Trichoepithelioma Treatment & Management

Author: Victor G Prieto, MD, PhD; Chief Editor: William D James, MD

Background

Trichoepithelioma is a benign adnexal neoplasm. According to some authors,

trichoepithelioma may be a superficial form of trichoblastoma. The gene involved in the
familial form of trichoepithelioma is located on band 9p21.[1] Other cases are associated with
Brooke-Spiegler syndrome caused by mutations of the cylindromatosis oncogene (CYLD),
which maps to 16q12-q13.[2, 3, 4] A 2006 study has suggested that abnormalities in this gene
may result in one of 3 syndromes: Brooke-Spiegler syndrome, familial cylindromatosis, and
multiple familial trichoepithelioma.[5] Furthermore, some cases of patients with multiple
trichoepitheliomas appear to be sporadic and not related with familial incidence.[6]

A 2009 study reports a novel missense mutation in the CYLD gene, heterozygous nucleotide
G-->A transition at position 2,317 in exon 17, in a Chinese family with multiple familial
trichoepithelioma.[7] Additionally, a novel splicing mutation in the CYLD gene (IVS12 + 1 G-
->A) has been reported in a Taiwanese family with multiple familial trichoepithelioma.[8

Pathophysiology

The gene associated with the familial type of trichoepithelioma links to the short arm of
chromosome 9. Because several tumor suppressor genes (ie, p16, p15, and the gene for the
basal cell nevus syndrome) are in this region, the gene for the development of familial
trichoepithelioma also encodes for a tumor suppressor. If altered, cellular proliferation may
be up-regulated because of a poorly functioning or absent tumor suppressor. Studies have
indicated that CYLD encodes a deubiquitinating enzyme that negatively regulates the nuclear
factor (NF)–kappaB and c-Jun N-terminal kinase (JNK) pathways.[9] Due to the presence of
significant numbers of Merkel cells within the tumor nest and the detection of a sheath of
CD34-positive dendrocytes around the tumor nests, it appears that trichoepithelioma
differentiates toward or derives from hair structures, particularly the hair bulge. Rare
instances of tumors resembling trichoepithelioma have been reported in animals.[10]
Epidemiology

One dermatopathology laboratory reported 2.14 and 2.75 cases of trichoepithelioma per year
(9000 specimens). Since trichoepithelioma is inherited in an autosomal dominant fashion,
males and females receive the gene equally, but because of lessened expressivity and
penetrance in men, most patients are women. Trichoepithelioma typically occurs in young to
aging adults; however, the hereditary form may be seen in younger individuals. A single case
study has reported a congenital lesion of desmoplastic trichoepithelioma.[11

Prognosis

Slow growth is characteristic of trichoepithelioma. Partial removal may result in persistence

or recurrence. Although rare, trichoepitheliomas can develop high-grade carcinomas and
mixed (epithelial/sarcomatous) tumors.[12, 13]
Familial trichoepithelioma has shown an
aggressive, recurrent behavior in rare cases.

In cases of multiple trichoepitheliomas, the lesions may cause disfigurement because of

involvement of the face. The rare cases of trichoepithelioma described as having aggressive
behavior (ie, ulceration, recurrence) are probably follicular tumors within the basal cell nevus
syndrome and not trichoepithelioma.

Patient Education

Inform the patient that some degree of scarring will be present after trichoepithelioma
treatment. Slow-growing, single or multiple papules or nodules are typically observed on the
face, as demonstrated in the image below.
Characteristic clinical morphologic features. Notice the numerous, small papules,
predominantly close to the midline. The occurrence of multiple trichoepitheliomas is
transmitted as an autosomal dominant trait. Lesions first appear in childhood and gradually
increase in number. In patients with multiple trichoepitheliomas, interview the patient's
family for a familial history of trichoepithelioma.

Physical

The lesions are rounded, skin-colored, firm papules or nodules that are 2-8 mm in diameter.
The lesions are located mainly on the nasolabial folds, the nose, the forehead, the upper lip,
and the scalp; 50% of lesions occur on the face and the scalp. Occasionally, lesions also occur
on the neck and the upper part of the trunk. Heller et al report a rare case of trichoepithelioma
of the vulva.[14]

Ulceration is rare. In the autosomal dominant form, multiple trichoepitheliomas may be

present, usually on the nasolabial folds. In some cases, the distribution is dermatomal. An
association may exist with other cutaneous tumors (eg, cylindroma or Brooke-Spiegler
syndrome, spiradenoma, basal cell carcinoma, ungual fibromas) or dystrophia unguis
congenita. Trichoepithelioma may be part of the Rombo syndrome (ie, vermiculate
atrophoderma, milia, hypotrichosis, trichoepithelioma, basal cell carcinoma, peripheral
vasodilatation). Solitary giant trichoepithelioma presents as a large, polypoid lesion, usually
in the lower part of the trunk or in the gluteal area.

Familial cases appear to be related to a mutation in a gene encoding a tumor suppressor

located on band 9q21. Additionally, the gene involved in basal cell carcinoma (PTCH, human
patched gene located on band 9q22.3) appears to participate in the pathogenesis of
trichoepithelioma.[15] Brooke-Spiegler syndrome patients have a high incidence of multiple
skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These
patients may show mutations of the CYLD gene (cylindromatosis gene) that map to 16q12-
q13.[16]

Diagnostic Considerations

Histologic differential diagnoses (see Histologic Findings) are as follows:

 Basal cell carcinoma

  Microcystic adnexal carcinoma
 Trichoadenoma
 Tumor of follicular infundibulum
 Basaloid follicular hamartoma

Differential Diagnoses

 Basal Cell Carcinoma

 Colloid Milium
 Cylindroma
 Miliaria
 Follicular Infundibulum Tumor
 Milia
 Steatocystoma Multiplex
 Syringoma
 Trichilemmal Cyst (Pilar Cyst)
 Trichilemmoma
 Trichofolliculoma

Approach Considerations

In vivo studies such as high-definition optical coherence tomography have been applied to
distinguish trichoepithelioma from other cutaneous tumors.[17] If necessary, genetic studies
may be used to detect the abnormalities in band 9p21 in trichoepithelioma patients.

Procedures

Perform a shave or small punch biopsy to allow a histologic diagnosis of trichoepithelioma.

Ensure that the biopsy sample is sufficiently deep to allow the dermatopathologist to study
most of the lesion in cases of a solitary trichoepithelioma. In particular, a shave biopsy of a
plaquelike lesion on the lip may result in identifying the superficial portion of a microcystic
adnexal carcinoma (an aggressive adnexal neoplasm) as a trichoepithelioma. Some adnexal
carcinomas may show a very limited degree of cytologic atypia. In such cases, only by
examining the periphery of the lesion with the characteristic infiltrative pattern allows correct
diagnosis.
Histologic Findings

As many as 30% of trichoepitheliomas connect with the overlying epidermis, but in general
they are circumscribed, dermal nodules.

In the upper dermis, multiple nodules are composed of uniform, basaloid cells, frequently
with central, keratin-filled cysts, as in the images below.

Well-circumscribed, superficial lesion composed of clusters of basaloid cells within a fibrous

stroma. This arrangement of epithelial cells and stroma is described as organoid.

The cystic spaces contain keratin. Notice the lack of mitotic figures or apoptotic bodies.

Peripheral palisading is present, but artifactual clefting is uncommon. Apoptotic and mitotic
figures are rarely present; central necrosis or atypical mitotic figures are not a feature. The
stroma is generally fibrous, with little myxoid component. Calcification is common, typically
associated with the rupture of the keratinous cysts. A distinctive feature is the papillary-
mesenchymal body (fibroblastic aggregate resembling abortive follicular papillae), as shown
in the image below.[18]
It occurs in the same population as the classic type and presents as a plaque located in the
same anatomical areas as the classic form. Histologically, it shows narrow strands of tumor
cells, a desmoplastic stroma, and keratinous cysts, as shown in the image below.

Approach Considerations

Treatment of the trichoepithelioma lesion is primarily surgical. Laser and radiofrequency

have been used with diverse results. A Brazilian study of several types of cutaneous tumors
reported only a partial response for trichoepithelioma to 5% imiquimod cream.[34] Other
studies suggest the possibility of targeted therapies, such as antitumor necrosis factor-alpha[35]
or targeting mammalian target of rapamycin (mTOR) and hypoxia signaling pathways.[36]

Surgical Care

Solitary lesions can be excised. In the case of multiple tumors, this surgical approach may not
be feasible. Split-thickness skin grafting, dermabrasion, and laser surgery have been
proposed, but the results of these procedures vary.[37, 38, 39] Management of either form (ie,
solitary, multiple/hereditary) by superficial biopsy is usually adequate.

Recurrence of solitary trichoepithelioma is uncommon. When the multiple facial lesions are
surgically flattened by dermabrasion or laser therapy, they tend to regrow into elevated
papules or nodules. This regrowth may occur rapidly within months, or it may take several
years. Some patients find a prolonged cosmetic improvement to be worthwhile even if
repeated procedures are necessary.
Ensure that the patient is informed about the possibility of scarring. As with many benign
skin neoplasms, the patient is mainly concerned about the aesthetic appearance of the lesion.
Scarring may result from all available methods for tumor removal. In patients with multiple
lesions, treating 1 or 2 of the lesions and showing the patient the final result may be helpful
before embarking on extensive aggressive therapy.

Complications

The persistence or recurrence of trichoepitheliomas is a complication, and scarring may occur

after treatment.

Prevention

No preventive measures for trichoepithelioma are known.

Sebaceous Adenoma Treatment & Management

Author: Dirk M Elston, MD; Chief Editor: William D James, MD

Background

Sebaceous glands are oil-producing glands present in the dermis of mammalian skin.
Sebaceous glands are usually attached to hair follicles and are part of a complex skin-adnexal
unit known as the folliculoapocrine (sweat) apparatus. The glands are present over the entire
body, with the exception of the palms of the hands and the soles of the feet; they are most
abundant on the scalp and central face.

Skin adnexal tumors with sebaceous differentiation are uncommon, difficult to classify, and
may be controversial. The main controversy concerns the microscopic features, which vary
from well-to-poorly differentiated and sometimes undifferentiated varieties. A spectrum of
morphologic features can be encountered within the same neoplasm. Most reports include
few cases. Large series of cases for comparison and follow-up have not been published.

Because of the intimate association of sebaceous glands with other adnexal structures in the
folliculosebaceous-apocrine unit, many sebaceous neoplasms show complex histopathologic
features with mixed sebaceous, pilar (hair), and apocrine (sweat) gland differentiations.
Therefore, the term sebaceous neoplasm is necessary to include these complex skin adnexal
tumors with varying degrees of sebaceous differentiation. The term sebaceous neoplasm
includes benign and malignant tumors with different degrees of sebaceous differentiation.
The following terms are recognized within this category: sebaceous adenoma, sebaceous
epithelioma (sebaceoma), sebaceous carcinoma, basal cell carcinoma with sebaceous
differentiation, sebocrine adenoma, and sebomatricoma.

Skin lesions containing benign sebaceous gland proliferation (eg, sebaceous hyperplasia),
congenital hamartomas (eg, nevus sebaceus), and lesions with ectopic sebaceous structures
(eg, Fordyce spot, Montgomery tubercles) are generally not considered to be true sebaceous
neoplasms.[1]

When patients with numerous SAs and/or other neoplasms with sebaceous differentiation
have an associated internal malignancy, the clinical condition is known as Muir-Torre
syndrome.
Pathophysiology

The sebaceous gland is a secretory structure consisting of sebaceous lobules and ducts.
Although the sebaceous gland is a glandular adnexal structure, it is topographically and
ontogenetically related to the hair sheath. Therefore, antigenic similarities exist between the
isthmus of the outer hair sheath and the germinative basaloid cells of the sebaceous gland.
Sebaceous glands are most abundant in the skin of the head and neck regions, particularly in
the central face, but they are also present throughout the hair-bearing areas of the body and
the mucocutaneous junction, including the labium minus. The eyelids have modified
sebaceous glands (ie, Zeis glands of cilia associated with eyelashes, meibomian glands within
the tarsal plates of the upper and lower eyelids).[2]

Using transmission electron microscopy, a small number of melanocytes can be identified

that synthesize melanin-containing organelles (melanin granules) in the ducts and acini of
human sebaceous glands.[3]

Ectopic sebaceous glands, known as the Fordyce condition, commonly occur on the
vermilion border of the lips and on the buccal mucosa of adults; these structures are not
considered sebaceous neoplasias.

As one of the skin's adnexal structures, the sebaceous gland is intimately associated with hair
(pilar) and arrector pili muscle. Because of the intimate association of sebaceous glands with
hair and apocrine ducts, many sebaceous neoplasms show complex histopathologic features
with various elements of pilar and sweat gland differentiation.

Pilar and sebaceous neoplasms share a common expression for both high and low molecular
weight cytokeratin that is not seen in most eccrine or apocrine tumors, pointing to similar
cellular differentiation patterns of hair and sebaceous structures. Furthermore, the
architectural features of sebaceous tumors resemble those of pilar neoplasms, and not those of
sweat gland tumors. Many antigens associated with sweat gland neoplasms, including S-100
protein, CA72.4, gross cystic disease fluid protein 15 (GCDFP-15), and carcinoembryonic
antigen (CEA), are absent in sebaceous tumors.[4]

Mature sebocytes express antigenicity for epithelial membrane antigen (EMA) and related
substances. Some studies have reported selective labeling of sebocytes and their neoplasms
for nuclear androgen receptor protein (ARP), but with some contradictory results. Reactivity
for immunoglobulin A, lipase, milk fat globule–associated (ovarian carcinoma–associated)
sebaceous antigen OV-2, and OKM5 (CD36) antigen may be selective for sebaceous
lesions.[5, 6, 7]

All sebaceous glands are derived from the embryonal stratum germinativum (epidermal basal
layer), which gives rise to the epidermis and epidermal appendages.

During the 13th to 15th weeks of intrauterine life, part of the primary epithelial germ
develops into pilosebaceous pegs; later, their outgrowths form hair and sebaceous glands.
Sebaceous glands are found next to hair follicles and arrector pili muscles. Arising in the 15th
to 20th weeks of gestation, the most superior bud on the primitive pilosebaceous germ
develops into the apocrine gland, which is a specialized sweat structure. These integral
structures are known as folliculosebaceous-apocrine units. Development of sebaceous glands
begins in the scalp and the face at the beginning of the second trimester (80-mm stage) and
progresses in a cephalo-caudal direction.

Any sebaceous gland in the body has the potential to develop into sebaceous neoplasms.
These tumors are cutaneous adnexal tumors that show varying degrees of sebaceous
differentiation.

Sebaceous adenoma is defined as a benign epithelial neoplasm composed of sebaceous

gland–like structures or tumors with well-recognized sebaceous differentiation by
microscopic examination

Epidemiology

No reported increased incidence of sebaceous adenoma has occurred in any particular

geographical location. No reported predisposition is reported for any particular race.
Sebaceous adenomas affect men and women equally. Sebaceous adenomas frequently appear
on the face or scalp of middle-aged and older individuals, after age 50 years. The mean age at
onset is 60 years.

History
Patients with sebaceous adenomas typically experience a gradual onset of small, usually less
than 0.5 cm in diameter (2-4 mm), smooth, yellow, sometimes speckled papules with central
umbilication on the skin of the face or scalp over a period of several months.

Some middle-aged and older individuals may have multiple papules (as described above) or
nondescript papules on their faces or other parts of their skin surface.

Physical

Sebaceous adenomas range from less than 1 cm (usually 2-4 mm) to greater than 5 cm in
maximum dimension. Tumors most frequently appear as a yellow, speckled, smooth-
surfaced, circumscribed papule or nodule (see image below).

A biopsy-proven sebaceous adenoma on the forehead of a 64-year-old man. The tumor

appeared as a dome-shaped, elevated nodule with a circumscribed margin. It measured 8 mm
in diameter, with a smooth, shiny, yellow, and speckled appearance. The tumor had a history
of slow growth, and the patient had noticed it for more than a year. Note the pearly
appearance and the presence of a few capillaries traversing the tumor surface, a feature
closely mimicking the clinical appearance of that of a basal cell carcinoma. The total surgical
removal of this tumor was uneventful. The patient has not experienced a recurrence.

At times, these tumors have a polypoid appearance or central umbilication. Sebaceous

adenomas sometimes present as tan or pink-to-red papules.

Tumors are commonly located on the face, the scalp, and the neck. Occasionally, tumors may
be seen at other sites, including the trunk and the legs.

The clinical impression prior to the time of biopsy is usually that of basal cell carcinoma or a
nondescript papule without definitive clinical diagnosis. See the image below.
Multiple sebaceous neoplasms on the skin of the chest and the trunk of a 62-year-old man.
The tumors were biopsy-proven sebaceous tumors with varying degrees of sebaceous
differentiation. The patient was found to have a well-differentiated adenocarcinoma of the
colon by subsequent colonoscopy, CT scan, and MRI examination.

Procedures

A biopsy of skin tumors performed for histopathologic examination provides an accurate

diagnosis of sebaceous neoplasms, including sebaceous adenomas.[13]

Histopathologic examination of specimens obtained from polypectomy and laryngoscopy of

patients with suspected Muir-Torre syndrome confirms the presence or the absence of occult
internal malignancy.[14] Peripheral blood smear, bone marrow examination, and lymph node
biopsy may assist in detecting an associated hematologic malignancy in these patients.

Medical Care

Recognizing the presence of sebaceous neoplasms can help identify patients with Muir-Torre
syndrome; then, early treatment of an associated occult malignancy may be started.

Surgical Care

Surgical treatment of sebaceous adenomas is aimed at completely removing the tumor and
preventing regrowth of the tumorous tissue.

Prognosis

Sebaceous adenomas are benign tumor growths that derive from sebaceous glands. Solitary
tumors are treated by complete surgical removal with a 100% cure rate. Incomplete removal
has occasionally resulted in local recurrence.
When multiple sebaceous adenomas are associated with Muir-Torre syndrome, visceral
carcinomas, including adenocarcinomas of the colon, stomach, duodenum, hematologic
system, genitourinary tract, endometrium, and larynx (in decreasing order of frequency) may
also be present. The most significant feature of Muir-Torre syndrome is the favorable
prognosis of each of the associated carcinomas.[23]

However, some of these malignancies have metastatic potential; deaths due to internal
malignancies have been reported. The Mayo clinic has established a scoring system to
determine the risk of associated disease. The scoring system includes age at presentation of
the initial sebaceous neoplasm, the total number of sebaceous neoplasms, any personal
history of a Lynch-related cancer, and family history of Lynch-related cancers. Patients with
a score of 3 or more were more likely to have Muir-Torre syndrome.[24]
Cylindroma

Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD

Background

Cylindromas are benign skin appendage tumors. They can be seen in conjunction with
spiradenomas and trichoepitheliomas. Cases of spiradenocylindromas, demonstrating
characteristics of both spiradenoma and cylindroma in the same tumor mass, have also been
observed, suggesting similar derivation of both tumors.

They most commonly occur on the head and neck as solitary or multiple tumors. Solitary
cylindromas occur sporadically and typically are not inherited. Multiple tumors are observed
in an autosomal dominantly inherited manner. When nodules enlarge and coalesce on the
scalp, they form the distinctive turban tumor feature.

Malignant cylindromas are very rare. Malignant transformation may develop within solitary
cylindromas, or they may complicate the multiple variant (more common)

Pathophysiology

Cylindromas are appendage tumors previously thought to be of apocrine differentiation.

While phenotypic features differ between cylindromas and spiradenomas, recent studies have
shown immunohistological and cytomorphological overlap, with both tumors exhibiting
apocrine, eccrine, secretory, and ductal features. Therefore, the cellular origin of cylindromas
remains unknown. Cylindromas are most likely a very primitive sweat gland tumor
differentiating toward either the eccrine or apocrine line.

Brooke-Spiegler syndrome (BSS) has been described as an autosomal dominant disease

characterized by the development of multiple skin appendage tumors such as cylindromas,
trichoepitheliomas, and spiradenomas, with a variable preponderance of any of the
aforementioned subsets. Other lesions reported with BSS include parotid basal cell
adenomas, organoid nevi, syringomas, and basal cell carcinomas. Despite variable phenotypic
expressions of a predominant tumor in BSS, the gene responsible for multiple cylindromas,
CYLD, is localized to band 16q12-q13. The mechanism of genotypic similarity and
phenotypic variance is not yet understood.[1, 2]
In 2006, Zhang et al[3] reported a large consanguineous Chinese family with BSS
demonstrating intrafamily phenotypic variability. Upon examination, some persons only
manifested discrete, small, skin-coloured growths, while the proband manifested an
expansion of multiple large growths on the nose and numerous dome-shaped papules on the
scalp. Biopsy showed both trichoepitheliomas and cylindromas in the affected persons. By
sequence analysis, Zhang et al identified a recurrent mutation 2272C→T (R758X) of the
CYLD gene in the affected familial persons that had been previously identified in other ethnic
kindreds with familial cylindromatosis.

Epidemiology

The exact international incidence of cylindromas is not known. A case of Brooke-Spiegler

syndrome that included cylindroma was reported in China in 2013. No racial disparity is
reported for cylindromas. The incidence of cylindroma is more common in females than in
males. Female-to-male ratios of 6:1 and 9:1 have been reported. Solitary cylindromas are
lesions that affect middle-aged and elderly persons. Multiple, inherited cylindromas usually
begin in early adulthood and increase in size and number throughout life.

History

The solitary form usually begins in middle age or later as a slow-growing, rubbery nodule
exhibiting no symptoms. The dominantly inherited, multiple variety appears shortly after
puberty as numerous, rounded nodules of various sizes ranging from several millimeters to
larger than 6 cm. Lesions grow slowly, and additional lesions develop over time. Loss of
CYLD can be linked with development of salivary gland cancers. Brooke-Spiegler syndrome
(BSS) associated with unilateral hearing loss has been reported.[14] BSS manifesting with
pegged teeth has been reported.[15]

Physical

Except for BSS, pertinent findings are largely limited to the skin. Histologically similar
tumors have been found in the breast, parotid glands, salivary glands, lacrimal gland of the
eye, Bartholin glands, the brain, lungs, and kidneys. An interesting case of cylindroma was
reported on the breast in 2013.[16] Solitary lesions are firm, rubbery nodules with pink, red, or
sometimes blue coloring that range in size from a few millimeters to several centimeters. The
multiple form has numerous masses of pink, red, or blue nodules, sometimes resembling
bunches of grapes or small tomatoes (sometimes called a tomato tumor). Dermal cylindromas
are noted, some which can be in the deep dermis.[17] The solitary form is typically found on
the head and neck. The multiple form most commonly occurs on the head and neck but can
also be seen on the trunk and the extremities.

Procedures

A skin biopsy may be performed. Light microscopy with ordinary hematoxylin and eosin
(H&E) staining is sufficient for diagnosis of cylindroma.

Surgical Care

For solitary lesions, the treatment of choice is surgical excision. Other treatments include
electrodesiccation/curettage and cryotherapy. For small cylindromas, the carbon dioxide laser
may be used.[23] Retamar et al used carbon dioxide laser to treat facial trichoepitheliomas in 2
patients, with good results.[24] Multiple cylindromas usually require extensive plastic surgery
that may be obviated by progressively excising a group of nodules in multiple procedures

Prognosis

Most cylindromas are benign but some are malignant and potentially lethal27; at least 14
reports have described malignant transformation. The prognosis is not good with malignancy
because visceral metastasis frequently follows.

Multiple cylindromas can cover the entire scalp and cause the disfiguring turban tumor
appearance, which necessitates extensive reconstructive surgery
Trichoepithelioma
Hillary Johnson MD PhD, Mirin Robles MD, Hideko Kamino MD, Ruth F Walters MD, Arnold
Lee MD PhD, Miguel Sanchez MD
Dermatology Online Journal 14 (10): 5
Department of Dermatology, New York University

Abstract

A 29-year-old man presented with a long-standing history of asymptomatic, skin-colored,

facial papules and nodules. Histopathologic examination of a representative papule
demonstrated trichoepithelioma. The patient had a history of a brother with a similar
phenotype, which suggests a diagnosis of familial trichoepithelioma. Linkage and mutational
analyses support genetic heterogeneity of familial trichoepithelioma, possibly sharing a
clinical spectrum with Brooke-Spiegler syndrome and familial cylindromatosis since each
entity has been associated with mutations the CYLD gene.

History

A 29-year-old Puerto Rican man presented to the Dermatology Clinic at Bellevue Hospital
Center in September, 2007, with multiple, skin-colored, facial papules that began to first
appear in childhood and then increased in size and number during adolescence. The papules
have been intermittently pruritic and slightly tender only after scratching. He reported that his
brother and mother had similar lesions. The patient denied a family history of additional
cutaneous disorders or neoplasms. He has been otherwise healthy without medical problems,
medications, or any systemic complaints upon review of systems. The patient presented with
a biopsy specimen from a facial papule from a private dermatologist. Past treatment using an
unknown laser therapy was unsuccessful.

Figure 1 Figure 2
Physical Examination

Numerous, 2-to-3-mm, skin-colored, dome-shaped papules were present on the forehead,

cheeks, nose, and chin. Larger 3-to-4-mm papules coalescing to plaques were concentrated
bilaterally on the mid-face along the nasal creases and the cutaneous upper lip. The trunk,
buttocks, and extremities were unaffected. Lab, none.

Histopathology

In the reticular dermis, there are aggregates and branching strands of uniform basaloid cells
with peripheral palisading of the nuclei arranged within a prominent fibrous stroma. One
focus exhibits a papillary mesenchymal body with hair bulb formation. Stromal clefts and
cysts lined by squamous epithelium with infundibular keratinization are present. The tumor
shows no connection to an unremarkable epidermis.

Comment

Trichoepithelioma is a benign adnexal neoplasm that is considered a hamartoma of folliculo-

sebaceous differentiation. It may erupt sporadically as solitary lesions or in multiplicity.
Numerous trichoepitheliomas occur in an autosomal dominantly inherited genodermatosis
called multiple familial trichoepithelioma (MFT) or familial trichoepithelioma (FT).
Historically, epithelioma adenoids cysticum and Brooke-Fordyce or Brooke syndrome have
been ascribed to this disorder [1, 2].

Multiple familial trichoepithelioma, familial cylindromatosis (FC), and Brooke-Spiegler

syndrome (BSS in which patients are predisposed to trichoepithelioma, cylindroma, and
spiradenoma) each have been associated with missense mutations in the cylindromatosis
(CYLD) gene on chromosome 16q12-q13 in a number of families [3, 4, 5, 6]. Current
evidence indicates that these inherited skin disorders may exist on a clinical spectrum rather
as than distinct entities. Families have been described in which the identical germline
mutation in the CYLD gene produces either the MFT or the FC phenotype [7, 8, 9, 10, 11].
However, MFT may be even more genetically heterogeneous since one family with MFT
possessed a defect mapped to chromosome 9p21 in genetic linkage analysis that has not been
reproduced in other lineages, and no gene mutations in this locus have yet been identified
[12]. CYLD has been postulated to function as a tumor suppressor since loss of
heterozygosity of a wild-type allele has been associated with development of
trichoepithelioma. A deubiquitinating enzyme, CYLD has been shown to regulate signal
transduction pathways whose activities are responsive to levels of ubiquitination of
component proteins in the NF-kB and JNK signaling pathways. For example, CYLD can
remove K63-linked polyubiquitin chains from tumor necrosis factor receptors TRAF2,
TRAF6, and NEMO and thereby negatively regulate the cytokine-induced NF-kB pathway
for cellular homeostasis [13, 14].

Classically, MFT presents with numerous, skin-colored, firm, well-demarcated papules or

small nodules that are often distributed symmetrically on the face, with increased
concentration on the nose and along the central face. The center of the papule may be
depressed or umbilicated. Occasionally, trichoepitheliomas will occur on the scalp, neck, or
upper trunk. They commonly appear in childhood or adolescence. There is no apparent
predilection for gender or ethnicity [15]. While typically unassociated with malignant
conditions, rare association with basal-cell carcinoma has been reported [16, 17, 18, 19]. One
Japanese family included members with MFT, who also experienced fatal cerebrovascular
accidents although the clinical association may not be generalized [20]. Patients with MFT
often present with disfigurement since the trichoepitheliomas tend to grow in size and
number over time and contribute to psychosocial challenges.

Histopathologic diagnosis of classical trichoepithelioma (non-desmoplastic) is usually made

based on established criteria. Papillary mesenchymal bodies (follicular germinative
differentiation) and keratinizing cystic spaces surrounded by keratinocytes (follicular
infundibular or isthmic differentiation) are surrounded by an adherent fibrocystic stroma.
Overall, the specimen displays relative symmetry and lack of atypia. Difficulties can arise in
distinguishing trichoepithelioma, particularly in small biopsy specimens, from less typical
keratotic variants of basal-cell carcinoma. Staining with lymphoid markers (CD34, CD23),
cytokeratin expression (CK5, CK14, CK17, and CK19), cell membrane glycoproteins (Ber-
Ep-4), and cell-cycle regulatory protreins (Ki-67, PCNA, p53, and bcl2) have been used to
distinguish these neoplasms with variable success and reproducibility [21, 22].

Treatment of MFT relies on a variety of ablative techniques with variable results and the risk
of scars. Report of clinical improvement, with minimizing the appearance of the lesions, has
been demonstrated after several treatments using the high energy pulsed or continuous wave
carbon dioxide lasers. Other destructive methods, which include cryotherapy, dermabrasion,
electrodesiccation and curettage, and radiation, have been employed with modest results [23,
24]. One case report showed lessening of lesions without scars in an 11-year-old girl treated
with topical imiquimod cram and tretinoin 1 percent gel over a three-year period [25]. In
another report, treatment with isotretinoin for 12 weeks failed to affect the trichoepitheliomas
of a patient with concurrent cystic acne [26]. However, additional evidence is needed to
determine the utility of these potential therapies.
Multiple facial cylindromas: A case report
Amiya Kumar Nath MD, Carounanidy Udayashankar MD
Dermatology Online Journal 18 (2): 8
Indira Gandhi Medical College and Research Institute, Puducherry Pondicherry, Pondicherry, India

Abstract

Cylindroma is a benign skin appendageal tumor arising from pluripotent stem cells in the
folliculo-sebaceous-apocrine unit. Multiple cylindromas are usually seen as a component of
Brooke-Spiegler syndrome (BSS) or as the only skin lesions of familial cylindromatosis (FC).
The usual site of occurrence of such tumors is the scalp. We report a case of multiple
cylindromas involving the face without any other feature of BSS and no family history
supporting the possibility of FC. Multiple cylindromas of 7 years duration, confirmed by
histopathological examination of multiple biopsies, were seen on the face of a 70-year-old
woman. There was no history of similar lesions in any of her family members. Examination
of the scalp revealed no lesions. Surgical excision of the larger lesions was performed to
improve the facial appearance of the patient. This case is being reported for the unusual
occurrence of multiple cylindromas only on the face without any features of BSS or FC.

Introduction

Brooke-Spiegler syndrome (BSS, OMIM# 605041), familial cylindromatosis (FC, OMIM#

132700), and multiple familial trichoepithelioma (MFT, OMIM# 601606) were originally
described as distinct entities with each having a unique OMIM number [1, 2, 3]. Patients with
BSS are predisposed to multiple skin appendage tumors such as cylindroma,
trichoepithelioma, and spiradenoma. FC is characterized by cylindromas and MFT by
trichoepitheliomas as the only tumor type [1, 4, 5, 6]. However, because these disorders show
overlapping phenotypic features, and because different manifestations of each have been
described within a single family, many consider these disorders to represent a phenotypic
spectrum of a single disease entity. This contention is further strengthened by the fact that
mutation in a single CYLD gene is responsible for all three syndromes [1, 5]. Multiple
cylindromas without the other components of BSS appear to be exceedingly rare, if they
occur at all [7]. However, components of BSS may be present in clinically separate lesions or
in different histopathology foci, which may be missed if the lesion representing the admixture
is not biopsied. However, in some close cases the distinction between BSS and FC would
seem best clinically because a histopathological admixture may be missed and CYLD
identification also may not help. We noted a case of multiple cylindromas occurring
unusually only on the face without any other clinical or histopathological components of BSS
in a elderly women. The onset of her tumors at 63 years of age is well beyond the age of
occurrence of skin lesions of BSS or FC. Because a careful family tree charting did not reveal
any other family member with similar skin lesions, we describe this condition as multiple
non-familial facial cylindromatosis.
Case report

A 70-year-old woman presented with multiple asymptomatic

swellings over the face for the past 7 years with a progressive
increase in size and number over the years. Some lesions
grew significantly in the last 6 months producing visible
facial disfigurement; for this reason she sought our
consultation. There was no history of similar lesions in any of
her family members.

On examination, multiple, rounded, smooth surfaced, firm,

non-tender, freely mobile skin colored to reddish papules and Figure 1
nodules of varying sizes (3 mm to 4 cm) were seen on the
face (forehead, nose and chin, pre-auricular region, and along Figure 1. Multiple cylindromas on
the jaw-line). There was tendency to develop a grouping of the face
lesions in the preauricular regions (Figure 1). Examination of Figure 1a. Right side
scalp revealed no lesions. Examination of other areas of the Figure 1b. Left side, with a
skin, mucosa, nails, and hair showed no abnormalities. tendency to grouping in the
preauricular regions

Figure 2 Figure 3

Figure 2. Non-encapsulated tumor composed of closely set tumor lobules forming mosaic-like
masses giving a jigsaw-puzzle appearance. The tumor lobules are separated from each other
by thin bands of hyaline material. (H&E, x100)

Figure 3. Higher magnification showing two types of cells: larger cells with a moderate
amount of cytoplasm and a vesicular nucleus in the center of the tumor lobule and small cells
with little cytoplasm and compact nuclei in the periphery. (H&E, x400)

Excisional biopsy of a nodule revealed a non-encapsulated tumor composed of closely set

tumor lobules forming mosaic-like masses giving a jigsaw-puzzle appearance. The tumor
lobules were separated from each other by thin bands of hyaline material (Figure 2). On
higher magnification two types of cells were seen – larger cells with a moderate amount of
cytoplasm and a vesicular nucleus in the center of the tumor lobule and small cells with little
cytoplasm and compact nuclei in the periphery. The small cells were seen surrounding duct-
like spaces and masses of hyaline material within a few tumor lobules (Figure 3). A diagnosis
of cylindroma was made based on the typical histopathological findings.
Surgical excision of the larger lesions was performed to improve the facial appearance of the
patient and all those lesions revealed cylindroma on histopathology.

Discussion

Cylindroma is a benign cutaneous appendageal tumor that most often affects the scalp, with a
strong predilection for middle-aged and elderly females [8]. It occurs more often as a solitary
lesion [9]. Lesions on the face and neck away from the scalp margin are unusual; in less than
10 percent of cases these may occur on the trunk and limbs [2]. The rate of growth is slow
and the tumors seem to stop growing after reaching a certain size. The tumors are generally
asymptomatic, but an occasional patient may have pain [2]. Cases with multiple lesions tend
to be dominantly inherited [9] and clinically present as multiple, smooth, firm, pink to red,
somewhat pedunculated nodules of various sizes [2]. In such cases, new tumors continue to
develop over the years. Scalp lesions may be present in large numbers and cover the entire
scalp like a turban (turban tumor, considered to be the most florid and disfiguring feature of
BSS, is fortunately seldom observed) [9]. A rare variant with multiple lesions in linear array
has been reported [9].

The origin of cylindromas appears to be from pluripotent stem cells in the folliculo-
sebaceous-apocrine unit [1, 8, 9]. Mutation in CYLD gene (a tumor suppression gene) on
chromosome 16q12–q13 is responsible for tumorogenesis in the affected patients through
constitutive NF-κB activation (e.g. owing to the inability of mutated CYLD to downregulate
this activation) [8]. Loss of heterozygosity at the CYLD locus has been found in both
inherited and sporadic tumors [1]. It has been reported to follow radiotherapy epilation of the
scalp [2].

Histopathologically, cylindromas are poorly circumscribed dermal tumors composed of

numerous islands of epithelial cells, separated often only by their hyaline sheath and a narrow
band of collagen, giving a jigsaw-puzzle appearance [7, 9]. They exhibit multiple molecular
defects in their basement membrane zone, including the lack of mature hemidesmosomes,
defective processing of laminin 5, and abnormalities in collagen IV alpha 1- and alpha 5-
chain expression [8]. Two types of basaloid cells constitute the islands: relatively
undifferentiated cells with small, dark-staining nuclei present predominantly at the periphery
of the islands, often in a palisade arrangement. More differentiated cells with large, light-
staining nuclei present in the center of the islands [9]. In addition, tubular lumina are often
present. The lumina are lined by cells that usually have the appearance of ductal cells [9].

Local aggressive behavior and malignant transformation are uncommon and usually
associated with long-standing turban tumors of the scalp [7, 10]. However, metastasis of
malignant tumors is very rare [7].

Sporadic, solitary cylindromas are not inherited; they appear in adulthood and occur either on
the scalp or the face [9]. BSS is autosomal dominant in inheritance with a high penetarnce of
60 percent to 100 percent [3]. In BSS and FC, lesions usually develop in early adult life (2nd
or 3rd decades of life [3]), but may occur even in childhood or adolescence [7]. In BSS, the
different types of tumor mostly adhere to specific predilection sites on the body [4].
Trichoepitheliomas are commonly encountered on the central face in the perinasal area,
whereas spiradenomas usually develop on the upper trunk. Cylindromas mostly manifest on
the head and neck as multiple lesions [4]. Phenotypic and histopathological variations may
occur between the different members of the affected family, with elder members tending to
have more numerous and larger lesions [3]. Spiradenomas usually manifest as solitary,
reddish-to-pink nodules on the trunk, whereas both cylindroma and trichoepithelioma present
in groups of partly coalescing and confluent tumors [4]. We ruled out BSS/FC in our case by
the absence of family history, late onset of the lesions, and the absence of trichoepitheliomas
or spiradenomas clinically and in multiple histopathological sections.

There is no curative therapy yet available for multiple cylindromas. Currently, surgical
excision or laser ablation is the treatment of choice in multiple cylindromas [3, 4]. Total scalp
and forehead excision with coverage by skin grafts has been described in patients with turban
tumors [4]. Recently, a therapeutic attempt has been made to treat single cylindroma in BSS
with topically applied salicylic acid at varying concentrations. Salicylic acid acts by
interfering with the NF-κB signaling pathway [4].

References
1. Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, Celebi JT. Mutations in the CYLD
gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma:
lack of genotype-phenotype correlation. J Invest Dermatol 2005;124:919-20. [PubMed]

2. Calonje E. Tumours of the Skin Appendages. In: Burns T, Breathnach S, Cox N, Griffiths C, eds.
Rook’s Textbook of Dermatology, 8th edn., Singapore: Wiley-Blackwell 2010: 53.28-53.29.

3. Layegh P, Sharifi-Sistani N, Abadian M, Moghiman T. Brooke-Spiegler syndrome. Indian J Dermatol

Venereol Leprol 2008;74:632-4. [PubMed]

4. Parren LJ, Bauer B, Hamm H, Frank J. Brooke-Spiegler syndrome complicated by unilateral hearing
loss. Int J Dermatol 2008;47 Suppl 1:56-9. [PubMed]

5. Accessed from http://www.omim.org/entry/605041 on 12.10.2011.

6. Accessed from http://www.omim.org/entry/132700 on 12.10.2011.

7. Weedon D. Tumors of cutaneous appendages. Weedon’s Skin Pathology, 3rd Edn., China: Churchill
Livingstone Elsevier 2010: 785-786.

8. Massoumi R, Podda M, Fässler R, Paus R. Cylindroma as tumor of hair follicle origin. J Invest
Dermatol 2006;126:1182-4. [PubMed]

9. Klein W, Chan E, Seykora JT. Tumors of the epidermal appendages. In: Elder DE, Elenitsas R,
Johnson BL, Murphy GF, eds. Lever’s Histopathology of the Skin, 9th edn., Philadelphia: Lippincott
Williams & Wilkins 2005: 897-898.

10. Nair PS. A clinicopathologic study of skin appendageal tumors. Indian J Dermatol Venereol Leprol
2008;74:550. [PubMed]

© 2012 Dermatology Online Journa

Brooke-Spiegler syndrome
Carolyn Kim MD, Olympia I Kovich MD, Jonathan Dosik MD
Dermatology Online Journal 13 (1): 10
New York Univeristy Department of Dermatology

Abstract

A 46-year-old woman with Brooke-Spiegler syndrome has multiple cutaneous adnexal

neoplasms on her face and scalp. One of the lesions has concurrent features of cylindroma,
trichoepithelioma, and spiradenoma in the same specimen. Etiology, clinical features,
malignant transformation, and treatment modalities for Brooke-Spiegler syndrome are
reviewed.

Clinical synopsis

A 46-year-old woman presented with numerous lesions on her face and scalp. She reported
that the lesions started as isolated, small bumps on her face when she was in her early
twenties, and slowly grew more numerous until the bumps appeared as cobblestoned skin.
Approximately 10 years after the onset of facial lesions, she noticed small nodular growths
on her scalp. Over the past decade, she has had multiple excisions of the scalp nodules and
experienced continual growth of new lesions. All of the lesions are asymptomatic. Her
parents and her teenage children are unaffected.

Along the hairline and on the forehead, temples, nose, medial aspects of the cheeks,
nasolabial folds, and upper lip areas were numerous, small, 1-3 mm, flesh-colored, nontender,
nonpruritic papules. On the scalp are multiple 5-7 mm, firm, dome-shaped, nontender
nodules, with no associated loss of hair.

Figure 1 Figure 2
Histopathology reveals circumscribed aggregates of small epithelial cells that are partially
rimmed by eosinophilic basement membrane material. Additionally, there is a proliferation of
basaloid cells arranged as branching cords with focal follicular differentiation.

Comment

Brooke-Spiegler syndrome is an uncommon disease with a predisposition to develop

cutaneous adnexal neoplasms such as cylindromas, trichoepitheliomas, spiradenomas,
trichoblastomas, basal-cell carcinomas, follicular cysts, organoid nevi, and malignant
transformation of pre-existing tumors in the affected individuals [1]. Brooke-Spiegler
syndrome is inherited in autosomal-dominant fashion, although expression and penetrance
are variable. Lesions usually begin to appear in the second or third decades and gradually
increase in number and size throughout adult life. Women are affected more frequently than
are men. Mutations in the CYLD tumor-suppressor gene have been implicated in the
phenotype diversity [2].

Cylindromas, trichoepitheliomas, and spiradenomas, which are the most commonly observed
tumors, are typically located on the head and neck. Scalp cylindromas can become numerous
and may eventually cover the entire scalp, which results in the so-called turban tumors and
may result in partial or complete hair loss. Although cylindromas are usually benign
neoplasms, malignant transformation to cylindrocarcinomas is rare but well documented. The
malignant cylindroma is locally aggressive, often metastasizes, and requires careful followup
surveillance [3, 4]. Trichoepitheliomas are usually numerous and located on the face. In
addition to neoplasms of the skin appendages, patients with Brooke-Spiegler syndrome also
are at risk for developing tumors of the salivary glands, such as basal-cell adenomas and
adenocarcinomas of the parotid glands and minor salivary glands [5].

Multiple trichoepitheliomas may be seen also in two other rare syndromes: Rombo syndrome
(vermicular atrophoderma, milia, hypotrichosis, basal-cell carcinomas, trichoepitheliomas,
and peripheral vasodilatation with cyanosis) and Bazex syndrome (follicular atrophoderma,
hypotrichosis, occasional trichoepitheliomas, basal-cell carcinomas, and localized or
generalized hypohidrosis) [6].

The histolopathologic spectrum of Brooke-Spiegler syndrome is broad and encompasses

benign adnexal neoplasms of apocrine, follicular, and sebaceous differentiation, which can
occur independently and conjointly. The most unusual findings are neoplasms with hybrid
features, such as spiradenocylindromas, spiradenoma-trichoepitheliomas, cylindroma-
trichoepitheliomas, and even the concurrence of all three adnexal tumors in one lesion [1, 7].

Treatment methods for adnexal neoplasms include excision, dermabrasion,

electrodesiccation, cryotherapy, and radiotherapy. In addition, successful treatment with
lasers such as the argon, CO2, and erbium:Yag plus CO2 have been reported [8]. Medical
treatments for cylindromas that are currently being tested include sodium salicylate and
prostaglandin A1, which are thought to restore growth control by inhibiting NF-B activity
[9].

References
1. Kazakov DV, et al. Brooke-Spiegler syndrome: report of a case with combined lesions containing
cylindromatous, spiradenomatous, trichoblastomatous, and sebaceous differentiation. Am J
Dermatopathol 2005;27:27
2. Gutierrez PP, et al. Phenotype diversity in familial cylindromatosis: a frameshift mutation in the
tumor suppressor gene CYLD underlies different tumors of skin appendages. J Invest Dermatol
2002;119:527

3. Hu G, et al. A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome. J

Invest Dermatol 2003; 121:732

4. De Francesco V, et al. Carcinosarcoma arising in a patient with multiple cylindromas. Am J

Dermatopathol 2005;27:21

5. Bowen S, et al. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial

cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation. J
Invest Dermatol 2005;124:919

6. Szepietowski JC, et al. Brooke-Spiegler syndrome. J Eur Acad Dermatol Venereol 2001;15:346

7. Ly H, et al. Case of the Brooke-Spiegler syndrome. Australas J Dermatol 2004;45:220

8. Rallan D, Harland CC. Brooke-Spiegler syndrome treatment with laser ablation. Clin Exp Dermatol
2005;30:355

9. Brummelkamp TR, et al. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by
activating NF- B. Nature 2003; 424: 738

© 2007 Dermatology Online Journal

Syringoma

Author: Christopher R Shea, MD; Chief Editor: Dirk M Elston, MD

Background

Syringoma is a benign adnexal neoplasm formed by well-differentiated ductal elements. The

name syringoma is derived from the Greek word syrinx, which means pipe or tube.

Based on Friedman and Butler’s classification scheme, 4 variants of syringoma are

recognized: (1) a localized form, (2) a form associated with Down syndrome, (3) a
generalized form that encompasses multiple and eruptive syringomas, and (4) a familial form.

Pathophysiology

Syringoma is generally considered a benign neoplasm that differentiates along eccrine lines.

Enzyme immunohistochemical tests demonstrate the presence of eccrine enzymes such as

leucine aminopeptidase, succinic dehydrogenase, and phosphorylase. The
immunohistochemical pattern of cytokeratin expression indicates differentiation toward both
the uppermost part of the dermal duct and the lower intraepidermal duct (ie, sweat duct
ridge). However, distinguishing between eccrine and apocrine ducts is sometimes difficult,
and many tumors that were traditionally thought to be eccrine have been shown to have
apocrine differentiation. Electron microscopy of syringomas demonstrates ductal cells with
numerous short microvilli, desmosomes, luminal tonofilaments, and lysosomes.[1] The
histogenesis of syringomas is most likely related to eccrine elements or pluripotential stem
cells.

Some investigators have suggested that cases of eruptive syringoma may represent a
hyperplastic response of the eccrine duct to an inflammatory reaction rather than a true
adnexal neoplasm.[2] In this setting, these authors propose the term syringomatous dermatitis
for such cases. Likewise, the scalp "syringomas" seen in scarring alopecia represent a reactive
proliferation in response to the fibrosis.

Epidemiology

Syringomas affect approximately 1% of the population. A racial or ethnic predilection has not
been reported. Females are affected by syringomas more often than males. Syringomas
usually first appear at puberty; additional lesions can develop later.

Prognosis

Syringomas are benign and are largely of cosmetic significance. With treatment, syringomas
ideally should be destroyed with minimal scarring and no recurrence. See Surgical Care.

History

Syringomas are usually asymptomatic. However, rare cases have been associated with
pruritus, especially in the setting of perspiration or when localized to the vulva.[3]
Uncommonly, the patient may have a family history of similar lesions. Rarely, syringomas
may be associated with the Brooke-Spiegler syndrome, an autosomal dominant disease
characterized by the development of multiple cylindromas, trichoepitheliomas, and
occasional spiradenomas.[4] Other associations include Nicolau-Balus syndrome,
characterized by milia and atrophoderma vermiculatum,[5] and Costello syndrome,
characterized by various other cutaneous manifestations such as hyperkeratosis,
hyperpigmentation, papillomas, and deep palmoplantar creases, as well as craniofacial,
musculoskeletal, and neurologic abnormalities.[6] In rare cases, syringoma can be associated
with steatocystoma multiplex.[3] The incidence of syringoma appears notably increased in
association with Down syndrome.[7, 8, 9]

Appearance

Syringomas are skin-colored or yellowish, generally small, dermal papules (see image
below).

The multiple, small, yellow papules in the lower lid and upper part of the cheek correspond to
syringomas. The blue cyst in the inner canthus is an eccrine hidrocystoma. Courtesy of Mark S.
Brown, MD, University of South Alabama Medical Center.

Sometimes, the lesions may appear translucent or cystic. The surface of syringomas can be
rounded or flat. Syringomas are usually smaller than 3 mm in diameter. However, rare cases
of giant syringoma have been reported.[10] Eruptive syringomas typically appear as
hyperpigmented papules on the chest, penile shaft, or vulva.

Distribution

Syringomas are usually multiple, sometimes arranged in clusters, and symmetrically

distributed. Most commonly, syringomas are limited to the upper parts of the cheeks and
lower eyelids.

Other characteristic sites for syringomas include the axilla, chest, abdomen, penis, and vulva.
Case reports have described syringomas limited to the dorsa of the hands.[11] In the variant of
eruptive syringoma, multiple lesions appear simultaneously, typically on the chest and lower
abdomen. The eruptive variant may involve the penis[12] and intertriginous areas.[13] Rarely,
syringomas appear as unilateral, linear, nevoid lesions.[14]
Differential diagnoses and related conditions

In rare instances, scalp syringomas are associated with scarring alopecia.[15] Clinically,
syringomas on the face must be distinguished from trichoepitheliomas and basal cell
carcinomas. Lesions on the eyelids may be confused with xanthelasmas. Eruptive syringomas
on the trunk can resemble disseminated granuloma annulare. Microcystic adnexal carcinoma
can masquerade as syringoma.[16] Plaque-type lesions have been described and may be
mistaken for microcystic adnexal carcinoma.[17] Lesions of Fox-Fordyce disease (multiple
pruritic follicular papules) should be differentiated from syringomas.[18]

Procedures

An adequately deep biopsy is required to rule out microcystic adnexal carcinoma. Clinical
follow-up with consideration of rebiopsy for persistent or recurrent lesions is indicated

Surgical Care

The main reason for treatment is cosmetic; in particular, patients commonly seek treatment
for syringomas of the eyelids and cheeks, which may be conspicuous. The goal of therapy for
syringomas should be the destruction of the tumor with minimal scarring and no recurrence.
However, because syringomas are embedded within the dermis, complete removal is often
unsuccessful and recurrence is common.[23]

No comparative studies and no long-term follow-up studies are available on which to base
definitive recommendations for syringoma treatment. Possible treatments include the
following:

 Surgical excision with primary suturing

 Scissor excision with secondary intention healing
 Electrocautery[24]
 Electrodesiccation and curettage
 Carbon dioxide laser using the pinhole method of application or Er:YAG laser
ablation[25, 26, 27]
 Fractionated carbon dioxide laser ablation[28]
 Cryotherapy
 Dermabrasion
 Trichloroacetic acid
 Oral isotretinoin and topical tretinoin[23]
 Application of topical atropine[23