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CHAPTER 1

Tumours of the Nasal Cavity and


Paranasal Sinuses

Although the nasal cavity and paranasal sinuses occupy a rel-


atively small anatomical space, they are the site of origin of
some of the more complex, histologically diverse group of
tumours in the entire human body. These include neoplasms
derived from mucosal epithelium, seromucinous glands, soft
tissues, bone, cartilage, neural/neuroectodermal tissue,
haematolymphoid cells and the odontogenic apparatus. Many
of the tumours are similar to those found elsewhere in the body
but a few, such as the olfactory neuroblastoma, are unique to
this site.
WHO histological classification of tumours of the nasal cavity and
paranasal sinuses
Malignant epithelial tumours Benign tumours
Squamous cell carcinoma 8070/3 Myxoma 8840/0
Verrucous carcinoma 8051/3 Leiomyoma 8890/0
Papillary squamous cell carcinoma 8052/3 Haemangioma 9120/0
Basaloid squamous cell carcinoma 8083/3 Schwannoma 9560/0
Spindle cell carcinoma 8074/3 Neurofibroma 9540/0
Adenosquamous carcinoma 8560/3 Meningioma 9530/0
Acantholytic squamous cell carcinoma 8075/3
Lymphoepithelial carcinoma 8082/3 Tumours of bone and cartilage
Sinonasal undifferentiated carcinoma 8020/3 Malignant tumours
Adenocarcinoma Chondrosarcoma 9220/3
Intestinal-type adenocarcinoma 8144/3 Mesenchymal chondrosarcoma 9240/3
Non-intestinal-type adenocarcinoma 8140/3 Osteosarcoma 9180/3
Salivary gland-type carcinomas Chordoma 9370/3
Adenoid cystic carcinoma 8200/3 Benign tumours
Acinic cell carcinoma 8550/3 Giant cell lesion
Mucoepidermoid carcinoma 8430/3 Giant cell tumour 9250/1
Epithelial-myoepithelial carcinoma 8562/3 Chondroma 9220/0
Clear cell carcinoma N.O.S. 8310/3 Osteoma 9180/0
Myoepithelial carcinoma 8982/3 Chondroblastoma 9230/0
Carcinoma ex pleomorphic adenoma 8941/3 Chondromyxoid fibroma 9241/0
Polymorphous low-grade adenocarcinoma 8525/3 Osteochondroma (exostosis) 9210/0
Neuroendocrine tumours Osteoid osteoma 9191/0
Typical carcinoid 8240/3 Osteoblastoma 9200/0
Atypical carcinoid 8249/3 Ameloblastoma 9310/0
Small cell carcinoma, neuroendocrine type 8041/3 Nasal chondromesenchymal hamartoma

Benign epithelial tumours Haematolymphoid tumours


Sinonasal papillomas Extranodal NK/T cell lymphoma 9719/3
lnverted papilloma Diffuse large B-cell lymphoma 9680/3
(Schneiderian papilloma, inverted type) 8121/1 Extramedullary plasmacytoma 9734/3
Oncocytic papilloma Extramedullary myeloid sarcoma 9930/3
(Schneiderian papilloma, oncocytic type) 8121/1 Histiocytic sarcoma 9755/3
Exophytic papilloma Langerhans cell histiocytosis 9751/1
(Schneiderian papilloma, exophytic type) 8121/0
Salivary gland-type adenomas Neuroectodermal
Pleomorphic adenoma 8940/0 Ewing sarcoma 9260/3
Myoepithelioma 8982/0 Primitive neuroectodermal tumour 9364/3
Oncocytoma 8290/0 Olfactory neuroblastoma 9522/3
Melanotic neuroectodermal tumour of infancy 9363/0
Soft tissue tumours Mucosal malignant melanoma 8720/3
Malignant tumours
Fibrosarcoma 8810/3 Germ cell tumours
Malignant fibrous histiocytoma 8830/3 Immature teratoma 9080/3
Leiomyosarcoma 8890/3 Teratoma with malignant transformation 9084/3
Rhabdomyosarcoma 8900/3 Sinonasal yolk sac tumour (endodermal sinus tumour) 9071/3
Angiosarcoma 9120/3 Sinonasal teratocarcinosarcoma
Malignant peripheral nerve sheath tumour 9540/3 Mature teratoma 9080/0
Borderline and low malignant potential tumours Dermoid cyst 9084/0
Desmoid-type fibromatosis 8821/1
Inflammatory myofibroblastic tumour 8825/1 Secondary tumours
Glomangiopericytoma
(Sinonasal-type haemangiopericytoma) 9150/1
Extrapleural solitary fibrous tumour 8815/1

__________
1
Morphology code of the International Classification of Diseases for Oncology (ICD-O) {821} and the Systematized Nomenclature of Medicine (http://snomed.org).
Behaviour is coded /0 for benign tumours, /3 for malignant tumours, and /1 for borderline or uncertain behaviour.

10 Tumours of the nasal cavity and paranasal sinuses


TNM classification of carcinomas of the nasal cavity and paranasal
sinuses
TNM classification 1,2 N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in
greatest dimension
TNM classification of carcinomas of the nasal cavity and sinuses # N2 Metastasis as specified in N2a, 2b, 2c below
T Primary tumour N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but
TX Primary tumour cannot be assessed not more than 6 cm in greatest dimension
T0 No evidence of primary tumour N2b Metastasis in multiple ipsilateral lymph nodes, none more than
Tis Carcinoma in situ 6 cm in greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none more
Maxillary sinus than 6 cm in greatest dimension
T1 Tumour limited to the antral mucosa with no erosion or destruction N3 Metastasis in a lymph node more than 6 cm in greatest dimension
of bone Note: Midline nodes are considered ipsilateral nodes.
T2 Tumour causing bone erosion or destruction, including extension
into hard palate and/or middle nasal meatus, except extension to M Distant metastasis
posterior antral wall of maxillary sinus and pterygoid plates MX Distant metastasis cannot be assessed
T3 Tumour invades any of the following: bone of posterior wall of M0 No distant metastasis
maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, M1 Distant metastasis
pterygoid fossa, ethmoid sinuses
T4a Tumour invades any of the following: anterior orbital contents, skin Stage grouping
of cheek, pterygoid plates, infratemporal fossa, cribriform plate, Stage 0 Tis N0 M0
sphenoid or frontal sinuses Stage I T1 N0 M0
T4b Tumour invades any of the following: orbital apex, dura, brain, Stage II T2 N0 M0
middle cranial fossa, cranial nerves other than maxillary division of Stage III T1, T2 N1 M0
trigeminal nerve V2, nasopharynx, clivus T3 N0, N1 M0
Stage IVA T1, T2, T3 N2 M0
Nasal cavity and ethmoid sinus T4a N0, N1, N2 M0
T1 Tumour restricted to one subsite of nasal cavity or ethmoid sinus, Stage IVB T4b Any N M0
with or without bony invasion Any T N3 M0
T2 Tumour involves two subsites in a single site or extends to involve Stage IVC Any T Any N M1
an adjacent site within the nasoethmoidal complex, with or without
bony invasion
T3 Tumour extends to invade the medial wall or floor of the orbit,
maxillary sinus, palate, or cribriform plate
T4a Tumour invades any of the following: anterior orbital contents, skin
of nose or cheek, minimal extension to anterior cranial fossa,
pterygoid plates, sphenoid or frontal sinuses
T4b Tumour invades any of the following: orbital apex, dura, brain,
middle cranial fossa, cranial nerves other than V2, nasopharynx,
clivus

N Regional lymph nodes 3


NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis

__________
1
{947,2418}.
2
A help desk for specific questions about the TNM classification is available at www.uicc.org/index.php?id=508 .
3 The regional lymph nodes are the cervical nodes

WHO and TNM classification 11


Tumours of the nasal cavity and L. Barnes
L.L.Y. Tse
M. Brandwein-Gensler
H.D. Curtin
paranasal sinuses: Introduction J.L. Hunt P. Boffetta

Anatomy formed by the perpendicular plate of the sinonasal tumour stage - violation of the
ethmoid bone posteriorly and the septal cribriform plate signifies direct extension
The nasal cavities are separated in the cartilage anteriorly. The vomer completes of the tumour into the anterior cranial
midline by the nasal septum. Each cavity the posteroinferior portion of the septum. fossa. The crista galli is a distinctive
is wide caudally, and narrow cranially. The septum is lined by relatively thin, cil- pointed bony landmark that extends from
The roof of the nasal cavity is formed by iated respiratory mucosa, which may the midline of the cribriform plate upward
the thin (0.5 mm) cribriform plate. The regularly undergo squamous metaplasia. into the floor of the anterior cranial fossa.
floor is the hard palate, formed by the The underlying thin lamina propria, The perpendicular plate of the ethmoid
palatine processes of the maxillae and although containing seromucinous bone extends downward from the cribri-
the horizontal portions of the palatine glands, is tethered to the septal carti- form plate to contribute to the nasal sep-
bones. The lateral nasal wall contains the lage, restricting reactive polyp formation. tum. The medial wall of each ethmoid
maxillary and ethmoid ostia, plus three or labyrinth is formed by a thin lamella of
four turbinates. These turbinates are del- The frontal sinus bone from which arise the middle, supe-
icate scroll-like projections of bone and These paired sinuses reside between the rior, and supreme turbinates. The lateral
vascular soft tissue that become smaller internal and external cranial tables and ethmoid wall is formed by the thin lamina
as they ascend in the nasal cavity. They drain either via a nasofrontal duct into the papyracea, which separates the ethmoid
attach to the lateral nasal wall anteriorly, frontal recess or more directly into the cells from the orbit. This is yet another
and have a free edge posteriorly. The anterior infundibulum, or less often, into important landmark for tumour staging.
turbinates are covered with a thick the anterior ethmoid cells, which in turn Tumour violation of the lamina papyracea
mucous membrane and contain a dense, will open into the infundibulum of the may necessitate including the orbit and
thick-walled venous plexus. The upper bulla ethmoidalis. globe with the surgical resection. This
margins of the nasal fossa are bound lat- area should be sampled in a maxillecto-
erally by the superior nasal turbinate and Ethmoid complex my specimen a) if the globe has not been
adjacent lateral nasal wall, and medially This paired complex of sinuses contains removed (as the lamina papyracea rep-
by the nasal septum. This region is the 3-18 cells that are grouped as anterior, resents the lateral orbital margin), or b) if
olfactory recess and it has a yellowish middle, or posterior, according to the orbital exenteration has been performed.
epithelium, the olfactory mucosa (OM). location of their ostia. There is an inverse The roof of the ethmoid complex is
This mucosa contains bipolar olfactory relationship between the number and formed by a medial extension of the
nerve fibers that cross through the cribri- size of the cells. Generally, the posterior orbital plate of the frontal bone, which
form plate. The terminal axons of the cells are both larger and fewer than the projects to articulate with the cribriform
olfactory nerves extend to the free sur- anterior cells. Each ethmoid labyrinth lies plate. This is often referred to as the
face of the epithelium, where they between the orbit and the upper nasal fovea ethmoidalis.
expand into knob-like protrusions bear- fossa. The left and right groups of eth-
ing cilia (olfactory cilia). Bowmans moid cells are connected in the midline Sphenoid sinus
glands, or olfactory glands, within the by the cribriform plate (nasal roof) of the The average adult sphenoid sinus meas-
lamina propria appear similar to serous ethmoid bone. The cribriform plate is an ures 20 mm high, 23 mm long, and 17
minor salivary glands. important landmark in evaluation of mm wide. The relationship of the posteri-
The nasal cavity and paranasal sinuses or extension of the sphenoid in relation to
are lined by Schneiderian mucosa, con- the sella turcica is variable. The sphe-
sisting of pseudostratified columnar cili- noid sinus septum is usually in the mid-
ated epithelium with interspersed goblet line, and anteriorly aligned with the nasal
cells. The lamina propria within the septum. However, it can also deviate far
paranasal sinuses, especially the maxil- to one side creating two unequal sinus
lary antrum, is loose and well vascular- cavities. With the exception of the sinus
ized, with seromucinous glands, and can roof, the other sinus walls are of variable
easily become polypoid as a result of thickness depending on the degree of
edema. The goblet cell component of the pneumatization. The sphenoid roof is
mucosal surface and seromucinous thin, often measuring only 1 mm. (planum
glands is variable. In chronic sinusitis, sphenoidale), and is vulnerable to perfo-
goblet cell hyperplasia can result in a Fig. 1.1 Normal coronal T1 WI shows foramen ration during surgery. The sinus roof
papillary mucosal lesion. rotundum (white arrow) and entrance to the Vidian relates to the floor of the anterior cranial
The major portion of the nasal septum is canal (black arrow). fossa, anteriorly; the optic chiasm and

12 Tumours of the nasal cavity and paranasal sinuses


the sella turcica, posteriorly. The lateral
sphenoid wall is related to the orbital
apex, the optic canal, the optic nerve,
and the cavernous sinus, containing the
internal carotid artery. The sinus floor is
the roof of the nasopharynx, and the
anterior sinus wall is the back of the
nasal fossa.

Maxillary sinus
The maxillary sinus lies within the body of
Fig. 1.2 Malignancy of ethmoid and nasal cavity. Fig. 1.3 Malignancy of upper nasal cavity invading
the maxillary bone. Behind the orbital Coronal CT with contrast. The tumour erodes the orbital fat and extending intracranially. The tumour
rims, each sinus roof/orbital floor slants cribriform plate and fovea ethmoidalis (white (white arrow) extends through the roof of the eth-
obliquely upward so that the highest arrowhead). The lamina papyracea is eroded (black moid and along the roof of the orbit (white arrow-
point of the sinus is in the posteromedial arrowhead) but the fat (white arrow) medial to the head). The tumour bulges (black arrow) the perior-
portion, lying directly beneath the orbital medial rectus (MR) is normal. The orbital fat is not bita near the medial rectus but breaks through into
apex. The medial antral wall is the inferi- invaded. The margin (black arrow) of the tumour in the orbital fat more superiorly (black arrowhead).
or lateral wall of the nasal cavity (party the maxillary sinus is separable from the obstructed Note that the tumour enhances intermediately and
wall). The curved posterolateral wall secretions because of different densities. less intensely than the mucosa.
separates the sinus from the infratempo-
ral fossa. The anterior sinus wall is the
facial surface of the maxilla that is perfo- sinuses {2378}. Malignant neoplasms of and sinonasal cancer, in particular squa-
rated by the infraorbital foramen below this region may lead to significant mor- mous cell carcinoma. Exposure to
the orbital rim. The floor of the sinus is bidity and disfigurement. Thorotrast, a radioactive contrast agent,
lowest near the second premolar and The incidence of cancer of the nasal cav- represents an additional risk factor.
first molar teeth and usually lies 3-5 mm ity and paranasal sinuses (sinonasal
below the nasal floor. The lower expan- cancer) is low in most populations
sion of the antrum is intimately related to (<1.5/100,000 in men and <1.0/100,000 Imaging
dentition. The location of the maxillary in women). Higher rates are recorded in
sinus ostia, is high on the medial wall. Japan and certain parts of China and Modern imaging plays a key role in the
They drain through the ethmoidal India. Squamous cell carcinomas are the evaluation of sinonasal tumours {2423}.
infundibulum and then the nasal fossa. commonest. Time trends have shown in The anatomy of the lesion can be defined
This pattern of drainage in the erect posi- most populations a stable incidence or a with the exact margins clearly delineated
tion is accomplished by intact ciliary small decline in recent decades. in almost every case. Imaging is a domi-
action. The maxillary hiatus is a bony nant factor in determining surgical
window leading to the interior of the max- approach and is an integral part of radi-
illary sinus. The hiatus is normally partial- Etiology ation therapy planning. Computed
ly covered by portions of four bones: the tomography (CT) and magnetic reso-
perpendicular plate of the palatine bone, Occupational exposure to wood dust, in nance imaging (MRI) provide significant
posteriorly; the lacrimal bone, anterosu- particular to dust of hard woods such as information about the texture, the mar-
periorly; the inferior turbinate, inferiorly, beech and oak, is the main known risk gins, the effect on bone and even the
and above the turbinate attachment, the factor for sinonasal cancer. The increase vascularity. In addition, some findings
uncinate process of the ethmoid bone. in risk (in the order of 5-50 fold) is are typical for a particular diagnosis, and
strongest for adenocarcinomas and for although biopsy is still required for ascer-
cancers originating from the sinuses. The taining the nature of the lesion, the imag-
Epidemiology effect is present after 40 or more years ing appearance may help limit the list of
since first exposure and persists after differential diagnoses.
Carcinomas of the nasal cavity and cessation of exposure. An increased risk
paranasal sinuses account for 0.2-0.8% of sinonasal cancer has been shown Staging and surgical planning
of all malignant neoplasms and 3% of among workers in nickel refining and The spread of a sinonasal tumour
those occurring in the head and neck chromate pigment manufacture, but not intracranially or into the orbit and the
{169,2378}. Sixty percent of sinonasal among workers exposed to these metals relationship of tumour to the optic nerve
tumours originate in the maxillary sinus, in other processes, such as plating and and carotid artery are important features
20-30% in the nasal cavity, 10-15% in the welding. Among other suspected occu- that can be delineated with imaging.
ethmoid sinus, and 1% in the sphenoid pational carcinogens are formaldehyde, Tumour can invade the orbit through the
and frontal sinuses {1493,2186}. When diisopropyl sulfate and dichloroethyl sul- lamina papyracea or the roof of the max-
considering the paranasal sinuses alone, fide. illary sinus. Even if the bony wall is
77% of malignant tumours arise in the A relatively weak (relative risks in the apparently destroyed, orbital fat may not
maxillary sinus, 22% in the ethmoid sinus range 2-5) but consistent association has be invaded {515}. A smooth bowing of
and 1% in the sphenoid and frontal been shown between tobacco smoking the soft tissue interface with the orbital fat

Introduction 13
A B
Fig. 1.4 Sinonasal polyps with multiple obstructed sinuses. A Axial T1 WI after intravenous gadolinium. The Fig. 1.5 Sinonasal polyps. Coronal T2WI. The
enhancing mucosa (arrowheads) lines the obstructed sphenoid sinus (S). The sinus was also dark on T2WI secretions in the sinus (S) are dark indicating high
indicating high protein and long standing obstruction. B Coronal T1WI shows cascading polyps filling the protein desiccated secretions. Compare to high
nasal cavity. The secretions in the maxillary sinus (S) are dark and the lining mucosa (white arrowhead) is signal of the edematous mucosa. Intact nasal sep-
visible. The nasal septum (black arrow) is intact. Hard palate - (black arrowhead), minor salivary glands at tum (black arrow), crista galli (white arrow).
roof of mouth (G), olfactory bulb (white arrow).

suggests that the lesion is contained by Radiographic signs the nasal cavity or the medial maxillary
periorbital fascia. Infiltration or irregulari- Bone changes can give an indication of sinus {534}. In the lower maxilla, odonto-
ty of this margin suggests extension into the aggressiveness of a tumour {2038}. genic lesions should be considered.
the fat or true orbital invasion. The thin In general, slowly growing lesions, such Such lesions arise in the bone of the
line of fat between the medial rectus as Schneiderian papillomas, appear to alveolar process and as they grow ele-
muscle and the lamina papyracea is a push bone as they slowly remodel the vate the floor of the maxillary sinus. Fibro-
key landmark in the evaluation of orbital osseous structure. More aggressive osseous lesions enter the differential
extension of ethmoid neoplasms. lesions, such as squamous cell carcino- diagnosis when a radiodense lesion aris-
The key landmarks for the assessment of ma, can aggressively destroy bony walls es from or follows the contour of bone.
intracranial extension of tumour are the leaving only a few remaining fragments Correlation of imaging studies with histo-
roof of the ethmoid, the cribriform plate {2425}. Occasionally, however, malignant logic appearance is crucial in the evalu-
and the crista galli. Elevation or frank lesions can cause bowing rather than ation of bony lesions.
invasion of the dura may be evaluated infiltrating destruction of bone {2424}.
using MRI. The integrity of the thin plates of bone in
A tumour in the maxillary sinus region the ethmoid sinus as well as the bony
may extend posteriorly and laterally walls of the sphenoid sinus and the bony
through the bony wall into the ptery- nasal septum also suggests that malig-
gopalatine fossa and the infratemporal nancy is unlikely.
fossa. Tumour can invade the ptery- Mineralization can be seen in several
gopalatine fossa area either by direct tumours, such as ring-like calcifications
extension or by following the nerves. in cartilage lesions as well as calcifica-
From there, perineural extension of tions in olfactory neuroblastomas {2130}.
tumour in the foramen rotundum and Meningioma can cause hyperostosis and
Vidian canal may result in intracranial can also calcify.
spread {516}. Tumour location plays a significant role in
Tumour may spread from the sphenoid differential diagnosis. Tumours in the
sinus region, laterally into the cavernous region of the cribriform plate and upper
sinus through the very thin layer of bone nasal cavity suggest diagnoses such as
separating these two structures. If the olfactory neuroblastoma or meningioma.
bone is intact, the tumour is likely con- Inverted Schneiderian papilloma occurs
tained within the sinus. predominantly along the lateral wall of

14 Tumours of the nasal cavity and paranasal sinuses


Squamous cell carcinoma B.Z. Pilch
J. Bouquot
L.D.R. Thompson

Definition tumours and only about 3% of malignan- {131,502}. Squamous cell carcinoma of
A malignant epithelial neoplasm originat- cies of the head and neck {169,2758}. the nasal vestibule should be considered
ing from the mucosal epithelium of the The disease appears to be more com- a carcinoma of the skin rather than
nasal cavities or paranasal sinuses that mon in Japan than in the West {2205}. It sinonasal mucosal epithelium {2566}.
includes a keratinizing and a non-kera- is extremely rare in children, and men are
tinizing type. more commonly affected (about 1.5 Clinical features
times) than women. Patients are general- Symptoms include nasal fullness, stuffi-
ICD-O codes ly about 55-65 years of age {502,2758}. ness, or obstruction; epistaxis; rhinor-
Squamous cell carcinoma 8070/3 rhea; pain; paraesthesia; fullness or
Verrucous carcinoma 8051/3 Etiology swelling of the nose or cheek or a palatal
Papillary squamous cell carcinoma Reported risk factors have included bulge; a persistent or non-healing nasal
8052/3 exposure to nickel, chlorophenols, and sore or ulcer; nasal mass; or, in
Basaloid squamous cell carcinoma textile dust, prior Thorotrast instillation, advanced cases, proptosis, diplopia, or
8083/3 smoking, and a history or concurrence of lacrimation {131,502,2758}. Radiologic
Spindle cell carcinoma 8074/3 sinonasal (Schneiderian) papilloma. studies such as CT scan or MRI may
Adenosquamous carcinoma Human papillomavirus (HPV) has been delineate the extent of the lesion, the
8560/3 found in some cases, especially those presence of bony invasion, and exten-
Acantholytic squamous cell associated with inverted Schneiderian sion to neighbouring structures such as
carcinoma 8075/3 papilloma {303}, but a definite etiologic the orbit, pterygopalatine or infratempo-
role has not been clearly established. ral spaces.
Synonyms Formaldehyde, despite the results of ani-
Keratinizing squamous cell carcinoma: mal experiments, has not been found to Macroscopy
squamous cell carcinoma. be a definite risk factor in humans Sinonasal squamous cell carcinomas
Nonkeratinizing carcinoma: Schneider- {502,1443,1571,2205,2904}. may be exophytic, fungating, or papil-
ian carcinoma, cylindrical cell carcino- lary; friable, haemorrhagic, partially
ma, transitional (cell) carcinoma, Localization necrotic, or indurated; demarcated or
Ringertz carcinoma, respiratory epithelial Sinonasal squamous cell carcinomas infiltrative.
carcinoma. occur most frequently in the maxillary
sinus (about 60-70%), followed by the Tumour spread and staging
Epidemiology nasal cavity (about 12-25%), ethmoid Nasal cavity carcinomas can spread to
Sinonasal squamous cell carcinoma is sinus (about 10-15%) and the sphenoid adjacent sites in the nasal cavity or to the
rare, accounting for <1% of malignant and frontal sinuses (about 1%) ethmoid sinus, or can extend to involve

A B
Fig. 1.6 A Non-keratinizing papillary squamous cell carcinoma. Multiple complex papillary projections lined by thickened epithelium. Lymphocytic response is pres-
ent at the pushing border of infiltration. B Squamous cell carcinoma, non-keratinizing. Islands of cohesive tumour cells invading into the underlying stroma. Surface
carcinoma in-situ is seen.

Squamous cell carcinoma 15


A B
Fig. 1.7 A Nasal verrucous carcinoma "Church-spire" type hyperkeratosis, parakeratosis and a broad pushing border of infiltration in a non-atypical epithelium sup-
port the diagnosis. B Basaloid squamous cell carcinoma. A characteristic feature is the presence of comedonecrosis in the center of the neoplastic lobules.
Surface is ulcerated.

the contralateral nasal cavity, bone, max- form or ribbon-like growth pattern. It exophytic mass of very well-differentiat-
illary sinus, palate, skin and soft tissues invades into the underlying tissue with a ed, keratinized epithelium {899,1955,
of the nose, lip, or cheek, cribriform smooth, generally well-delineated bor- 2118,2278}. The maxillary sinus is the
plate, or cranial cavity. Maxillary sinus der. Therefore, definite evidence of stro- most common site, followed by the nasal
carcinomas may spread to the nasal cav- mal invasion may be difficult to appreci- fossa. Rare nasopharyngeal lesions have
ities, palate, other paranasal sinuses, ate, although a degree of invasion by encroached on the nasal sinus
skin or soft tissues of the nose or cheek, irregular small nests or strands may be {1199,1872}.
orbit, cranial contents, or the ptery- present. There is typically a lack of matu- Papillary squamous cell carcinoma
gopalatine and infratemporal spaces ration in the epithelial nests or ribbons, {2488} is an exophytic squamous cell
{131,2418}. Lymph node metastases are as in transitional cell carcinoma of the uri- carcinoma with a papillary configuration
less common than in squamous cell car- nary tract, which this tumour subtype composed of thin fingers of tumour sur-
cinomas of other sites in the head and resembles. Cytologic atypia is present to rounding fibrovascular cores.
neck. a significant degree. As its name implies, Basaloid squamous cell carcinoma is
this tumour does not generally evince uncommon in the sinonasal tract {2786}.
Histopathology histologic evidence of keratinization, It is an aggressive variant of squamous
Keratinizing squamous cell carcinoma although some degree may be seen. cell carcinoma that is characterized by
This tumour is histologically identical to When keratinization is significant, there is rounded nests of cytologically highly
squamous cell carcinomas of other morphologic overlap with keratinizing atypical and mitotically-active basaloid
mucosal sites in the head and neck. squamous cell carcinoma. Occasional epithelial cells, with high nuclear/cyto-
There is histologic evidence of squa- mucus-containing cells can be seen. The plasmic ratios and hyperchromatic
mous differentiation, in the form of extra- tumour may be moderately or poorly dif- nuclei. There is often comedo-type
cellular keratin or intracellular keratin ferentiated; the latter type is difficult to necrosis. A pseudoglandular or strand-
(pink cytoplasm, dyskeratotic cells) recognize as squamous, and must be like arrangement, reminiscent of the
and/or intercellular bridges. Tumour cells differentiated from olfactory neuroblas- architecture of an adenoid cystic carci-
are generally apposed to one another in tomas or neuroendocrine carcinomas. noma, is often present, as is the produc-
a mosaic tile arrangement. The tumour tion of basement membrane-like materi-
may be arranged in nests, masses, or as Variants of squamous cell carcinoma al. Squamous differentiation is invariably
small groups of cells or individual cells. Variants of squamous cell carcinoma are present, either in basaloid nests, as sep-
Invasion occurs as blunt projections or rare in the sinonasal tract. They are simi- arate foci of tumour, or as surface epithe-
ragged, irregular strands. There is often lar to the analogous tumours occurring lial carcinoma or carcinoma in-situ.
a desmoplastic stromal reaction. The with greater frequency in other sites in Spindle cell carcinoma is characterized
carcinomas may be well, moderately, or the head and neck and are more com- by a biphasic pattern of squamous cell
poorly differentiated. pletely described in the corresponding carcinoma as well as a generally much
sections. larger component of malignant spindled
Non-keratinizing (cylindrical cell, transi- Verrucous carcinoma of the nasal and cells, reminiscent of a sarcoma. The
tional) carcinoma paranasal sinuses is very rare. It is a low- squamous component may be scant or
This is a distinctive tumour of the grade variant of squamous cell carcino- even inapparent on light microscopy. In
sinonasal tract characterized by a plexi- ma characterized by a papillary or warty the latter circumstance, immunohisto-

16 Tumours of the nasal cavity and paranasal sinuses


chemical or ultrastructural evidence of
epithelial differentiation is required for the
diagnosis. The spindle cell component is
characteristically immunohistochemically
vimentin-positive, and keratin positivity
may be scant, difficult to demonstrate, or
even absent.
Adenosquamous carcinoma is uncom-
mon in the sinonasal tract, and is more
completely described in the sections on
oral and laryngeal tumours. Briefly, it is
generally considered as a variant of
squamous cell carcinoma in which a sur-
face mucosal component of squamous
cell carcinoma is present. There is also a
component of carcinoma with definite
glandular differentiation in the form of
ductules or tubules, often intimately
admixed with the squamous cell carcino-
ma. The mere presence of intracellular
mucin is not sufficient for the diagnosis. Fig. 1.8 Schneiderian papilloma with keratinization is associated with an area of malignant transformation
into a squamous cell carcinoma with severe cytologic atypia.
Acantholytic squamous cell carcinoma is
exceedingly rare in the sinonasal tract.

Precursor lesions Prognosis and predictive factors to be large and extensive when diag-
Precursor lesions for sinonasal squa- Patients with nasal squamous cell carci- nosed. Prognosis correlates with stage.
mous cell carcinomas are considerably nomas generally present earlier than Patients with the non-keratinizing type of
less well defined than for oral or laryn- patients with maxillary cancers and, not carcinoma tend to do better than those
geal carcinomas. The sinonasal surprisingly, fare better than the latter with the keratinizing type {502}. The over-
Schneiderian (inverted) papilloma group. Nasal squamous cell carcinomas all 5-year survival of patients with maxil-
appears to be a precursor lesion; the fre- rarely metastasize to lymph nodes, and lary sinus squamous carcinoma is about
quency of association has been estimat- recurrences, when they occur, do so 42% {131}.
ed at about 10% {173}. Although squa- quickly {131}. Advanced local disease
mous metaplasia may precede the worsens the prognosis. The overall 5-
development of sinonasal squamous year survival for nasal squamous cell
carcinoma, a predisposing role for such carcinomas is about 60%. Squamous
metaplasia in the development of carci- carcinomas of the maxillary sinus have a
noma has not been clearly established. more ominous prognosis. They are likely

Squamous cell carcinoma 17


Lymphoepithelial carcinoma W.Y.W. Tsang
J.K.C. Chan

Definition are more common in the nasal cavity nent than that seen in nasopharyngeal
Lymphoepithelial carcinoma is a poorly than in the paranasal sinuses, although carcinoma. In some cases, the inflamma-
differentiated squamous cell carcinoma both sites may be involved simultaneous- tory cells may even be sparse
or histologically undifferentiated carcino- ly. The tumours may show local invasion {1216,1480}. The epithelial nature of the
ma accompanied by a prominent reac- of the palate, orbit, and base of skull. tumour can be confirmed by immunos-
tive lymphoplasmacytic infiltrate, mor- taining for pan-cytokeratin and epithelial
phologically similar to nasopharyngeal Clinical features membrane antigen. EBV encoded RNA
carcinoma. Patients present with nasal obstruction, (EBER) is strongly expressed by the
bloody nasal discharge or epistasis. tumour cells in most cases
ICD-O code 8082/3 Intracranial extension of tumour may {801,1216,1480,1558,2910}.
cause proptosis and cranial nerve palsy
Synonyms {1216,1480}. There may be cervical Differential diagnosis
Undifferentiated carcinoma; undifferenti- lymph node and/or distant metastasis at Sinonasal lymphoepithelial carcinoma
ated carcinoma with lymphocytic stroma; presentation. Examination and biopsy of must be distinguished from the vastly
undifferentiated carcinoma of nasopha- the nasopharynx is required to exclude more aggressive sinonasal undifferentiat-
ryngeal type; lymphoepithelioma-like loco-regional spread from a primary ed carcinoma (SNUC). The presence of
carcinoma nasopharyngeal carcinoma. lymphoplasmacytic infiltrates, although
helpful, cannot be relied on solely in
Epidemiology Histopathology making the distinction. SNUC is charac-
Sinonasal lymphoepithelial carcinoma is The tumour infiltrates the mucosa in the terized by tumour cells with nuclear pleo-
rare, and most reported cases have orig- form of irregular islands and sheets, usu- morphism, high mitotic rate and frequent
inated from Southeast Asia, where ally without a desmoplastic stroma. The necrosis. EBV status is also helpful since
nasopharyngeal carcinoma is also tumour cells possess relatively monoto- SNUC, except for rare cases from
prevalent {1216,1480,1558,2910}. It nous vesicular nuclei with prominent Asians, are EBV-negative {1216,1480,
affects adults in the fifth to seventh nucleoli. The cytoplasm is lightly 1558}. Other important differential diag-
decades, and there is a male predomi- eosinophilic, with indistinct cell borders, noses are malignant melanoma and non-
nance of approximately 3:1. resulting in a syncytial appearance. The Hodgkin lymphoma.
tumour cells may also appear plump
Etiology spindly, with streaming of nuclei. Prognosis and predictive factors
Nearly all sinonasal lymphoepithelial car- Intraepithelial spread of tumour may The tumour responds favourably to local-
cinomas show a strong association with sometimes be seen in the overlying regional radiotherapy even in the pres-
Epstein-Barr virus (EBV) epithelial lining. Necrosis and keratiniza- ence of cervical lymph node metastasis
{801,1216,1480,1558,2910}. tion are usually not evident. The tumour is {623,1216,1480}. Distant metastasis
infiltrated by variable numbers of lym- (most often to bone), however, is associ-
Localization phocytes and plasma cells. In general, ated with a poor prognosis.
Sinonasal lymphoepithelial carcinomas the inflammatory infiltrate is less promi-

A B
Fig. 1.9 Primary lymphoepithelial carcinoma of the nasal cavity. A The intimate intermingling of the carcinoma cells with lymphoid cells imparts a lymphoma-like
appearance. B Large carcinoma cells with indistinct cell borders, vesicular nuclei and prominent nucleoli are admixed with numerous small lymphocytes..

18 Tumours of the nasal cavity and paranasal sinuses


Sinonasal undifferentiated carcinoma H.F. Frierson, Jr.

Definition sinus symptoms, usually of relatively Immunohistochemistry


A highly aggressive and clinicopatholog- short duration, including nasal obstruc- The carcinoma is immunoreactive for
ically distinctive carcinoma of uncertain tion, epistaxis, proptosis, periorbital pan-cytokeratins and simple keratins
histogenesis that typically presents with swelling, diplopia, facial pain, and symp- (CK7, CK8 and CK19), but not CK4,
locally extensive disease. It is composed toms of cranial nerve involvement. CK5/CK6 and CK14 {801}. Less than half
of pleomorphic tumour cells with fre- of the cases have been reported to be
quent necrosis, and should be differenti- Macroscopy positive for epithelial membrane antigen,
ated from lymphoepithelial carcinoma The tumour is usually larger than 4 cm. It neuron specific enolase, or p53 {350}.
and olfactory neuroblastoma. is fungating, with poorly defined margins, The tumour is negative for CEA, while
bone destruction, and invasion of adja- positivity for synaptophysin, chromo-
ICD-O code 8020/3 cent structures {2038}. granin, or S100 protein is only rarely
observed {350,1216}.
Synonym Tumour spread and staging
Anaplastic carcinoma In addition to involvement of multiple Electron microscopy
sinuses, the neoplasm destroys sinus Ultrastructurally, cells with occasional
Epidemiology walls and orbital bones. Penetration into small desmosomes and rare dense core
The tumour is rare, with fewer than 100 the cranial cavity is frequent. Less often, granules have been noted {819}.
reported cases. The age range is broad there is extension into the nasopharynx
(third to ninth decade), and the median or oral cavity. The tumour can metasta- Histogenesis
age is in the sixth decade {350,1216}. size to cervical lymph nodes and distant This is a tumour of uncertain histogene-
There is a male predominance (2-3:1). sites (such as liver, lung, bone) {1216}. sis, but with unique clinicopathologic
characteristics. It should be differentiat-
Etiology Histopathology ed from other specific types of carcino-
The neoplasm is typically negative for Sinonasal undifferentiated carcinoma ma and non-epithelial tumours with
Epstein-Barr virus {350,1216}. Some forms nests, lobules, trabeculae and round cells.
cases have occurred after prior radiation sheets, in the absence of squamous or
therapy for nasopharyngeal carcinoma glandular differentiation. Severe dyspla- Prognosis and predictive factors
{1216}. sia of the overlying surface epithelium Despite aggressive management, the
has been noted in a few instances. prognosis is poor, with median survival of
Localization The nuclei are medium to large-sized, less than 18 months {350,1216}, and 5-
The nasal cavity, maxillary antrum, and surrounded by small amounts of year survival of less than 20% {856}.
ethmoid sinus are typically involved eosinophilic cytoplasm that lacks a syn- Recent results suggest that more promis-
alone or in combination. The neoplasm cytial quality. The nucleoli are variable in ing outcome may be achieved by com-
also commonly extends to other contigu- size, but most often, they are single and bining chemoradiation and radical resec-
ous sites. prominent. The mitotic rate is very high tion {1802}.
and there is often prominent tumour
Clinical features necrosis and apoptosis. Lymphovascular
Patients have multiple nasal/paranasal invasion is often prominent.

A B C
Fig. 1.10 Sinonasal undifferentiated carcinoma. A Small nests of tumour cells with or without interconnections are frequently observed. B The cells usually have
prominent nucleoli. The mitotic rate is high. C Conspicuous invasion of vascular spaces.

Sinonasal undifferentiated carcinoma 19


Adenocarcinoma A. Franchi
M. Santucci
B.M. Wenig

These are glandular malignancies of the sinonasal malignancies is difficult to Localization


sinonasal tract, excluding defined types ascertain. Most series report a pro- ITACs involve the ethmoid sinus, nasal
of salivary gland carcinoma. Two main nounced male predominance, possibly cavities and maxillary sinus in approxi-
categories are recognized: (1) intestinal- because of occupational exposure. mately 40%, 27% and 20% of cases,
type adenocarcinoma, and (2) non-intes- Patients have ranged in age from 12 to respectively. In the nasal cavities, the
tinal-type adenocarcinoma, which can 86 years at the time of diagnosis (mean inferior and middle turbinates are the
be further divided into low-grade and 58 years) {124}. sites of predilection. For larger destruc-
high-grade subtypes. Overall, adenocar- tive lesions it may be impossible to
cinomas and salivary-type carcinomas Etiology ascertain the exact site of origin.
comprise 10-20% of all sinonasal primary The causal relationship of wood dust and Advanced tumours tend to invade the
malignant tumours. leather dust with the development of orbit, the pterygopalatine and infratem-
sinonasal ITACs has been established by poral fossae, and the cranial cavity.
several epidemiological studies from dif- About 10% of cases show lymph node
Intestinal-type ferent countries {1594}. In this setting, involvement at presentation {124,1341,
adenocarcinomas dust particle size is important because 2234}.
those smaller than 5 m reach the lower
Definition respiratory tract, while larger particles Clinical features
A primary malignant glandular tumour of are accumulated in the nasal mucosa. Most patients present with unilateral
the nasal cavity and paranasal sinuses However, the carcinogens involved in the nasal obstruction, rhinorrhea and epis-
histologically resembling adenocarcino- onset of ITACs in wood workers and taxis. Advanced tumours may cause
ma or adenoma of the intestines, or leather workers have not yet been clear- pain, neurologic disturbances, exoph-
exceptionally normal small intestinal ly identified. Biologically active sub- thalmos and visual disturbances.
mucosa. stances which can be present in wood
and leather dusts include alkaloids, Imaging
ICD-O code 8144/3 saponins, stilbenes, aldehydes, Computed tomography (CT) and mag-
quinones, flavonoids, resins, oil, steroids, netic resonance imaging (MRI) are used
Synonyms terpenes, fungal proteins, and tannins for diagnosis of early lesions, defining
Colonic-type adenocarcinoma, enteric- {1341}. the extent of disease and detection of
type adenocarcinoma. Association has also been reported for early recurrence. CT best shows sites of
agricultural workers, food manufacturers, bone destruction, while MRI best delin-
Epidemiology and motor-vehicle drivers among men, eates soft tissue extension {1537}.
The frequency of intestinal type adeno- and for textile occupations among
carcinomas (ITACs) among primary women {1443}.

A B
Fig. 1.11 Intestinal-type adenocarcinoma A Well differentiated intestinal type adenocarcinoma shows a papillary growth pattern and occasional tubular glands. B
Higher power view of a moderately differentiated intestinal type adenocarcinoma, showing glandular structures formed by cylindrical and goblet cells.

20 Tumours of the nasal cavity and paranasal sinuses


A B C
Fig. 1.12 Intestinal-type adenocarcinoma A Mucinous intestinal-type adenocarcinoma invading bone. The tumour has an alveolar architecture and strands of neo-
plastic cells with clear mucus-containing cytoplasm are present within mucus pools. B Mucinous intestinal-type adenocarcinoma showing small glands and solid
islands floating in abundant mucous substance. C Mucinous intestinal-type adenocarcinoma formed by signet ring cells.

Macroscopy growth with isolated tubule formation, Mucus extravasation may elicit an inflam-
ITACs present as an irregular exophytic marked increase in number of smaller matory response that can include multin-
pink or white mass bulging in the nasal cuboidal cells with nuclear pleomor- ucleated giant cells. {799}.
cavity or paranasal sinus, often with a phism, round vesicular nuclei, prominent The mixed type (transitional) is com-
necrotic friable appearance. Some nucleoli and increased mitotic figures. posed of an admixture of two or more of
lesions are gelatinous. Analogous to colonic adenocarcinoma, the previously defined patterns.
some ITACs are predominantly com- Irrespective of the histologic type, ITACs
Histopathology prised of abundant mucus and are clas- histologically simulate normal intestinal
Two classifications of ITACs have been sified as the mucinous type. The muci- mucosa and may include villi, Paneth
proposed. Barnes divided these tumours nous type (alveolar goblet cell and signet cells, enterochromaffin cells and muscu-
into 5 categories: papillary, colonic, ring) includes two growth patterns. In laris mucosae {1739}. In rare instances,
solid, mucinous and mixed. Kleinsasser one pattern, there are solid clusters of the tumour is so well differentiated that it
and Schroeder divided ITACs into four cells, individual glands, signet ring cells, is composed of well-formed villi lined by
categories: papillary tubular cylinder cell short papillary fronds with or without columnar cells resembling normal
(PTCC) types I-III (I = well-differentiated, fibrovascular cores; mucin is predomi- resorptive cells; in some cases, bundles
II = moderately-differentiated, III = poor- nantly intracellular and a mucomyxoid of smooth muscle cells resembling mus-
ly-differentiated) {799,804,1333}, alveo- matrix may be present. The other pattern cularis mucosae may also be identified
lar goblet type, signet-ring type and tran- shows the presence of large, well-formed under the villi.
sitional type. Either classification is glands distended by mucus and extra-
acceptable, but for simplicity the Barnes cellular mucin pools {799,804,1333}. In Immunohistochemistry
classification is preferred and will be the the latter type, pools of extracellular ITACs are diffusely positive for epithelial
one utilized in this description. The most mucin are separated by thin connective markers including pancytokeratin,
common histologic types seen in associ- tissue septa creating an alveolar type epithelial membrane antigen, B72.3, Ber-
ation with wood workers as well as in pattern. Predominantly cuboidal or gob- EP4, BRST-1, Leu-M1, and human milk
sporadic cases are the papillary and let tumour cells are present in single lay- fat globule (HMFG-2) {1687}. They show
colonic types {124,1333}. ers at the periphery of mucus lakes. CK20 positivity (73%) and variable CK7
The papillary type (papillary tubular
cylinder cell I or well-differentiated ade-
nocarcinoma), which accounts for Table 1.1 Classification and survival of intestinal-type adenocarcinoma
approximately 18% of cases, shows a
predominance of papillary architecture Barnes {124} Klesinsasser and Schroeder 3-year cumulative
{1333} survivalb
with occasional tubular glands, minimal
cytologic atypia, and rare mitotic figures. Papillary-type PTCC-Ia 82%
The colonic type (papillary tubular cylin-
der II or moderately-differentiated adeno- Colonic-type PTCC-II 54%
carcinoma), representing approximately
40% of cases, shows a predominance of Solid-type PTCC-III 36%
tubulo-glandular architecture, rare papil-
lae, increased nuclear pleomorphism Mucinous type Alveolar goblet 48%
and mitotic activity. Signet-ring 0%
The solid type (papillary tubular cylinder
Mixed Transitional 71%
III or poorly-differentiated adenocarcino-
ma), representing approximately 20% of aPTCC, papillary tubular cylinder cell
cases, shows a loss of differentiation, bSurvival data derived from Kleinsasser and Schroeder {1333}
characterized by solid and trabecular

Adenocarcinoma 21
reactivity (43% to 93% of cases) {800}. p16(INK4a). A close association Sinonasal non-intestinal-type
CDX-2, a nuclear transcription factor between TP53, p14(ARF) and adenocarcinoma
involved in the differentiation of intestinal p16(INK4a) gene deregulation has been
epithelial cells and diffusely expressed in found in tumours from individuals occu-
ICD-O code 8140/3
intestinal adenocarcinomas, is common- pationally exposed to dusts {2013}.
ly expressed in ITACs {800}. Information Synonyms
on CEA staining in ITACs is conflicting Prognosis and predictive factors Sinonasal low-grade adenocarcinoma,
{1687,2660}. Scattered or groups of Sinonasal ITACs are generally locally terminal tubulus adenocarcinoma,
chromogranin-positive cells are frequent- aggressive tumours with frequent local sinonasal tubulopapillary low-grade ade-
ly identified {1687}; these neuroen- failure (about 50% of cases), whereas nocarcinoma.
docrine cells may express a variety of metastasis to cervical lymph nodes and
hormone peptides, including serotonin, spread to distant sites are infrequent Definition
cholecystokinin, gastrin, somatostatin (about 10% and 20%, respectively) Adenocarcinomas arising in the
and leu-enkephalin {163}. {124,799,804,1333}. The 5-year cumula- sinonasal tract that are not of minor sali-
tive survival rate is around 40%, with vary gland origin and do not demon-
Electron microscopy most deaths occurring within 3 years. strate histopathologic features of the
ITAC demonstrates features of the intes- Since most patients present with sinonasal intestinal-type adenocarcino-
tinal epithelium {163}. Columnar cells advanced local disease, clinical staging ma. These adenocarcinomas are divided
present regular microvilli with cores of generally has no relevant prognostic sig- into low- and high-grade subtypes.
microfilaments that combine to form a nificance.
band that inserts into the zonula The histologic subtype has been identi- Epidemiology
adherens of the junctional complexes. fied as indicative of clinical behaviour in Sinonasal non-intestinal-type adenocar-
Glycocalyceal bodies as characteristic different series {124,799,804,1333}. The cinomas predominantly occur in adults
of intestinal-type epithelium may be iden- papillary type (papillary tubular cylinder but have been identified over a wide age
tified between the microvilli. Endocrine cell adenocarcinoma I = well-differenti- range from 9-80 years {1044}. The aver-
cells with neurosecretory granules, ated adenocarcinoma) has a more indo- age patient age at presentation of low-
Paneth cells with large exocrine gran- lent course, with little tendency to distant grade adenocarcinomas is 53 years
ules, and goblet cells containing several spread (5-year survival rate of about while that of high-grade ones is 59 years
mucin droplets in the apical cytoplasm 80%). Conversely, the solid type (papil- {1044}. There is a slight male predomi-
are present in variable numbers. lary tubular cylinder cell adenocarcino- nance for the low-grade adenocarcino-
ma III = poorly differentiated adenocarci- mas but a more marked male predilec-
Precursor lesions noma) and mucinous type adenocarcino- tion in the high-grade ones {1044}.
The frequent presence of squamous ma have a very poor survival. Other fac-
metaplasia and/or dysplasia of the tors that have been associated with a Etiology
sinonasal epithelium in the vicinity of the more aggressive behaviour are: H-RAS There are no known occupational or envi-
tumour impairs mucociliary clearance, mutation, chromogranin expression and ronmental etiological factors.
resulting in prolonged contact of carcino- c-erbB-2 expression {855,1687,2012}.
genic substances with the mucosa Although it has been suggested that Localization
{2789}. ITACs occurring in occupational The low-grade non-intestinal-type adeno-
exposed individuals have a better prog- carcinomas predilect to the ethmoid
Histogenesis nosis than sporadic ITACs {124}, this has sinus (to a lesser extent as compared
It has been hypothesized that ITAC not been confirmed in other reports with the intestinal-type), and the high-
derives from a stem cell capable of {799}. grade non-intestinal-type adenocarcino-
undergoing differentiation into various mas predilect to the maxillary sinus
type of epithelial cells (resorptive cells,
goblet cells, neuroendocrine cells,
Paneth cells) {1739}.

Genetics
Genetic data are limited {2012,2013,
2218,2829}. K-RAS or H-RAS mutation
has been detected in only about 15% of
cases {2012,2218}. TP53 mutations are
reported in 18-44% of cases
{2013,2829}; mutations consist more fre-
quently of C:G to A:T transitions and
involve the CpG dinucleotides. Other
gene alterations include loss of heterozy-
gosity (LOH) at 17p13 and 9q21, and Fig. 1.13 Sinonasal high-grade non-intestinal-type adenocarcinoma. Solid areas of the tumour show
promoter methylation of p14(ARF) and marked nuclear pleomorphism as well as an area of comedo-type necrosis.

22 Tumours of the nasal cavity and paranasal sinuses


A B
Fig. 1.14 Sinonasal (mucosal) non-intestinal-type adenocarcinoma. A Complex glandular growth and focal papillary architecture. B The glands are lined by a sin-
gle layer of cuboidal to columnar appearing cells with uniform, round nuclei, single small identifiable nucleoli and eosinophilic appearing cytoplasm.

A B
Fig. 1.15 Sinonasal low-grade non-intestinal-type adenocarcinoma. A Complex glandular growth including back-to-back glands lacking an intervening fibrovascu-
lar stroma is characteristically seen. B The glands are comprised of a single layer of nonciliated columnar cells with uniform, round nuclei, granular eosinophilic
cytoplasm. The cells vary from orderly linear arrangement to stratification with loss of nuclear polarity.

{1044}. Either tumour type may also orig- Histopathology malignancy to be made.
inate in the nasal cavity, other paranasal The low-grade non-intestinal-type adeno- The high-grade non-intestinal-type ade-
sinuses, or in multiple sinonasal sites in carcinomas are circumscribed or inva- nocarcinomas are invasive tumours with
various combinations {1044}. sive, and have a glandular or papillary a predominantly solid growth pattern, but
growth. Numerous uniform small glands glandular and papillary patterns can also
Clinical features or acini are arranged in a back-to-back be present. These tumours are charac-
For low-grade adenocarcinomas, or coalescent pattern with little or no terized by moderate to marked cellular
patients primarily present with nasal intervening stroma. Occasionally, large, pleomorphism, high mitotic activity,
obstruction and epistaxis. Pain is an irregular cystic spaces can be seen. The including atypical forms, and necrosis.
infrequent feature {1044}. The duration of glands are lined by a single layer of non-
symptoms ranges from 2 months to five ciliated, cuboidal to columnar cells with Prognosis and predictive factors
years, with a median of 5.5 months. uniform, round nuclei which may be limit- The treatment for sinonasal non-intestin-
For high-grade adenocarcinomas, the ed to the basal aspect of the cells or may al-type adenocarcinomas is complete
presenting symptoms include nasal demonstrate pseudostratification with surgical excision generally via a lateral
obstruction, epistaxis, pain and facial loss of nuclear polarity. The cytoplasm is rhinotomy; depending on the extent and
deformity (e.g., proptosis). The duration eosinophilic. Cellular pleomorphism is histology of the neoplasm, the surgery
of symptoms ranges from two weeks to mild to moderate. While occasional mitot- varies from local excision to more radical
five years with a median of 2.5 months ic figures may be seen, atypical mitoses procedures (maxillectomy, ethmoidecto-
{1044}. and necrosis are absent. Variants include my and additional exenterations).
papillary, clear cell and oncocytic adeno- Radiotherapy may be utilized for exten-
Macroscopy carcinomas. Multiple morphologic pat- sive disease or for higher-grade neo-
The appearance varies, including well terns may be present in a single neo- plasms. The low-grade neoplasms have
demarcated to poorly-defined and inva- plasm. Despite the relatively bland histol- an excellent prognosis, while high-grade
sive, flat to exophytic or papillary growths ogy, the complexity of growth, absence neoplasms have a dismal prognosis with
with a tan/white to pink colour and a fri- of myoepithelial/basal cell component, a 3-year survival rate of only approxi-
able to firm consistency. absence of encapsulation and invasion mately 20% {1044}.
into the submucosa permit a diagnosis of

Adenocarcinoma 23
Salivary gland-type carcinomas J.W. Eveson

Salivary gland neoplasms of the


sinonasal tract are uncommon, and the
majority are malignant {1039}. For details
see Chapter 5 on tumours of salivary
glands.

ICD-O codes
Adenoid cystic carcinoma 8200/3
Acinic cell carcinoma 8550/3
Mucoepidermoid carcinoma A B
8430/3 Fig. 1.16 Adenoid cystic carcinoma. A CT scan shows a nasal sinus mass focally extending into the bone.
Epithelial-myoepithelial carcinoma B The tumour (T) is inhomogenous and extends from the maxillary sinus into the infratemporal (black arrow-
8562/3 head) and the pterygopalatine fossa (black arrow). Perineural spread follows the Vidian cana (white arrow-
Clear cell carcinoma 8310/3 head).

Adenoid cystic carcinoma Mucoepidermoid carcinoma Epithelial-myoepithelial carcinoma


Adenoid cystic carcinoma is the most Mucoepidermoid carcinomas are rare at Epithelial-myoepithelial carcinoma is rare
frequent malignant salivary gland-type this site, and should be distinguished in the sinonasal tract. Cases have been
tumour of the sinonasal tract. The age from the more aggressive variants of reported to involve the nasal septum,
range is from 11-92 years {1039}. The squamous cell carcinoma, especially nasal cavity and maxillary sinus
majority develop in the maxillary sinus adenosquamous carcinoma {1039, {1011,1221,1450,2506}. Signs and
(about 60%) and nasal cavity (about 1291,2588}. symptoms are non-specific but have
25%) {130}. The disease is often insidi-
ous, and symptoms include nasal
obstruction, epistaxis, and pain, paraes-
thesia or anaesthesia. Swelling of the
palate or face, and loosening of the teeth
may be the presenting symptom. Many
tumours are large and extensively infiltra-
tive at the time of diagnosis. These
tumours can be difficult to detect on plain
film radiographs and often extend widely
through bone before there is radiograph-
ical evidence of osseous destruction. In
addition, the true extent of tumour spread
is often underestimated by imaging tech-
niques. The long-term prognosis is poor A
and the 10-year survival rate is only 7%
{2444}. Most patients die as a result of
local spread rather than metastatic dis-
ease {2799}.

Acinic cell carcinoma


Acinic cell carcinoma is rare in the
sinonasal tract and cases have been
reported in the nasal cavity {996,1950,
2014,2244,2698} and maxillary sinuses B C
{829,2860}. The signs and symptoms are
Fig. 1.17 Adenoid cystic carcinoma of nasal cavity. A Solid as well as tubular growth patterns are seen. B
non-specific but they include nasal An intact surface mucosa overlying the cribriform and cystic patterns of a sinonasal adenoid cystic carci-
obstruction and epiphora. noma. C A high power illustrating the relatively bland nuclear appearance with an intermediate to high
nuclear to cytoplasmic ratio. Palisading is noted, along with small gland or tubule formation, in addition to
the larger cyst-like spaces.

24 Tumours of the nasal cavity and paranasal sinuses


Fig. 1.18 Clear cell carcinoma. Fig. 1.19 Mucoepidermoid carcinoma. A low grade mucoepidermoid carcinoma has variable sized mucus
filled cystic spaces lined by mucocytes and intermediate cells.

included the formation of polypoid mass-


es and nasal obstruction.

Clear cell carcinoma


Clear cell carcinoma, N.O.S., of the
sinonasal tract is rare {1757,1874} and it
is important to exclude metastatic renal
clear cell carcinoma {1664,2918}.
Microscopically, these tumours consist of
closely packed, polygonal clear cells
arranged in sheets and theques. They
Fig. 1.20 Mucoepidermoid carcinoma. Solid epithe- Fig. 1.21 Mucoepidermoid carcinoma. The mucin
contain glycogen but no mucin.
lial growth pattern with occasional mucocytes production (left) can be accentuated with a muci-
(left); predominant cystic pattern with numerous carmine stain where both the intracytoplasmic and
Other tumours mucocytes and a few intermediate cells (right). extracellular mucin is highlighted (right)
A variety of other salivary gland-type car-
cinomas have been rarely reported in the
nasal cavity and paranasal sinuses. Table 1.2 Sinonasal glandular tumours*
These include: malignant myoepithe-
lioma {2918}, carcinoma ex pleomorphic Tumour types No of cases Percentage
adenoma {435}, polymorphous low-
Pleomorphic adenoma 73 23%
grade adenocarcinoma {1536} and basal
cell adenocarcinoma {785}. Oncocytic tumours 7 2%

Low-grade adenocarcinoma 67 21%


(including acinic cell carcinoma)

Mucoepidermoid carcinoma 17 5%

Adenoid cystic carcinoma 54 17%

High grade adenocarcinoma 93 30%

Total 311 100%

* Modified from Heffner {1039}

Salivary gland-type carcinomas 25


Neuroendocrine tumours B. Perez-Ordonez

Neuroendocrine tumours are very rare in


the nasal cavity, paranasal sinuses or
nasopharynx. The recognizable types
are typical carcinoid, atypical carcinoid
and small cell carcinoma neuroen-
docrine type. It is unclear whether large
cell neuroendocrine carcinoma that cor-
responds to the pulmonary counterpart
occurs in these sites. There are also rare
cases that do not fit these categories,
and the diagnostic label neuroen- Fig. 1.22 Sinonasal small cell carcinomas, neu- Fig. 1.23 MRI of a small cell carcinoma, neuroen-
docrine carcinoma, not otherwise speci- roendocrine type (SCCNET) are aggressive docrine type (SCCNET) involving the superior nasal
fied may be applied. tumours with a mortality rate of > 60% despite mul- cavity, ethmoid and sphenoid sinuses, with exten-
timodal therapy. (DOD, dead of disease; AWD, sive invasion of skull base and frontal lobe.
alive with disease; AND, alive no disease; DOC,
Carcinoid tumour dead other causes).
with smoking or radiation. The age range
ICD-O codes type is a high-grade carcinoma com- is from 26-77 years with a mean of 49
Typical carcinoid 8240/3 posed of small to intermediate sized years.
Atypical carcinoid 8249/3 cells resembling those of small cell carci-
noma of pulmonary or extrapulmonary Localization
Typical and atypical carcinoids of the origin. Necrosis, large numbers of apop- SCCNET most commonly arise in the
nasal cavity and paranasal sinuses are totic cells, high mitotic rate, and lack of superior or posterior nasal cavity, and
exceedingly rare, possibly because they neurofibrillary stroma are microscopic often extend into the maxillary or ethmoid
are under-reported or have been includ- hallmarks of this tumour. sinuses. Primary tumours of the maxillary
ed under other non-descriptive cate- or ethmoid sinuses without nasal involve-
gories, such as neuroendocrine carci- ICD-O code 8041/3 ment can be seen in approximately 45%
noma {1676,2007,2384,2776}. They are of cases. Secondary involvement of the
otherwise similar to carcinoids in other Synonyms nasopharynx is present in a minority of
sites. Small cell carcinoma, small cell neuroen- patients. Advanced tumours may invade
Patients have ranged in age from 13-65 docrine carcinoma, oat cell carcinoma, the skull base, orbit, or brain.
years, and present with nasal obstruc- poorly differentiated neuroendocrine car-
tion, epistaxis and/or facial pain. Most cinoma. Clinical features
tumours arise in the nasal cavity but may The most common symptoms are epis-
extend into adjacent sinuses. A patient Epidemiology taxis and nasal obstruction, followed by
with two carcinoids - nasal and pul- SCCNET of the sinonasal tract is a rare facial pain, palpable facial mass, and
monary - has been described {2384}. tumour with no sex, racial, or geographic exophthalmos. Rare tumours have shown
Another individual with the Multiple predilection and no known association elevated serum levels of ACTH, calci-
Endocrine Neoplasia Type I (MEN1) has
been reported to have a carcinoid of the
sphenoid sinus {2776}.
Paucity of cases and lack of significant
follow-up preclude definitive statements
about the prognosis. The tumours are at
least locally aggressive.

Small cell carcinoma, neuroen-


docrine type (SCCNET)
A B
Definition Fig. 1.24 Sinonasal carcinoid tumour. A Trabecular and insular patterns. B Diffuse and strong staining for
Small cell carcinoma, neuroendocrine neuron specific enolase (NSE).

26 Tumours of the nasal cavity and paranasal sinuses


A A

B B

C C
Fig. 1.25 Small cell carcinoma, neuroendocrine type (SCCNET) A Typical sinonasal SCCNET showing con- Fig. 1.26 Sinonasal SCCNET. A Patchy but strong
fluent sheets of tumour cells surrounding vessels of nasal mucosa. B Sinonasal SCCNET composed of small staining for synaptophysin. Note the extensive
cells with high nucleo/cytoplasmic ratio and extensive apoptosis. The nuclei are hyperchromatic and lack tumour necrosis. B Diffuse and strong keratin
visible nucleoli. C Sinonasal SCCNET with perineural invasion and numerous hyperchromatic apoptotic expression. Note the characteristic perinuclear
cells. "dot". C Diffuse staining for CD56.

tonin, pro-gastrin releasing peptide (pro- poor prognosis and frequent local recur- mary head and neck small cell carcino-
GRP), or antidiuretic hormone with syn- rence and distant metastasis despite mas was only 14.5 months {845}. Follow-
drome of antidiuretic hormone and multimodal therapy. Among twenty up data have shown a local recurrence
hyponatremia {1259,1901,2042}. reported patients {849,1259,1358,1901, rate of 45% and a distant metastasis rate
2009,2042,2134,2153,2728,2742}, of 35%. Common sites of metastases
Pathology twelve (60%) died of disease, three include cervical lymph nodes, lung, liver,
See Chapter 3 under Neuroendocrine (15%) were alive with no evidence of dis- bone marrow, and vertebrae.
Neoplasms of the Larynx. An important ease, four were alive with disease (20%),
differential diagnosis is olfactory neuro- and one died of other causes. In a study
blastoma. of extrapulmonary small cell carcinomas
{845}, which included seven cases
Prognosis and predictive factors involving the paranasal sinuses, the
SCCNET are aggressive tumours with a median survival of 14 patients with pri-

Neuroendocrine carcinomas 27
Schneiderian papillomas L. Barnes
L.L.Y. Tse
J.L. Hunt

Table 1.3 Distribution of Schneiderian papillomas


The ectodermally derived ciliated respi-
ratory mucosa that lines the nasal cavity References Total cases Inverted Oncocytic Exophytic
and paranasal sinuses, so-called
Schneiderian membrane, gives rise to Hyams {1158} 315 149 10 156
three morphologically distinct types of
papillomas. These are referred to individ- Michaels and Young {1714} 191 139 16 36
ually as inverted, oncocytic, and exo-
phytic papillomas or, collectively, as Buchwald et al. {302} 82 58 5 19
Schneiderian papillomas.
Sarkar et al. {2246} 35 24 9 2
As a group, the Schneiderian papillomas
are uncommon, representing only 0.4- Weiner et al. {2737} 105 82 2 21
4.7% of all sinonasal tumours {1423}.
Total 728 (100%) 452 (62%) 42 (6%) 234 (32%)

lnverted papilloma
(Schneiderian papilloma,
inverted type) Etiology of sophisticated molecular techniques,
Although a viral origin of inverted papil- 131 (38%) were positive. Whether the
Definition lomas has long been suspected, viral virus is a passenger or etiologically relat-
A papilloma derived from the inclusions have never been unequivocal- ed to the papilloma is unclear {1596}.
Schneiderian membrane in which the ly demonstrated by light or electron Epstein-Barr virus (EBV) DNA has been
epithelium invaginates into and prolifer- microscopy. In addition, they are almost identified in 65% of inverted papillomas
ates in the underlying stroma. invariably negative when stained for by polymerase chain reaction (PCR),
human papillomavirus (HPV) by the raising the possibility that this virus might
ICD-O code 8121/1 immunoperoxidase technique. HPV be involved in its pathogenesis {1596}. A
genomes, however, have been demon- subsequent study utilizing in-situ hybridi-
Synonyms strated in inverted papillomas by in situ sation found no evidence of EBV in the
Inverting papilloma, Schneiderian papil- hybridization or the polymerase chain tumour cells, suggesting that the report-
loma, papillomatosis reaction, particularly HPV 6 and 11, ed PCR positivity might be related to the
sometimes HPV 16 and 18, and excep- presence of EBV-positive lymphocytes in
Epidemiology tionally, HPV 57. The frequency of finding the tissues {842}. There is no known
Inverted papillomas are two to five times the virus by these specialized tech- association of inverted papilloma with
more common in males, and are found niques is highly variable, ranging any- allergy, inflammation, smoking, noxious
primarily in the 40-70 year age group. where from 0-100% {127}. In a collective environmental agents or occupation
They are distinctly uncommon in chil- review of 341 inverted papillomas evalu- {1158}.
dren. ated for the presence of HPV by a variety

A B
Fig. 1.27 Inverted papilloma. Coronal CT. The Fig. 1.28 Inverted papilloma. A Specimen removed intact. Note the opaque yellow-tan nodular polypoid
tumour bows the bone. The calcification (white appearance. B Cut surface of the lesion shown in A. Close inspection shows well-demarcated islands of
arrowhead) may represent a sclerotic fragment of epithelium which extend endophytically into the stroma.
inferior turbinate.

28 Tumours of the nasal cavity and paranasal sinuses


Localization {1158}. Whether all of these ectopic On physical examination, inverted papil-
Inverted papillomas characteristically cases are bona fide inverted papillomas lomas present as pink, tan, or grey; non-
arise from the lateral nasal wall in the is uncertain. translucent; soft to moderately firm, poly-
region of the middle turbinate or ethmoid Although overwhelmingly unilateral, rare poid growths with a convoluted or wrin-
recesses, and often extend secondarily cases of bilateral inverted papillomas kled surface.
into the sinuses, especially the maxillary have been described {211}. Such occur-
and ethmoid and, to a lesser extent, the rence, however, should always arouse Imaging
sphenoid and frontal. Isolated lesions of the suspicion of septal erosion and per- Findings on imaging vary with the extent
the paranasal sinuses without nasal foration from unilateral disease. of disease. Early on, there may be only a
involvement however, do occur. Almost soft tissue density within the nasal cavity
none arise primarily on the nasal septum Clinical features and/or paranasal sinuses. Later, with
{1297}. Signs and symptoms more extensive disease, unilateral opaci-
Exceptionally, inverted papillomas may Nasal obstruction is the most common fication and thickening of one or more of
arise in sites other than the sinonasal presenting symptom. Other manifesta- the sinuses is common, as are expansion
tract. They have been recorded in the tions include nasal drainage, epistaxis, and displacement of adjacent structures.
middle ear-mastoid {2757}, pharynx anosmia, headaches (especially frontal), Pressure erosion of bone may also be
{2499}, nasopharynx {81}, and lacrimal epiphora, proptosis, and diplopia. Pain, apparent and must be distinguished from
sac {2217}. It has been suggested that on the other hand, is an uncommon initial the destructive invasion associated with
ectopic migration of the Schneiderian complaint, occurring in only about 10% malignancy, such as de novo carcinoma
membrane during embryogenesis could of all cases. When present, it should or carcinoma arising in and/or associat-
account for these aberrant papillomas in always arouse suspicion of secondary ed with an inverted papilloma.
sites contiguous with the sinonasal tract infection or malignant change.

A B

C D
Fig. 1.29 Inverted papilloma A Low magnification showing hyperplastic aggregates of well-demarcated squamous and respiratory epithelium extending through-
out the stroma. Note the absence of mucoserous glands. B Papilloma composed partially of hyperplastic, ciliated respiratory epithelium. Note the epithelial trans-
migration of neutrophils and the delicate basement membrane. C HPV nuclear and cytoplasmic reactivity can be seen in some inverted papillomas, usually in the
same nuclei which exhibit features of "koilocytic" atypia (right). D Inverted papilloma and carcinoma. Note the inverted papilloma on the left and the normal ciliat-
ed respiratory epithelium of the sinonasal track in the middle of the illustration. The carcinoma at the right shows both in-situ and invasive components.

Schneiderian papillomas 29
of the inverted papilloma to the develop-
ment of the carcinoma is 63 months
(range, 6 months to 13 years) {1477}.
Carcinomas complicating inverted papil-
loma vary from well to poorly differentiat-
ed and exhibit a broad range of behav-
iour. Some are in situ and of little conse-
quence, whereas others are locally
aggressive or may even metastasize.
A B The carcinomas may actually arise within
the papilloma, as evidenced by a grada-
Fig. 1.30 Oncocytic Schneiderian papilloma. A Note the yellow-tan appearance and fine papillary excres-
cences in some of the fragments. Close inspection of the cut surface of the fragment in the top center part tion of histological changes ranging from
of the illustration shows an inverted component to the papilloma. B The epithelium is oncocytic and there dysplasia to carcinoma in-situ to frankly
are prominent intra-epithelial mucous cells, cysts and microabscesses. invasive carcinoma; whereas in others,
the carcinoma is merely associated with
a histologically bland inverted papilloma.
Histopathology as scaffolds to extend into the stroma. Staining for CD44s may be helpful in
Inverted papillomas are composed As inverted papillomas enlarge, they identifying a malignant component. It is
exclusively or almost exclusively of may obstruct the drainage of nearby diffusely expressed in typical inverted
hyperplastic ribbons of basement mem- sinuses. As a result, it is not uncommon papillomas, whereas its expression is
brane-enclosed epithelium that grow to also find ordinary nasal polyps in reduced or absent in the associated car-
endophytically into the underlying stro- inverted papilloma specimens. They can cinomatous component {1175}.
ma. Infrequently, a minor exophytic com- usually be identified grossly by their There is no correlation between the num-
ponent may be seen. The epithelium is more myxoid appearance and the fact ber of local recurrences of an inverted
multilayered, usually 5-30 cells thick, and that they will transilluminate, whereas papilloma and the subsequent develop-
formed of squamous or ciliated columnar inverted papilloma will not. ment of carcinoma. There is some evi-
(respiratory epithelial) cells admixed with Rarely, an inverted papilloma will exhibit dence, however, to suggest that HPV 16
mucocytes. Nonkeratinizing squamous focal surface changes reminiscent of a and 18 may be more carcinogenic than
or transitional-type epithelium tends to verruca vulgaris; that is, it shows focal HPV 6 and 11 {1334}.
predominate, and is frequently covered papillary squamous epithelial hyperpla- Preliminary data suggest that alterations
by a single layer of ciliated columnar sia with marked keratosis and/or parak- in TP53, manifested by an increased pro-
cells. An occasional case may be com- eratosis, with a prominent granular cell tein expression or genetic mutation, can
posed almost entirely of respiratory layer, and often contains numerous vac- be used to predict which lesions are at
epithelium. Gradations between these uolated cells suggestive of koilocytes. risk for malignant change {715,765}.
two extremes are not uncommon, result- Although this might be a viral effect,
ing in a transitional epithelium reminis- immunohistochemical stains for HPV are Differential diagnosis
cent of that seen in the urinary tract. All of invariably negative. When this change is The differential diagnoses include nasal
these epithelial types may be present in observed, the diagnosis of inverted polyp with squamous metaplasia, respi-
the same lesion, and their proportions papilloma with focal verrucous hyperpla- ratory epithelial adenomatoid hamartoma
may vary widely in different lesions or sia is appropriate and the patient should (REAH) and invasive carcinoma.
even in different areas of the same papil- be followed closely for possible develop- Nasal polyps with squamous metaplasia
loma. Mitoses are not numerous and, if ment of carcinoma, either verrucous car- show thickening and hyalinization of the
present at all, are seen primarily in the cinoma or squamous cell carcinoma. basement membrane, a prominent com-
basal and parabasal epithelium. ponent of normal seromucinous glands
Ten to 20% of inverted papillomas may Inverted papilloma and carcinoma and, often, a large number of stromal
show focal surface keratinisation, and 5- Inverted papillomas are occasionally inflammatory cells. These features are
10% varying degrees of dysplasia {127}. complicated by carcinomas, especially typically absent in inverted papilloma. In
These are not necessarily signs of malig- squamous cell carcinoma and, to a much addition, the surface epithelium of nasal
nancy, but they should alert the patholo- lesser extent, verrucous, mucoepider- polyps is thin, contains more mucocytes,
gist of the need of thorough evaluation of moid, spindle and clear cell carcinomas, and does not show the characteristic
the papilloma. The stroma ranges from as well as adenocarcinomas. The inci- epithelial transmigration of neutrophils.
dense and fibrous to loose and myxoid, dence of malignant change in individual In contrast to inverted papilloma, REAH
with or without an inflammatory compo- series of inverted papillomas has ranged occurs primarily on the posterior nasal
nent. The inflammatory cells, especially from 2-27% {127}. In a collective review septum rather than the lateral nasal wall
neutrophils, often transmigrate through of 1390 inverted papillomas reported in and/or paranasal sinuses {2766}. REAH
the epithelium. Basement membrane the literature, 150 (11%) were associated is also composed of numerous glands
thickening is not typically seen. Normal- with carcinoma and, of these, 61% of the lined by respiratory epithelial cells, sur-
appearing seromucinous glands are carcinomas were synchronous and 39% rounded by thick hyalinized basement
sparse to absent, because the neoplas- metachronous {127}. For metachronous membranes, features not seen in invert-
tic epithelium uses the ducts and glands carcinomas, the mean interval from onset ed papilloma.

30 Tumours of the nasal cavity and paranasal sinuses


nasal obstruction and intermittent epis-
taxis.

Histopathology
The oncocytic papilloma exhibits both
exophytic and endophytic patterns of
growth. The epithelium is multilayered, 2-
8 cells thick, and is composed of tall
columnar cells with swollen, finely granu-
lar cytoplasm reminiscent of oncocytes.
The high content of cytochrome c oxi-
dase and presence of numerous mito-
chondria ultrastructurally clearly estab-
Fig. 1.31 Oncocytic papilloma. Stratified columnar epithelium with oncocytic features and small neutrophilic lish their oncocytic character {129}. The
microabscesses are characteristic. nuclei are either small dark and uniform
or slightly vesicular with barely dis-
cernible nucleoli. Cilia in varying stages
Invasive carcinoma can be distinguished Oncocytic papilloma of regression may be observed in a few
from inverted papilloma by the presence (Schneiderian papilloma, of the outermost cells.
of the following features: cellular pleo- oncocytic type) The epithelium characteristically con-
morphism, atypical mitoses, keratin tains numerous small cysts filled with
pearls, loss of basement membranes, Definition mucin or neutrophils (microabscesses).
and stromal invasion associated with an A papilloma derived from the The stroma varies from edematous to
inflammatory-desmoplastic response. Schneiderian membrane composed of fibrous, and may contain modest num-
both exophytic fronds and endophytic bers of lymphocytes, plasma cells, and
Prognosis and predictive factors invaginations lined by multiple layers of neutrophils, but few eosinophils.
Though histologically benign, they have columnar cells with oncocytic features. Seromucinous glands are sparse to
an unlimited growth potential and, if neg- Intraepithelial microcysts containing absent.
lected, can cause considerable morbidi- mucin and neutrophils are characteristic.
ty or even death by extending into con- Oncocytic papilloma and carcinoma
tiguous structures. Attempts to remove ICD-O code 8121/1 Four to 17% of all oncocytic papillomas
these lesions intranasally by snare and harbour a carcinoma {1158,1266,1611,
avulsion have resulted in recurrence (or Synonyms 2723}. Most of these are squamous, but
persistence) rates of 0-74% (average, Oncocytic Schneiderian papilloma, cylin- mucoepidermoid, small cell and
60%) {1442}. drical cell papilloma, columnar cell papil- sinonasal undifferentiated carcinomas
The preferred treatment for most lesions loma, papillomatosis. have also been described.
is a lateral rhinotomy and medial maxil- As in inverted papilloma, the carcinoma
lectomy with meticulous removal of all Epidemiology complicating oncocytic papilloma may
mucosa in the ipsilateral paranasal Oncocytic papilloma is equally distrib- arise within the papilloma, as evidenced
sinuses. With this approach, the recur- uted between the sexes, and the majori- by a gradation of histologic changes
rence rate is usually <20% {1442}. ty of the patients are aged over 50 years. ranging from dysplasia to in situ to inva-
Selected small tumours can be effective- sive carcinoma, or it may only be associ-
ly removed by a less aggressive Etiology ated with the papilloma. Prognosis
approach using endoscopic sinonasal In contrast to exophytic and inverted depends on the histologic type, degree
surgery. Recurrences typically appear papillomas, HPV has not been identified of invasion, and the extent of tumour. In
within 2-3 years of therapy but, in some in oncocytic papillomas {127}. some instances, the carcinoma is in situ
instances, are delayed for many years. and of little consequence to the patient,
Attempts to correlate histological fea- Localization whereas others are locally aggressive
tures with risk of recurrence have result- Oncocytic papilloma almost always and may metastasize.
ed in conflicting data {1158,1442,2417}. occurs unilaterally on the lateral nasal
Even those with prominent mitotic activi- wall or in the paranasal sinuses, usually Differential diagnosis
ty and dysplasia do not invariably show the maxillary or ethmoid. It may remain The intraepithelial mucin-filled cysts of an
an increased recurrence or malignancy. localized, involve both areas, or if neg- oncocytic papilloma are often mistaken
Nevertheless, dysplasia, especially if lected, extend into contiguous areas for rhinosporidiosis. In rhinosporidiosis,
moderate to severe, demands thorough such as the orbit or cranial cavity. the organisms are not limited to the
microscopic evaluation of all resected epithelium but also involve stroma, and
tissue to avoid overlooking small foci of Clinical features do not induce a diffuse oncocytic
carcinoma. The association between Oncocytic papilloma presents as a change.
presence of HPV and the risk of recur- fleshy, pink, tan, red-brown, or grey pap- Oncocytic papilloma is also occasionally
rence is debatable {185,839}. illary or polypoid growth associated with confused with a low-grade papillary ade-

Schneiderian papillomas 31
nocarcinoma. The presence of intact
basement membranes and absence of
infiltrative growth are features that indi-
cate a benign lesion. In addition, the
presence of intraepithelial mucin-filled
cysts and microabscesses and the strat-
ified oncocytic epithelium of a papilloma
are rarely seen in a low-grade adenocar-
cinoma.
A B
Prognosis and predictive factors
The clinical behaviour parallels that of
the inverted papilloma. If inadequately
excised, at least 25-35% will recur, usu-
ally within 5 years. Smaller tumours can
be resected endoscopically.

Exophytic papilloma
(Schneiderian papilloma,
exophytic type) C D
Fig. 1.32 Exophytic papilloma. A Papillary growth arising from the nasal septum. B Higher magnification
Definition showing the hyperplastic non-keratinizing squamous epithelium with scattered clear (mucous) cells. C
A papilloma derived from the Small neutrophilic abscess can be seen within the epithelium on occasion. D Koilocytic change (nuclear
Schneiderian membrane composed of chromatin condensation, perinuclear halo and accentuation of the cell border) seen in exophytic papillo-
papillary fronds with delicate fibrovascu- mas.
lar cores covered by multiple layers of
epithelial cells. Involvement of the paranasal sinuses is Differential diagnosis
practically non-existent. Bilateral lesions Exophytic papillomas must be distin-
ICD-O code 8121/0 are exceptional. guished from the much more common,
keratinizing cutaneous papillomas (e.g.
Synonyms Clinical features verruca vulgaris) occurring in the nasal
Fungiform papilloma, everted papilloma, Epistaxis, unilateral nasal obstruction, vestibule. The lack of extensive surface
transitional cell papilloma, septal papillo- and the presence of asymptomatic mass keratinization, presence of mucocytes,
ma, squamous papilloma, papillomato- are the typical presenting symptoms. On and presence of ciliated and/or transi-
sis, Ringertz tumour physical examination, they appear as tional epithelium help to confirm a diag-
papillary or warty, grey, pink or tan, non- nosis of exophytic papilloma. The pres-
Epidemiology translucent growths attached to the nasal ence of seromucinous glands and septal
Exophytic papillomas are 2-10 times septum by a relatively broad base. cartilage further indicate that the lesion is
more common in men, and occur in indi- of mucosal rather than cutaneous origin.
viduals between 20 and 50 years of age Histopathology
(2-87 years) {1158,1908}. Most exophytic papillomas range up to Prognosis and predictive factors
about 2 cm. Microscopically, they are Complete surgical excision is the treat-
Etiology composed of papillary fronds with ment of choice. Inadequate excision
There is increasing evidence to suggest fibrovascular cores covered by epitheli- rather than multiplicity of lesions proba-
that exophytic papillomas may be etio- um, 5-20 cells thick, that vary from squa- bly accounts for the local recurrence of
logically related to HPV, especially types mous to transitional (intermediate) to cili- 22-50% {1158,1908}.
6 and 11, rarely types 16 and 57b. In a ated pseudostratified columnar (respira-
collective review of exophytic papillomas tory). Scattered mucocytes are common.
evaluated for the presence of HPV by in Surface keratinization is absent or scant,
situ hybridization and/or the polymerase unless the lesion has been irritated or if
chain reaction, about half of the cases the papilloma is unusually large and
were HPV positive {131}. hangs into the nasal vestibule, where it is
exposed to the drying effect of air.
Localization Mitoses are rare and never atypical.
Exophytic papillomas arise on the lower Unless infected or irritated, the stroma
anterior nasal septum with no significant contains few inflammatory cells.
lateralization. As they enlarge, they may
secondarily involve, but only infrequently Malignant change in exophytic papilloma
originate from the lateral nasal wall. is exceptional {301,1908}.

32 Tumours of the nasal cavity and paranasal sinuses


Respiratory epithelial adenomatoid B.M. Wenig

hamartoma

Definition Associated complaints include allergies. membrane. Atrophic glandular alter-


Benign nonneoplastic overgrowth of ations may be present in which the
indigenous glands of the nasal cavity, Macroscopy glands are lined by a single layer of flat-
paranasal sinuses and nasopharynx Lesions are typically polypoid or exo- tened to cuboidal epithelium. Small reac-
associated with the surface epithelium, phytic with a rubbery consistency, tan- tive seromucinous glands can be seen.
and devoid of ectodermal neuroectoder- white to red-brown appearance, measur- The stroma is oedematous or fibrous,
mal, and/or mesodermal elements. ing up to 6 cm in greatest dimension and contains a mixed chronic inflamma-
{933,2766}. tory cell infiltrate.
Synonyms Additional findings may include inflam-
Glandular hamartoma; seromucinous Histopathology matory sinonasal polyps, hyperplasia
hamartoma. The lesions are dominated by a glandu- and/or squamous metaplasia of the sur-
lar proliferation composed of widely- face epithelium unrelated to the adeno-
Epidemiology spaced, small to medium-sized glands matoid proliferation, osseous metaplasia,
Hamartomas of the sinonasal tract and separated by stromal tissue. In areas, the rare association with inverted type
nasopharynx are uncommon. The major- glands arise in direct continuity with the Schneiderian papilloma, and rare associ-
ity of them are of pure epithelial type (res- surface epithelium, which invaginate ation with a solitary fibrous tumour
piratory epithelial adenomatoid hamar- downward into the submucosa. The {2766}.
toma) {2766}, although pure mesenchy- glands are round to oval, and composed
mal hamartomas or mixed epithelial- of multilayered ciliated respiratory Prognosis and predictive factors
mesenchymal hamartomas may also epithelium often with admixed muco- Conservative but complete surgical exci-
rarely occur {14,106,933,2766}. cytes. Glands distended with mucus can sion is curative.
Respiratory epithelial adenomatoid be seen. A characteristic finding is stro-
hamartomas predominantly occur in mal hyalinization with envelopment of
adult patients with a decided male pre- glands by a thick, eosinophilic basement
dominance; patients range in age from
the 3rd to 9th decades of life, with a
median age in the 6th decade {2766}.

Etiology
Respiratory epithelial adenomatoid
hamartomas often arise in the setting of
inflammatory polyps, raising a possible
developmental induction secondary to
the inflammatory process {2766}.

Localization A B
The majority occur in the nasal cavity, in
particular the posterior nasal septum;
involvement of other intranasal sites
occurs less often and may be identified
along the lateral nasal wall, middle mea-
tus and inferior turbinate {2766}. Other
sites of involvement include the
nasopharynx, ethmoid sinus, and frontal
sinus. Most are unilateral, but some may
be bilateral. C D
Fig. 1.33 Respiratory epithelial adenomatoid hamartoma (REAH). A The glandular proliferation arises in
Clinical features direct continuity with the surface epithelium with invagination downward into the submucosa. Clusters of
Patients present with nasal obstruction, seromucinous glands are seen (arrow). B Pseudostratified epithelium with cilia within the adenomatoid
nasal stuffiness, epistaxis and/or chronic collections of a REAH hamartoma. C Cilia along the luminal border of the cells (arrows). D Atrophic
(recurrent) rhinosinusitis. The symptoms changes in which the glands are lined by a single layer of flattened to cuboidal-appearing epithelium. Note
may occur over months to years. the prominent thickened stromal hyalinization enveloping the glands.

Adenomatoid hamartoma 33
Salivary gland-type adenomas J.W. Eveson

Among glandular tumours of the


sinonasal tract, about one-quarter of
cases are benign, and practically all of
them are salivary gland-type neoplasms
{1039}. For details see Chapter 5 on
Tumours of salivary glands.

ICD-O codes
Pleomorphic adenoma 8940/0
Myoepithelioma 8982/0
Oncocytoma 8290/0

Pleomorphic adenoma
Most patients are between 20 and 60
years of age. Signs and symptoms are
non-specific, and include unilateral nasal Fig. 1.34 Pleomorphic adenoma of nasal cavity. Tumour is circumscribed, and lies above the cartilage.
obstruction, epistaxis and a discernible
mass. The tumour may resorb bone and
extend into the maxillary sinuses. Most
cases arise from the submucosa of the
bony or cartilaginous nasal septum, but
some arise in the lateral nasal wall
{483,974,1210,1506}. The size varies
from 0.5-5 cm {483} and tumours usually
form polypoid, sessile swellings.
Microscopically, they are unencapsulat-
ed, and tend to be cellular with predomi-
nance of modified myoepithelial cells
often of plasmacytoid hyaline type; stro-
mal elements are sparse. Exceptionally,
focal skeletal muscle differentiation can
occur {1419}. If treated by wide surgical
excision, recurrence is uncommon {483}.
Fig. 1.35 Pleomorphic adenoma of nasal cavity. Tumour typically rich in modified myoepithelial cells.
Myoepithelioma
Myoepithelioma, including the spindle
cell variant, of the sinonasal tract is very
rare {188}.

Oncocytoma
Oncocytomas of the sinonasal tract are
rare, and most arise from the nasal sep-
tum {1039}. They are usually small, but
some extend posteriorly and can cause
bone resorption {470,480,998}. The
nasolacrimal duct may be involved, A B
causing unilateral epiphora and purulent Fig. 1.36 Pleomorphic adenoma A A highly cellular tumour with myxochondroid matrix material (lower left).
rhinorrhoea {555}. Those examples that The cells are monotonous and plasmacytoid. B The myxochondroid matrix has a lacunar space (left), while
have behaved aggressively {470} are short trabeculae of epithelial cells are seen within a more myxoid area.
more appropriately considered low-
grade oncocytic adenocarcinomas
rather than adenomas {449,605,1044}.

34 Tumours of the nasal cavity and paranasal sinuses


Malignant soft tissue tumours L.D.R. Thompson
J.C. Fanburg-Smith

Fibrosarcoma more paranasal sinuses, while origination epithelial invagination into the tumour can
confined to the nasal cavity alone is less be prominent, simulating an inverted
Definition common {168,345,826,1041,1317, 2438}. papilloma. Spindle cells are arranged in
A malignant tumour of fibroblastic/myofi- The infantile-type fibrosarcoma in the compact fascicles, intersected by various
broblastic phenotype. sinonasal tract is exceedingly uncommon amounts of delicate thin to dense keloid-
in the sinonasal tract and occurs near the like collagen. The cell bundles are
ICD-O code 8810/3 choana {349,1041, 1317}. arranged at acute angles to one another,
occasionally giving rise to a herring-
Synonyms Clinical features bone or chevron pattern, while in most
Fibromyxosarcoma; chondromyxofibro- Nearly all patients have nasal obstruc- areas there is a more subtle fasciculation.
sarcoma. tion, often associated with epistaxis, A prominent storiform pattern is not seen.
while pain, sinusitis, nasal discharge, There is a marked variability in the cellu-
Epidemiology swelling, anosmia, and proptosis are less larity within and between tumours. The
The incidence of sinonasal tract fibrosar- common. The median duration of symp- cells are fusiform with a centrally placed
comas is difficult to determine because toms is quite short. hyperchromatic, needle-like nucleus sur-
the diagnosis is often one of exclusion. rounded by tapering cytoplasm which is
These tumours are rare, accounting for Macroscopy often indistinct, creating a syncytial
<3% of all non-epithelial tumours. The tumours are smooth, nodular, pedun- appearance to the fascicles. Most
However, they are considered the sec- culated, fungating or ulcerating. The sinonasal tract fibrosarcomas are low
ond most common soft tissue sarcoma lesions range in size between 2 and 8 grade. Nuclear pleomorphism is usually
after rhabdomyosarcoma in the head cm, with the cut surface revealing a cir- slight to moderate, but occasionally
and neck {168,345,349,826,1041,1317, cumscribed but not encapsulated, prominent. Mitotic figures are found in
2511}. They occur in all ages, with a fleshy, homogeneous white-tan to yellow- variable numbers. Haemorrhage and
peak in the 5th decade. There is a 3:2 pink mass, variably firm dependent upon necrosis can be found in the poorly differ-
female:male gender predilection {168, the collagen content. Necrosis and entiated forms, with areas of myxoid
345,826,1041,1317,2438,2511}. haemorrhage may be present in higher- degeneration. Focal osteo-cartilaginous
grade tumours. differentiation has been described {168,
Etiology 345,826,1041,1317,2438}. Fibrosarcomas
A few patients have developed fibrosar- Histopathology are immunoreactive with vimentin, and
coma within the field of prior irradiation. The tumours are unencapsulated, some- sometimes focally with actin {1041}.
times sharply circumscribed, although
Localization often infiltrative and occasionally ulcerat-
Most fibrosarcomas originate in one or ing. Bone invasion is common. Surface

A B
Fig. 1.37 Fibrosarcoma. A Short, angular intersections (herringbone or chevron) are most characteristic of a low grade fibrosarcoma. B Sweeping fascicles of min-
imally pleomorphic spindled cells can occasionally be seen. The overlying surface epithelium is unremarkable, including the presence of cilia.

Malignant soft tissue tumours 35


Macroscopy
Tumours are generally smooth, nodular
or pedunculated (polypoid), with a num-
ber being fungating or ulcerating. The
cut surface reveals a fleshy, homoge-
neous white-tan to yellow-pink mass with
necrosis and haemorrhage, measuring
up to 8 cm in maximum dimension {714}.

Tumour spread and staging


Sinonasal MFH can directly extend into
nasopharynx, orbit, and pituitary fossa
{1032,1707} and commonly metastasizes
to lungs, bones, liver, {1707,2426} and
only rarely to lymph nodes {279,1032,
1707}.
Fig. 1.38 Malignant fibrous histiocytoma. Remarkably pleomorphic cells with atypical mitotic figures.
Histopathology
Sinonasal MFH are generally infiltrative
Differential diagnosis myofibroblasts or undifferentiated mes- and ulcerative, but can occasionally be
The differential diagnoses include malig- enchymal cells. circumscribed. Pleomorphic MFH, the
nant fibrous histiocytoma, spindle cell most frequent morphologic subtype of
carcinoma, spindle malignant melanoma, ICD-O code 8830/3 MFH in the sinonasal tract, is character-
malignant peripheral nerve sheath ized by spindled to pleomorphic cells in
tumour, monophasic synovial sarcoma, Synonyms a storiform growth pattern, with easily
rhabdomyosarcoma, glomangiopericy- Fibroxanthosarcoma, malignant fibrous identified mitotic figures, including atypi-
toma, desmoid fibromatosis, and nodular xanthoma, myxofibrosarcoma, myxoid cal forms, and necrosis. The cells are
fasciitis {168,826,1041, 2332}. malignant fibrous histiocytoma fusiform with tapering indistinct cyto-
plasm. Tumour giant cells with multiple
Histogenesis Epidemiology nuclei may be found.
The (myo)fibroblast is considered the Although once considered the most
progenitor cell for these tumours. common sarcoma of adults, the frequen- Immunohistochemistry
cy of its diagnosis has diminished since MFH are usually positive for vimentin and
Prognosis and predictive factors the introduction of immunohistochemistry focally for actins. Importantly, MFH is a
Surgery is the treatment of choice, often has allowed assignment of some pleo- diagnosis of exclusion and is generally
followed by radiation therapy, yielding an morphic sarcomas to specific sarcoma negative for desmin, skeletal muscle
overall long-term survival of 75% in low entities. Only 3% of MFH occur in the specific markers, S100 protein, HMB-45,
grade and localized tumours. The high head and neck, with 30% of these arising epithelial markers and lymphoid mark-
incidence of recurrence (about 60%) is in the sinonasal area {2187}. MFH rarely ers.
perhaps related to the complexity of the occurs in the nasopharynx {1032,1923}.
anatomy of the sinonasal tract and con- Sinonasal MFH most commonly occurs in Differential diagnosis
sequent difficulties of complete excision. adults with a male predominance {2433}. The differential diagnoses include
Recurrence usually precedes metasta- fibrosarcoma, rhabdomyosarcoma,
sis, which occurs in about 15% of cases, Etiology leiomyosarcoma, monophasic synovial
most commonly to the lungs and bones Many sinonasal and nasopharyngeal sarcoma, malignant peripheral nerve
and only rarely to lymph nodes. Poor MFH are a result of previous radiation, sheath tumour, spindle cell carcinoma,
prognostic factors include male gender, after a long latency period {1180,1345}. spindle cell malignant melanoma and
large tumour size, involvement of more anaplastic large cell lymphoma.
than one contiguous site (nasal cavity Localization
and sinus, multiple sinuses), high histo- The maxillary sinus is most commonly Prognosis and predictive factors
logic grade, and positive surgical mar- affected, followed by the ethmoid sinus- Compared with other anatomical sites,
gins {168,345,826,1041,1317,2438}. es and nasal cavity, whereas the frontal MFHs of the head and neck generally
and sphenoid sinuses and nasopharynx have a slightly lower rate of recurrence
are affected far less commonly {279,536, and metastasis {133}.
Malignant fibrous histiocytoma 581,1032,1923,1936,2256,2426,2433}.

Definition Clinical features


Malignant fibrous histiocytoma (MFH) is Symptoms include mass, swelling, facial pain,
currently used as a diagnosis of exclu- loose teeth, epistaxis, and nasal obstruction
sion for sarcomas composed largely of {279,1707,2015,2187,2426, 2433}.

36 Tumours of the nasal cavity and paranasal sinuses


Leiomyosarcoma
Definition
A malignant tumour of smooth muscle
phenotype.

ICD-O code 8890/3

Epidemiology
Only a small number of sinonasal
leiomyosarcomas have been reported
{151,824,840,1144,1395,1416,1529,
2147,2240,2553}, accounting for <1% of all
non-epithelial tumours. They occur in all
ages, with a peak in the 6th decade (mean,
53 years) without a gender difference.

Etiology
There are a few reported cases with a
prior history of radiation {824,1416,2147}
or chemotherapy (cyclophosphamide
specifically) {1416,2147}.
Fig. 1.39 Leiomyosarcoma. A spindle cell neoplasm with "cleared" cytoplasm, immediately adjacent to the
nucleus, is seen below an intact surface mucosa. Mitotic figures are seen.
Localization
Involvement of both the nasal cavity and
paranasal sinuses is more common than
involvement of the nasal cavity alone
{824,840,1144,1395,1416,1529,1745}.

Clinical features
Nearly all patients have nasal obstruc-
tion, frequently associated with epistaxis
and pain, while nasal discharge,
swelling, and blurred vision are less
common. The duration of symptoms is A B
usually long {824,840,1144,1395,1416, Fig. 1.40 Leiomyosarcoma. A A high power shows short, "cigar-like" nuclei with small cytoplasmic clearing
1529,2147,2240,2553}. There is usually adjacent to the nucleus. There are atypical mitotic figures. B Desmin reactivity in the remarkably pleomor-
phic tumour cells can help to confirm the smooth muscle differentiation.
no lymphadenopathy. Plain radiographs
show opacification of the nasal cavity or
sinus(es), often suggesting sinusitis composed of right-angle intersecting tudinally oriented parallel fibrils within the
{1144,1395,1529,2553}. bundles of spindle cells. Palisading, cytoplasm. Tumour cells are diffusely
storiform and haemangiopericytoma- and strongly immunoreactive for
Macroscopy like patterns can occur. The tumours vimentin, actin (smooth muscle or mus-
These tumours range in size up to 7 cm, are hypercellular, but coagulative cle-specific), desmin and h-caldesmon.
with an average of about 4 cm. They are tumour necrosis and haemorrhage can There is generally no reactivity with ker-
more likely infiltrative than circum- create a hypocellular appearance. The atin, CD34, CD117, S-100 protein or
scribed, and occasionally polypoid. The tumour cells have elongated, vesicular HMB-45 {1144,1395,2702}. The Ki-67
surface is typically ulcerated and crust- to hyperchromatic, lobulated or indent- index is usually >15% {1144}.
ed. These bulky tumours have a cut sur- ed nuclei with blunt ends (cigar-
face which reveals a soft to firm, grey- shaped). The cytoplasm is fibrillary and Electron microscopy
white and fleshy appearance. eosinophilic, with frequent perinuclear Electron microscopy reveals variable
Haemorrhage, necrosis and cystic vacuolation. Mitoses, both typical and features of smooth muscle cells, includ-
change are common. atypical, are present to a variable ing myofilaments arranged in parallel
degree {824,840, 1144,1395,1416,1529, arrays, dense bodies within the fila-
Histopathology 2147,2240,2553}. ments, cell junctions, pinocytotic vesi-
Leiomyosarcomas are infiltrative neo- cles and basal lamina {1395,1529,1933}.
plasms accompanied by surface ulcera- Histochemistry and immunoprofile
tion. Bone or cartilage invasion is more Intracytoplasmic glycogen can be Differential diagnosis
frequent than surface or seromucinous demonstrated with a PAS stain. Masson The differential diagnoses include
gland invasion. Leiomyosarcomas are trichrome stain demonstrates red, longi- sinonasal glomangiopericytoma, periph-

Malignant soft tissue tumours 37


A B
Fig. 1.41 Rhabdomyosarcoma A Nasal alveolar rhabdomyosarcoma, with typical alveolar pattern. B The tumour cells are ovoid and have hyperchromatic nuclei
and scant eosinophilic cytoplasm.

eral nerve sheath tumour, fibrosarcoma, Epidemiology {825}. The alveolar subtype is fleshy to
spindle cell carcinoma and melanoma Approximately 40% of rhabdomyosarco- firm tan-grey.
{824,840,1144,1395,1416,1529,2147,22 mas occur in the head and neck {1978},
40,2553,2603}. with about 20% in the nasal cavity, Tumour spread and staging
nasopharynx, and nasal sinuses {2745}. These tumours often spread to contigu-
Genetic susceptibility Rhabdomyosarcoma is the most com- ous sites including base of the skull, tem-
There are isolated cases of children with mon sarcoma in childhood. The embry- poral bones, and orbit {724,825}. About
leiomyosarcomas who have preexisting onal subtype predominates in children, 40% metastasize to lymph nodes, bones,
hereditary retinoblastomas {627}. while the alveolar subtype predominates and lungs, and less commonly bone
in adults {825,1273}. The pleomorphic marrow, soft tissue, liver and brain
Prognosis and predictive factors subtype is rare {836,837}. There is an {1441,1856}. The tumours are staged
About half of the reported cases develop overall slight male predominance {825}. according to the Intergroup
local recurrence, often within one year, Rhabdomyosarcoma Study. Group I
and nearly 1/3 of these patients will sub- Localization includes local disease, Group II residual
sequently develop metastasis (mostly to The nasopharynx is more commonly disease or local spread, Group III incom-
the lungs and liver). Complete surgical involved than the sinonasal tract plete resection or biopsy with gross
excision is difficult to achieve, and radia- {326,724}. In adults, rhabdomyosarcoma residual disease, and Group IV metasta-
tion and chemotherapy are used with is more common in the ethmoid sinuses, tic disease at onset {613}. Most adult
variable results. {824,1416,2501}. followed by the maxillary sinuses and sinonasal and nasopharyngeal rhab-
Poor prognostic factors include involve- nasopharynx {1856}. domyosarcomas are staged as Group III
ment of more than one contiguous site, or IV at presentation {1856}.
large tumour size (>5 cm), high mitotic Clinical features
count (>20/10 high power field), tumour Signs and symptoms include difficulty in Histopathology
necrosis, and tumour stage {824,840, breathing, epistaxis, facial swelling, visu- Embryonal rhabdomyosarcoma has
1144,1395,1416,1529,2147,2240,2553}. al disturbances, and sinusitis often of round to spindled cells with hyperchro-
short duration. Tumours may appear as a matic nuclei. Larger rhabdomyoblasts
Rhabdomyosarcoma large, polypoid sinonasal mass or may with eosinophilic cytoplasm are usually
occasionally protrude as a gelatinous identified, but cross striations are difficult
Definition mass from the nares {825}. to recognize. Myxoid stroma is common.
A malignant tumour of skeletal muscle CT and MRI imaging delineate the size The spindle cell variant, characterized by
phenotype. and extent of the tumour {1453,2846}. spindled cells in fascicular to storiform
The botryoid type shows grape-like rings growth patterns, can be deceptively
ICD-O code 8900/3 and heterogeneous enhancement {980}. bland. The botryoid variant is polypoid
(Also see subtypes: 8910/3, 8912/3, with a submucosal hypercellular cambi-
8920/3, 8901/3 in WHO Tumours of Soft Macroscopy um layer, a myxoid hypocellular zone,
Tissue) The embryonal subtype is generally and a deep cellular component.
poorly circumscribed, fleshy, pale and Alveolar rhabdomyosarcoma typically
Synonyms tan; the spindle cell variant is firm, has fibrous septa separating clusters of
Myosarcoma, malignant rhabdomyoma, fibrous, and tan-yellow with a whorled cut loosely cohesive groups of small to medi-
rhabdosarcoma, embryonal sarcoma, surface. The botryoid variant has a um round tumour cells with hyperchro-
rhabdomyoblastoma grape-like or polypoid appearance matic nuclei and scant eosinophilic cyto-

38 Tumours of the nasal cavity and paranasal sinuses


A B
Fig. 1.42 Sinonasal rhabdomyosarcoma. A This macroscopic image demonstrates the similarity between a sinonasal polyp and a rhabdomyosarcoma. B Irregular
islands of tumour in stroma may mimic carcinoma. Desmin and skeletal muscle markers can aid in the diagnosis of rhabdomyosarcoma.

plasm. Multinucleated giant cells with myf4) {2619}. CD99 can be positive in olfactory neuroblastoma, and mucosal
overlapping peripheral nuclei are often 16% of cases {1084}. malignant melanoma.
present. The solid variant grows in
sheets and lacks septa. Rarely, the Electron microscopy Somatic genetics
tumour can be composed exclusively or Electron microscopy shows some Embryonal rhabdomyosarcoma shows
predominantly of clear cells. A mixed degree of skeletal muscle differentiation allelic loss at 11p15 {271,925}. Alveolar
alveolar and embryonal pattern may ranging from well-formed Z-bands to rhabdomyosarcoma has a consistent
occur. incomplete sarcomeres with thick and translocation, usually t(2:13) (PAX3-
Mitotic figures are usually easy to identi- thin filaments and ribosome-myosin com- FKHR), or less commonly t(1;13) (PAX7-
fy. Pleomorphism is occasionally plexes {724,837}. FKHR) which can be performed on
observed focally. After treatment, there is paraffin-embedded sections {141}.
often increased cytodifferentiation, with Differential diagnosis
the cells exhibiting abundant The differential diagnoses of embryonal Genetic susceptibility
eosinophilic fibrillary cytoplasm {2644}. rhabdomyosarcoma include sinonasal Germline mutations of TP53 in Li-
Pleomorphic rhabdomyosarcoma is rare polyp with stromal atypia {1840} and var- Fraumeni syndrome are found in some
and uncommon in this location. ious sarcomas. The differential diag- children with rhabdomyosarcoma.
noses of alveolar rhabdomyosarcoma
Immunohistochemistry include various round blue cell tumours, Prognosis and predictive factors
There is immunoreactivity for desmin, including lymphoma, sinonasal undiffer- Prognosis is determined by patient age,
muscle specific actin, myoglobin, fast entiated carcinoma, small cell carcinoma histologic subtype, and tumour clinical
myosin, nuclear MyoD1 and nuclear of neuroendocrine type, mesenchymal group {2123}. Younger patients have a
myogenin (skeletal muscle myogenin, chondrosarcoma, PNET/Ewing sarcoma, more favourable prognosis than older

A B
Fig. 1.43 A Alveolar rhabdomyosarcoma of nasal cavity. After chemotherapy, there is increased cytodifferentiation to rhabdomyoblasts. B An embryonal rhab-
domyosarcoma demonstrates remarkably atypical spindle cells with small amounts of eosinophilic cytoplasm.

Malignant soft tissue tumours 39


ICD-O code 9120/3 Lymph node and distant metastasis is
not common at presentation.
Synonyms
Malignant haemangioendothelioma; Macroscopy
malignant angioendothelioma; lymphan- The tumours range up to 8 cm, with a
giosarcoma, haemangiosarcoma. mean of about 4 cm. They are nodular,
polypoid and morulated, soft and friable,
Epidemiology purple to red, often ulcerated with asso-
Angiosarcoma is uncommon, accounting ciated haemorrhage or clot and necrosis
for less than 1% of all sinonasal tract {823,1848,2633,2795,2812}.
malignancies {89,1603,1640,1848}. They
Fig. 1.44 Alveolar rhabdomyosarcoma showing
scant cytoplasm surrounding atypical nuclei. There occur in all ages, with a peak in the 5th Histopathology
are small areas of eccentric eosinophilic cyto- decade, and a male predilection Most sinonasal angiosarcomas are histo-
plasm (left). The tumour cells are strongly (male:female = 2:1). Females tend to be logically low-grade. They infiltrate the
immunoreactive to desmin (right). younger at presentation by up to a adjacent tissues and bone, accompa-
decade {823,1848,2633,2795,2812}. nied by necrosis and haemorrhage. They
comprise tortuous anastomosing vascu-
patients in all rhabdomyosarcoma sub- Etiology lar channels that dissect the stroma, cap-
types. Currently, the 5-year survival is 44- Radiation exposure {1556,1603,1848}, illary-sized vessels and cavernous vas-
69%, and 90% for clinical Group I dis- Thorotrast, arsenic and vinyl chloride are cular spaces. The lining endothelial cells
ease {322,1084}. Adults have a poor reported risk factors {2795}. range from flat to plump spindly to
prognosis, with 5-year survival of <10% epithelioid, and often form papillary tufts.
{1841,1856}. Embryonal rhabdomyosar- Localization Intracytoplasmic vacuoles (neolumen),
coma has a better prognosis than alveo- The maxillary sinus is most frequently often containing erythrocytes, are char-
lar rhabdomyosarcoma {2123}. Botryoid affected. Other sites that may be acteristic of the epithelioid variant. The
and spindle cell variants {346} have a involved primarily or secondarily include degree of nuclear pleomorphism is vari-
better prognosis than embryonal rhab- the nasal cavity and other paranasal able. Mitotic figures, including atypical
domyosarcoma. Furthermore, alveolar sinuses {823,1848,2633,2795,2812}. forms, are variably present {823,1848,
rhabdomyosarcomas with PAX7/FKHR 2633,2795,2812}.
are thought to have better prognosis than Clinical features
PAX3/FKHR tumours {1298}. Patients present with recurrent epistaxis, Immunohistochemistry
profound pallor, a mass lesion, pain Angiosarcomas are immunoreactive for
Angiosarcoma (including headache, otalgia, tooth- CD34, CD31, Factor VIII R-Ag and
ache), nasal obstruction, sinusitis, nasal vimentin, and focally keratin (especially
Definition discharge (often described as foul- the epithelioid variant) and actin {2812}.
A malignant neoplasm of vascular phe- smelling and blood tinged), paraesthesia
notype whose constituent tumour cells and/or loose teeth. The duration of symp- Differential diagnosis
have endothelial features. toms ranges from weeks to months, but The differential diagnoses include granu-
is generally short (median, 4 months). lation tissue, intravascular papillary

A B
Fig. 1.45 Angiosarcoma. A A richly vascularized tumour abuts the cartilage. Many ramifying vascular channels are filled with erythrocytes. B A benign duct (right
lower) is surrounded by a vascular neoplasm with "neolumen" formation and intraluminal erythrocytes. Note the mitotic figure.

40 Tumours of the nasal cavity and paranasal sinuses


endothelial hyperplasia, haemangioma, Clinical features
nasopharyngeal angiofibroma, angiolym- Presenting symptoms include mass,
phoid hyperplasia with eosinophilia, glo- pain, epistaxis, deviation or swelling of
mangiopericytoma, Kaposi sarcoma, tonsils, nasal obstruction, and sinusitis
malignant melanoma, carcinoma and {27,1319,1891,1964,2119}.
large cell lymphoma {30,1388,1976,
2469,2764}. Macroscopy
MPNST is generally globoid to fusiform,
Prognosis and predictive factors pseudoencapsulated, cream-grey and
Patients are usually treated by surgical firm, occasionally associated with sur-
resection with radiation and/or face ulceration. Infiltration into the sur-
Fig. 1.46 Nerve sheath tumour of maxillary nerve.
chemotherapy. Recurrences are com- The nerve (arrow) at the entrance to foramen rounding soft tissues and bone is com-
mon (50%), likely due to incomplete exci- rotundum is enlarged compared to opposite side. mon. The tumours are often large (>5
sion or possible multifocality. Metastasis This is similar to the appearance expected for per- cm) and may be attached to a nerve.
is uncommon, and the predilection sites ineural spread of malignancy. Note the carotid Foci of cyst formation, necrosis and/or
are the lung, liver, spleen, and bone mar- artery (arrowhead). haemorrhage are frequent.
row {1976}. The outcome is more
favourable compared with the almost Tumour spread and staging
uniformly fatal outcome for cutaneous head and neck sarcomas {1231,1562}, Local extension into contiguous struc-
and soft tissue angiosarcomas {823, arising de novo or less commonly in the tures along the path of the trigeminal
1848,2633,2795,2812} setting of neurofibromatosis type 1 (NF1) nerve or through the foramen ovale are
{1059,1231,1795}. De novo MPNST characteristic {1452}. MPNSTs metasta-
peaks in the fourth decade, while those size to the lungs, bones, and/or liver,
Malignant peripheral nerve in the setting of NF1 occur at an earlier {1041} while the epithelioid variant tends
sheath tumour age. There is a female predominance for to involve regional lymph nodes {1437}.
de novo sinonasal MPNST {1041}, and a
Definition male predominance in NF1-associated Histopathology
A malignant tumour of nerve sheath phe- MPNST {774}. MPNSTs can either be spindled (95%) or
notype. epithelioid (5%) {1437}. At low magnifica-
Etiology tion, both types show alternating areas of
ICD-O code 9540/3 Radiation and possibly immunosuppres- dense cellularity with less cellular myxoid
sion may be etiologic factors {1562} areas. Geographic necrosis and perivas-
Synonyms cular accentuation of tumour cells are
Neurogenic sarcoma, malignant schwan- Localization common. The tumour cells are fusiform
noma, neurofibrosarcoma. They commonly arise from the oph- and plump, arranged in tightly packed
thalmic and maxillary branches of the fascicles woven into a vague herring-
Epidemiology trigeminal (5th) cranial nerve, but can bone pattern, while in other areas the
Malignant peripheral nerve sheath involve all of the sinonasal tract and cells are wavy with fibrillar cytoplasmic
tumours (MPNSTs) comprise 2-14% of all nasopharynx {756,1153,1795,2018}. extensions, arranged in a loose myxoid

Fig. 1.47 Epithelioid malignant peripheral nerve sheath tumour (MPNST) of nasal cavity. Tumour composed Fig. 1.48 Epithelioid malignant peripheral nerve
of short fascicles of plump spindly or polygonal cells. sheath tumour of nasal cavity.

Malignant soft tissue tumours 41


A B
Fig. 1.49 Malignant peripheral nerve sheath tumour. A Increased cellularity with focal haemorrhage and hyperchromatic and atypical nuclei. B Highly cellular
tumour with atypical spindle cell population with slightly wavy nuclei. Note focal necrosis at the lower right corner.

background matrix. Focal palisading of tive for desmin and other skeletal muscle Genetic susceptibility
nuclei may be present. The tumour cells markers. MPNST of the sinonasal tract may be
are variably pleomorphic, with a high associated with NF1, typified by germline
nuclear to cytoplasmic ratio and mitotic Differential diagnosis mutation of the NF1 tumour suppressor
activity. Many sinonasal tract MPNSTs, in The differential diagnoses include syn- gene located on chromosome 17 {454}.
contrast to those occurring in other ovial sarcoma, fibrosarcoma, spindle cell
anatomic sites, are histologically and carcinoma, leiomyosarcoma and mucos- Prognosis and predictive factors
biologically low-grade {1041}. An origin al malignant melanoma {1041,2550, Surgery is the treatment of choice,
from a nerve may or may not be appar- 2603}. although radiation and chemotherapy
ent. MPNST with rhabdomyoblasts are may have a palliative role. De novo
known as malignant Triton tumours. Precursor lesions sinonasal MPNSTs have a 5-year survival
MPNST may arise from neurofibroma rate of about 90%, which is superior to
Immunohistochemistry (especially in the setting of NF1) and only that of 50-65% for MPNSTs arising in
The spindle cell variant is usually focally exceptionally from classic schwannoma. other anatomic locations
positive for S100 protein and occasional- {1041,1562,2715}. However, NF1-associ-
ly positive for glial fibrillary acidic protein Somatic genetics ated sinonasal MPNSTs have a 5-year
(GFAP). However, up to 30% of MPNST Both NF1 alleles must be inactivated for survival rate of only about 15% {2119}.
may be negative for S100 protein MPNST to occur in NF1. Malignant pro- Poor prognostic factors include male
{2784A}. The epithelioid variant is dif- gression from neurofibroma in NF1 is gender, high tumour cellularity and high
fusely immunoreactive for S100 protein related to alterations of genes controlling mitotic activity {1041}.
and may mimic malignant melanoma, cell cycle regulation, including TP53
{583,756,2603} but other melanoma {1459} and CDKN2A (which encodes
markers are negative. In malignant Triton p16) {1361,1895}.
tumour, the rhabdomyoblasts are posi-

42 Tumours of the nasal cavity and paranasal sinuses


Borderline and low malignant potential L.D.R. Thompson
J.C. Fanburg-Smith
tumours of soft tissues B.M. Wenig

Desmoid-type fibromatosis
Macroscopy Prognosis and predictive factors
Definition The lesion is tan-white, glistening, and Fibromatosis can be locally aggressive
A locally aggressive, cytologically bland rubbery to firm, and is often infiltrative. It and involve contiguous structures, with
tumour of (myo)fibroblastic phenotype. measures up to 7 cm. Fibromatosis may approximately 20% recurrence rate, but
be multicentric, especially in the setting it does not metastasize {514,903,2643}.
ICD-O code 8821/1 of Gardner syndrome {562}. Recurrence generally occurs within the
first few years and is related to inade-
Synonyms Histopathology quacy of surgical margins {514,903,
Extra-abdominal desmoid, extra-abdomi- This is an infiltrative growth with low to 2643}.
nal fibromatosis, desmoid tumour, aggres- moderate cellularity, comprising broad
sive fibromatosis, juvenile desmoid-type fascicles of bland-looking spindle cells
fibromatosis, infantile fibromatosis. and collagen fibers often arranged in a Inflammatory myofibroblastic
uniform direction. Elongated blood ves- tumour
Epidemiology sels are frequently observed running par-
Although 15% of cases of desmoid-type allel to each other. ICD-O code 8825/1
fibromatosis occur in the head and neck, The spindle cells have a myofibroblastic
the sinonasal tract is uncommonly appearance, with low nuclear to cyto- Inflammatory myofibroblastic tumour
involved {6,903,2643}. All ages can be plasmic ratio and uniformly bland ovoid uncommonly occurs in the sinonasal
affected, especially children {903}. There nuclei with indistinct nucleoli. Mitotic fig- tract {2429}. Please see corresponding
is a male predilection {903}. ures are infrequent and never atypical. section in Tumours of the hypopharynx,
The matrix is collagenized to focally myx- larynx and trachea.
Localization oid, and keloid-like collagen may be
The maxillary sinus and turbinates are present. The main differential diagnoses
usually affected, and the involvement can include hypertrophic scar and fibrosar- Glomangiopericytoma
occasionally be bilateral {514,826, 903}. coma. (Sinonasal-type haemangio-
Diagnosis does not require immunohisto- pericytoma)
Clinical features chemistry, but vimentin and actins are
Symptoms include nasal obstruction, positive. Desmin may be focally positive. Definition
epistaxis, mass, facial pain, tooth dis- A sinonasal tumour demonstrating
placement, and a non-healing tooth Genetic susceptibility perivascular myoid phenotype.
extraction site {514,826,903}. Fibromatosis can be part of Gardner syn-
drome {562}. ICD-O code 9150/1

Fig. 1.50 Desmoid-type fibromatosis. Heavily colla- Fig. 1.51 Glomangiopericytoma. Characteristic diffuse growth within the submucosa, with effacement of the
genized stroma with spindle cells with bland nuclei normal components of the submucosa and preservation of mucoserous glands. The overlying respiratory
and elongated vessels. epithelium remains intact.

Borderline and LMP tumours of soft tissues 43


philic cytoplasm. Mild nuclear pleomor-
phism and occasional mitotic figures
may be present, but necrosis is not
found. Extravasated erythrocytes, mast
cells, and eosinophils are nearly ubiqui-
tously present. Occasionally, tumour
giant cells, fibrosis or myxoid degenera-
tion may be seen.

Immunohistochemistry
Immunohistochemically, glomangioperi-
A B cytoma is distinctly different from soft tis-
sue haemangiopericytoma by yielding
diffuse reactivity for actins, factor XIIIA
and vimentin, and lacking strong diffuse
staining for CD34. Bcl-2, FVIII-R Ag,
CD99 and CD117 are negative {343,
638,1364,2070,2600}.

Differential diagnosis
The differential diagnoses include hae-
mangioma, solitary fibrous tumour, glo-
C D mus tumour, leiomyoma, synovial sarco-
ma and leiomyosarcoma.
Fig. 1.52 Glomangiopericytoma. A A characteristic histomorphologic feature is the presence of prominent
perivascular hyalinization. B Tumour cells are ovoid or polygonal. Note the delicate interspersed vascular
Histogenesis
spaces. C Streaming short spindly cells. Vascular spaces may not be obvious. D Immunostaining for mus-
cle-specific actin is mainly in vessels and focally in tumour cells. This tumour has been known as haeman-
giopericytoma-like tumour or sinonasal
haemangiopericytoma, but it is clinically,
Synonyms show nasal cavity or paranasal sinus morphologically and biologically distinct
Sinonasal haemangiopericytoma; hae- opacification by a polypoid mass lesion, from soft tissue-type or dura-based hae-
mangiopericytoma-like tumour, sinonasal frequently accompanied by sinusitis, mangiopericytoma {446,544,773,936,
glomus tumour; haemangiopericytoma. bone erosion and sclerosis {482,2600, 1723,1724,2276,2386,2689}. The pro-
2729}. posed cell of origin is a modified perivas-
Epidemiology cular glomus-like myoid cell.
Sinonasal glomangiopericytomas Macroscopy
predilect to the nasal cavity and paranasal The generally polypoid tumours range up Prognosis and predictive factors
sinuses, where they comprise <0.5% of all to 8 cm, with a mean size of about 3 cm. Sinonasal glomangiopericytoma is indo-
neoplasms {343,482,2600}. There is a The tumours are beefy red to greyish lent, with an overall excellent survival
very slight female predominance. All ages pink, soft, edematous, fleshy to friable (>90% 5-year survival) achieved with
can be affected (in-utero to 86 years), but masses, often demonstrating haemor- complete surgical excision. Recurrence,
the peak is in the 7th decade. rhage. which develops in up to 30% of cases,
may occur many years after the initial sur-
Localization Histopathology gery {216,343,638,649,2600}. Aggressive-
Tumours most frequently arise unilateral- This is a subepithelial well-delineated but behaving glomangiopericytomas (malig-
ly in the nasal cavity alone, although unencapsulated cellular tumour, effacing nant glomangiopericytomas) are uncom-
extension into paranasal sinuses can or surrounding the normal structures. It is mon {216,343,482, 556,1779,2600}, and
occur. Isolated paranasal sinus involve- comprised of closely packed cells, form- usually exhibit the following features: large
ment is uncommon. Rarely, large ing short fascicles and sometimes size (>5 cm), bone invasion, profound
tumours may appear to arise bilaterally exhibiting a storiform, whorled or pal- nuclear pleomorphism, increased mitotic
{216,343,482,638,649,681,1364,1779, isaded pattern, interspersed with many activity (>4/10 high power fields), necro-
1846,2276,2600,2729}. vascular channels. The latter are in the sis, and proliferation index >10%
form of capillary-sized to large patulous {216,343,1364, 2600}.
Clinical features spaces that may have a staghorn or
The majority of patients present with antler-like configuration. A prominent
nasal obstruction, epistaxis, or non-spe- peritheliomatous hyalinization is charac-
cific findings, such as a mass, polyp, dif- teristic. The neoplastic cells are uniform,
ficulty breathing, sinusitis, headache and elongated to oval, and possess vesicular
nasal congestion, present for an average to hyperchromatic, round to oval to spin-
duration of <1 year. Imaging studies dle-shaped nuclei, and lightly eosino-

44 Tumours of the nasal cavity and paranasal sinuses


A B
Fig. 1.53 Solitary fibrous tumour of nasal cavity. A Circumscribed tumour beneath epithelium. B Bland-looking spindly cells are tightly intertwined with collagen
fibers.

Extrapleural solitary fibrous polypoid and firm. It is composed of a synovial sarcoma, and fibrosarcoma.
tumour variably cellular proliferation of bland Complete surgical removal yields the best
spindle-shaped cells with nondescript patient outcome. Occasional cases may
ICD-O code 8815/1 growth pattern associated with ropy potentially show a malignant behaviour
Solitary fibrous tumours are tumours of keloidal collagen bundles and interlaced {158,834,997,1706,2600,2800, 2914}.
CD34-positive fibroblasts which often thin-walled vascular spaces. The latter See WHO Classification of Tumours of
show a prominent haemangiopericytoma- may be prominent and exhibit a haeman- Soft Tissue and Bone {775}.
like vascular pattern. They are exceeding- giopericytoma-like pattern. Solitary
ly uncommon in the upper respiratory fibrous tumours are immunoreactive for
tract, where they comprise <0.1% of all CD34 and bcl-2, and generally lack actin
neoplasms. All ages can be affected with- immunoreactivity. The diagnosis rests on
out a gender predilection. Tumours can a combination of architectural, cytomor-
affect the nasal cavity, nasopharynx or phologic, and immunophenotypic fea-
paranasal sinuses. Patients present with tures. The differential diagnoses include
nasal obstruction, epistaxis or other non- sinonasal glomangiopericytoma, fibrous
specific symptoms. The tumour is usually histiocytoma, leiomyoma, schwannoma,

A B
Fig. 1.54 Solitary fibrous tumour A Cytologically bland cells are arranged in streaming fashion, with collagen deposited between the cells. Haemorrhage is seen..
B A solitary fibrous tumour strongly and diffusely immunoreactive for CD34.

Borderline and LMP tumours of soft tissues 45


Benign soft tissue tumours J.C. Fanburg-Smith
L.D.R. Thompson

Myxoma Localization activity is scarce. Mucinous degenera-


The turbinates are affected most fre- tion, hyalinization or fibrosis, and
Myxoma is a benign soft tissue tumour quently, {824,1144,1307,1535,1796, adipocytes can be seen, but these fea-
characterized by bland spindle shaped 2114,2635,2695} with isolated cases tures are usually focal and more likely
cells enbedded in hypovascular, myxoid reported in the paranasal sinuses alone seen in larger lesions {1144,1535,1796,
stroma. For details see Chapter 6 or in combination with the nasal cavity 2695}. Vascular leiomyoma (angiomy-
(Odontogenic tumours). {1842}. oma) contains capillary, cavernous or
venous vascular spaces, with the smooth
Clinical features muscle cells being associated with the
Leiomyoma Nearly all patients have nasal obstruc- vessel walls and represents the most
tion, although nasal discharge, epistaxis, common type of benign smooth muscle
Definition headaches and pain are also common tumour in this region.
A benign tumour of smooth muscle phe- {824,2114,2635,2695}.
notype. Immunoprofile
Macroscopy The tumour cells are diffusely and strong-
ICD-O code 8890/0 These tumours have an average size of 2 ly immunoreactive for actins, desmin,
cm, but rare ones may be as large as 10 h-caldesmon and vimentin. The Ki-67
Synonyms cm. They are sessile or polypoid, with a index is usually <5% {1144}.
Angioleiomyoma; vascular leiomyoma; smooth, well circumscribed border.
leiomyoblastoma Differential diagnosis
Histopathology The differential diagnoses include
Epidemiology Leiomyomas are located in the submu- sinonasal glomangiopericytoma, hae-
Primary leiomyomas of the sinonasal cosa, separated from a typically intact mangioma, peripheral nerve sheath
tract are very rare {824,975,1144,1307, mucosa. They are composed of spindled tumour and leiomyosarcoma.
1535,1796,2114,2635,2695}. There is a cells arranged in orderly fascicles,
peak in the 6th decade, although men whorls and intersecting bundles. The Prognosis and predictive factors
are younger than women by a decade at cells have elongated, vesicular to stip- Complete excision is curative.
initial diagnosis. There is a female pled nuclei with blunt ends (cigar-
predilection, with a ratio of 3.5:1. shaped), surrounded by spindled, bipo-
lar, fibrillar eosinophilic cytoplasm. They Haemangioma
Etiology are highly differentiated, with little or no
Other than prior radiation, there are no atypia, although rare cells may exhibit Definition
known risk factors. nuclear pleomorphism {2695}. Necrosis A benign neoplasm of vascular pheno-
and invasion are absent, and mitotic type.

A B
Fig. 1.55 A Myxoma. The stellate cells have thin processes which extend out into the background mucinous matrix. B Vascular leiomyoma. Spindle tumour cells
are identified scrolling off thick muscle-walled vessels.

46 Tumours of the nasal cavity and paranasal sinuses


ICD-O code 9120/0 Symptoms are usually present for a short Venous haemangiomas are composed of
duration {658,823,1037,1189,1270,1738, thick-walled veins with abundant smooth
Synonyms 2056,2333,2753}. muscle, but rarely occur in this location.
Lobular capillary haemangioma; pyo-
genic granuloma; capillary haeman- Macroscopy Immunoprofile
gioma; cavernous haemangioma; epulis The tumours range up to 5 cm, with a The tumour cells are immunoreactive for
gravidarum. mean size of <1.5 cm. Grossly, they Factor VIII related antigen, CD34, CD31
appear as a red to blue submucosal soft, and Ulex europaeus I lectin. The prolifer-
Epidemiology compressible, flat or polypoid lesion, ated blood vessels are enwrapped by
Mucosal haemangiomas of the nasal often with an ulcerated surface. actin-positive pericytes.
cavity, paranasal sinuses and nasophar- Cavernous haemangiomas are spongy
ynx account for 10% of all head and neck on sectioning {658,823,1037,1189,1270, Differential diagnosis
haemangiomas and approximately 25% 1738,2056,2333,2753}. Haemangiomas should be distinguished
of all non-epithelial neoplasms of this from granulation tissue, telangiectasia,
anatomical region. The haemangiomas Histopathology vascular malformations, vascular polyps
occur in all ages, although there is a Haemangiomas are usually localized and (haemorrhagic type), papillary endothe-
peak in children and adolescent males, can be divided into capillary and cav- lial hyperplasia, angiofibroma, bacillary
females in the reproductive years, and ernous types based on the size of the angiomatosis, angiolymphoid hyperpla-
then an equal distribution beyond 40 blood vessels. Haemangiomatosis is a sia with eosinophilia, glomus tumour,
years of age. Patients with cavernous more diffuse lesion often involving con- sinonasal glomangiopericytoma, lym-
haemangiomas tend to be men in the 5th tiguous structures {823,1270,2126}. phangioma, Kaposi sarcoma, and
decade {166,167,658,823,1037,1189, Lobular capillary haemangioma is a cir- angiosarcoma. Haemangioma can be
1270,1738,2056,2333}. cumscribed lesion comprising lobules of distinguished from granulation tissue by
capillaries lined by plump endothelial the lobular arrangement of the capillaries
Etiology cells and supported by prominent peri- in the former and the more parallel
Lobular capillary haemangioma (pyo- cytes. The lobules are separated by a arrangement of vessels in the latter. The
genic granuloma) has an association fibromyxoid stroma. The cellularity of the distinction between a haemangioma and
with injury and hormonal factors (preg- lobules may be quite high. Mitotic figures telangiectasia may be difficult but is facil-
nancy or oral contraceptive use) {2158}. are often observed, but are never atypi- itated in a patient with a known family his-
cal. The surface epithelium often forms tory of hereditary haemorrhagic telang-
Localization collarettes around the lesion {658, iectasia (Osler-Weber-Rendu syndrome)
The septum is most frequently affected 823,1037,1189,1270,1738,2056,2333}. If {658,823,1037,1189,1270,1738,2056,
(specifically, the anterior septum in the lesion is ulcerated and inflamed, the 2073,2333,2600}.
Littles area), followed by the turbinate term pyogenic granuloma has been
(usually the tip) and the sinuses {658, applied. Prognosis and predictive factors
823,1037,1189,1270,1738,2056,2753}. Cavernous haemangiomas are frequent- Haemangiomas are generally easy to
ly intraosseous or involve the turbinates remove, although larger tumours may be
Clinical features or lateral nasal wall. They are composed complicated by excessive bleeding.
Patients present with unilateral epistaxis of multiple, large thin-walled, dilated They should be removed in all ages,
and/or an obstructive painless mass. blood vessels separated by scant fibrous especially in children since aplasia of the
Sinus lesions present as sinusitis, prop- stroma {658,823,1037,1189,1270,1738, nasal cartilages may cause eventual dis-
tosis, mass, anaesthesia or pain. 2056,2333}. figurement. If the tumour is pregnancy-

A B
Fig. 1.56 Haemangioma. A A lobular arrangement around large patulous vessels is seen in this lobular capillary haemangioma. B Cavernous haemangioma with
large, dilated vascular spaces and an intact surface epithelium.

Benign soft tissue tumours 47


B

A C
Fig. 1.57 Schwannoma. A A well circumscribed spindle cell neoplasm has focal degeneration with a lymphoid cuff. B Nuclear palisading around fibrillar cellular
processes is characteristic for a peripheral nerve sheath tumour. C Hyalinized vessel next to a Verocay body with palisaded nuclei.

related, regression will often occur after Clinical features may result in only a thin rim of recogniza-
parturition. Multiple recurrences are The presenting symptoms include ble tumour. Cellular variants exhibit only
more common in children if the lesional obstruction, rhinorrhea, epistaxis, anos- the Antoni A pattern, but no fascicular
bed is not completely eradicated. mia, headache, dysphagia, hearing loss, growth or Verocay bodies.
facial or orbital swelling, and pain
{2018,2351}. Immunoprofile
Schwannoma The tumour cells are strongly and dif-
Macroscopy fusely immunoreactive for S100 protein.
Definition Sinonasal schwannoma ranges in size CD34 only stains some more slender
A usually encapsulated, benign tumour up to 7 cm. It is a well-delineated but cells in the Antoni B areas. Neurofilament
composed of differentiated, neoplastic non-encapsulated globular, firm to rub- is absent. GFAP and keratins may be
Schwann cells. bery yellow-tan mass. The cut surfaces positive.
show tan-grey, yellowish, solid to myxoid
ICD-O code 9560/0 and cystic tissue, commonly with haem- Prognosis and predictive factors
orrhage. Schwannoma is a benign tumour with a
Synonyms very low recurrence potential. Malignant
Neurilemoma, neurilemmoma, benign Tumour spread and staging transformation is exceptional {1690}.
peripheral nerve sheath tumour. The tumour can expand into the orbit,
nasopharynx, pterygomaxillary fossa
Epidemiology and cranial cavity {2351}. Neurofibroma
Less than 4% of schwannomas involve
the nasal cavity and paranasal sinuses Histopathology Definition
{1091,2351}, and they occur in middle- Schwannoma is composed of cellular A benign tumour of peripheral nerve
aged adults with an equal gender distri- Antoni A areas with Verocay bodies and sheath phenotype with mixed cellular
bution {2351}. hypocellular myxoid Antoni B areas. The components, including Schwann cells,
cells are fusiform with elongated fribillary perineurial hybrid cells and intraneural
Localization cytoplasm, and buckled to spindled fibroblasts.
Sinonasal schwannomas arise from the nuclei which show little pleomorphism,
branches of the trigeminal (5th) nerve although scattered large pleomorphic or ICD-O code 9540/0
and autonomic nervous system, and bizarre cells can be present in some
most commonly involve the ethmoid and cases. Nuclear palisading is often evi- Epidemiology
maxillary sinuses, followed by the nasal dent in some foci. There are frequently Neurofibromas are extremely rare in the
cavity, sphenoid and frontal sinuses small to medium-sized vessels with ecta- sinonasal tract. In NF1-related neurofi-
{1023,1091,2018,2351}. Cellular sia, thrombosis and perivascular hyalin- bromas, patients tend to be younger, with
schwannoma tends to be located in the ization in the Antoni B areas. Extensive a male predominance {2745}. For the
midline. degenerative changes can occur, and more common sporadic neurofibromas,

48 Tumours of the nasal cavity and paranasal sinuses


A B
Fig. 1.58 Neurofibroma. A A central "circumscribed" area has cellular and hypocellular areas. There is nerve tissue noted at the periphery. B "Wavy" nuclei with
bundles of collagen separated by a myxoid, degenerated stroma.

all ages may be affected, although submucosal location with an intact sur- not associated with NF1 {1091,1095,
patients tend to be older with an equal face epithelium {61,1095}. 2018}.
gender distribution.
Histopathology Prognosis and predictive factors
Localization Neurofibromas are generally submucosal Neurofibromas are benign and have a
The tumour arises from the ophthalmic or paucicellular lesions. They are com- very low recurrence rate. A small per-
maxillary branches of the trigeminal (5th) posed of spindled cells with wavy, dark- centage of cases may undergo malig-
nerve and is most commonly located in staining nuclei and scanty cytoplasm, in nant transformation.
the maxillary and ethmoid sinuses and/or a background of wavy collagen fibres,
nasal cavity {288}. Plexiform neurofibro- myxoid stroma and mast cells. The cen-
ma may occur in the sinonasal area tre of the lesion usually shows residual Meningioma
where it is found in the maxillary sinus neurites.
{817}, usually associated with NF1. Definition
Immunoprofile A benign neoplasm of meningothelial
Clinical features The tumour is diffusely immunoreactive cells.
Symptoms include epistaxis, rhinor- for S100 protein, but the proportion of
rhoea, swelling, mass, obstruction, and positive cells is lower than that in ICD-O code 9530/0
pain {61,2018}. schwannoma. CD34 stains the admixed
fibroblasts. Epidemiology
Macroscopy Primary extracranial (ectopic, extracal-
The tumour is firm, glistening, grey-tan, Genetic susceptibility varial) meningiomas of the sinonasal
fusiform, and sometimes polypoid, in a Sinonasal neurofibromas are generally tract are rare, comprising <0.5% of non-

A B
Fig. 1.59 Meningioma. A Meningothelial growth and "whorling". Note the squamous mucosa intimately associated with the meningioma. B "Whorling" of cytologi-
cally bland meningeal cells is prominent in this meningioma.

Benign soft tissue tumours 49


epithelial neoplasms {814,873,1109, fragments of bone are frequently visible. Differential diagnosis
1781,2019,2221,2599}. They should be The differential diagnoses include carci-
distinguished from intracranial menin- Tumour spread and staging noma, melanoma, aggressive psammo-
giomas with extracranial/extraspinal Primary extra-cranial meningiomas have matoid ossifying fibroma and follicular
extension into the sinonasal tract {721, not been reported to metastasize {814, dendritic cell sarcoma/tumour {2599,
814,2599}. Any age can be affected, and 873,2019,2599}. 2771}.
there is a slight female predilection. Men
tend to be younger than women by about Histopathology Histogenesis
a decade. Sinonasal meningiomas can exhibit a Meningiomas are derived from arachnoid
variety of histological patterns, most cap cells located extra-cranially within
Localization commonly meningotheliomatous, char- the sheaths of nerves or vessels.
Sinonasal tract meningiomas involve acterized by lobules of cells with whorl
both the nasal cavity and paranasal formation, indistinct cell borders, and Prognosis and predictive factors
sinuses more frequently than either loca- bland nuclei with delicate chromatin Complete surgical extirpation is some-
tion alone. Most tumours are left-sided {1329,2599}. Intranuclear pseudoinclu- times difficult, and accounts for the up to
{814,873,1109,1781,2019,2221,2599}. sions and psammoma bodies are com- 30% recurrence rate {1109,2019,2599}.
mon. Other variants can also occur in the The rare deaths are related to compro-
Clinical features sinonasal tract, such as transitional, mise of mid-facial structures or compli-
Symptoms include a mass (often poly- metaplastic (lipidized cells within cations of surgery, rather than the
poid), nasal obstruction, epistaxis, tumour), and psammomatous type aggressive nature of the tumour.
sinusitis, pain, headache, seizure, {1329}. Histologic features (such as hypercellu-
exophthalmos, periorbital edema, visual larity, nuclear pleomorphism, necrosis),
disturbance, ptosis, and facial deformity Immunoprofile proliferation index and progesterone
{814,873,1109,1781,2019,2221,2599}. Meningiomas are immunoreactive for receptor status do not influence progno-
Symptoms are present for an average of epithelial membrane antigen and sis {1138,1139,1426,1666,2599}.
4 years. vimentin, but usually negative for cytok-
eratin, although rare lesions can exhibit
Macroscopy focal and weak cytokeratin immunoreac-
The tumours range up to 8 cm, with a tivity. They are frequently positive for
mean of about 3 cm. They may infiltrate progesterone receptor (50%) and occa-
bone and rarely ulcerate the mucosa. sionally for oestrogen receptor (25%).
The cut surface is grey-white, tan or pink, Glial fibrillary acidic protein and smooth
gritty, firm to rubbery. Calcifications and muscle actin are negative.

50 Tumours of the nasal cavity and paranasal sinuses


Malignant tumours of bone and K. Saito
K.K. Unni
cartilage

Chondrosarcoma, including drosarcoma involves the mandible and


mesenchymal maxilla almost equally.
chondrosarcoma
Clinical features
Definition Patients with involvement of the nose
Chondrosarcoma is a malignant tumour present with nasal obstruction. Painful
of hyaline cartilage. swelling is common with other sites of
Mesenchymal chondrosarcoma is a involvement.
malignant small round cell neoplasm with
focal cartilaginous differentiation, and Imaging A
often with a pericytomatous vascular pat- On plain radiographs, both tumours
tern. show osteolysis with stippled calcifica-
tion, cortical destruction and possible
ICD-O codes soft tissue extension. Computerized
Chondrosarcoma 9220/3 tomograms and magnetic resonance
Mesenchymal chondrosarcoma images are useful in evaluating the
9240/3 extent of disease {463}.

Synonym Macroscopy
Polyhistioma Chondrosarcomas are lobulated pale-
blue glistening masses that may show B
Epidemiology cystic change. Mesenchymal chon-
These tumours are rare in the facial drosarcomas have the fish-flesh appear-
skeleton. Chondrosarcomas account for ance of high-grade sarcomas; chalky
<16% of all sarcomas of the nasal cavity, foci of calcification may offer a diagnos-
paranasal sinuses and nasopharynx tic clue.
{256,463,1367,4045}. Chondrosarcoma
affects older adults, with a male predilec- Histopathology
tion. Chondrosarcomas are often lobulated,
Mesenchymal chondrosarcoma is and show round to oval cells in lacunae
extremely rare, and affects young adults, with a blue chondroid matrix that may C
with a female predilection. show myxoid changes. Most are low- Fig. 1.62 Mesenchymal chondrosarcoma. A Small
grade. Increased cellularity and perme- cells with scant cytoplasm arranged in a "haeman-
Localization ation of the intertrabecular spaces of giopericytoma-like" pattern around open vascular
Chondrosarcoma involves the alveolar bone, if identified, are the most important channels without chondroid matrix identified in this
portion of the maxilla, the maxillary sinus features that distinguish chondrosarco- field. B Normal Haversian bone is invaded by
or the nasal septum. Mesenchymal chon- ma from chondroma. Radiological corre- chondrosarcoma which blends with areas of undif-
ferentiated mesenchymal cells (lower right). C The
chondroid matrix shows lacunar spaces filled with
the same nuclei identified in the mesenchymal
component. Vague lacunar spaces surround the
undifferentiated mesenchymal cells which display
coarse nuclear chromatin in irregularly shaped
nuclei. From P.D. Knott et al. {1343}.

lation is required for a definitive diagno-


sis {4045}.
Mesenchymal chondrosarcomas show a
mixture of hyaline cartilage and small
Fig. 1.60 Chondrosarcoma. CT shows a destructive Fig. 1.61 Chondrosarcoma. Glistening pale blue round to oval cells with hyperchromatic
lesion arising in nasal cavity invading into maxillary fragments of cartilage. nuclei, frequently arranged in a pericy-
sinus. Note focal calcification. tomatous vascular pattern. These cells

Malignant tumours of bone and cartilage 51


Fig. 1.63 CT of an osteosarcoma of the maxilla. The Fig. 1.64 CT of an unusual osteosarcoma arising in Fig. 1.66 Osteosarcoma. Gross specimen of
destructive lesion extends into soft tissue, produc- nose. The mineral present suggests cartilage dif- osteosarcoma. The tumour is fleshy and surrounds
ing a sunburst pattern of tumour bone. ferentiation. the root of a tooth.

are frequently immunoreactive for CD99. ICD-O code 9180/3 out pain and loosening of teeth.
The relative amounts of the two elements On plain radiograph, the tumour is usual-
are quite variable. The chondroid lobules Synonym ly lytic but may be sclerotic or mixed. In
have the appearance of well-differentiat- Osteogenic sarcoma over half of the lesions, there is soft tissue
ed chondrosarcoma. extension. Computerized tomogram is
Epidemiology better in demonstrating matrix mineral-
Prognosis and predictive factors Osteosarcomas of the jaws are very rare, ization and soft tissue extension {1457}.
Chondrosarcomas are associated with with an incidence of 0.7 per million {868}.
an excellent prognosis if the lesions are They are extremely rare in other head Macroscopy
completely resected. Approximately 20% and neck sites. Patients are a decade The tumours vary from the lobulated blue
of patients die of tumour, most often with older than those with extragnathic colour of cartilage to fleshy white to
uncontrolled local recurrence osteosarcomas {455,868,1366}. There is densely sclerotic masses.
{2223,4045} a modest male predilection.
Mesenchymal chondrosarcoma is a Histopathology
high-grade tumour with an unpredictable Etiology Osteosarcomas of the jaws are generally
prognosis. Patients with tumour of the Over 10% of tumours are post-radiation, better differentiated than extragnathic
facial skeleton do better than those with including Thorotrast exposure. osteosarcomas. There is commonly
tumours of the remainder of the skeleton chondroblastic differentiation, character-
{2687}. Localization ized by lobules of atypical-appearing
The maxilla and the mandible are affect- chondrocytes in lacunae. There is a typi-
ed almost equally. In the maxilla, the cal condensation of nuclei toward the
Osteosarcoma alveolar ridge and the antrum are pre- periphery of the lobules, where sheets of
dominantly involved, whereas in the spindle cells may be seen. The centre of
Definition mandible, the body is the main site. the chondroid lobules shows bone for-
Osteosarcoma is a primary malignant mation in the form of trabeculae.
tumour of bone in which the neoplastic Clinical features The remainder show osteoblastic or
cells produce osteoid or bone. Symptoms include swelling with or with- fibroblastic features. It is unusual to see
benign giant cells within the tumour.

Prognosis and predictive factors


Some studies have shown that patients
with osteosarcoma of the jaws have a
better survival than those with extrag-
nathic osteosarcomas {455,1366}.
However, some other studies {206,868}
have not confirmed this finding.
Complete surgical resection is associat-
ed with better prognosis.

Fig. 1.65 Osteoblastic osteosarcoma with a typical filigree pattern of osteoid formation.

52 Tumours of the nasal cavity and paranasal sinuses


Benign tumours of bone and G. Jundt
F. Bertoni
cartilage K.K. Unni
K. Saito
L.P. Dehner

Fibrous dysplasia Epidemiology


Giant cell tumour (GCT) accounts for
See Chapter 6 for details. about 5% of all bone tumours. Most
cases occur in patients between 20 and
50 years {523,775,1146,1369}. CGT is
Giant cell lesion slightly more common in women than in
men {523,775,2831}.
Synonym
Giant cell granuloma. Localization
In the skull, in the absence of Paget dis-
Extragnathic giant cell lesion may rarely ease, the bones developing from endo-
involve the paranasal sinuses {2161, chondral ossification, i.e. sphenoid, eth-
2243,2479,2648,2839}. Symptoms moid and temporal bone, are almost
include pain, visual disturbances, exoph- exclusively involved {207,496,870,875}.
thalmos, epistaxis, lacrimation, anaes-
thesia and swellings {728,1867,2322, Clinical features Fig. 1.67 Giant cell tumour. Large geographic oste-
2839}. Signs and symptoms olytic lesion (OL) at the base of the skull with an
Plain radiographs show nonspecific Clinical symptoms of GCTs depend on irregular dorsal margin.
osteolytic defects. Their extent and pos- the site of occurrence. Sphenoidal
sible impingement on brain or orbital lesions are associated with headache, the sphenoid sinus or the sella turcica,
contents is better visualized in cross sec- diplopia and vision impairment or cranial displacing the pituitary gland, is best
tional studies (CT, MRI) {2322,2839}. nerve palsies (II, III, IV, V, VI and combi- seen on cross-sectional studies (CT,
Brown tumour of hyperparathyrodism nations). Temporal bone involvement MRI) {983,2177,2556}.
should be excluded. causes deafness (conductive: middle
Please refer to Chapter 6 for details. ear and mastoid; sensorineural com- Histopathology
bined with vertigo: petrous bone), The tumour is characterized by abundant
retroauricular pain, or swelling {676, multinucleated osteoclastic giant cells,
Giant cell tumour of bone 2328}. Duration of symptoms ranges with up to 50-100 nuclei, that are evenly
from weeks to years {207}. distributed among sheets of stromal
Definition cells. In some areas, ovoid to plump
An aggressive but benign neoplasm Imaging spindled stromal cells are more promi-
containing spindle-shaped stromal cells, On plain radiographs and CT, GCT pres- nent, and giant cells may be lacking.
mononuclear round to oval cells resem- ents with a nonspecific expansile and Regressive changes, including fibrosis,
bling histiocytes, and abundant evenly destructive osteolysis, generally lacking foam cell aggregates, haemosiderin
distributed osteoclastic giant cells. any matrix mineralization. The lesion deposits, and even necrosis may be
shows contrast enhancement on CT present. Small foci of reactive woven
ICD-O code 9250/1 {207,2177,2806}. A soft tissue mass in bone are often seen. Mitoses are easily

A B C
Fig. 1.68 Central giant cell lesion/granuloma. A Osteodestructive lesion of the right maxillary sinus extending into the nasal cavity, eroding the orbital floor and
destroying the alveolar process of the maxilla with protrusion into the oral cavity.. B On T1 images the signal intensity is low. C Fluid levels are indicative for a
pseudocystic (ABC-like) component.

Benign tumours of bone and cartilage 53


A B
Fig. 1.69 Giant cell tumour. A Clustering of multinucleated giant cells. On the right are remnants of Rathke`s pouch with ciliated columnar epithelium. B Densely
packed giant cells with up to 20 nuclei. Intermingled are macrophages and oval stromal cells.

found in the mononuclear cells, but atyp- Chondroma Localization


ical ones do not occur and, if present, The osteomas may be single or multiple;
are a strong indicator for progression to Chondromas of the sinonasal tract are central or on the bone surface, where
malignant GCT {272}. Intravascular extremely rare, and any cartilaginous they can be sessile or rarely pedunculat-
growth, particularly in the tumour periph- tumour greater than 2 cm occurring in ed. They occur most commonly in the
ery, may be noted, but has no prognostic this site should be considered potentially frontal and ethmoid sinuses. The maxil-
relevance {207,775,2831}. malignant until proven otherwise. lary and sphenoid sinuses are infre-
quently involved. In the jaws, the angle of
Histogenesis ICD-O code 9220/0 the mandible is more frequently involved
The ovoid to plump spindled stromal than the coronoid process or condyle.
cells represent the active proliferating
tumour cell pool {2190}, capable of Osteoma Clinical features
secreting cytokines and differentiation Osteomas are often asymptomatic and
factors, including receptor activator of Definition incidentally discovered. However they
nuclear factor ligand (RANKL) {2207}. A benign lesion composed of mature can produce pain or symptoms related to
These factors attract monocytes, the bone with a predominantly lamellar struc- the location. Multiple jaw osteomas are a
second cell type in GCT, and promote ture. frequent component of the Gardner syn-
fusion to osteoclasts, the third cell type in drome (a form of familial adenomatous
GCT. The monocytes and osteoclast-like ICD-O code 9180/0 polyposis), being found in 70-90% of
giant cells represent a non-neoplastic patients.
tumour component {775,2831}. Synonyms Osteomas are radiodense, sharply
In the jaws and calvaria, the terms exos- defined, well-circumscribed lesions
Genetics tosis and osteoma have been used inter- occurring in either a central or peripheral
Cytogenetic studies reveal telomeric changeably {131}. The term osteoma location.
associations (TAS) as the most frequent should be used in a restricted sense lim-
chromosomal aberration {272}. Some ited to lesions of the paranasal sinuses, Macroscopy
GCTs show rearrangements in 16q22 or facial bones and orbit, although it has The lesion is a well-circumscribed white
17p13, similar to aneurysmal bone cyst, been used in the literature to describe bony mass, which is occasionally poly-
which is often associated with GCT. calvarian and mandibular ivory exosto- poid or exophytic.
These rearrangements may indicate the sis, surface (juxtacortical) osteoma of the
possible presence of an aneurysmal long bones, torus palatinus and torus Histopathology
bone cyst component {775}. mandibularis. Osteoma is characterised by compact
cortical bone with scanty intervening
Prognosis and predictive factors Epidemiology fibrovascular stroma. In some cases,
GCT of the skull is a locally aggressive Among patients with sinonasal radi- there is a peripheral rim of dense sclerot-
lesion. Treatment consists of complete ographs taken for a variety of reasons, ic lamellar bone surrounding trabeculae
removal, if possible. Radiotherapy is also up to 1% have been found to have osteo- of lamellar or occasionally woven bone
applied {207,1146}. Histologically malig- mas. It may occur at any age, but espe- separated by fibrofatty vascular tissue.
nant GCT of the skull has been rarely cially in young adults. There is a 2:1 male
described, sometimes associated with predominance. Genetic predisposition
Paget disease {365,1474}. The presence of multiple osteomas is an

54 Tumours of the nasal cavity and paranasal sinuses


important clue that the patient may have tumours occurring outside the head and by salicylates. It is very rare in the head
Gardner syndrome. neck. Females are more commonly and neck. It occurs in young patients
affected than males. (first three decades), with male predomi-
Prognosis and predictive factors nance. On plain radiographs, dense cor-
No therapy is required unless the lesion Localization tical sclerosis surrounds a radiolucent
causes cosmetic or functional problems. More than half of the lesions occur in the nidus. Histologically, the nidus shows
A local resection is the treatment of coronoid process of the mandible. The interconnected, ossified woven bone
choice in such circumstances. condyle can also be involved. rimmed by osteoblasts. Fibrous tissue,
vessels and multinucleated giant cells
Clinical features are identified in between the bony tra-
Chondroblastoma and Osteochondroma involving the coronoid beculae. See WHO Classification of
chondromyxoid fibroma process or the condyle causes difficulty Tumours of Soft Tissue and Bone {775}.
in opening the mouth or dysfunction of
ICD-O codes the temporomandibular joint. On plain
Chondroblastoma 9230/0 radiographs, flaring of the cortex in con- Osteoblastoma
Chondromyxoid fibroma 9241/0 tinuity with the underlying bone and vary-
ing degrees of calcification and/or ossifi- ICD-O code 9200/0
Chondroblastomas and chondromyxoid cation are present. The cartilaginous cap
fibromas are rare in the head and neck is of variable thickness. Definition
{177,988,1024,1120,1185,1348,1349, A rare, benign, bone-forming tumour in
1356,1466,2559,2683,2730}. See WHO Macroscopy which osteoblasts rim woven bony tra-
Classification of Tumours of Soft Tissue A cartilaginous cap covers the bony pro- beculae, forming a mass usually over 2
and Bone {775}. trusion. cm.

Histopathology Epidemiology
Osteochondroma (exostosis) The cap consists of hyaline cartilage, Osteoblastoma is rare, and 90% of cases
and the osteochondral junction resem- occur below the age of 30 years. It is
Definition bles the growth plate. A well-defined more common in males.
A pedunculated or sessile exophytic zone of enchondral ossification matures
bony projection with a cartilaginous cap. into cancellous bone with marrow. Localization
The bony component is continuous with In the head and neck, the most common
the underlying bone. Prognosis and predictive factors site of involvement is the jaws, followed
Excision is curative. No recurrence or by the cervical vertebrae and the skull
ICD-O code 9210/0 malignant transformation has been {1570}. The mandible is affected about
reported in osteochondromas of the two to three times more often than the
Epidemiology jaws. maxilla. Most arise in the body of the
Osteochondroma is one of the most com- mandible, rarely in the midline or coro-
mon lesions of the long and flat bones. It noid process.
may be solitary or multiple. In the facial Osteoid osteoma
bones, osteochondromas are very rare Clinical features
and almost invariably single. ICD-O code 9191/0 Osteoblastomas of the jaw cause
Osteochondromas of the facial skeleton swelling and toothache, and in the cervi-
have not been reported in the setting of Osteoid osteoma is a benign bone-form- cal spine, pain, scoliosis and nerve root
multiple hereditary exostoses. ing tumour of limited growth potential, compression. In contrast to osteoid
The mean age at diagnosis is 40 years, usually less than 1.5 cm, typically asso- osteoma, the pain is rarely nocturnal and
which is older than that of patients with ciated with nocturnal pain that is relieved not relieved by salicylates.

A B C
Fig. 1.70 A Osteoma of the right parietal bone. Mature lamellar bone with osteon-like structures. B Osteoid osteoma. Osteoblasts surround the trabeculae. C Nidus
of an osteoblastoma, showing a single layer of osteoblasts lining the bony trabeculae.

Benign tumours of bone and cartilage 55


whose mixed chondroid, stromal, and
cystic features are morphologically simi-
lar to the chest wall hamartoma.

Epidemiology
There are only 12 reported cases
{45,1140,1284,1311,1678}. A pleuropul-
monary blastoma was diagnosed in one
of these children {1678}. One infant with
A B the prenatal detection of hydrocephalus
also had absence of the corpus callosum
Fig. 1.71 Nasal chondromesenchymal hamartoma. A Multiple tumour fragments with a mucosal surface
and nodules of cartilage. B Cartilaginous nodule, surrounded by cellular stroma. and hypoplasia of the cerebellar vermis.
The age range is newborn to 16 years
with most cases presenting in the first
On plain radiographs, osteoblastoma is a as secondary aneurysmal bone cyst-like year of life, often before 3 months of age.
sharply circumscribed, oval-round lytic changes. At the periphery, there is no There is a male predilection of approxi-
lesion. It may have a mixed lytic and permeative growth pattern. The histolog- mately 3:1.
sclerotic pattern, reflecting the degree of ic features are identical to cementoblas-
mineralization of the matrix. A reactive toma. Tumours showing direct continuity Clinical features
bony shell is detected at the periphery. with the root of a tooth are preferably Signs and symptoms
Radiographic features indistinguishable termed a cementoblastoma. Respiratory difficulty, the discovery of an
from malignant lesions are reported in intranasal mass and/or facial swelling are
about one-third of cases. Prognosis and predictive factors the most common presenting features.
Curettage or local excision is the treat- The respiratory distress is detected in the
Macroscopy ment of choice. In the few cases with immediate neonatal period or develops
It is a red and gritty lesion often with cyst recurrence, a further conservative treat- later during feedings with accompanying
formation. The border between the ment will control the disease. cyanosis. A unilateral mass in the nasal
tumour and the host bone is very sharp. cavity is the most consistent finding on
physical examination.
Histopathology Ameloblastoma
Woven bony trabeculae, rimmed by Imaging
osteoblasts are haphazardly distributed Ameloblastomas are very rare in the A mass density in the nasal cavity and/or
within a richly vascularized fibrous stro- sinonasal tract and nasopharynx {1554, the contiguous paranasal sinuses is
ma accompanied by osteoclast-like giant 2257}. See Chapter 6 on odontogenic noted on radiographic examination.
cells. Mitotic figures may be present, but tumours for details. Magnetic resonance or computed tomo-
without atypical forms. Degenerative graphic imaging discloses a dense mass
nuclear atypia is occasionally present. ICD-O code 9310/0 with or without calcifications or a hetero-
When large plump osteoblasts with geneous signal in a lesion with cystic fea-
prominent nucleoli predominate, the tures. Extension or involvement of the
tumour is often referred to as epithelioid Nasal chondromesenchymal maxillary and/or ethmoid sinuses and
osteoblastoma or aggressive osteoblas- hamartoma erosion into the anterior cranial fossa are
toma. However, these histologic features other accompanying changes.
are not necessarily indicative of aggres- Definition
sive behaviour. Rarely, focal areas of hya- A tumefactive process arising in the Macroscopy
line cartilage may be identified, as well nasal cavity and/or paranasal sinuses Multiple solid and cystic fragments of tis-

A B C
Fig. 1.72 Ameloblastoma. A An intact respiratory surface is subtended by a complex ameloblastic neoplasm with many lobules displaying a central stellate retic-
ulum surrounded by the palisaded columnar ameloblastic epithelium. B Reverse polarity of the hyperchromatic columnar nuclei away from the basement mem-
brane and towards the stellate reticulum. C Granular cell ameloblastoma showing islands of granular cells.

56 Tumours of the nasal cavity and paranasal sinuses


sues, some with identifiable foci of carti-
lage reflect the piecemeal nature of the
resection in most cases. The precise site
of origin of the mass has varied from the
nasal septum, upper nasal cavity or floor
of the anterior cranial fossa.

Histopathology
All tumours have had nodules of carti-
lage varying in size, contour and degree
of differentiation. Some nodules resem-
ble the chondromyxomatous nodules of
a chondromyxoid fibroma, whereas oth-
ers are well-differentiated cartilaginous
nodules. At the periphery of the chon-
droid nodules, there is a loose spindle
cell stroma or an abrupt transition to A
hypocellular fibrous stroma. Other areas
can have a fibro-osseous appearance
with a prominent cellular stromal compo-
nent and small ossicles or trabeculae of
immature woven bone resembling
fibrous dysplasia. Yet another common
pattern is a cellular stroma with hyalin-
ized nodules with or without perivascular
stromal cells displaying a pericytoma-
tous pattern. Cellular myxoid foci are
similar in some respects to cranial/nodu-
lar fasciitis. The aneurysmal bone cyst-
like areas are surrounded by a stroma
rich in multinucleated giant cells.

Immunoprofile
The cartilage, mature or immature, is B
immunoreactive for S-100 protein. The Fig. 1.73 Nasal chondromesenchymal hamartoma. A Loose spindle cell proliferation with a myxoid back-
spindled stroma is immunoreactive for ground. B The interface between the immature chondroid tissue and stroma resembles a chondromyxoid
smooth muscle actin and vimentin. fibroma.

Differential diagnosis sinuses and is associated with the


The differential diagnosis depends on Carney complex in some cases. None of
the particular combination of microscop- the patients with nasal chondromes-
ic features present in the biopsy or resec- enchymal hamartoma are known to have
tion. Since cartilage is the dominant the Carney complex {1678}.
component, differential diagnoses
include chondromyxoid fibroma and Prognosis and predictive factors
chondroblastoma {1858}. Other differen- Information on the clinical behaviour is
tial diagnoses may include aneurysmal incomplete, but prognosis is apparently
bone cyst, fibrous dysplasia, cranial favourable. There is some capacity for
fasciitis and osteochondromyxoma continued local growth when the resec-
{334}. Interestingly, the latter tumour may tion is incomplete.
be congenital, may involve the paranasal

Benign tumours of bone and cartilage 57


Haematolymphoid tumours A.C.L. Chan
J.K.C. Chan
M.M.C. Cheung
S.B. Kapadia

Non-Hodgkin lymphoma peripheral T-cell lymphomas, such as suppression are also EBV-related {511}.
anaplastic large cell lymphoma, can also
Definition occur in the sinonasal region. Localization
Primary non-Hodgkin lymphomas (NHL) Lymphomas of the nasal cavity are often
of the nasal cavity or paranasal sinuses Lymphomas presenting in the paranasal locally destructive, with obliteration of the
are defined as lymphoid cell neoplasms sinuses are frequently B-cell lymphomas, nasal passages and maxillary sinuses. In
in which the bulk of disease occurs in with diffuse large B-cell lymphoma particular, extranodal NK/T cell lym-
these anatomic sites. (DLBCL) being the most common phoma can involve the adjacent alveolar
{5,551,1837}. Other B-cell lymphomas bone, hard palate, orbit and nasophar-
Synonyms that can involve the sinonasal regions ynx in over half of the cases {1948}.
Most cases described in the past as include Burkitt lymphoma, follicular lym- Lymphomas of the paranasal sinuses
polymorphic reticulosis, malignant mid- phoma, extranodal marginal zone B-cell commonly show bony destruction and
line reticulosis, lethal midline granuloma lymphoma of MALT type, and mantle cell local extension to adjacent structures
or angiocentric immunoproliferative lymphoma {5}. Please also refer to the including the orbit, palate, nasal cavity,
lesion, are now reclassifiable as extran- section of non-Hodgkin lymphomas in nasopharynx, and soft tissues in the
odal NK/T cell lymphoma of nasal-type. Chapter 4 on tumours of the oral cavity cheek and infratemporal fossa {511,
and oropharynx. 1836,1837}. Maxillary sinus is the most
Epidemiology NHL of the nasal cavity and paranasal commonly involved paranasal sinus.
Malignant lymphoma is the second most sinus is primarily a disease of adults, with
common malignancy of the nasal cavity male predominance. Patients with extra- Clinical features
and paranasal sinuses, following squa- nodal NK/T cell lymphoma of nasal-type Patients may present with nasal obstruc-
mous cell carcinoma {1013}. It accounts have a male to female ratio of 3:1, and a tion, epistaxis, nasal discharge, pain and
for 14% of all cancers in these sites median age of 53 years {420}. Patients nasal swelling or facial swelling. Locally
{1013}. with DLBCL are generally one decade advanced cases can cause destruction
Although many different types of NHL older (median age 63 years), and the of midline facial structures. The nasal
can occur in the nasal cavity, the most male to female ratio is 1.2:1 {5,420}. septum or palate may be perforated.
common lymphoma type is extranodal Children may rarely present with NHL of Extension to the orbits can lead to prop-
NK/T cell lymphoma of nasal-type, espe- the nasal cavity and the paranasal sinus- tosis and visual disturbance. Regional
cially in Asian populations {5,420}. The es, with Burkitt lymphoma being the most lymph node involvement may occur in
relatively high prevalence of this lym- common type {2808}. some patients. Occasional patients have
phoma type in Asians and Latin systemic symptoms including fever and
Americans also accounts for the higher Etiology weight loss. Haemophagocytic syn-
overall incidence of nasal lymphomas in The etiology is unknown, but extranodal drome with pancytopenia occurs at pres-
these populations as compared with NK/T cell lymphoma of nasal-type is entation in a minority of patients with
Caucasian populations {58,2104}. Other strongly associated with Epstein-Barr extranodal NK/T cell lymphoma of nasal-
virus (EBV) irrespective of the ethnic type {420,2533}.
background of the patients {68,376,
1107,1263,1347,2671,2828}. There is
only a weak association between B-cell
lymphomas in the nasal cavity and the
paranasal sinuses with EBV {376,511,
2617,2740}.
Immunosuppression (e.g. post-trans-
plant, HIV infection) is associated with an
increased risk of developing NHL,
including in the nasal cavity and
paranasal sinuses. Although the majority
Fig. 1.74 Extranodal NK/T cell lymphoma of nasal
of the cases in immunosuppressed
cavity in a 69-year-old patient who presented with patients are DLBCL {511,2068}, extran- Fig. 1.75 CT scan of nasal NK/T cell lymphoma. The
painful nasal swelling. MRI showed tumour odal NK/T cell lymphoma of nasal-type tumour involves the nasal cavity mainly on the left
involvement of the left nasal cavity, left ethmoidal has also been reported {328}. Most of the side, with extension to the medial part of the left
and maxillary sinuses. NHL that arise in the setting of immuno- maxillary sinus and the left ethmoidal sinuses.

58 Tumours of the nasal cavity and paranasal sinuses


A B
Fig. 1.76 Nasal NK/T cell lymphoma. A In this example, the mucosa is intact and expanded by a diffuse infiltrate of lymphoma cells. B The mucosal lymphoid infil-
trate is destructive, resulting in separation and loss of mucosal glands.

A B
Fig. 1.77 Nasal NK/T cell lymphoma. A This case shows marked pseudoepitheliomatous hyperplasia, mimicking squamous cell carcinoma. B Note angiocentric
and angiodestructive growth.

Tumour spread and staging type is characterized by a diffuse lym- Immunoprofile and genetics
The majority (80%) of patients with extra- phomatous infiltrate expanding the nasal The lymphoma most commonly exhibits
nodal NK/T cell lymphoma of nasal-type or paranasal sinus mucosa, with wide an NK-cell immunophenotype of CD2+,
have localized disease at presentation separation and destruction of the mucos- surface CD3(Leu4)-, cytoplasmic CD3+,
(Stage IE/IIE) {420,1500,1505}. Bone al glands, which may undergo a peculiar CD56+ {1196}. CD43 and CD45RO are
marrow involvement at presentation is clear cell change. Extensive coagulative commonly positive, but other T-cell mark-
uncommon {2810}. Although extranodal necrosis and frequent apoptotic bodies ers (including CD5) and NK-cell markers
NK/T cell lymphoma often shows local- are very common, as are ulceration, (CD16, CD57) are usually negative. The
ized disease at presentation, spread to angiocentricity, angiodestruction and fib- tumours commonly exhibit a cytotoxic
other sites (such as skin, gastrointestinal rinoid deposits in vessel walls. The lym- phenotype with expression of perforin,
tract, liver, lymph node, testis) during the phoma cells vary in size in different TIA1, and granzyme B {662,1773,1878,
course of disease is common. cases, ranging from small through medi- 1935}. Fas (CD95) and Fas ligand
Most of the patients (75%) with DLBCL of um-sized to large. Some nuclei have an expression are frequent, and may
the nasal cavity and the paranasal sinus- irregular outline, while others can be account for the extensive necrosis
es present with low clinical stage (IE/IIE) round or oval. The cells have a moderate {1877,1935}. Expression of the various
{420,511}. In contrast to extranodal NK/T amount of pale cytoplasm, and cytoplas- NK cell receptors is variable. P-glycopro-
cell lymphoma, cervical lymph node mic azurophilic granules can be identi- tein/MDR1 is often expressed (90%), and
involvement is more frequent at presen- fied in Giemsa-stained touch prepara- may explain the poor response to
tation (60%), and the common sites of tions. Some cases are associated with a chemotherapy {2838}. The T-cell recep-
relapse are lymph node, liver and lung rich inflammatory infiltrate, consisting of tor genes are often in germline configu-
{420}. small lymphocytes, histiocytes, plasma ration {1196}. Practically all cases
cells and eosinophils. Occasionally (>95%) are associated with EBV
Extranodal NK/T cell lymphoma pseudoepitheliomatous hyperplasia of {68,376,1107,1263,1347,2671,2828}.
the overlying squamous epithelium may The virus is best demonstrated in the
ICD-O code 9719/3 occur, mimicking well differentiated tumour cells by in situ hybridization for
squamous cell carcinoma. EBER (EBV-encoded early RNAs) {376}.
Extranodal NK/T cell lymphoma of nasal- The EBV is in clonal episomal form, pro-

Haematolymphoid tumours 59
A B C
Fig. 1.78 Nasal NK/T cell lymphoma: the cytological spectrum. A Predominantly small cells that are slightly larger than small lymphocytes. Most cells show mild
nuclear foldings. B Predominantly large cells. There are many intermingled apoptotic bodies. C This example is predominated by small lymphoid cells. The admix-
ture of plasma cells may give the impression of a reactive inflammatory process (so-called polymorphic reticulosis). Note presence of mitotic figures.

viding additional evidence of the clonal ilarly presents with destructive nasal In DLBCL of the nasal cavity or
nature of the lesion {1107,1693}. lesion, simultaneous pulmonary involve- paranasal sinuses, the mucosa shows
Some cases are CD56 negative, but are ment may be present. There is serologic dense, diffuse and interstitial infiltration
still classified as extranodal NK/T cell positivity for cytoplasmic anti-neutrophil by large or medium-sized lymphoid cells.
lymphoma provided they express T-cell cytoplasmic antibody (c-ANCA), and the There may or may not be ulceration and
markers and cytotoxic markers, and are main histologic findings are chronic necrosis. Occasional cases show
EBV positive. These cases may show inflammation with microabscesses and angioinvasion. The tumour cells may
clonally rearranged T-cell receptor genes histiocytic infiltrate, in the absence of resemble centroblasts or immunoblasts,
and may represent a neoplasm of cyto- atypical lymphoid cells. or have a non-specific blastoid appear-
toxic T-lymphocytes {426}. T-cell lym- In those examples of extranodal NK/T ance. The nuclei are round, multilobated
phomas which lack cytotoxic markers or cell lymphomas dominated by small cells or irregularly folded, with multiple small
evidence of EBV infection are diagnosed with minimal atypia, a definitive diagno- membrane-bound nucleoli or single cen-
as peripheral T-cell lymphoma unspeci- sis can be difficult to make. An angio- tral prominent nucleolus. The tumour
fied. Lymphoblastic lymphoma of proba- centric infiltrate with expansion of the cells express pan-B markers (e.g. CD20,
ble NK-cell lineage (or so-called blastic mucosa and mucosal gland destruction, CD79a). Extramedullary myeloid sarco-
NK-cell lymphoma) with expression of coupled with prominent necrosis, should ma, plasmacytoma, undifferentiated car-
CD56 and TdT and no EBV association raise suspicion for the diagnosis of extra- cinoma and amelanotic melanoma may
has also been described in the nasal nodal NK/T cell lymphoma. Confirmation resemble DLBCL, but these entities can
cavity, but this is an entity distinct from of the diagnosis can be made by demon- be readily distinguished by appropriate
the extranodal NK/T cell lymphoma of strating sheets of CD3+, CD56+ and immunohistochemical stains.
nasal-type {1352,1838}. EBER+ cells.
Some non-lymphoid CD56+ small round Histogenesis
Differential diagnosis cell tumours (e.g. olfactory neuroblas- Most cases of extranodal NK/T cell lym-
Since the tumour cells of extranodal NK/T toma, Ewing sarcoma/primitive neuroec- phoma of nasal-type are activated NK-
cell lymphoma can be masked by a todermal tumour, rhabdomyosarcoma) cell neoplasms, while some appear to be
prominent inflammatory infiltrate, the also enter in the differential diagnoses. neoplasms of cytotoxic T-cells {425}.
lesion can be mistaken as an infective, However, these can be easily excluded DLBCL are mature B-cell neoplasms at
inflammatory or granulomatous lesion by appropriate immunohistochemical either the germinal centre or post-germi-
(including Wegener granulomatosis). It is stains {1532}. nal centre stage of differentiation.
not uncommon that a definitive diagnosis
can only be reached after repeated biop- Diffuse large B-cell lymphoma Somatic genetics
sies. While Wegener granulomatosis sim- ICD-O code 9680/3 A number of cytogenetic abnormalities

Table 1.4 Non-Hodgkin lymphomas in the nasal cavity or paranasal sinuses: differences in distribution according to cell lineage.

Primary in nasal cavity Primary in paranasal sinuses

NK/T- or T-cell lymphomas B-cell lymphomas NK/T- or T-cell lymphomas B-cell lymphomas
(mostly DLBCL) (mostly DLBCL)

Asian series {420,1837} 71% 29% 18% 82%

Western series {5} 54% 46% 25% 75%

DLBCL = diffuse large B-cell lymphoma

60 Tumours of the nasal cavity and paranasal sinuses


A B C
Fig. 1.79 Nasal NK/T cell lymphoma. A In situ hybridization for EBER shows nuclear labeling in practically all lymphoma cells. B The lymphoma cells show
immunoreactivity for CD3. Surface CD3 as detected on frozen section is negative (not shown). C The lymphoma cells show membrane staining for CD56.

A B C
Fig. 1.80 Nasal large B cell lymphoma. A Centroblastic morphology, characterized by cells with round nuclei and membrane-bound nucleoli. B This example is
dominated by very large pleomorphic cells with prominent nucleoli. C There is diffuse and uniform immunostaining for CD20.

have been reported in extranodal NK/T and son of a family with known pesticide not been studied in detail in sinonasal
cell lymphoma of nasal-type, most com- exposure {1354}. DLBCL. A Western series reporting treat-
monly isochromosome 1q, isochromo- ment results of lymphomas of the nasal
some 6p, partial deletion of 6q, and aber- Prognosis and predictive factors cavity and the paranasal sinuses showed
ration at 11q {2606,2811}. Comparative Radiotherapy and/or systemic that the International Prognostic Index is
genomic hybridization and loss of het- chemotherapy is the treatment of choice the only significant predictor for freedom
erozygosity studies have suggested fre- for localized disease. {420-422,1505, from progression rate {1550}.
quent DNA loss at 1p, 6q, 11q, 12q, 13q, 1550}. Treatment of DLBCL follow protols
17p, whole X, and frequent gain at 1p, 2q, for similar tumours elsewhere in the body, Extramedullary plasmacytoma
6p, 10q, 11q, 12q, 13q, 17q, 19p, 20q, Xp as some series showed that chemothera-
{1346,2382,2383}. Overall, the most fre- py might be beneficial {1550,2091}. Definition
quent changes are del(6)(q21-25), The overall survival for extranodal NK/T A mass-forming lesion of monoclonal
del(17)(p12-p13), del(13)(q14-q34) and cell lymphoma of nasal-type is only 30- plasma cells that occurs outside the
gain of 1p32-pter {422}. P53 protein over- 50% {420-422,1312,1838}. In patients bone and bone marrow. By definition,
expression occurs in 45-86% of cases achieving complete remission, local patients with primary extramedullary
{1496,2104,2105}, but P53 mutation is relapse occurs in one-third to one-half of plasmacytoma (EMP) do not have evi-
less common (24-48%) {1496,2105}. cases {421,1312}, and systemic failure is dence of underlying multiple myeloma.
TP53 mutation has been associated with also common {421}. Factors associated
large cell morphology and advanced with a worse outcome include: advanced ICD-O code 9734/3
stage {2105}. FAS gene mutation is fre- stage, poor performance status, B symp-
quently observed {2331,2534}. Aberrant toms, and bulky disease {422}. There is Epidemiology
methylation of promoter CpG region of no conclusive evidence to suggest that The mean age of patients with EMP of the
P73 gene occurs in 94% of cases {2381}, the histologic grading of NK/T cell lym- head and neck is 60 years (range 34-78
and its detection by methylation-specific phoma can predict the clinical outcome. years), with a male predominance 4:1
polymerase chain reaction may be helpful Expression of cutaneous lymphocyte {1267}.
for monitoring residual disease or early antigen (CLA) may be associated with a
relapse {2380}. There are no molecular worse prognosis, but this finding has yet Localization
data on DLBCL specifically occurring in to be confirmed {2863}. Most frequent sites of envolvement are
the sinonasal tract. The prognosis is slightly more favourable nasal cavity, paranasal sinuses and
for DLBCL compared with extranodal nasopharynx {433,827,1267,1613,1972,
Genetic susceptibility NK/T cell lymphoma of nasal-type {420}. 2347,2656,2746}.
Extranodal NK/T cell lymphoma of nasal- The overall survival for DLBCL is 35-60%
type has been reported in both the father {420,511,1550}. Prognostic factors have

Haematolymphoid tumours 61
A B C
Fig. 1.81 Extramedullary plasmacytoma. A Poorly-differentiated plasmacytoma. Note mononuclear and multinucleated neoplastic plasma cells with prominent
nucleoli. B Immunoperoxidase staining of plasmacytoma shows monoclonal kappa staining in cytoplasm of neoplastic plasma cells. C Immunoperoxidase staining
shows absence of staining for lamda light chains in neoplastic plasma cells.

Clinical features Histopathology Differential diagnosis


EMP tends to be solitary, with multiple There is a diffuse infiltrate of neoplastic Well-differentiated EMP should be distin-
tumours present in only 10% of cases at plasma cells in the subepithelial tissue, guished from reactive plasma cell prolif-
diagnosis. The presenting features of accompanied by a scant vascularized erations, either non-specific or associat-
head and neck EMP are: soft tissue mass stroma, and rarely blood lakes. There ed with specific disorders, such as
(80%), airway obstruction (35%), epis- can be deposits of amyloid or rhinoscleroma or Rosai-Dorfman dis-
taxis (35%), local pain (20%), proptosis immunoglobulin in the stroma. ease. Reactive plasmacytic proliferations
(15%), nasal discharge (10%), regional The tumour can be well, moderately or show a polyclonal pattern of
lymphadenopathy (10%), and cranial poorly differentiated {18,1267}. Well-dif- immunoglobulin staining.
nerve palsy (5%). The mean duration of ferentiated EMP is characterized by uni- Moderately or poorly-differentiated EMP
symptoms is about 4.5 months. The form normal-looking to mildly atypical can cause significant difficulties in dis-
tumour ranges in size from 2-5 cm. The plasma cells. Intracytoplasmic crystals tinction from large cell lymphoma, carci-
appearance varies from grey to red, soft can be abundant in some cases. Dutcher noma, melanoma, extramedullary
to firm, and sessile or pedunculated. bodies are sometimes seen. Moderately- myeloid sarcoma and olfactory neurob-
EMP bleeds easily and is usually smooth differentiated EMP comprises moderate- lastoma. The occasional positive staining
without mucosal ulceration. Cervical ly atypical plasma cells that vary in size. for cytokeratin can lead to a misdiagno-
lymph nodes are enlarged in only 10% of Poorly-differentiated (anaplastic) EMP sis of carcinoma. A high index of suspi-
patients {2500}. Occasional primary EMP comprises large cells that are often bare- cion for EMP should be raised for any
may be associated with serum parapro- ly recognizable as being plasma cells. poorly differentiated neoplasm occurring
teinaemia. An underlying multiple myelo- The nuclei often show significant varia- in the upper aerodigestive tract. Features
ma should always be excluded. tion in size, and can be round or irregu- suggestive of the diagnosis include
larly folded. The chromatin pattern eccentrically placed nuclei, coarsely
Macroscopy ranges from vesicular to finely granular to clumped clock-face chromatin in some
EMP is lobulated, smooth or nodular, and coarsely clumped. Nucleoli can be nuclei, and amphophilic cytoplasm with
has a fleshy or rubbery consistency. prominent. The cytoplasm is amphophilic a paranuclear hof. The diagnosis can be
and eccentrically located, and a paranu- confirmed by immunohistochemistry or
clear hof (Golgi zone) may be present. in-situ hybridization for immunoglobulin
Table 1.5 Sites of occurrence for head and neck Mitotic figures are frequent. Some tumour mRNA to look for monotypic light chain
extramedullary plasmacytomas cells can be multinucleated. expression {18}.
Site Frequency
Immunohistochemistry Prognosis and predictive factors
Immunohistochemically, the plasma cells The mainstay of treatment for primary
Nasal cavity 28%
Paranasal sinuses 22% express cytoplasmic immunoglobulin with EMP is radiotherapy. The prognosis of
Nasopharynx 22% light chain restriction. CD20 is negative in primary EMP is far more favourable than
Tonsil 7% most cases, and some cases express that associated with myeloma {1267}.
Larynx 5% CD79a. PAX-5 is negative, while Oct-2 Approximately 20% of patients with pri-
Pharynx 5% and Bob.1 are frequently positive. There mary EMP will develop multiple myelo-
Soft palate 3% is usually expression of CD38, CD138 and ma, but it is not possible to predict which
Salivary gland 2% VS38, markers characteristically positive cases will progress.
Thyroid 1% in but not specific for plasma cells.
Tongue 1%
Epithelial membrane antigen is commonly
Gingiva 1%
Cervical lymph node 1%
positive, and rare cases can show cytok- Extramedullary myeloid
Miscellaneous sites, e.g. eratin immunoreactivity (often with a dot sarcoma
trachea, subcutaneous tissue 2% pattern). Leukocyte common antigen,
CD31 or CD56 is sometimes positive. ICD-O code 9930/3

62 Tumours of the nasal cavity and paranasal sinuses


A B C
Fig. 1.82 Extramedullary myeloid sarcoma of nasal cavity. A In this case, some eosinophilic myelocytes (right field) are evident among primitive myeloid cells which
show a fine cytoplasmic granularity. B This example comprises a uniform population of primitive myeloid cells (blasts). The nuclear membranes are delicate and
the chromatin pattern is fine. Distinction from malignant lymphoma can be difficult on morphologic grounds. C The neoplastic cells show strong and uniform
immunostaining for myeloperoxidase, supporting the presence of granulocytic differentiation (same case as B).

Extramedullary myeloid sarcoma, also entiation shows a myeloperoxidase -, Langerhans cell histiocytosis
known as granulocytic sarcoma, is a CD68/PGM1+ immunophenotype. The
tumour mass of myeloblasts or immature pan-T marker CD43 is commonly ICD-O code 9751/1
myeloid cells occurring outside the bone expressed and may lead to a misdiagno-
marrow or bone. It can precede, co-exist sis of T-cell lymphoma. Langerhans cell histiocytosis may occa-
with or follow the presentation of acute sionally present with nasal obstruction
myeloid leukaemia. It can also arise as due to facial bone involvement {1183}.
blastic transformation of an underlying Histiocytic sarcoma For details see Chapters 4 on tumours of
chronic myeloproliferative disease or the oral cavity and oropharynx and 7 on
myelodysplastic syndrome. ICD-O code 9755/3 tumours of the ear.
The most common sites for occurrence
of extramedullary myeloid sarcoma are Histiocytic sarcoma, defined as a malig-
lymph node and skin, but involvement of nant proliferation of cells showing mor- Juvenile xanthogranuloma
the nasal cavity and paranasal sinuses phologic and immunophenotypic fea-
has also been reported {1701,2204}. The tures of mature tissue histiocytes, is a This histiocytic proliferation may mimic
tumour mass comprises diffuse sheets of rare tumour that can occasionally pres- tumours of Langerhans cells. It common-
blast cells, which often show a single file ent in the nasal cavity {2043}. The large ly presents as skin nodules in infants and
pattern of infiltration in some areas. The pleomorphic tumour cells have eccentri- children, but rare extracutaneous cases
blast cells have round or ovoid nuclei, cally-located round, ovoid, indented or involving the nasal cavity and paranasal
very fine chromatin, small but distinct grooved nuclei, and abundant sinuses have also been reported {568,
nucleoli, and a small to moderate amount eosinophilic cytoplasm that may show 2245}. Some of the histiocytes have
of lightly eosinophilic cytoplasm. There fine vacuolation. Phagocytosis is rare. foamy cytoplasm, and frequently there
can be better-differentiated cells with Histologic distinction from large cell lym- are scattered Touton giant cells and
eosinophilic cytoplasmic granules. phoma is difficult, except that the cyto- spindly cells within the infiltrate of nonde-
Intermingled eosinophilic myelocytes plasm tends to be voluminous and script mononuclear cells. The histiocytes
and metamyelocytes, if present, can pro- eosinophilic. in juvenile xanthogranuloma express
vide an additional clue to the diagnosis. The diagnosis depends on the demon- CD68 and factor XIIIa. In contrast to
Giemsa-stained touch preparations are stration of histiocytic differentiation (gran- Langerhans cells, they are negative for
excellent for identification of cytoplasmic ular staining for CD68 and lysozyme), in S100 protein and CD1a.
azurophilic granules as well as Auer the absence of expression of pan-B
rods, if present. Not uncommonly, markers (e.g. CD19, CD20, CD22,
extramedullary myeloid sarcoma is mis- CD79a), pan-T markers (e.g. CD3), Rosai-Dorfman disease
diagnosed as malignant lymphoma. myeloid markers (e.g. MPO),
Langerhans cell marker CD1a, and follic- Rosai-Dorfman disease (sinus histiocyto-
Immunohistochemistry ular dendritic cell markers (e.g. CD21, sis with massive lymphadenopathy) is an
The tumour cells show chloroacetate CD35). Since CD68 or lysozyme per se is uncommon reactive condition of
esterase activity in approximately 75% of not totally specific for histiocytic lineage, unknown etiology, characterized by pro-
cases. Immunohistochemically, they it is preferable to demonstrate additional liferation of distinctive histiocytes that
express various myeloid markers (such haematolymphoid markers such as usually exhibit emperipolesis of lympho-
as myeloperoxidase, CD13, CD33, LCA/CD45, CD4,CD43 or CD163 to con- cytes. The tumour masses can mimic
CD117, CD68/KP1, neutrophil elastase firm the diagnosis. The frequent expres- lymphoma or other malignancies both
and lysozyme), with myeloperoxidase sion of CD43 may lead to a misdiagnosis clinically and histologically. The patients
being most sensitive and specific. of T-cell lymphoma. A small proportion of are commonly children or young adults
Myeloid sarcoma with monocytic differ- cases can express S100 protein. who present with massively enlarged

Haematolymphoid tumours 63
A B

C D
Fig. 1.83 Rosai-Dorfman disease of nasal cavity. A Low to medium magnification typically reveals alternating bands of dark-staining and light-staining cells. B The
presence of spindly cells in a vague storiform growth pattern may lead to a misdiagnosis of fibrohistiocytic tumour. C The characteristic histiocytes are usually
much larger than the typical histiocytes with round nuclei, distinct nucleoli, abundant light-staining cytoplasm, and indistinct cell borders. There are typically many
admixed plasma cells. D Immunostaining for S100 protein selectively highlights the distinctive histiocytes. Both the nuclei and cell bodies are stained, while the
phagocytosed lymphocytes become much more evident because of the negative staining.

cervical lymph nodes. Extranodal tion of histiocytes can exhibit atypical or of disease or with stable disease.
involvement is frequent (about 40% of irregular nuclei, and may lead to a misdi- However, some patients may develop
cases), especially the upper aerodiges- agnosis of malignancy such as histiocyt- recurrent disease in the original site or
tive tract {791,923,1378,2760}. The ic sarcoma or melanoma. The dark areas other body sites.
patients with upper aerodigestive tract consist of large aggregates of plasma
disease present with nasal obstruction, cells and small lymphocytes. Fibrosis is
sinusitis, epistaxis, facial pain or saddle usually a prominent feature in extranodal
nose deformity. disease, and the fibrotic bands can
Histologically, low magnification exami- impart a nodular appearance. Together
nation reveals alternating pale and dark- with spindling of some of the cells, the
staining areas. The pale areas show pro- histologic features may strongly mimic
liferation of a distinctive type of very those of fibrohistiocytic tumours or
large histiocytes with large round nuclei, inflammatory pseudotumours. Immuno-
distinct nucleoli, and voluminous lightly histochemically, the large histiocytes co-
eosinophilic cytoplasm whose borders express S100 protein and the histiocytic
are often difficult to define. Some histio- marker CD68, and are negative for
cytes show emperipolesis, with lympho- CD1a.
cytes, plasma cells or neutrophils in the Most cases are treated by excision
cytoplasm. These characteristic histio- alone, with steroid, radiotherapy and
cytes can be few in number in extranodal chemotherapy having been given in a
sites. The lesion may be mistaken for minority of cases. In general, the progno-
rhinoscleroma. In some cases, a propor- sis is excellent, most patients being free

64 Tumours of the nasal cavity and paranasal sinuses


Neuroectodermal tumours B.M. Wenig
P. Dulguerov
M.L. Prasad
J.C. Fanburg-Smith
S.B. Kapadia L.D.R. Thompson

Ewing sarcoma (EWS) /


Primitive neuroectodermal
tumour (PNET)
Definition
A high-grade, primitive, round cell
tumour of neuroectodermal phenotype.
EWS and PNET represent a group of
small round cell neoplasms with variable
degrees of neuroectodermal differentia- A B
tion, and are considered together in this Fig. 1.84 Ewing sarcoma (EWS). A A "small blue round cell" tumour is comprised of intermediate sized cells
section under the rubric of EWS/PNET. with scant cytoplasm, although there are an increased number of mitotic figures. B While non-specific, the
neoplastic cells are strongly and diffusely immunoreactive with CD99. The nuclei have very delicate nuclear
ICD-O codes chromatin, with margination to the periphery.
Ewing sarcoma 9260/3
PNET 9364/3
and neck, with about 20% of these aris- obstruction {2069}. The tumour can be
Synonyms ing in the sinonasal tract {2122}. On rare polypoid when arising from the nasal
Peripheral neuroepithelioma, peripheral occasion, older adults may be affected cavity {2069}. Bony erosion may or may
neuroectodermal tumour, peripheral neu- {2611}. There is a very slight male pre- not be present {2069}.
roblastoma dominance {2122}.
Macroscopy
Epidemiology Localization EWS/PNET is a grey-white and glistening
Sinonasal Ewing sarcoma / primitive neu- Sinonasal EWS/PNET most commonly tumour with haemorrhage and often
roectodermal tumour (EWS/PNET) is occurs in the maxillary sinus {1518} and ulceration {2069}. It tends to be much
rare. This is mostly a tumour of children nasal fossa {1424,2069}. smaller than that arising in other sites.
and young adults, with a peak in the 3rd
decade {2211}. In children, approximate- Clinical features Tumour spread and staging
ly 20% of EWS/PNET occur in the head Symptoms include pain, mass, and Intranasal tumours usually spread into

A B
Fig. 1.85 Olfactory neuroblastoma. A CT with intravenous contrast. The tumour (T) extends through the floor of the anterior fossa. The lamina papyracea is bowed
but the orbital fat (arrow) is normal indicating that the periorbita has not been breached. B T1 weighted image. The tumour (T) obstructs the sphenoid sinus. The
right side shows secretions with low protein (white arrow). The left has higher protein and higher signal (black arrow). Carotid artery (C)

Neuroectodermal tumours 65
the paranasal sinuses {2069}. When sinonasal undifferentiated carcinoma, Synonyms
metastases develop, they are mainly to lymphoma, olfactory neuroblastoma, and Esthesioneuroblastoma, esthesioneuro-
the lungs and bone {2122}. Staging is pituitary adenoma. cytoma, esthesioneuroepithelioma, olfac-
according to the Clinical Groups of the tory placode tumour.
Intergroup Rhabdomyosarcoma Study Histogenesis
{2122}. A pluripotential fetal neuroectodermal ICD-O code 9522/3
cell is considered the progenitor.
Histopathology Epidemiology
The tumour is composed of densely dis- Somatic genetics Olfactory neuroblastoma is an uncom-
tributed, uniform, small to medium sized, Most EWS/PNET have a characteristic mon neoplasm representing approxi-
round cells with a high nuclear to cyto- t(11;22) with EWS/FLI1 juxtaposition or mately 2-3% of sinonasal tract tumours.
plasmic ratio and fine chromatin. Mitotic other translocations involving EWS The incidence has been estimated at 0.4
activity is high, and coagulative necrosis {2646}. Molecular analysis by PCR or per million {2584}. Patients range in age
is common. Some cases show more FISH is helpful in diagnosis. from as young as 2 years to 90 years,
densely clumped chromatin or a greater and a bimodal age distribution has been
degree of nuclear pleomorphism. Homer Genetic susceptibility noted in the 2nd and 6th decades of life
Wright rosettes are rare. Sinonasal EWS/PNET has been reported {625,626,663,1159}. Both genders are
in association with retinoblastoma {627, affected equally. No racial predilection
Immunoprofile 1330}. has been noted.
The immunophenotype includes reactivi-
ty for CD99 (MIC2, O13, HBA-71, p30/32, Prognosis and predictive factors Etiology
and 12E7), {2472} vimentin, and on EWS/PNET has much better prognosis in There are no known etiologic agent(s) for
occasion focally for keratins. Some the head and neck than in other anatom- human olfactory neuroblastoma.
cases express neural markers, such as ic sites {2122}. Size and stage are the Injection of diethylnitrosamine in Syrian
synaptophysin, S100 protein, NSE, neu- most important prognostic factors. hamsters and N-nitrosopiperidine in rats
rofilament protein, GFAP, and chromo- Tumours demonstrating the EWS/FLI1 has produced tumours histologically
granin. Fli-1 (one portion of the gene fusion are reported to have a better prog- identical to human olfactory neuroblas-
fusion product of EWS/FLI1) can be nosis than those with less common gene toma {1078,2697}.
detected by immunohistochemistry. fusion types {552}. With improvements in
imaging techniques and multimodality Localization
Electron microscopy treatment, a 5-year survival of 60-70% The most common site of origin is in the
Electron microscopy reveals, to a vari- can be achieved {23}. upper nasal cavity in the region of the
able extent, interdigitating neuritic cribriform plate. Included in the areas of
processes, neurofilaments, microtubules, the proposed origin are Jacobsons
neurosecretory granules and glycogen Olfactory neuroblastoma organ (vomeronasal organ), sphenopala-
{1743,2069}. tine (pterygoid palatine) ganglion, olfac-
Definition tory placode, and the ganglion of Loci
Differential diagnosis A malignant neuroectodermal tumour (nervus terminalis). Ectopic origin in
The differential diagnoses include malig- thought to originate from the olfactory lower nasal cavity or within one of the
nant melanoma, melanotic neuroectoder- membrane of the sinonasal tract. paranasal sinuses (e.g., maxillary sinus)
mal tumour, rhabdomyosarcoma, may occur. Olfactory neuroblastoma may

A B
Fig. 1.86 Olfactory neuroblastoma. A Tumour lobules separated by a highly vascularized stroma. B Olfactory neuroblastoma accompanied by the hyperplasia of
the olfactory epithelium.

66 Tumours of the nasal cavity and paranasal sinuses


A B

C D
Fig. 1.87 Olfactory neuroblastoma. A Lobules of tumour separated by fibrovascular septa. B The lobules of tumour are separated by dense fibrovascular tissue. A
large pseudorosette (Homer Wright) shows a central area of neurofibrillary matrix. C A high grade olfactory neuroblastoma showing a true Flexner-Wintersteiner
rosette and increased mitotic figures. D The "small blue round cell" neoplasm has scant cytoplasm surrounding variably hyperchromatic nuclei. Granular nuclear
chromatin can be seen. Mitotic figures are noted in higher grade lesions.

on occasion present as an intracranial extending across the cribriform plate. Histopathology


(frontal lobe) mass with involvement of The extent of disease is best determined Characteristically, the tumours are local-
the superior aspect of the cribriform by pre- and postcontrast MR imaging in ized to the submucosa, growing in cir-
plate or rarely, occur intracranially with which there is intense signal in T2- cumscribed lobules or nests separated
no intranasal component {987}. weighted images with marked enhance- by a richly vascularized fibrous stroma.
ment of T1-weighted images after Less often the tumour shows a diffuse
Clinical features gadolinium injection {2815}. Details of growth pattern. The overwhelming major-
Signs and symptoms bone erosion (lamina papyracea, cribri- ity of tumours are not associated with an
The main presenting symptoms are uni- form plate and fovea ethmoidalis) are in-situ component. The neoplastic cells
lateral nasal obstruction (70%) and epis- better demonstrated by CT scan. have uniform, small round nuclei with
taxis (46%); less common manifestations Calcifications producing a speckled pat- scant cytoplasm, dispersed (salt and
include anosmia, headache, pain, tern on radiographic studies can be pepper) coarse to fine nuclear chro-
excessive lacrimation and ocular distur- identified. Angiographic studies disclose matin and inconspicuous nucleoli.
bances. Typically, these tumours are a hypervascular neoplasm. Nuclear pleomorphism, mitotic activity
slow-growing resulting in long-standing and necrosis are usually absent.
symptomatology, the mean delay Macroscopy However, in higher-grade tumours,
between the appearance of the first The gross appearance includes a glis- nuclear pleomorphism with prominent
symptom and the diagnosis being 6 tening, mucosa-covered, soft, polypoid, nucleoli, increased mitotic activity and
months {626}. often highly vascularized mass varying necrosis may be present. The cells do
from a small nodule measuring less than not have distinct borders and are sur-
Imaging 1 cm to a large mass filling the nasal cav- rounded by a neurofibrillary matrix,
The radiologic features include the pres- ity and extending into paranasal sinuses, which corresponds to tangles of neuronal
ence of a dumbbell-shaped mass orbit and/or cranial cavity. cell processes. Rosettes of the Homer

Neuroectodermal tumours 67
Table 1.6 Hyams histologic grading system for olfactory neuroblastoma

Microscopic Features Grade 1 Grade 2 Grade 3 Grade 4

Architecture Lobular Lobular Lobular Lobular


Pleomorphism Absent to Slight Present Prominent Marked
Neurofibrillary matrix Prominent Present May be present Absent
Rosettes Present* Present* May be present** May be present**
Mitoses Absent Present Prominent Marked
Necrosis Absent Absent Present Prominent
Glands May be present May be present May be present May be present
Calcification Variable Variable Absent Absent

NF-neurofibrillary; *Homer Wright rosettes (pseudorosettes); **Flexner-Wintersteiner rosettes (true neural rosettes)

Wright type (pseudorosettes) and persed (salt and pepper) nuclear chro- all the histologic grades. The cellular infil-
Flexner-Wintersteiner type (true neural matin and inconspicuous nucleoli. The trate is characterized by pleomorphic
rosettes) can be identified in up to 30% cells do not have distinct borders; rather, nuclei often with prominent eosinophilic
and less than 5% of tumours, respective- the nuclei are surrounded by a neurofib- nucleoli and an indistinct cytoplasm.
ly. The Homer Wright pseudorosettes rillary material suggesting cytoplasmic Necrosis is commonly seen and there is
represent the presence of cells in an extension. Homer Wright rosettes are fre- increased mitotic activity, including atyp-
annular arrangement surrounding central quently seen. Varying amounts of calcifi- ical mitoses. Rosettes are uncommon.
neurofibrillary matrix; distinct cell mem- cation may be noted. Interlobular fibrous The neurofibrillary component is general-
branes are not present. Flexner- stroma is often extremely vascular. ly absent. Calcification is absent. Of note
Wintersteiner rosettes are gland-like Mitotic activity and necrosis are absent. is that in any given tumour there may be
structures in which the annular arrange- Grade II tumours share many of the his- histologic diversity with mixed (overlap-
ment of cells includes the presence of a tologic features described for Grade I ping) features.
distinct cell membrane. Perivascular lesions but the neurofibrillary element is In general, the lower grade olfactory neu-
pseudorosettes can be seen but are of less well defined, and the neoplastic roblastomas are readily recognizable
no diagnostic utility. Uncommon findings nuclei show increased pleomorphism. and diagnostic by light microscopy.
include stromal calcifications, ganglion Scattered mitoses can be seen. Grade III Adjunct studies, particularly in the higher
cells, melanin-containing cells and diver- tumours may retain a lobular architecture histologic grade tumours, may assist in
gent differentiation. The latter may with a vascular stroma. These hypercel- the diagnosis. The advent of immunohis-
include the presence of glandular (ade- lular tumours are characterized by cells tochemistry has diminished the role of
nocarcinoma-like), squamous, teratoma- that are more anaplastic, hyperchromat- histochemical stains, but silver stains
tous and rhabdomyoblastic differentia- ic, and have increased mitotic activity as such as Bodian, Grimelius and
tion {1096,1734,2404}. compared to Grade I or II tumours. Churukian-Schenk may still be of assis-
Necrosis is seen. The neurofibrillary tance.
Grading component may be focally present, but is
The microscopic grading {1159} includes much less conspicuous as compared to Immunoprofile
four grades: Grade I is the most differen- Grades I or II tumours. Flexner- The most consistently expressed marker
tiated and includes lobular architecture Wintersteiner rosettes are uncommon. is neuron specific enolase (NSE).
with intercommunication of the neoplasm Calcification is absent. Grade IV tumours Reactivity is also present in a majority of
between lobules. The neoplastic cells may also retain the overall lobular archi- cases for synaptophysin, neurofilament
are well-differentiated with uniform, small tecture, but the neoplastic element is the protein (NFP), class III beta-tubulin, and
round nuclei with scant cytoplasm, dis- most undifferentiated and anaplastic of microtubule-associated protein. S-100

A B C
Fig. 1.88 Olfactory neuroblastoma. A A true Flexner-Wintersteiner rosette is surrounded by intermediate sized cells with scant cytoplasm and prominent nuleoli. A
mitotic figure is present. B Immunostaining shows strong staining for synaptophysin. C Immunostaining shows the characteristic S100 protein+ sustentacular cells
wrapping around the tumour islands.

68 Tumours of the nasal cavity and paranasal sinuses


high nuclear to cytoplasmic ratio, high
mitotic activity, confluent necrotic areas
and individual cell necrosis are readily
apparent as well as lymphovascular and
perineural invasion. Characteristically,
crush artifacts of the neoplastic cells are
seen. Squamous cell foci may occasion-
ally be present; glandular or ductal dif-
ferentiation is rarely seen. Although
A B uncommon, neural-type rosettes similar
to those seen in olfactory neuroblastoma
can be seen in association with small cell
carcinoma. The overall light microscopic
findings should allow for differentiating
small cell carcinoma from olfactory neu-
roblastoma in most cases, but immuno-
histochemical evaluation may be
required in some cases. The immunohis-
tohemical profile of small cell carcinoma
includes variable reactivity for cytoker-
C D atin, chromogranin, synaptophysin, neu-
Fig. 1.89 Olfactory neuroblastoma Grade III / IV. A Tumour nests comprised of cell and with nuclear pleo- ron specific enolase (NSE), S-100 protein
morphism, increased mitotic activity and individual cell necrosis. B Higher magnification shows the pres- and thyroid transcription factor-1 (TTF-1).
ence of enlarged nuclei with moderate to marked pleomorphism, prominent nucleoli, absence of identifiable Cytokeratin reactivity may include a
neurofibrilllary matrix, and increased mitotic figures, including atypical mitoses. C The immunohistochem- punctate paranuclear or globoid pattern.
ical antigenic profile typically shows absence of cytokeratin and presence of NSE. D S100 protein is limit- The tumour usually is negative for cytok-
ed to sustentacular cells along the periphery of the neoplastic lobules.
eratin, and the positive cases do not
show a punctate paranuclear or globoid
protein staining typically is limited to the with a 9 + 2 microtubule pattern, microvil- pattern. In contrast to olfactory neurob-
sustentacular cells situated along the li, and junctional complexes. lastoma, NSE reactivity in small cell car-
periphery of the neoplastic lobules, cinoma is more likely to be focal than dif-
although such cells may be sparse in the Differential diagnosis fusely positive, and the S100 protein
higher-grade tumours. In addition, The differential diagnosis of olfactory staining, if present, is dispersed through-
immunoreactivity may be present for neuroblastoma includes the group of out the cellular proliferation and not limit-
chromogranin, glial fibrillary acidic pro- small round cell malignant neoplasms ed to sustentacular cells. Olfactory neu-
tein (GFAP), and Leu-7. that can occur in the sinonasal tract, i.e., roblastoma is also negative for TTF-1.
Cytokeratin is usually negative, but some sinonasal undifferentiated carcinoma,
cases can show some positive cells. lymphoma, rhabdomyosarcoma, mucos- Genetics
Epithelial markers, including epithelial al malignant melanoma and neuroen- Studies on cytogenetic aberrations in
membrane antigen (EMA) and carci- docrine carcinomas. This discussion will olfactory neuroblastoma are sparse
noembryonic antigen (CEA) are absent. be limited to neuroendocrine carcino- {2612,2521}. Studies have found partial
Leucocyte common antigen (LCA), mas; for the others the reader may refer gains of chromosome material on 8q,
HMB-45, desmin and CD99 are absent. to the specific sections detailing these while the other findings are conflicting.
Proliferation marker studies using Ki-67 specific tumour types. Inclusion of olfactory neuroblastoma
and MIB-1 have shown a high prolifera- Neuroendocrine carcinomas (NEC) within the Ewing sarcoma family of
tive index of 10-50% and flow cytometric include, among different tumour types, tumours {2428} or the primitive neuroec-
analysis shows frequent polyploidy/ane- the carcinoid tumour, atypical carcinoid todermal tumours (PNET) {1865} has
uploidy {2560,2682}. tumour and small cell carcinoma. NEC of been proposed {2467} because of the
the sinonasal tract are extraordinarily identification, in certain cases, of translo-
Electron microscopy rare, and in contrast to the larynx, the cation t(11:22), which is regarded as
Electron microscopy evaluation is a use- most common subtype is small cell car- specific molecular abnormality for Ewing
ful adjunct in the diagnosis and includes cinoma. By light microscopy, small cell sarcoma {575}. Recent studies using
the presence of dense core neurosecre- carcinoma typically is a submucosal immunohistochemistry, fluorescent in situ
tory granules measuring 50-250 nm in hypercellular proliferation growing in hybridization and reverse transcriptase
diameter and neurite-like cell processes sheets, cords and ribbons; the distinct PCR have failed to confirm this translo-
containing neurofilaments and neuro- lobular pattern of olfactory neuroblas- cation in olfactory neuroblastoma {72,
tubules {1096,2567,2682}. In addition, toma is absent. The cells are small and 1384,1709,2001}. Therefore, olfactory
Schwann-like cells and junctional com- hyperchromatic with oval to spindle- neuroblastoma should be considered an
plexes may be identified. When identi- shaped nuclei, absent nucleoli and mini- entity distinct from PNET and the Ewing
fied, olfactory rosettes show apical cilia mal cytoplasm. Cellular pleomorphism, sarcoma family of tumours.

Neuroectodermal tumours 69
Histogenesis Table 1.7 Clinical staging for olfactory neuroblastoma {663,1243}
Proposed sources of origin of olfactory
Stage Extent of Tumour 5-Year survival
neuroblastoma include Jacobsons
vomero-nasal organ, the sphenopalatine A Tumour confined to the nasal cavity 75-91%
ganglion, the ectodermal olfactory pla-
code, Locis ganglion, autonomic ganglia B Tumour involves the nasal cavity plus 68-71%
in the nasal mucosa, and the olfactory one or more paranasal sinuses
epithelium. While a neuronal neural
crest origin is supported by the presence C Extension of tumour beyond the sinonasal cavities 41-47%
of neurofilaments in olfactory neuroblas-
toma {2634}, until recently {335}, few
arguments linked olfactory neuroblas- inserted under the OMP gene promoter with increased morbidity (i.e., tumour
toma directly to the olfactory epithelium. region {2307}: these mice did not devel- recurrence, metastasis) and mortality
The olfactory neuroepithelium is a unique op olfactory neuroblastoma but adrenal (i.e., decreased survival) {2560,2682}.
neurosensory organ because olfactory and sympathetic ganglia neuroblastoma. The majority of tumours behave as local-
neurons are continuously replaced Therefore, the currently available evi- ly aggressive lesions mainly involving
throughout adult life by new ones dence links olfactory neuroblastoma with adjacent structures (orbit and cranial
{941,942}. Three types of cells are classi- the basal progenitor cells of the olfactory cavity). Local recurrence and distant
cally recognized in the olfactory epitheli- epithelium. metastasis may occur years following the
um: the basal cells, located against the initial diagnosis. Approximately 15-70%
basement membrane, the olfactory neu- Prognosis and predictive factors of patients will experience local recur-
rosensory cells, and the sustentacular Complete surgical eradication (craniofa- rence, 10-25% will have cervical lymph
supporting cells, the processes of which cial resection that includes removal of node metastasis, and approximately 10-
extend on the luminal surface. The glo- the cribriform plate) followed by full 60% will experience distant metastasis
bose basal cells constitute a stem cell course radiotherapy is the treatment of {131,663}. The more common sites of
compartment, which confers to this tis- choice {625,626,1777}. Limited success metastases include lymph nodes, lungs,
sue its peculiar ability to regenerate not using chemotherapeutic modalities have and bone. All histologic grades have the
only physiologically but also when been achieved for advanced unre- capacity to metastasize.
injured by trauma or environmental sectable tumours and/or for disseminat-
insults {1631,2690}. The globose basal ed disease {2705}. High-dose
cells express {1747} neural cell adhesion chemotherapy, including platinum-based Melanotic neuroectodermal
molecule (NCAM) {513} and mammalian protocols and autologous bone marrow tumour of infancy
homologue of Drosophila achaete-scute transplantation have resulted in long-
(MASH) gene {958}. These progenitor term survival {634,1919,2064}. The over- Definition
cells differentiate into olfactory neurosen- all 5-, 10- and 15-year survival rates have Melanotic neuroectodermal tumour of
sory cells, which exhibit a progressive been reported to be 78%, 71% and 68%, infancy (MNTI) is a rare neoplasm of
maturation from the basal membrane to respectively {634}. Initial multimodality infants with a biphasic population of neu-
the epithelial surface {1631,1884}. Each therapy is associated with 5-year survival roblastic cells and pigmented epithelial
layer can be characterized by specific of 80% for low-grade tumours and 40% cells.
olfactory- and neuron specific markers. for high-grade tumours {1777}. The
Immature olfactory cells express majority of the recurrences occur within ICD-O code 9363/0
{1631,2690} GAP43, a 24 kD membrane- the first two years {625}. The most fre- [if benign]
associated protein kinase C involved in quent recurrence is local, with rates
polyphosphoinositide turnover {197}. As around 30%. Prognosis has traditionally Synonyms
these cells mature, they send axons to been correlated to clinical staging with 5- Melanotic progonoma, retinal anlage
the olfactory bulb and migrate towards year survival of 75-91%, 68-71% and 41- tumour, melanotic ameloblastoma
the surface, they express olfactory mark- 47% for Stage A, B and C tumours,
er protein (OMP) {1630} and NCAM, but respectively {663,1243}. More recently, Epidemiology
not GAP43 {1631,1884,2690}. complete tumour resection was found to The tumour is very rare. It characteristi-
Recently, olfactory neuroblastomas were be of more prognostic importance than cally occurs in infants, with 80% of cases
found to express HASH, the human clinical staging {1740}. <6 months of age and 95% <1 year of
homologue of the MASH gene {335}, Other factors purportedly implicated in age, with a 2:1 female predominance
while staining negative for OMP. So far, prognosis include histologic grading, {1269}.
HASH has only been demonstrated in proliferation rate and ploidy.
medullary thyroid carcinoma and certain Histologically lower grade tumours Localization
small cell lung carcinoma {111}. Further (Grades I and II) have been reported to More than 85% of patients have a mass
indirect evidence that olfactory neurob- have a better 5-year survival than higher- involving craniofacial sites: maxilla
lastoma originates from olfactory stem grade tumours (Grades III, IV) {1159}. (70%), mandible (10%), skull (10%), neu-
cells can be derived from transgenic High proliferation indices and high rate of rocranial dura or brain (1%).
mice in which, the SV40T oncogene was ploidy/aneuploidy have been correlated Occasionally other sites, such as the epi-

70 Tumours of the nasal cavity and paranasal sinuses


A B

C D
Fig. 1.90 Melanotic neuroectodermal tumour. A Section of maxilla shows tumour infiltration of bone. Note fibrous stroma containing neoplastic cellular infiltrate.
B Dual population of neoplastic cells, including smaller blue neuroblastic cells and larger pigmented epithelial cells. C There is a trabecular, tubular, or alveolar
arrangement of the biphasic cell population, with the larger pigmented cells surrounding groups of the smaller round, "blue" neuroectodermal cells. The trabeculae
are separated by a dense collagenous stroma. D Note spatial relationship of larger pigmented epithelial cells surrounding smaller neuroblastic cells.

didymis (4%), skin (3%), uterus (1%), of smaller neuroblastic cells. The latter Electron microscopy
and mediastinum (1%) may be involved possess small, round hyperchromatic The small cells demonstrate neurosecre-
{1269,2026}. nuclei and scant or fibrillary cytoplasm. tory granules and neuritic processes,
The epithelial cells have larger, vesicular and the large cells contain melanosomes
Clinical features nuclei and abundant cytoplasm, most and premelanosomes {517,571,1269}.
Patients present with a rapidly growing containing melanin granules. Mitoses
pigmented mass, which is usually locat- and necrosis are rare or absent. Differential diagnosis
ed in the anterior alveolar ridge of the The differential diagnoses include alveo-
maxilla. The duration of symptoms Immunoprofile lar rhabdomyosarcoma, malignant lym-
ranges from 2 weeks to 5 months (mean MNTI shows polyphenotypic expression phoma, EWS/PNET, metastatic neurob-
2 months) {1269}. Infrequently, there are of neural, melanocytic and epithelial lastoma, immature teratoma and malig-
elevated levels of vanilmandelic acid, markers, but without photoreceptor dif- nant melanoma. Primary melanoma,
which normalize following adequate ther- ferentiation. Occasionally glial and rhab- especially mucosal, is extremely rare in
apy. domyoblastic differentiation may be infants, should show S100 protein
seen. The larger cell (epithelial) compo- immunoreactivity, and lacks epithelial
Macroscopy nent is immunoreactive for cytokeratin, markers. Neuroblastomas may rarely be
The tumours range from 1-10 cm (mean, HMB-45, vimentin, and sometimes pigmented, but lack the dual cell popula-
3.5 cm), and are smooth, firm to hard, epithelial membrane antigen tion and usually show diffuse immunore-
and grey to blue-black {1269}. {1269,2026}. Neuron-specific enolase, activity for neuroendocrine markers.
CD57/Leu-7 and dopamine-beta-hydrox-
Histopathology ylase are often positive in both the small Histogenesis
This is a nonencapsulated mass com- neuroblastic cells and large cells. The A neural crest origin is proposed {145,
posed of a dual population of small neu- small cells may express synaptophysin, 517,571,1232,1269,2026}.
roblastic cells and larger melanin-con- glial fibrillary acidic protein focally, and
taining epithelial cells in a vascularized desmin focally. The tumour cells are neg- Prognosis and predictive factors
dense fibrous stroma {1269,2026}. The ative for chromogranin, desmin, CEA, The treatment of choice is complete local
epithelial cells show alveolar or tubular retinol-binding protein, neurofilaments, excision {1269,1657,2092}. Radiothera-
arrangement, and often surround nests alpha-fetoprotein, and S100 protein. py and chemotherapy are to be avoided,

Neuroectodermal tumours 71
A B

C D
Fig. 1.91 Malignant melanoma. A This macroscopic view of a mucosal malignant melanoma of the septum demonstrates black pigment and the typical polypoid
nature of the tumour. Note the well defined border at the base of the tumour. B The vast majority of tumours demonstrate a "Grenz" zone of separation between the
surface and the malignant infiltrate (left), although pagetoid spread and surface epithelium involvement is appreciated (right). C Atypical plasmacytoid cells with
eccentrically placed nuclei with prominent nucleoli and intranuclear cytoplasmic inclusions. A "Hof" zone is easily identified (left). Rhabdoid cells have abundant
opaque eosinophilic cytoplasm arranged eccentrically from the atypical nuclei (right upper). Prominent, magenta nucleoli are common (right lower). D
Characteristic peritheliomatous growth with areas of degeneration noted between the vessels (left). A storiform or cartwheel pattern with increased mitotic fig-
ures (right).

unless there is evidence of metastasis. Epidemiology paranasal sinuses and present as exten-
Despite its rapid growth and tendency to Sinonasal mucosal malignant sive skull base tumours {260,273,386,
destroy bone, MNTI pursues a benign melanomas are rare, accounting for less 484,500,560,807,930,1324,2603}.
clinical course in most cases than 1% of all melanomas {112,165}, and
{1269,2026}. However, if not totally <5% of all sinonasal tract neoplasms Clinical features
excised, local recurrences occur fre- {205,2603}. Both genders are equally Symptoms include nasal obstruction,
quently. About 7% of cases develop affected, without a race predilection, epistaxis, nasal polyp, pain, nasal dis-
metastases to sites such as the lymph although an increased incidence has charge of variable duration, and melan-
nodes, liver, bone, adrenal glands or soft been suggested in Japanese patients. orrhoea (coal flecked or brown nasal
tissue {2026}. The potential for recur- Malignant melanomas typically affect discharge) {273,386,930,1076,2603}.
rence or metastasis, however, cannot be older individuals in the 5-8th decade with
predicted from the clinical or pathologic a peak incidence in the 7th decade Macroscopy
features. {165,260,273,386,484,500,560,807,930, The lesions are large, bulky and polypoid
1076,2603}. tumours with a mean size of 2-3 cm, but
may be larger with involvement of multi-
Mucosal malignant melanoma Etiology ple paranasal sinuses. The vast majority
Formaldehyde exposure and tobacco are ulcerated. The cut surface varies
Definition smoking have been suggested as possi- from black and brown to light tan,
A malignant neoplasm derived from the ble etiologic factors {260,273,1318, depending upon the amount of melanin
melanocytes in the mucosa. 2603}. production {273,386,930,2603}.

ICD-O code 8720/3 Localization Tumour spread and staging


The nasal cavity is affected most fre- At presentation, 70-80% of cases are
Synonyms quently, followed by a combination of the localized, 10-20% have regional lymph
Melanosarcoma; melanoma nasal cavity and paranasal sinuses. node and <10% have distant metastasis
Large tumours may involve multiple {112,273,386,1324,2603}. However, dur-

72 Tumours of the nasal cavity and paranasal sinuses


A B
Fig. 1.92 Malignant melanoma. A Interlacing fascicles (left) and an undifferentiated to epithelioid pattern (right) can be seen in melanoma. B Focal melanin pig-
ment noted in an epithelioid mucosal malignant melanoma (left) while an S-100 protein immunohistochemical study stains both the nucleus and cytoplasm.

ing the course of disease, an additional cells are generally medium to large-sized 1472,1624,2603}. The tumours usually
20% may develop nodal metastasis and {260,273,386,484,1472,2603}. They have invade the subepithelial tissue and fre-
40-50% may develop distant metastasis a high nuclear to cytoplasmic ratio with quently extend into the bone, cartilage or
to lungs, brain, bone and/or liver pleomorphic nuclei containing prominent skeletal muscle.
{273,386,484,500,1324,2603}. eosinophilic nucleoli and intranuclear
There is currently no universally accept- cytoplasmic inclusions. Nuclear molding Immunoprofile
ed staging system. However, the most can be present. The cytoplasm is usually Malignant melanoma expresses S100
common and prognostically significant densely eosinophilic, and variably con- protein and vimentin {1472,1661}, and
staging system in use is: stage I- local- tains melanin pigment. Mitoses, includ- variably HMB45, tyrosinase, melan-A
ized tumours, stage II- tumours with ing atypical forms, are frequent and eas- and microphthalmia transcription factor.
lymph node metastases, and stage III- ily identifiable. Vascular invasion and Neuron specific enolase, CD117, CD99,
tumours with distant metastasis {1076}. neurotropism may be identified in up to synaptophysin, CD56, and CD57 have
Tumour thickness or depth of invasion 40% of cases. An inflammatory infiltrate been reported to be occasionally posi-
cannot be accurately assessed due to admixed with pigment-laden histiocytes tive, but epithelial membrane antigen,
the lack of a well-defined reference point is commonly identified within or adjacent cytokeratins, and muscle markers are not
for the surface in the respiratory mucosa, to the tumour. Tumour cell necrosis is expressed {260,273,484,1472,1661,
frequent ulceration, tissue fragmentation common, particularly in tumours display- 2603}.
and poorly oriented specimen ing a peritheliomatous or pseudopapil-
{273,386,2603}. lary growth pattern. Other growth pat- Differential diagnosis
terns include solid, alveolar or sarcoma- Sinonasal mucosal malignant melanoma
Histopathology toid. may morphologically masquerade as a
The tumours are comprised of epithe- Intraepithelial melanocytic atypia variety of benign and malignant neo-
lioid, spindled, plasmacytoid, rhabdoid, (melanoma in-situ) is sometimes seen in plasms, such as small blue round cell
and/or multinucleated tumour cells. The the overlying epithelium {260,273,386, neoplasms, pleomorphic neoplasms

A B
Fig. 1.93 Melanoma in situ, associated with primary mucosal melanoma of the maxillary sinus. A A portion of the respiratory epithelium is replaced by melanoma
in situ and shows melanophages in the superficial lamina propria. B Anti-tyrosinase antibody (T311) strongly decorates the invasives tumour cells (bottom) as well
as melanoma cells in the sinonasal respiratory epithelium.

Neuroectodermal tumours 73
A B

C D
Fig. 1.94 Heterotopic central nervous system tissue. A Mucosal glands are subtended by reactive glial tissue composed of neuropil separated by dense, more
brightly eosinophilic fibrous connective tissue. Astrocytes are not seen. B S-100 positivity in nuclei and cytoplasm of subepithelial glial cells. C The left side demon-
strates a number of "gemistocytic-type" astrocytes within glial tissue, the right image shows classic neuroglial tissue without significant fibrosis or inflammatory
cells. D Trichrome stain highlights the neural tissue red, while the reactive background fibrosis is blue (left). GFAP immunoreactivity is present in glial tissue, but
not in the surrounding soft tissues (right).

(sinonasal undifferentiated carcinoma, Local recurrence is frequent (67%-92%), Epidemiology


anaplastic large cell lymphoma, may be repeated, and is a harbinger of Most patients present at birth, and 90%
angiosarcoma), or various sarcomas adverse prognosis {273,386,560,1324, of cases are diagnosed by age of 2
{260,273,386,1472,1661,2603}. 2603}. Most tumours progress to region- years. There is no gender predilection.
Metastatic melanoma to the sinonasal al and distant metastasis resulting in
tract, although highly uncommon, must poor 5-year disease-specific survival that Localization
always be excluded, as the prognosis is may range from 17- 47% {165,260,273, The lesion is situated externally on or
even poorer. Presence of intraepithelial 386,560,1076,1324,2310,2603}. Other near the bridge of the nose in 60% of
atypical melanocytes favours primary poor prognostic factors include cases, within the nasal cavity in 30% of
melanoma {386,1624,2603}. advanced age, obstructive symptoms, cases, and in both sites in 10% of cases.
tumour size >3 cm, location in paranasal In the latter cases, communication of the
Histogenesis sinuses and nasopharynx, vascular inva- intra- and extranasal components is
Melanocytes, distributed throughout the sion into skeletal muscle and bone, high through a defect in the nasal bone.
upper respiratory tract are considered mitotic count, marked cellular pleomor-
the progenitor of primary sinonasal phism and distant metastasis {165,273, Clinical features
mucosal malignant melanoma. 500,1324,2081,2310,2603}. Extranasal heterotopic CNS tissue pres-
ents as a smooth noncompressible sub-
Genetic susceptibility cutaneous mass over the dorsum of the
Patients with sinonasal mucosal malig- Heterotopic central nervous nose. The intranasal lesions usually pres-
nant melanoma do not seem to be part of system tissue (nasal glioma) ent with nasal obstruction or nasal defor-
dysplastic nevus syndrome or xeroder- mity. Heterotopic CNS tissue may occur
ma pigmentosum kindreds {273,2603}. Definition at other sites, such as the paranasal
A mass of heterotopic neuroglial tissue sinuses, nasopharynx {2289}, pharynx,
Prognosis and predictive factors presenting in and around the nose. tongue, palate, tonsil and orbit, and may
Surgery is the cornerstone of therapy, be referred to as facial glioma. One-
although wide free margins of resection Synonyms third of pharyngeal heterotopic CNS tis-
are difficult to achieve. Radiation therapy Nasal glioma, nasal glial heterotopia sues are associated with cleft palate or
has a palliative role {500,2078,2603}. choanal stenosis.

74 Tumours of the nasal cavity and paranasal sinuses


A helpful clinical sign is the absence of plexus, ependyma-lined clefts and pig- differentiates the latter from the former.
expansion or pulsation of the mass fol- mented retinal epithelium are seen,
lowing compression of the ipsilateral especially those of the palate and Histogenesis
jugular vein (negative Furstenberg test), nasopharynx. It is a congenital malformation in which
due to lack of connection of the mass The glial tissue can be confirmed by there is anterior displacement of mature
with the CSF pathway. Importantly, radi- immunoreactivity for glial fibrillary acidic cerebral tissue that has lost connection
ographic imaging scans (CT and MRI) protein (GFAP) or S100 protein with the intracranial contents.
reveal a soft tissue mass without an {607,1273,1323,1991,2851}.
intracranial component or bony defect in Prognosis and predictive factors
the floor of the anterior cranial fossa. Differential diagnosis Adequate excision offers a cure in most
The histologic differential diagnoses cases, but incomplete excision can be
Macroscopy mainly include nasal encephalocele and, accompanied by recurrence (15-30%).
The lesion appears as a polypoid, less frequently, a fibrosed nasal polyp. In There is no local aggressive behaviour or
smooth, soft, grey tan, non-translucent contrast to heterotopic CNS tissue, malignant potential.
mass with encephaloid features. It usual- encephaloceles are herniations of
ly measures 1-3 cm. meningeal lined brain tissue that commu-
nicate with the intracranial ventricular Ectopic pituitary adenoma
Histopathology system and subarachnoid space through
The lesion is non-encapsulated, com- a bony defect in the skull {1134}. Nasal This lesion is described in Chapter 2 on
posed of large or small islands of glial tis- encephalocele is composed of CNS tis- tumours of the nasopharynx.
sue with evenly spaced astrocytes and sue with easily found neurons. However,
interlacing bands of vascularized fibrous in nasal encephalocele of long-standing
connective tissue. The glial tissue and in recurrences, the excessive fibrous
merges with the collagen of the stroma or tissue relative to the amount of glial cells
dermis. Mitoses are absent. At times, the and absence of neurons may make it
astrocyte nuclei may appear enlarged or impossible to distinguish from hetero-
multinucleated. Long-standing or recur- topic CNS tissue.
rent lesions tend to contain a consider- Long-standing heterotopic CNS tissue
able amount of fibrous tissue. Neurons may be mistaken for a fibrosed nasal
are rare or absent. Rarely, choroid polyp {1258}. The absence of glial tissue

Neuroectodermal tumours 75
Germ cell tumours A. Cardesa
M.A. Luna

Malignant germ cell tumours and terato- the sinonasal tract of a 13-month-old boy. immature tissue with blastomatous fea-
carcinosarcoma exhibiting histologic fea- The malignant component was a squa- tures, while embryonal carcinoma, chori-
tures similar to germ cell tumours of the mous cell carcinoma {1379}. The tumour ocarcinoma or seminoma is absent.
gonads arise on rare occasions in the was locally aggressive and recurred after
sinonasal tract. Immature teratomas and surgery. There was no further recurrence Synonyms
teratomas with malignant transformation 2 years after chemotherapy {1379}. Malignant teratoma, blastoma, teratocar-
are tumours of infancy and early child- cinoma, teratoid carcinosarcoma
hood, whereas sinonasal yolk sac tumour
and sinonasal teratocarcinosarcoma Sinonasal yolk sac tumour Epidemiology
have only been documented in adults. (endodermal sinus tumour) Sinonasal teratocarcinosarcoma is very
rare {755}. Approximately 60 cases have
ICD-O code 9071/3 been published {755,1042,1619,1970,
Immature teratoma 2339,2578,2749}. Patients are exclusive-
This is a tumour that has the histological ly adults, with age ranging from 18-79
ICD-O code 9080/3 features of embryonic yolk sac, indistin- years (mean 60 years). There is a
guishable from yolk sac tumour (endo- marked male predominance {1042}.
Immature teratomas are rare in the dermal sinus tumour) of the gonads.
sinonasal tract and nasopharynx, and Only two cases have been reported to Localization
are composed of variable quantities of arise in the sinonasal tract {1623}. Both It almost exclusively arises in the ethmoid
immature tissue elements, mostly neu- patients were adults (aged 34 and 43 sinus and maxillary antrum. One tumour
roepithelial, that are interspersed with years). In one case, there was an has been reported to arise in the roof of
mature and immature tissues derived admixed component of sinonasal the nasopharynx and another from the
from the three embryonic germ layers. nonkeratinizing carcinoma. The behav- dorsum of the tongue {1042}.
They are tumours of infancy and child- iour has been aggressive.
hood {2317}. Clinical features
Immature teratomas tend to be either Patients present with a short history of
solid-nodular or solid-cystic, while Sinonasal nasal obstruction and epistaxis {1042}.
mature teratomas are usually cystic. teratocarcinosarcoma Imaging studies reveal a nasal mass,
The tumour may contain cystic spaces occasionally accompanied by opacifica-
lined by ciliated pseudostratified epithe- Definition tion of the paranasal sinuses. Bone
lium as well as primitive neuroepithelium A complex malignant sinonasal neo- destruction may be seen.
with rosettes. Mitotic figures are frequent- plasm combining features of teratoma
ly present in the immature areas; howev- and carcinosarcoma. Benign and malig- Macroscopy
er, cellular atypia is not found. In infants nant epithelial, mesenchymal, and neural Tumours are usually bulky, soft to rub-
and children, a teratoma with malignant elements are typically present, including bery, and red-tan to purple.
transformation has to be excluded. In
adults, thorough sampling of the speci-
men is mandatory to rule out teratocarci-
nosarcoma. Immature teratomas rarely
behave in a malignant fashion {570}.

Teratoma with malignant


transformation
ICD-O code 9084/3

Teratoma with malignant transformation


is a neoplasm containing benign tissue
elements of all three germinal layers and,
in addition, a somatic malignancy. There Fig. 1.95 Yolk sac tumour of nasal cavity. Typical features of yolk sac tumour, with many hyaline globules.
is only a single reported case involving

76 Tumours of the nasal cavity and paranasal sinuses


A B
Fig. 1.96 Teratocarcinosarcoma. A Immature blastematous and glandular components are covered by a mixture of mature ciliated, mucinous and squamous epithe-
lia. B Foci of neural differentiation showing fibrillary matrix and ganglion-like cells.

Histopathology Immunoprofile origin, but probably arises from a primi-


There are multiple tissue types derived The undifferentiated/primitive component tive cell in the olfactory/sinonasal mem-
from two or three germ layers, exhibiting often shows positive immunoreaction for brane that not only reproduces the neu-
variable degrees of maturity. In addition, CD99 and occasionally synaptophysin roectodermal features of olfactory neu-
there are intermingled carcinomatous and S-100 protein {1970}. The spindle roblastoma, but also has the capacity to
and sarcomatous components {755, cell component is consistently positive differentiate into divergent types of
2319}. The epithelial component is usual- for vimentin, and sometimes desmin, somatic cells {1970}.
ly made up of keratinizing and nonkera- myoglobin, and glial fibrillary acidic pro-
tinizing squamous epithelium, pseudos- tein. The neuroepithelial component is Prognosis and predictive factors
tratified columnar ciliated epithelium, positive for neuron-specific enolase and Teratocarcinosarcomas are highly malig-
and glandular structures lined by either occasionally chromogranin, alfa-fetopro- nant. They are locally aggressive, rapidly
cuboidal or columnar cells that may tein, and cytokeratin. The epithelial com- invading soft tissue and bone as well as
show mucous differentiation. Nests of ponent is positive for cytokeratins, the orbit and cranial cavities. They also
immature squamous cells containing epithelial membrane antigen, and occa- have the potential to metastasize to
clear cells (fetal-appearing) are a com- sionally S-100 protein and glial fibrillary regional lymph nodes and distant sites,
mon finding and an important diagnostic acidic protein. mainly the lungs. The average survival is
clue {1042}. The carcinomatous compo- less than 2 years, with 60% of the
nent is usually glandular, but sometimes Differential diagnosis patients not surviving beyond 3 years
squamous. Neuroepithelial elements with Inadequate sampling may lead to erro- {1042}. Recurrences usually appear with-
rosettes and neuroblastoma-like areas neous diagnoses of olfactory neuroblas- in 3 years.
are present in most instances. The mes- toma, squamous cell carcinoma, undif-
enchymal areas range from immature tis- ferentiated carcinoma, adenocarcinoma,
sues (such as cartilage) to sarcomas malignant salivary gland-type tumours Mature teratoma
(such as rhabdomyosarcoma and and adenosquamous carcinoma {1042}.
fibrosarcoma). There may be a prolifera- Teratoma is the principal benign germ
tion of small round cells that are difficult Histogenesis cell tumour of the sinonasal region and
to classify. The tumour is unlikely to be of germ cell shows histologic features similar to its

A B C
Fig. 1.97 Teratocarcinosarcoma. A The adenocarcinoma is intimately associated with the sarcomatous portion, arranged in a "teratoma-like" distribution. Cytologic
atypia is present in both constituents of the neoplasm. B A primitive blastema-like component is immediately adjacent to a malignant glandular element that is jux-
taposed with a malignant, cellular spindle cell constituent. C An adenocarcinoma with primitive blastema-like cells (left). The primitive cells can sometimes be
arranged in a true rosette, similar to teratomas.

Germ cell tumours 77


counterparts in the gonads and in other
extragonadal locations.

Definition
Tumour composed of a variety of mature
tissues that are foreign to the site of
occurrence. There are typically tissues
derived from two or three germ layers.

ICD-O code 9080/0

Synonyms
Teratoid tumour, benign teratoma.

Epidemiology
Teratomas of the head and neck account
for only 6% of all teratomas {2558}.
Mature teratomas in the sinonasal tract A
are even more uncommon {955}. Most
cases occur in neonates and older
infants, with equal sex distribution
{955,1737}. Stillbirth, prematurity, fetal
malpresentation, dystocia, and maternal
polyhydramnios are frequent associa-
tions.

Localization
In the sinonasal tract, the maxillary
antrum and nasal cavity are affected
more often than the sphenoid sinus
{1036,1408,1778,1805,2312}. The
nasopharynx can also be the primary site
of involvement.

Clinical features
Facial deformity, nasal obstruction, and a
nasal mass are common manifestations. B
Occasional calcifications may be seen
on imaging {955,1805}. Teratomas may
be associated with other skull deformi-
ties, anencephaly, hemicrania, and
palatal fissures {8}.

Macroscopy
The tumours are usually cystic, but can
be solid or multilocular. They are com-
monly encapsulated masses that meas-
ure up to 7 cm.

Histopathology
Teratomas are composed of variable
admixtures of mature skin, skin
appendages, fat, glial tissue, smooth
muscle, cartilage, bone, minor salivary
glands, respiratory epithelium and gas- C
trointestinal epithelium. Neural tissues Fig. 1.98 Sinonasal mature teratoma. A Benign teratoma showing cysts lined by squamous epithelium and
are seen more often in sinonasal ter- cartilage in stroma. B Cartilage and respiratory mucosa in mature teratoma. C Teratoma containing mature
atomas than in teratomas of other sites. glial tissue.
Although the variegated histologic
appearance of mature teratomas is usu-

78 Tumours of the nasal cavity and paranasal sinuses


ally diagnostic, heterotopic CNS tissue old or less, and approximately a third are Histopathology
and meningocele should be considered present at birth {582}. Dermoid cysts are lined with mature ker-
in the differential diagnosis. The pres- atinizing squamous epithelium and fre-
ence of immature elements or any other Localization quently contain cutaneous appendages
germ cell tumour excludes mature ter- Dermoid cysts of the head and neck are in the cyst wall. This lesion is differentiat-
atoma. located more often in the subcutaneous ed from a teratoma by the limited variety
tissue of the lateral supraorbital ridge of tissue types and the absence of endo-
Histogenesis and nose. In the nose, they occur most dermal components. Epidermal inclusion
The most popular theories are derivation commonly in the bridge and always in cysts may resemble dermoid cysts but
from primordial germ cells or primitive the midline. The glabella, nasal tip, and do not contain adnexa and occur pre-
somatic cells that escaped the influence columella are less common sites dominantly in adults {99,582,2622}.
of organizers and inducers {2558}. {582,2891}. A few cases have been
described as originating in the paranasal Histogenesis
Prognosis and predictive factors sinuses {2622}. The most likely explanation for the
Complete surgical excision is curative. ontogeny of dermoid cysts is the reten-
Clinical features tion of ectodermal tissue along the lines
Nasal dermoid cysts manifest as a mid- of closure at junctions of bones, soft tis-
Dermoid cyst line nasal pit, fistula, or subcutaneous sues, and embryonic membranes
infected mass. They may cause broad-
Definition ening of the nasal bridge and occasion- Prognosis and predictive factors
A dermoid cyst is a developmental lesion ally cellulitis or purulent discharge. On Dermoid cysts are treated by complete
histogenetically and histologically com- palpation, the cysts are soft to fluctuant surgical excision. Recurrence is uncom-
posed of ectoderm and mesoderm, but with a pale yellowish-pink colour noted mon (<7%) {582,2891}.
no endoderm. beneath the thinned but intact epitheli-
um; when keratin debris and sebum fill
ICD-O code 9084/0 the lumen, they may have a doughy con-
sistency {99,582,822,2891}. Most
Synonyms patients do not have other congenital
Nasal dermoid sinus cyst, cystic der- malformations, but some do {2058}.
moid. Imaging studies are valuable in detect-
ing a potential intracranial component
Epidemiology and excluding an encephalocele {582,
Dermoid cysts of the nose comprise 3% 2622,2891}.
of all dermoids and about 10% of those
of the head and neck region {2891}. Macroscopy
There is a male predominance. More The cysts range up to 12 cm. The lumen
than half are detected in children 6 years contains cheesy, yellow-white material.

Germ cell tumours 79


Secondary tumours L. Barnes
L.L.Y. Tse
J. Hunt

Table 1.8 Most frequent sites of primary tumours


Definition Prognosis and predictive factors
that metastasize to the paranasal sinuses*
Tumours that involve the nasal cavity and Although the eventual outcome is usually
paranasal sinuses that originate from, Primary Tumour Frequency poor, prognosis depends, in part, on
but are not in continuity with, primary whether the sinonasal metastasis is iso-
malignant neoplasms of other sites. Kidney 40% lated or part of widespread disseminated
Leukaemias and lymphomas are exclud- Lung 9% disease. If the metastasis to the nasal
ed. Breast 8% cavity and sinuses is localized and treat-
Thyroid 8% ed aggressively, the average survival fol-
Prostate 7%
Epidemiology lowing discovery of the metastasis may
Miscellaneous 28%
Metastases to the nasal cavity and be as long as 20-30 months {1300}.
paranasal sinuses are rare {1300,2085} *Data derived from reference {2085}
and may occur in any age group. In a
review of 82 cases, the median age of
patients with metastatic tumours at diag-
nosis was 57 years (range 3 months to
76 years), and about 60% were males Table 1.9 Distribution of 168 tumours metastatic to
{202}. paranasal sinuses*

Sinus Frequency
Localization
The distribution of tumour among the Maxillary 33%
paranasal sinuses and the most frequent Sphenoid 22%
tumour types to metastasize to these Ethmoid 14%
sites are shown in the Table 1.8 and 1.9. Frontal 9%
In 10-15% of cases, the metastases are Multiple sinuses 22%
limited to the nasal cavity.
*Data based on reference {2085}

Clinical features
Metastases to the sinonasal tract are
haematogenous. They may be solitary or swelling, cranial nerve deficits and epis-
multifocal and ordinarily produce symp- taxis (especially metastatic renal and
toms indistinguishable from those of a thyroid carcinomas). In some instances,
primary tumour. These include nasal the metastasis may be the first manifes-
obstruction, headache, facial pain, visual tation of an otherwise clinically occult
disturbances, exophthalmos, facial carcinoma, usually renal cell carcinoma.

A B C
Fig. 1.99 Metastatic carcinoma. A Renal cell carcinoma metastatic to the maxillary sinus showing clear cells (due to accumulation of glycogen in the cytoplasm)
and prominent sinusoidal vascularity. B Secondary prostatic adenocarcinoma. A malignant epithelial proliferation is identified within the large, patulous vessels in
the sinonasal tract mucosa. C (Same case as B). The metastatic nature of the tumour (left) was confirmed when the prostate specific antigen (PSA) was strongly
and diffusely immunoreactive in the cytoplasm of tumour cells within vascular spaces (right).

80 Tumours of the nasal cavity and paranasal sinuses

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