ORIGINAL ARTICLE
Fine Needle Aspiration Biopsy of Soft Tissue Sarcomas
Utility and Diagnostic Challenges
Harsharan K. Singh,* Scott E. Kilpatrick,* and Jan F. Silverman†
Abstract: The role of fine needle aspiration biopsy (FNAB) as the
primary modality for the initial diagnosis of previously undiagnosed
soft tissue sarcomas presents several important challenges. Most
practicing pathologists are inexperienced with the wide array of soft
tissue neoplasms and their morphologic heterogeneity, making them
susceptible to misdiagnosis. However, in the hands of experienced
cytopathologists, FNAB in conjunction with ancillary techniques has
a diagnostic accuracy approaching 95% for the diagnosis of malig-
nancy. FNAB has been shown to have a diagnostic yield nearly iden-
tical with core needle biopsy while avoiding significant clinical com-
plications. Nevertheless, FNAB has certain limitations related to the
accurate histologic grading and subtyping of certain subgroups of sar-
comas. It may also be difficult to accurately distinguish between low-
grade sarcomas and benign or borderline cellular lesions, especially in
the spindle cell sarcoma subgroup. The aim of this review is to high-
light the utility and limitations of FNAB in the primary diagnosis of
soft tissue sarcomas, highlight diagnostically challenging lesions, and
comment on the limitations of FNAB in providing a “definitive” di-
agnosis.
Key Words: fine needle aspiration biopsy, soft tissue sarcoma, im-
munohistochemistry, cytogenetic analysis, subtyping, cytology
(Adv Anat Pathol 2004;11:24–37)
S oft tissue sarcomas are a heterogeneous group of uncom-
mon neoplasms that represent fewer than 1% of all malig-
nancies diagnosed in the United States each year. In children as
compared with adults, the incidence of soft tissue sarcomas is
higher as an overall percentage of childhood neoplasms.1 Fine
needle aspiration biopsy (FNAB) has become an important and
widely used diagnostic procedure for the evaluation and docu-
mentation of local recurrences, as well as metastases from pre-
viously diagnosed soft tissue sarcomas and for diagnosing be-
From the *Department of Pathology and Laboratory Medicine, The University
of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and †De-
partment of Pathology and Laboratory Medicine, Allegheny General Hos-
pital, Pittsburgh, Pennsylvania.
Reprints: Dr. Harsharan K. Singh, Department of Pathology and Laboratory
Medicine, CB#7525 UNC-CH School of Medicine, Chapel Hill, NC
27599 (e-mail: hsingh@med.unc.edu).
Copyright © 2003 by Lippincott Williams & Wilkins
24
nign nonneoplastic lesions and metastatic carcinomas in soft
tissue.2–4 But its role as the primary modality for the initial
diagnosis of soft tissue sarcomas is not as widely accepted by
all clinicians and pathologists. In childhood sarcomas, FNAB
is even more underutilized because many of these patients are
eligible for enrollment only in histogenetic-specific treatment
protocols [ie, Pediatric Oncology Group (POG)], which re-
quire accurate histologic subtyping.5–7 The two major factors
contributing to the lack of widespread usage of FNAB as the
diagnostic procedure of choice have been the inexperience of
cytopathologists with the wide spectrum of soft tissue neo-
plasms, coupled with overlapping morphologic appearances of
reactive and neoplastic lesions, making them susceptible to
misdiagnosis.8 Moreover, interpreting soft tissue FNAB mate-
rial requires considerable expertise, and a diagnosis of malig-
nancy may result in debilitating surgery (ie, limb amputation),
causing pathologists to potentially be hesitant in rendering a
definitive diagnosis.3,9 However, in the hands of experienced
cytopathologists, FNAB in conjunction with ancillary tech-
niques (immunohistochemistry, cytogenetics, flow cytometry,
and/ or electron microscopy) can afford a diagnostic sensitivity
and specificity approaching 95% for the diagnosis of a malig-
nancy and reported false-positive and false-negative rates
ranging from less than 1% to 4% for adequate speci-
mens.4,9,10,11,12 The selection of a biopsy technique should
take into account whether it can reliably provide pertinent di-
agnostic and prognostic information on which therapeutic de-
cisions can be based while avoiding complications such as dis-
ruption of the tumor bed.13,14 In this regard, FNAB compares
favorably with core needle biopsy having roughly the same
diagnostic accuracy in separating benign from malignant soft
tissue lesions.2,15 Several studies have shown that diagnostic
FNAB had an identical yield to core needle biopsy, and when
both were performed, the information from the needle core
“did not contribute to further patient management.”9,14,15
In a large study of FNAB of primary bone and soft tissue
sarcomas from 140 patients, of which 91 patients had FNAB of
previously undiagnosed soft tissue sarcomas, Kilpatrick and
colleagues showed no complications resulting from the FNAB
procedure and no recurrences in the FNAB needle track.13 In
this study, no false-positive diagnoses were made (benign tu-
mor diagnosed as malignant cytologically), and there was only
Adv Anat Pathol • Volume 11, Number 1, January 2004
Adv Anat Pathol • Volume 11, Number 1, January 2004 Fine Needle Biopsy of Soft Tissue Sarcomas

one true false-negative case (malignant tumor diagnosed as cy-
tologically benign), which had no adverse consequences for
the patient. It must be emphasized that in the cited studies, an
experienced cytopathologist was available on site for immedi-
ate interpretation and for determining the need for additional
material for ancillary studies (more FNAB passes for cell
block preparation, immunohistochemical staining, cytogenet-
ics, flow cytometry, and electron microscopy). It is our opinion
that if an on-site cytopathologist experienced at evaluating soft
tissue lesions is not available, then the advantages and diag-
nostic accuracy of FNAB can be compromised, and tissue bi-
opsy may be better to insure that adequate material would be
available for ancillary studies. Alternatively, the patient can be
referred to an institution where all diagnostic modalities and
options are available.13
Histologic grading of soft tissue sarcomas is important
for management and prognosis. Recent studies have shown
that histologic grade is valuable in predicting metastases.16 Ex-
cept for pediatric small round cell tumors, therapy is based
mainly on anatomic location and stage, the latter incorporating
histologic grade.13,17,18 Of the several reported grading sys-
tems, the National Cancer Institute (NCI) system as proposed
by Costa and later modified by Guillou and the Fédération Na-
tionale des Centers de Lutte Contré le Cancer (FNCLCC) sys-
tem are the most widely used and reproducible systems in the
United States and Europe.19–21 For pediatric small round cell
tumors, the POG system proposed by Parham and colleagues
and the similar NCI system incorporate the histologic subtype
and grade while “integrating the unique clinical and morpho-
logic features of pediatric sarcomas.”6,19 These systems are,
however, less applicable to FNAB specimens because they re-
quire assessment of the percentage of tumor necrosis and mi-
totic rates. Accurate assessment of these parameters is not pos-
sible on cytologic specimens. For FNAB specimens, several
studies recommend a classification approach that divides soft
tissue sarcomas into five major cytomorphologic subgroups or
subtypes based on the predominant cytologic appearance of
the specimen on aspiration smears: myxoid, spindle cell, pleo-
morphic, polygonal/epithelioid cell, and round cell. This sys-
tem has been shown to be applicable to FNAB specimens and

TABLE 1. Grading of Soft Tissue Sarcomas by Fine Needle Aspiration Biopsy*

Low Grade High Grade Potentially Low

(by Definition) (by Definition) or High Grade
Well-differentiated liposarcoma Small round cell tumors Leiomyosarcoma
Rhabdomyosarcoma
Myxoid liposarcoma Ewing sarcoma Gastrointestinal stromal tumor (GIST)
Mesenchymal chondrosarcoma
Extraskeletal myxoid chondrosarcoma Desmoplastic small round cell tumor
Malignant peripheral nerve sheath tumor
(MPNST)
Epitheloid hemangioendothelioma Adult pleomorphic sarcomas
Pleomorphic malignant fibrous
histiocytoma
Infantile fibrosarcoma Pleomorphic rhabdomyosarcoma Myxofibrosarcoma
Pleomorphic leiomyosarcoma
Kaposi sarcoma Pleomorphic liposarcoma Conventional fibrosarcoma
Extraskeletal osteosarcoma
Hemangiopericytoma
Round cell liposarcoma
Malignant granular cell tumor
Epithelioid sarcoma

Clear cell sarcoma

Alveolar soft part sarcoma

Angiosarcoma
3,13
*Based on the results of Kilpatrick et al.

© 2003 Lippincott Williams & Wilkins 25

Singh et al
is presented in Table 1.3,22 In most cases, once a cytomorpho-
logic subtype has been determined (ie, round cell, pleomorphic
sarcoma), the corresponding histologic grade in many cases is
definitional.
Recent guidelines published by the Association of Di-
rectors of Anatomic and Surgical Pathology (ADASP) for the
reporting of soft tissue sarcomas commented on the use of
needle biopsy in soft tissue tumor diagnosis, highlighting con-
cerns that “precise typing and grading are not possible,...prone
to sampling error and might not provide enough material for
diagnosis” (ie, ancillary studies).23 They also raised concerns
about potential sampling problems caused by the heterogene-
ity of soft tissue tumors, potentially leading to an underestima-
tion of the true histologic grade. However, there are only a few
studies documenting how well FNAB can subtype previously
undiagnosed soft tissue sarcomas, and the results vary widely,
with an average 50–70% success rate.3,4,9,10 In one of the larg-
est series, Kilpatrick and colleagues found the accuracy of
FNAB for histologic subtyping to be greater for pediatric sar-
comas (92%) (with the use of ancillary studies) than for adult
sarcomas (52%).13 In this study, cytogenetic analysis was ac-
curately performed using FNAB material to confirm the
t(11;22) translocation in two cases of Ewing sarcoma and the
t(x;18) translocation in three synovial sarcomas supporting the
FNAB morphologic impression. The authors further showed
that if one is able to subtype or at the least, place the sarcoma
into the proper cytomorphologic group using the approach il-
lustrated in Table 1, therapy at most institutions can proceed
appropriately. A crucial point that was raised in this study re-
lated to the proper evaluation of the role of FNAB in the diag-
nosis and management of sarcomas: “the accuracy of the tech-
nique for histologic subtyping is less important than the per-
centage of cases in which an FNAB diagnosis was sufficient
for definitive therapy.” In their series, the FNAB diagnosis was
sufficient to begin definitive therapy in 83% of patients with
soft tissue sarcomas. For most sarcomas, if the subtype (syno-
vial sarcoma, etc) or cytomorpologic group (pleomorphic sar-
coma, etc.) could be ascertained by cytologic examination,
then a specific grade was not needed for the initiation of treat-
ment because in most cases, the histologic grade is either
readily apparent or is definitional for certain histologic sub-
types (Table 1).17 There were also no sampling problems
caused by morphologic heterogeneity in the overwhelming
majority of the cases, largely because of a multidisciplinary
approach of reviewing imaging studies before FNAB to in-
crease diagnostic yield. More recently, Jones et al have shown
similar results supporting the opinion that FNAB can accu-
rately subtype and grade soft tissue sarcomas in most cases.14
In their series of 107 FNAB (77 with corresponding surgical
material available), only low-grade sarcomas were under-
graded in a significant minority of cases, reducing the utility of
FNAB when this group of neoplasms is encountered. This has
been our experience as well. Grading spindle cell sarcomas is
26
Adv Anat Pathol • Volume 11, Number 1, January 2004
often challenging, and separating some nonneoplastic spindle
cell proliferations from low-grade spindle cell sarcomas may
also be difficult. Others have found similar difficulties when
sampling lipomatous tumors and recommend that deeply
seated soft tissue lesions that appear predominantly fatty by
current imaging techniques should be evaluated by incisional
or excisional biopsy techniques.13,24
DIAGNOSTIC APPROACH
As with FNAB material from other sites, a multidisci-
plinary approach is critical when evaluating aspirated material
from soft tissue sarcomas. Specifically, besides patient age,
tumor size, mobility, anatomic location of the mass, and clini-
cal presentation (rapid versus slow growth), the radiographic
findings need to be correlated with the FNAB cytologic fea-
tures to narrow down the differential diagnoses and avoid mis-
diagnoses. Liu et al found that clinical history improved the
diagnostic accuracy in bone and soft tissue lesions “for all ob-
servers regardless of experience.”25 Kilpatrick et al docu-
mented that the clinical and radiographic histories are probably
more helpful for accurate subtyping of bone sarcomas (82%) in
comparison with soft tissue sarcomas (54%).13
Knowledge of the patient’s age (adult versus pediatric)
can help narrow down the differential diagnostic consider-
ations, as little overlap occurs in the groups of tumors that pre-
dominate in each general age group. Location of the mass
helps in that most primary soft tissue sarcomas are deep-seated
masses, whereas benign soft tissue neoplasms along with me-
tastases from carcinoma and melanoma, with few exceptions,
tend to present as subcutaneous or superficial masses.
The interpretative approach to FNAB of soft tissue
should mainly attempt to categorize lesions as to their potential
biologic behavior so that the appropriate initial triage and
therapeutic options can be adequately assessed. In general,
most soft tissue masses should be suspected to be benign until
proven otherwise because benign lesions far outnumber ma-
lignancies. Additionally, when malignancy is encountered,
primary soft tissue sarcomas are far less common than metas-
tases. Therefore, the possibility of a metastasis must be ex-
cluded before a diagnosis of a primary soft tissue sarcoma is
considered because metastatic sarcomatoid carcinoma or ma-
lignant melanoma can simulate a sarcoma. Most authors agree
that a definitive cytologic diagnosis must be based on a com-
bination of the cytologic findings (ie, adequate specimen, cy-
tomorphology) correlated with results of ancillary studies (im-
munohistochemistry, flow cytometry, cytogenetic analysis,
electron microscopy), along with the clinical and/or radio-
graphic data. Close interaction between the clinician and cyto-
pathologist is therefore an essential component to the success
of FNAB in the workup of soft tissue sarcomas.
Most authors recommend a cytologic approach that em-
phasizes the use of low- and high-power morphologic pattern
© 2003 Lippincott Williams & Wilkins
Adv Anat Pathol • Volume 11, Number 1, January 2004 Fine Needle Biopsy of Soft Tissue Sarcomas

recognition in the cytomorphologic evaluation. Primary soft
tissue sarcomas can be classified either by their cell lineage or
by their dominant cytomorphologic pattern. As previously
mentioned, we and others recommend dividing soft tissue sar-
comas into one of five major cytomorphologic subtypes based
on the predominant morphology: myxoid, spindle cell, round
cell, pleomorphic, and polygonal/epithelioid cell (Table
2).17,22 However, it should be recognized that overlapping cy-
tologic features can occur; therefore, some tumors could be
considered in the differential diagnosis of more than one cat-
egory. For example, features of synovial sarcoma could be
placed in the epithelioid/polygonal, small cell, and spindle cell
groups. In addition, it has been our experience that the
polygonal/epithelioid cell and spindle cell groups are the most
challenging to accurately subclassify and grade based solely
on cytomorphologic features.
Ancillary Studies
Nowhere has the use of immunohistochemistry and mo-
lecular genetic studies impacted the rendering of histogenetic-
specific diagnoses than in the childhood soft tissue sarcomas
and/or the small round cell group of sarcomas.1,5 This is espe-
cially important because the majority of pediatric patients are
enrolled in histogenetic-specific protocols (eg, POG) follow-
ing a diagnosis of sarcoma. Therefore, most authors agree that
the gold standard for diagnosis remains light microscopic
evaluation. Ancillary diagnostic procedures such as immuno-
histochemistry and cytogenetic studies can aid in rendering the
most specific subtyping of the majority of these sarcomas. In a
study by Kilpatrick et al, among 27 patients clinically eligible
for histogenetic-specific protocols, an accurate diagnosis was
rendered in 25 (92%) cases.5 However, this is probably not the
case in the pleomorphic sarcoma group of adults. In most pa-
thology practices, immunohistochemistry plays an important
role in the workup of small round cell, spindle cell, and
epithelioid/polygonal sarcomas; a panel of antibodies is also
used to separate soft tissue sarcomas from metastatic carci-
noma, malignant melanoma, and/or lymphoma. Table 3 out-
lines the immunohistochemical screening panels for the three
categories of tumors for which it is clinically most useful in the
rendering of an accurate diagnosis.
SELECT SOFT TISSUE SARCOMAS BASED ON
THE MAJOR
CYTOMORPHOLOGIC PHENOTYPES
Myxoid Sarcomas
Although myxoid change can be seen in a variety of soft
tissue tumors, it is not usually consistently seen as a dominant
feature of the tumor. From our experience, the most commonly
sampled entities on FNAB with a myxoid appearance are
myxoid liposarcoma, myxofibrosarcoma (myxoid malignant
fibrous histiocytoma), and extraskeletal myxoid chondrosar-
coma 22,26,27 (Fig. 1). The cytologic features of most of
these lesions have been previously reported.2,27–29 Myxoid
sarcomas consistently demonstrate abundant myxoid stroma
as an intricate part of the tumor. On Romanowsky-stained
(Diff-Quik stain) air-dried smears, the stroma imparts a

TABLE 2. Major Cytomorphologic Phenotypes of Soft Tissue Sarcomas

Polygonal*
Myxoid Spindle† Pleomorphic*† Round* (Epithelioid)
Myxoid liposarcoma Fibrous histiocytoma Pleomorphic MFH Rhabdomyosarcoma Epithelioid sarcoma
(childhood types)
Fibrosarcoma Pleomorphic liposarcoma Ewing sarcoma/PNET Clear cell sarcoma
(malignant melanoma
of soft parts)
Extraskeletal myxoid Leiomyosarcoma Extraskeletal
chondrosarcoma osteosarcoma
Myxofibrosarcoma Gastrointestinal stromal Pleomorphic Desmoplastic small Alveolar soft part
(myxoid MFH) tumor (GIST) rhabdomyosarcoma round cell tumor sarcoma
Low-grade fibromyxoid Synovial sarcoma‡ Pleomorphic Mesenchymal Malignant granular cell
sarcoma leiomyosarcoma chondrosarcoma tumor
MPNST Angiosarcoma Round cell liposarcoma
Metastatic spindle cell Small cell osteosarcoma
sarcomatoid carcinoma
*High-grade sarcomas by definition.
†Must exclude metastatic carcinoma, malignant melanoma, and lymphoma (immunohistochemistry pivotal for diagnosis).
‡May be included in either spindle cell or polygonal (epithelioid) categories. MFH, malignant fibrous histiocytoma; MPNST, malignant peripheral nerve
sheath tumor; PNET, primitive neuroectodermal tumor.

© 2003 Lippincott Williams & Wilkins 27

Singh et al Adv Anat Pathol • Volume 11, Number 1, January 2004

TABLE 3. Immunohistochemical Screening Panels for Common Soft Tissue Sarcomas

Round Cell Sarcomas Spindle Cell Sarcomas Epithelioid/Polygonal Cell Sarcomas

• Rhabdomyosarcoma • Synovial sarcoma* • Epithelioid sarcoma
MyoD1 and Desmin + CK +/−, S-100 +/− Cytokeratin +, EMA +, CD99+, Cytokeratin +, CD34+, Vimentin +,
S-100+ (30%), Desmin −, CD34 − S-100 −, CD30−, CD45−
• Ewing sarcoma/PNET
CD99+, CK+/−, FLI-1+, EMA−, S-100−, • MPNST • Clear cell sarcoma and metastatic
Desmin−, CD56− S-100+ (weak, focal), CD34+/−, malignant melanoma
Desmin −, Cytokeratin − S-100+, HMB-45+, Melan-A+, Cytokeratin −,
• Intraabdominal desmoplastic round cell tumor CD45−, CD30−
CK+, Desmin+, S-100−, CD99+/− • Leiomyosarcoma
Desmin+, muscle actin+, vimentin+, • Alveolar soft parts sarcoma
• Non-sarcomatous group: perinuclear cytokeratin+ MyoD1 and Myogenin+/−
Lymphoma: CD45+ CD99+/− • Dermatofibrosarcoma pertuberans • Nonsarcomatous group
Small cell carcinoma: CK +, NSE +, CD34+, Cytokeratin−, S-100−,
Synaptophysin+, Chromogranin A+/− Desmin−, muscle actin− Ki-1 Lymphoma: CD30+, CD45+/−,
Cytokeratin−, S-100−
Carcinoma: Cytokeratin +, S-100 variably +,
Melanoma: S-100+, HMB-45+, Melan-A+ vimentin +/−, CD30 and CD34+
*Poorly differentiated synovial sarcomas can have a round cell morphology. PNET, primitive neuroectodermal tumor; MPNST, malignant peripheral nerve
sheath tumor; pancytokeratin (AE1/AE3), EMA, epithelial membrane antigen; NSE, neuron-specific enolase.

brilliant magenta/purple to indigo blue color. At times, the
myxoid matrix can be so copious as to obscure the cellular
component.
Although liposarcomas are broadly divided into four
major groups—well differentiated, myxoid, round cell, and
pleomorphic—recent evidence including cytogenetic studies
suggests that myxoid and round cell liposarcomas represent
spectra of the same neoplasm. Myxoid LS represents a low-
grade sarcoma and round cell liposarcoma is a high-grade ag-
gressive sarcoma.30,31 Myxoid liposarcoma (myxoid LS) is the
most common malignant lipomatous tumor in adults, most of-
ten affecting adults 40–70 years of age. Myxoid liposarcoma
usually presents as a slow-growing painless mass, that often
occurs in the retroperitoneum and proximal extremities. The
presence of even small foci of a round cell component in an
otherwise myxoid LS portends worse long-term patient sur-
vival. The major cytomorphologic features of myxoid LS are:
1) the myxoid stromal fragments, 2) plexiform or “chicken
wire” vascular pattern, and 3) a uniform mononuclear cell
population, the latter including both univacuolated lipoblasts
and nonvacuolated oval to spindle cells. In a study using logis-
tic regression analysis, Layfield et al found the presence of
lipoblasts to be the only significant feature for rendering a di-
agnosis of myxoid LS.27 These cells were most often univacu-
olated or of the signet ring cell type rather than the classic mul-
tivacuolated cells seen in tissue sections. Lipoblasts, however,
are not a dominant feature in most cases and must be searched
for diligently on the smears.27,30 In the series by Layfield et al,
the plexiform vascular pattern could also be seen in cases of
myxofibrosarcomas (15%) and chondrosarcomas (6%) and,
therefore, was not as specific a diagnostic feature. The myxoid
stroma is typically distributed as discrete stromal fragments
rather than as a diffuse film of myxoid material seen which is in
myxomas and myxofibrosarcomas. In most FNAB samples, a
specific diagnosis of myxoid liposarcoma can be rendered.
The major limitation, however, is related to difficulties in
documenting the presence or absence of a round cell liposar-
coma component due to sampling.
Myxofibrosarcoma is a tumor of adults (older than 50
years) and occurs in the extremities, trunk, retroperitoneum,
and the head and neck region. Unlike the other sarcomas in this
group, myxofibrosarcoma often occurs in the subcutaneous fat
and dermis.28 Aspirates typically yield an abundant and diffuse
myxoid granular background with a variable cellular compo-
nent depending on the grade of the tumor. There is an inverse
relationship between the amount of stroma, the smear cellular-
ity, and the grade of the sarcoma. Low-grade lesions tend to be
hypocellular with mostly myxoid matrix and oval to spindle
cells. High-grade lesions are hypercellular with pleomorphic
cells including multinucleated tumor giant cells. Lesions con-
taining the latter have been referred to as myxoid malignant
fibrous histiocytoma (MFH). Layfield et al demonstrated via
logistic regression analysis that the presence of pleomorphic
giant cells and fibroblast like spindle cells were the only cyto-
logic features diagnostically useful for the separation of myxo-
fibrosarcoma from other myxoid lesions.27 For low-grade le-

28 © 2003 Lippincott Williams & Wilkins

Adv Anat Pathol • Volume 11, Number 1, January 2004 Fine Needle Biopsy of Soft Tissue Sarcomas

FIGURE 1. A,B, Myxoid liposarcoma characterized by discrete myxoid stromal fragments containing uniform oval to spindled
neoplastic cells transversed by arborizing blood vessels (A, Diff-Quik ⳯100; B, Diff-Quik ⳯400). C, Aspirate from low-grade
myxofibrosarcoma characterized by a diffuse granular film of background myxoid material with singly dispersed spindled hyper-
chromatic tumor cells, some which display cytoplasmic “tails” (Diff-Quik ⳯200). D, High-grade myxofibrosarcomas display higher
cellularity, increasing nuclear pleomorphism, and presence of multinucleated tumor giant cells. The amount of background
myxoid granular stroma also decreases as the tumor grade increases (Diff-Quik ⳯200).

sions, the major differential diagnostic considerations are in-
tramuscular myxoma (IM) and low-grade fibromyxoid
sarcoma (LGFS). The smears of low-grade myxofibrosarcoma
are more cellular than IM and demostrate more cytologic atyp-
ia. IM is usually a deep-seated lesion, whereas most low-grade
myxofibrosarcomas are present above the deep fascia. Lind-
berg et al reported on the FNAB features of three cases of
LGFS and concluded that the cytologic findings were not spe-
cific enough to allow a diagnosis by FNAB since the cytologic
features are similar to those of low-grade myxofibrosarco-
mas.32 Low-grade myxofibrosarcoma should show more
nuclear atypia than LGFS on aspiration smears. Because of the
decreased amount of stroma, high- grade lesions are difficult,
if not impossible, to distinguish from other adult pleomorphic
sarcomas including pleomorphic malignant fibrous histiocy-
toma and pleomorphic liposarcoma.26,30
Extraskeletal myxoid chondrosarcoma (EMS) is a rare,
slow-growing low-grade sarcoma most often seen in patients
older than 35 years of age and occurring in the deep soft tissues
of the thigh and popliteal fossa. Only case reports of the cyto-
pathologic characteristics of EMS exist with the largest series
consisting of only 5 cases.30,33,34 The most characteristic find-
ing on the smears is large fragments of intensely staining myx-
oid stroma which, in some cases, can obscure the cellular com-
ponent present. On Papanicolaou-stained smears, the stroma
appears transparent, and the cellular component may be better
evaluated. Smears are moderate to highly cellular with pre-
dominantly tight clusters of round to oval to spindled cells with
uniform nuclei, inconspicuous nucleoli, and moderate
amounts of finely vacuolated cytoplasm, the latter recapitulat-
ing the lacunae of chondrocytes. The major differential diag-
nosis is chordoma. Although strictly a neoplasm of bone, chor-
doma commonly infiltrates adjacent soft tissues, thereby,
simulating a primary soft tissue sarcoma. Smears are domi-
nated by copious amounts of intensely staining myxoid
stroma, which is typically interwoven between groups or indi-

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Singh et al Adv Anat Pathol • Volume 11, Number 1, January 2004

vidual cells. The stroma is more dense than that seen in the
other myxoid sarcomas and more closely resembles chondroid
stroma on the smears. The physaliphorous cell, which is the
only cytologic feature specific for chordoma, can be uni- or
multinucleated and is surrounded by large cytoplasmic vacu-
oles.27 Immunohistochemical staining for cytokeratin can be
extremely useful because chordomas show strong and diffuse
cytoplasmic positivity, whereas the other myxoid sarcomas are
negative.
Spindle Cell Sarcomas
The spindle cell sarcomas include synovial sarcoma,
malignant peripheral nerve sheath tumor (MPNST), leiomyo-
sarcoma, fibrosarcoma, Kaposi sarcoma, angiosarcoma, and
some forms of MFH (Fig. 2).22
In our experience, this group of lesions is the most diag-
nostically challenging because of the difficulties in accurately
separating benign lesions from low-grade sarcomas and accu-
rately subclassifying the sarcoma. Kilpatrick and Geisinger
have shown that the two major criteria used to designate a
FNAB specimen as a sarcoma, namely, moderate to high
smear cellularity and hyperchromatic nuclei in almost all
sampled cells, do not always allow accurate separation and/or
grading among the spindle cell sarcoma group.9 Benign mes-
enchymal lesions often demonstrate marked dyscohesive-
ness and hypercellularity that, in some cases, result in destruc-
tive changes clinically and radiographically mimick a sar-
coma.
Aspirates from MPNST are of moderate to high cellu-
larity with a predominance of single cells and, in some cases,

FIGURE 2. A,B, Aspirates from MPNST with enlarged spindled cells with bent, wavy, and serpentine nuclei and scant amounts of
tapering cytoplasm. Multinucleated tumor giant cells can be observed in high-grade lesions (A, Diff-Quik ⳯200; B, Diff-Quik
⳯400). (Reprinted with permission from McGee RS, Ward WG, Kilpatrick SE: Diagn Cytopathol 1997;17:298–305.) C, Synovial
sarcoma characterized by clusters and solitary ovoid to spindled tumor cells with uniform nuclei, scant cytoplasm, and small
inconspicuous nucleoli (Diff-Quik ⳯200). D, Unlike most sarcomas, aspirates from leiomyosarcoma typically demostrate cohesive
tissue fragments with parallel bundles of spindled cells with cigar-shaped nuclei and varying degrees of pleomorphism (Papani-
colaou ⳯400).

30 © 2003 Lippincott Williams & Wilkins

Adv Anat Pathol • Volume 11, Number 1, January 2004
loosely cohesive clusters of malignant cells. The spindled nu-
clei demonstrate characteristic wavy or bent nuclear shapes
with hyperchromasia, irregular nuclear membranes, and intra-
nuclear inclusions. The nuclear/cytoplasmic ratios tend to be
high and cells display cyctoplasmic ends. As the grade of the
sarcoma increases, multinucleated tumor giant cells and mito-
ses can be identified. In a series of 10 MPNST, Jimenez-
Heffernan et al reported on the cytologic characteristics of both
low and high grade lesions35. While all lesions could be rec-
ognized on the smears as malignant, only the low grade tumors
could be identified as having a neural origin. High grade le-
sions displayed an epithelioid/polygonal cell morphology in
two of the cases. Immunohistochemical staining against
smooth muscle actin, muscle specific actin, and S-100 can be
extremely useful in separating MPNST from other spindle
neoplasms such as schwannoma, leiomyosarcoma, malignant
fibrous histiocytoma, and synovial sarcoma. S-100 reactivity
is seen in only 50% of MPNST and tends to be weak and focal.
Diffuse S-100 positivity argues against a diagnosis of MPNST
and should suggest the diagnosis of a schwannoma. It should
be noted that ancient schwannomas may be misinterpreted as a
sarcoma based on their high smear cellularity, mitotic activity,
and large hyperchromatic and often multinucleated cells. At-
tention to chromatin detail, which displays degenerative
changes, along with more prominent cellular cohesion, should
help differentiate this lesion from MPNST. Likewise, cellular
schwannomas display predominantly cohesive cellular frag-
ments rather than single cells22. Correlation between the cyto-
logic features and the clinical information, ie, preexisting neu-
rofibroma, patient known to have a history of neurofibromato-
sis I, and origin of the tumor from a nerve trunk, can help to
support a diagnosis of MPNST, particularly in the high-grade
lesions.
Synovial sarcomas are relatively uncommon tumors af-
fecting young adults and most often occur in the extremities.
Biphasic and monophasic varieties occur, with the majority of
synovial sarcomas pathologically recognized being of the lat-
ter type. Aspiration smears are of high cellularity, comprised
of small cohesive clusters of overlapping densely packed cells,
branching tumor tissue fragments, as well as singly dispersed
cells in the background. The cells are monomorphic and range
from round to oval to slightly spindled in shape with finely
granular evenly dispersed chromatin, inconspicuous nucleoli,
and scant cytoplasm. Spindle cells dominate the aspirate
smears from histologically documented cases of biphasic sy-
novial sarcomas. Mitoses may be seen. The majority of aspi-
rated synovial sarcomas, regardless of subtype, lack an obvi-
ous epithelial component. The major differential diagnostic
considerations include MPNST, Ewing sarcoma, and malig-
nant hemangiopericytoma. Spindle cell tissue fragments are
less prominent in MPNST, which also contains spindle cells
with wavy or bent morphology displaying greater nuclear
pleomorphism. In Ewing sarcoma, most of the cells are singly
© 2003 Lippincott Williams & Wilkins
Fine Needle Biopsy of Soft Tissue Sarcomas
dispersed with only a few cell clusters identified. The FNAB
smears of hemangiopericytoma are also dominated by a uni-
form population of oval to spindle cells, and the characteristic
vascular pattern seen histologically is generally not obvious in
cytologic smears.36,37 Immunohistochemistry plays a pivotal
role in the rendering of a specific diagnosis by FNAB with
synovial sarcoma, demonstrating positivity for cytokeratin,
epithelial membrane antigen, and CD99. More than 90% of
cases of synovial sarcoma have the characteristic t(x;18) by
cytogenetic analysis which can be successfully demonstrated
on aspirated material13.
The retroperitoneum is the most common deep seated
site for leiomyosarcomas. Low grade lesions are most often
aspirated. Unlike the other spindle sarcomas, the cellularity is
low to moderate with a predominance of cohesive cell clusters
arranged in parallel bundles with cells displaying cigar shaped
nuclei, fibrillar cytoplasm, and indistinct nucleoli. The parallel
arrangement of cells is an important cytologic feature for a
diagnosis of leiomyosarcoma. High grade lesions still display
a predominance of cohesive cell clusters, however, increasing
nuclear pleomorphism, nucleoli, multi-nucleated giant cells,
and singly dispersed tumor cells are also present. Background
necrotic debris and mitoses can be seen in high grade leiomy-
osarcomas. Distinction of higher grade lesions from leiomyo-
ma can generally be made based on the smear cellularity and
nuclear abnormalities, however, it may be impossible to sepa-
rate a low grade leiomyosarcoma from leiomyoma based on
cytomorphology alone. The usefulness of mitotic counts for
separating benign from malignant smooth muscle tumors on
aspirated material as in histologic sections is believed to be
limited. High grade pleomorphic leiomyosarcomas containing
multinucleated tumor giant cells may be difficult to separate
from malignant fibrous histiocytoma (MFH). The use of im-
munohistochemical stains for desmin, caldesmon, and alpha
smooth muscle actin can be of diagnostic aid in their separa-
tion.
Because of their tendency to bleed, vascular lesions are
seldom aspirated except where nodular lesions are suspected
of being a metastasis. Malignant vascular neoplasms most of-
ten encountered in FNAB specimens include hemangiopericy-
tomas and angiosarcomas. The smears from hemangiopericy-
tomas are generally of high cellularity and composed of a uni-
form population of oval to spindled cells arranged in cohesive
tissue fragments. The characteristic perivascular proliferation
of cells seen in tissue sections can be identified in cell block
preparations from aspirated material as tissue fragments tra-
versed by branched, and dilated vascular channels. Minimal
cytologic atypia is seen in FNAB smears of hemangiopericy-
tomas A number of other soft tissue sarcomas can display focal
hemagiopericytomatous patterns and these include MFH,
synovial sarcoma, and leiomyosarcoma. In all of these cases,
characteristic cytomorphologic features of the specific sar-
coma are also seen. Hemangiopericytoma remains a diagnosis
31
Singh et al
of exclusion and cannot be reliably diagnosed by FNAB
alone.36
Aspirates from angiosarcomas tend to be hypocellular
with predominantly single cells in an abundant bloody back-
ground. Cells vary from spindled to oval to round with abun-
dant vacuolated cytoplasm and eccentric pleomorphic nuclei.
In some cases, intracytoplasmic hemosiderin can be identi-
fied.39 In a study of the cytomorphologic features of 11 angio-
sarcomas, Liu et al emphasized that the low smear cellularity is
“an inherent and helpful diagnostic feature of angiosarcomas
and is not due to sampling error.” From this series, they pro-
posed that when rare, single pleomorphic cells with eccentric
nuclei and abundant vacuolated cytoplasm are present in a
bloody background, the possibility of angiosarcoma should be
raised. Many of the cytologic features of angiosarcoma can be
seen in radiation-induced injury; therefore, when there is a
history of radiation therapy, tissue biopsy should be recom-
mended. A definitive diagnosis of angiosarcoma requires the
aid of immunohistochemical staining for factor VIII and CD34
or CD31, the latter being the most specific and sensitive
marker for diagnosing angiosarcoma. However, in the major-
ity of cases, insufficient material is usually present to perform
immunohistochemistry.
The prototype lesion of the fibrohistiocytic group of
spindle cell sarcomas is fibrosarcoma. The FNAB diagnosis is
one of exclusion because the smears may contain little to no
associated matrix and are frequently of moderate to high cel-
lularity. Smears contain large tissue fragments with bundles of
spindle cells. The degree of nuclear atypia correlating with the
tumor grade. Higher-grade sarcomas may show, in addition to
marked nuclear abnormalities, the presence of multinucleated
tumor giant cells, necrosis, hemorrhage, and frequent mitoses.
Fibrosarcoma may not be classifiable beyond a diagnosis of
spindle cell malignant neoplasm on FNAB specimens because
there is significant overlap of the cytologic features with fibro-
matoses, nodular fasciitis, leiomyosarcoma, spindle cell carci-
nomas, MFH, MPNST, and spindle cell predominant synovial
sarcoma. Aspirates from fibromatoses tend to be of low to
moderate cellularity and, most importantly, lack mitotic fig-
ures often seen in both low- and high-grade fibrosarcomas.
However, in our experience, the diagnosis of fibromatoses by
FNAB is usually not possible. Aspirates from nodular fasciitis,
in conjunction with the clinical findings, can be diagnosed by
FNAB. Smears are moderate to highly cellular with cells dis-
playing a characteristic tissue culture pattern set in a highly
metachromatic myxoid background admixed with inflamma-
tory cells.22 Ancillary studies with a panel of immunohisto-
chemical stains can help separate fibrosarcoma from leiomyo-
sarcoma (desmin-, muscle-specific actin-, and smooth muscle
actin-positive), MPNST (S-100 negative and N-CAM-
positive), and synovial sarcoma (cytokeratin negative, EMA
negative, and CD99-positive).
32
Adv Anat Pathol • Volume 11, Number 1, January 2004
Because metastases outnumber primary soft tissue sar-
comas, nonsarcomatous malignancies must be included in
the differential diagnosis of spindle cell sarcomas. Sarcoma-
toid carcinomas, mesotheliomas, malignant melanomas, and
examples of non-Hodgkin lymphomas associated with sclero-
sis present the most difficulty in accurate separation from pri-
mary spindle cell sarcomas. Smears are of moderate to high
cellularity with a predominance of highly atypical spindle
cells. Correlation with the past medical history and immuno-
histochemical stains are crucial in rendering an accurate diag-
nosis.
Pleomorphic Sarcomas
The majority of aspirates from this category of sarcomas
are from MFH and liposarcomas (Fig. 3A,B). In aspirated ma-
terial, the pleomorphic sarcomas are easily recognized as ma-
lignant and as high-grade sarcomatous lesions with moderate
to highly cellular smears containing predominantly dyscohe-
sive cells. If lipoblasts are identifiable, then a specific diagno-
sis of pleomorphic liposarcoma can be rendered on FNAB. In
most cases, the cytologic features are not diagnostic for sub-
typing beyond a diagnosis of “pleomorphic sarcomas, not oth-
erwise specified.” Kilpatrick et al have reported that, at pres-
ent, adult patients with pleomorphic sarcomas, regardless of
the histologic subtype, are treated similarly with complete sur-
gical excision and radiation therapy and/or chemotherapy.
This is due to the fact that prognosis and treatment responses
are approximately the same across the group. The overall
5-year survival across the group is 50–60%.3 Fletcher and col-
leagues, in a recent study reevaluating 100 cases of MFH, have
shown that there are prognostic subgroups among the lesions
previously categorized as pleomorphic MFH.40 The rate of
metastases varied among the subgroups with dedifferentiated
liposarcoma having a 15–20% incidence, high-grade myxofi-
brosarcoma (myxoid MFH) with a 30–35% rate, and the pleo-
morphic rhabdomyosarcoma and leiomyosarcoma groups hav-
ing the highest rate of metastases with much shorter relapse-
free survival.
Pleomorphic MFH is regarded as the most common soft
tissue sarcoma in adults. Its most distinctive feature, however,
has been the lack of any specific differentiation, and therefore,
the diagnosis has become essentially one of exclusion. Cur-
rently, the concept of MFH remains controversial, and it has
been shown that most lesions classified as MFH based on mor-
phology can be further subtyped (with the use of ancillary stud-
ies) into other pleomorphic sarcomas including pleomorphic
liposarcomas, rhabdomyosarcomas, and leiomyosarcomas or
even nonsarcomatous malignancies.40 Therefore, pleomorphic
MFH is now used to define a small group of undifferentiated
pleomorphic sarcomas where current diagnostic methods do
not reveal a definite line of differentiation.40
The most common differential diagnostic problems arise
in the separation of pleomorphic sarcomas from sarcomatoid
© 2003 Lippincott Williams & Wilkins
Adv Anat Pathol • Volume 11, Number 1, January 2004 Fine Needle Biopsy of Soft Tissue Sarcomas

FIGURE 3. A, Pleomorphic liposarcoma characterized by an aggregate of multivacuolated lipoblasts (Diff-Quik ⳯200). B, Multi-
nucleated tumor giant cell from an aspirate of MFH. Similar tumor cells can be seen in other pleomorphic sarcomas; therefore,
MFH should be a diagnosis of exclusion. C, Aspirate from clear cell sarcoma demonstrating round to oval tumor cells with
abundant clear to granular cytoplasm (Diff-Quik ⳯200). D, Aspirate of alveolar soft part sarcoma with large polygonal shaped cells
with round, eccentrically placed nuclei, prominent nucleoli, and abundant granular cytoplasm (Diff-Quik ⳯400).

carcinomas from various sites (lung, kidney, pancreas, thy-
roid), malignant melanoma, and anaplastic lymphoma. All of
these entities can present with highly cellular smears with a
predominance of dyscohesive cells that are markedly pleomor-
phic and sometimes multinucleated. Careful review of the
clinical history along with ancillary studies (panel of immuno-
histochemical stains) are crucial for accurate classification
(Table 3).
Polygonal/Epithelioid Cell Sarcomas
This category represents, by definition, high-grade sar-
comas and includes epithelioid sarcoma, alveolar soft part sar-
coma, clear cell sarcoma (malignant melanoma of soft parts),
and malignant granular cell tumors (Fig. 3C,D). This is also the
least frequently encountered group on FNAB specimens.
Smears are dominated by singly dispersed cells with
round/polygonal shapes and moderate to abundant cytoplasm.
Nuclei tend to be eccentrically located with one or more promi-
nent nucleoli. Bi- and multinucleated cells can be seen in most
cases. The cytomorphologic features among these entities
show considerable overlap necessitating the use of ancillary
studies with immunohistochemistry to make a specific diagno-
sis and for separation from nonsarcomatous malignancies. As-
pirates from clear cell sarcoma rarely display the characteristic
intranuclear pseudoinclusions and intracytoplasmic melanin.
As with malignant melanoma, the cells show diffuse and
strong cytoplasmic positivity for S-100 and less often for
HMB-45 and Melan-A. It is therefore not possible to separate
this entity from metastatic cutaneous malignant melanoma by
cytologic and immunohistochemical findings.41 Most cases of
clear cell sarcoma show the t(12;22) translocation that has not
been observed in cutaneous malignant melanoma. Metastatic
carcinoma also enters into the differential diagnosis and gen-
erally shows at least some cohesive clusters of malignant cells
along with positivity for epithelial markers by immunohisto-

© 2003 Lippincott Williams & Wilkins 33

Singh et al
chemistry. Epithelioid sarcomas are extremely rare, occurring
in the distal extremities of young adults. This tumor can be
misdiagnosed as a benign granulomatous process. Most cases
show positive staining for epithelial markers (low- and high-
molecular-weight cytokeratin) and vimentin. CD34 positivity
by immunohistochemistry is seen in approximately 50% of
cases and can help in differentiating epithelioid sarcoma from
metastatic carcinomas, which are almost always negative.
Muscle-specific markers and epithelial markers should sepa-
rate epithelioid sarcoma from rhabdomyosarcoma.
Alveolar soft part sarcoma is a rare tumor that mainly
affects adolescents and young adults, most commonly occur-
ring in the deep soft tissues of the thigh. On FNAB specimen
cell block preparations, the characteristic alveolar arrange-
ment of cells may be seen. The major differential diagnosis
includes alveolar rhabdomyosarcoma, metastatic carcinoma,
and granular cell tumor. Immunohistochemistry is extremely
useful in the separation of these entities because alveolar soft
part sarcoma often shows positivity for desmin and vimentin,
whereas metastatic carcinomas are positive for various epithe-
lial markers, and granular cell tumors characteristically reveal
diffuse S-100 positivity.
Round Cell Sarcomas
Round cell sarcomas predominate in the pediatric popu-
lation, and, in contrast to adult patients, definitive cell typing
is necessary for enrollment of patients in histogenetic-specific
protocols (ie, POG, etc.). These combined therapeutic proto-
cols have led to a significant increase in the disease-free
survival rates. The most common soft tissue small round cell
sarcoma is rhabdomyosarcoma. Other round cell sarcomas in-
clude extraskeletal Ewing sarcoma (ES)/primitive neuroecto-
dermal tumor (PNET), neuroblastoma, intraabdominal desmo-
plastic small round cell tumor, and lymphoma (Fig. 4).
All are uniformly characterized by the presence of sheets
of monomorphic round cells with minor architectural and cy-
tomorphologic features that can serve as clues to the correct
diagnosis. In rare cases, it may be difficult to impossible to
correctly classify this group of sarcomas by histologic exami-
nation. Therefore, one may presume that this problem is fur-
ther compounded when only cytologic material is evaluated.
However, as mentioned previously, correct cell typing is
often possible and achievable in 92% of all round cell sarco-
mas by FNAB with the judicious use of ancillary studies
(immunohistochemistry, electron microscopy, cytogenet-
ics).3,42 There have been numerous reports of the various cy-
tologic features for diagnosis of specific round cell sarco-
mas.1,22,43 In an effort to better define the diagnostic utility of
various features previously described in the literature, Layfield
et al performed logistic regression analysis of 59 cases for the
diagnosis of the more common round cell sarcomas (Ewing
sarcoma, rhabdomyosarcoma, neuroblastoma, Wilms tumor,
and lymphoma).44 Twenty-eight cytologic variables encom-
34
Adv Anat Pathol • Volume 11, Number 1, January 2004
passing nuclear, cytoplasmic, and architectural features were
analyzed as to their association with the histologic diagnostic
category to determine which characteristics were most predic-
tive. From their analysis, the most specific feature for the di-
agnosis of rhabdomyosarcoma was the presence of tadpole or
strap cells. In their absence, diagnosis was dependent on im-
munohistochemical and/or ultrastructural analysis. Aspirates
from rhabdomyosarcoma are highly cellular, and the appear-
ance partly depends on the specific histologic subtype. The
most recent classification includes 5 “prognostically signifi-
cant” subtypes, which are: spindle cell and botryoid embryonal
(superior prognosis); embryonal not otherwise specified (in-
termediate prognosis); alveolar, diffuse anaplastic, and undif-
ferentiated subtypes (poor prognosis). Most aspirates show a
predominant single cell population of primitive small cells
with scant cytoplasm and solitary nuclei. Embryonal rhabdo-
myosarcomas tend to have more abundant cytoplasm and mul-
tiple nuclei. Aspirates from alveolar rhabdomyosarcoma can
have admixed loose cell aggregates (better appreciated in cell
block preparations). Vacuolization of the cytoplasm has been
reported in up to 85% of rhabdomyosarcomas but is not diag-
nostic and can be seen in Ewing sarcoma and lymphoma as
well. In Layfield’s study, cytoplasmic vacuoles were strongly
associated with Ewing sarcoma and not with rhabdomyosar-
coma. Among the group of round cell sarcomas, Ewing
sarcoma/PNET is the most difficult to specifically diagnose by
cytomorphology alone. In most cases, it is the lack of diagnos-
tic criteria of the other round cell sarcomas that is used to make
a diagnosis of Ewing sarcoma/PNET. FNAB specimens char-
acteristically demonstrate high cellularity with single mono-
morphic cells with extremely high nuclear/cytoplasmic ratios.
Layfield et al found the scanty cytoplasm along with cytoplas-
mic vacuolization to be the most specific cytologic features for
a diagnosis of Ewing sarcoma.44 The nuclei are strikingly uni-
form, round with evenly dispersed chromatin, and have incon-
spicuous nucleoli. In some cases, pseudorosettes may be iden-
tified. Larger cells with vesicular chromatin (light cells) and
scant cytoplasm can also be seen. The differential diagnosis
includes neuroblastoma and lymphoma. Lymphoglandular
bodies, characteristically seen in lymphomas, are absent from
the background of aspirates of Ewing sarcoma. Background
neuropil, ganglion cells, and the presence of Homer-Wright
rosettes help to identify neuroblastoma. Immunohistochemical
staining for CD99 and FLI-1, although not entirely specific,
can aid in the diagnosis of Ewing sarcoma.45 Positive staining
for the MIC-2 oncogene can be seen in lymphoblastic lympho-
mas as well as Ewing sarcoma and is, therefore, less helpful.
Cytogenetic analysis for demonstrating the t(11;22) reciprocal
translocation has been successfully performed on aspirated
material.5
FNAB specimens from an intraabdominal site raise the
differential diagnosis of neuroblastoma, Burkitt lymphoma,
and intraabdominal desmoplastic small round cell tumor. The
© 2003 Lippincott Williams & Wilkins
Adv Anat Pathol • Volume 11, Number 1, January 2004 Fine Needle Biopsy of Soft Tissue Sarcomas

FIGURE 4. A, Alveolar rhabdomyosarcoma characterized by loose clusters and singly scattered small round cells with minimal
nuclear pleomorphism and scant cytoplasm (Diff-Quik ⳯200). B, Aspirates from embryonal rhabdomyosarcoma typically show
more cytologic variability and cells with more abundant cytoplasm. Bi- and multinucleated forms can be seen (Diff-Quik ⳯400).
C, Ewing sarcoma is characterized by a strikingly uniform population of round tumor cells with regular nuclear membranes and
very high nuclear/cytoplasmic ratios (Papanicolaou ⳯400). D, Neuroblastoma with rosette formation, characteristic neuropil, and
uniform small round tumor cells (Papanicolaou ⳯400).

latter is a highly aggressive sarcoma affecting male adoles-
cents. Aspirates from intraabdominal desmoplastic tumors
yield variable cellular smears because of the presence of
a desmoplastic stroma. The cellular composition is similar
to that seen in aspirates from Ewing sarcoma/PNET with
small round cells containing scant cytoplasm predominating.
Immunohistochemical staining reveals positive staining
for cytokeratin, desmin, and neuron-specific enolase. FNAB
specimens from neuroblastomas are highly cellular with a
predominant singly dispersed small round cell population.
Characteristic cytologic features include the presence of
pseudorosettes containing central neuropil, which may also be
seen in the background, and in some cases, ganglion cells
can be identified. In cases of Burkitt lymphoma, the smears
demonstrate a uniform population of blasts with more promi-
nent nucleoli and variable amounts of cytoplasm. Lympho-
glandular bodies can be easily identified in the background
and aid in the diagnosis. Cytogenetic analysis can be per-
formed on aspirated material to demonstrate the t(8;14) recip-
rocal translocation.
CONCLUSIONS
For the primary workup of soft tissue sarcomas, FNAB
has several major advantages that certainly outweigh its limi-
tations. It provides a rapid, relatively nontraumatic sampling
technique for both superficial and deep-seated lesions. Mul-
tiple samplings provide additional material for ancillary stud-
ies, especially when guided by immediate interpretation from
an experienced on-site cytopathologist.
FNAB, in conjunction with ancillary studies (immuno-
histochemistry, cytogenetics, flow cytometry, and/or electron
microscopy), can approach a diagnostic accuracy of 95% for

© 2003 Lippincott Williams & Wilkins 35

Singh et al
the diagnosis of a malignancy. FNAB compares favorably
with core needle biopsy, having approximately the same diag-
nostic accuracy in separating benign from malignant soft tissue
lesions.
When ancillary studies are incorporated, FNAB is ca-
pable of subtyping most malignant soft tissue tumors.
As with FNAB material from other sites, a team ap-
proach that integrates the clinical, radiographic, and morpho-
logic data cannot be overemphasized as a key component to the
success of this diagnostic modality.
From a practical standpoint, it may not be possible to
accurately separate low-grade spindle cell and myxoid sarco-
mas from benign neoplasms based on cytomorphology alone.
Even in this latter instance, FNAB still allows the rapid sepa-
ration of patients who will require tissue biopsy for a defini-
tive diagnosis, thereby obviating multiple clinic visits, elimi-
nating unnecessary procedures, and reducing the overall
costs.
REFERENCES
1. Geisinger KR, Silverman J. F., Wakely P. Pediatric Cytopathology.
1st ed. Chicago: American Society of Clinical Pathologists; 1994:259–
281.
2. Gonzalez-Campora R. Fine needle aspiration cytology of soft tissue tu-
mors. Acta Cytol. 2000;44:337–343.
3. Kilpatrick SE, Ward WG, Cappellari JO, et al. Fine-needle aspiration bi-
opsy of soft tissue sarcomas. A cytomorphologic analysis with emphasis
on histologic subtyping, grading, and therapeutic significance. Am J Clin
Pathol. 1999;112:179–188.
4. Abdul-Karim FW, Rader AE. Fine needle aspiration of soft-tissue lesions.
Clin Lab Med. 1998;18:507–540.
5. Kilpatrick SE, Ward WG, Chauvenet AR, et al. The role of fine-needle
aspiration biopsy in the initial diagnosis of pediatric bone and soft tissue
tumors: an institutional experience. Mod Pathol. 1998;11:923–928.
6. Parham DM, Webber BL, Jenkins JJ 3rd, et al. Nonrhabdomyosarcoma-
tous soft tissue sarcomas of childhood: formulation of a simplified system
for grading. Mod Pathol. 1995;8:705–710.
7. Parham DM. Pathologic classification of rhabdomyosarcomas and corre-
lations with molecular studies. Mod Pathol. 2001;14:506–514.
8. Recommendations for the reporting of soft tissue sarcomas. Association of
Directors of Anatomic and Surgical Pathology. Hum Pathol. 1999;30:
3–7.
9. Kilpatrick SE, Geisinger KR. Soft tissue sarcomas: the usefulness and
limitations of fine-needle aspiration biopsy. Am J Clin Pathol. 1998;110:
50–68.
10. Costa MJ, Campman SC, Davis RL, et al. Fine-needle aspiration cytology
of sarcoma: retrospective review of diagnostic utility and specificity. Di-
agn Cytopathol. 1996;15:23–32.
11. Wakely PE Jr, Kneisl JS. Soft tissue aspiration cytopathology. Cancer.
2000;90:292–298.
12. Bommer KK, Ramzy I, Mody D. Fine-needle aspiration biopsy in the
diagnosis and management of bone lesions: a study of 450 cases. Cancer.
1997;81:148–156.
13. Kilpatrick SE, Cappellari JO, Bos GD, et al. Is fine-needle aspiration bi-
opsy a practical alternative to open biopsy for the primary diagnosis of
sarcoma? Experience with 140 patients. Am J Clin Pathol. 2001;115:
59–68.
14. Jones C, Liu K, Hirschowitz S, et al. Concordance of histopathologic and
cytologic grading in musculoskeletal sarcomas: can grades obtained from
analysis of the fine-needle aspirates serve as the basis for therapeutic de-
cisions? Cancer. 2002;96:83–91.
15. Bennert KW, Abdul-Karim FW. Fine needle aspiration cytology vs.
needle core biopsy of soft tissue tumors. A comparison. Acta Cytol. 1994;
38:381–384.
36
Adv Anat Pathol • Volume 11, Number 1, January 2004
16. Coindre JM, Terrier P, Guillou L, et al. Predictive value of grade for me-
tastasis development in the main histologic types of adult soft tissue sar-
comas: a study of 1240 patients from the French Federation of Cancer
Centers Sarcoma Group. Cancer. 2001;91:1914–1926.
17. Kilpatrick SE. Histologic prognostication in soft tissue sarcomas: grading
versus subtyping or both? A comprehensive review of the literature with
proposed practical guidelines. Ann Diagn Pathol. 1999;3:48–61.
18. Pollock RE. The National Cancer Data Base report on soft tissue sarcoma.
Cancer. 1996;78:2247–2257.
19. Costa J, Wesley RA, Glatstein E, et al. The grading of soft tissue sarco-
mas. Results of a clinicohistopathologic correlation in a series of 163
cases. Cancer. 1984;53:530–541.
20. Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the Na-
tional Cancer Institute and French Federation of Cancer Centers Sarcoma
Group grading systems in a population of 410 adult patients with soft
tissue sarcoma. J Clin Oncol. 1997;15:350–362.
21. Trojani M, Contesso G, Coindre JM, et al. Soft-tissue sarcomas of adults;
study of pathological prognostic variables and definition of a histopatho-
logical grading system. Int J Cancer. 1984;33:37–42.
22. Geisinger KR, Abdul-Karim FW. Fine needle aspiration biopsies of soft
tissue tumors. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss’s
Soft Tissue Tumors. 4th ed. Saint Louis: Mosby; 2001:147–188.
23. Recommendations for the reporting of soft tissue sarcomas. Association of
Directors of Anatomic and Surgical Pathology. Mod Pathol. 1998;11:
1257-61.
24. Palmer HE, Mukunyadzi P, Culbreth W, et al. Subgrouping and grading of
soft-tissue sarcomas by fine-needle aspiration cytology: a histopathologic
correlation study. Diagn Cytopathol. 2001;24:307–316.
25. Liu K, Layfield LJ, Coogan AC, et al. Diagnostic accuracy in fine-needle
aspiration of soft tissue and bone lesions. Influence of clinical history and
experience. Am J Clin Pathol. 1999;111:632–640.
26. Wakely PE Jr. Myxomatous soft tissue tumors: correlation of cytopathol-
ogy and histopathology. Ann Diagn Pathol. 1999;3:227–242.
27. Layfield LJ, Liu K, Dodge RK. Logistic regression analysis of myxoid
sarcomas: a cytologic study. Diagn Cytopathol. 1998;19:355–360.
28. Kilpatrick SE, Ward WG. Myxofibrosarcoma of soft tissues: cytomor-
phologic analysis of a series. Diagn Cytopathol. 1999;20:6–9.
29. Kilpatrick SE, Inwards CY, Fletcher CD, et al. Myxoid chondrosarcoma
(chordoid sarcoma) of bone: a report of two cases and review of the lit-
erature. Cancer. 1997;79:1903–1910.
30. Kilpatrick SE, Ward WG, Bos GD. The value of fine-needle aspiration
biopsy in the differential diagnosis of adult myxoid sarcoma. Cancer.
2000;90:167–177.
31. Fletcher CD, Akerman M, Dal Cin P, et al. Correlation between clinico-
pathological features and karyotype in lipomatous tumors: a report of 178
cases from the Chromosomes and Morphology (CHAMP) Collaborative
Group. Am J Pathol. 1996;148:623–630.
32. Lindberg GM, Maitra A, Gokaslan ST, et al. Low grade fibromyxoid sar-
coma: fine-needle aspiration cytology with histologic, cytogenetic, im-
munohistochemical, and ultrastructural correlation. Cancer. 1999;87:
75–82.
33. De Las Casas L, Singh HK, Halliday BE, et al. Myxoid chondrosarcoma
of the sphenoid sinus and chondromyxoid fibroma of the iliac bone: Cy-
tomorphologic features of two distinct and uncommon myxoid lesions.
Diagn Cytopathol. 1999;22:383–389.
34. Niemann TH, Bottles K, Cohen MB. Extraskeletal myxoid chondrosar-
coma: fine-needle aspiration biopsy findings. Diagn Cytopathol. 1994;11:
363–366.
35. Jimenez-Heffernan JA, Lopez-Ferrer P, Vicandi B, et al. Cytologic fea-
tures of malignant peripheral nerve sheath tumor. Acta Cytol. 1999;43:
175–183.
36. Chhieng D, Cohen JM, Waisman J, et al. Fine-needle aspiration cytology
of hemangiopericytoma: A report of five cases. Cancer. 1999;87:190–
195.
37. Geisinger KR, Silverman J. F., Cappellari J.O., Dabbs D.J. Fine needle
aspiration cytology of malignant hemangiopericytoma with ultrastruc-
tural and flow cytometric analysis. Arch Pathol Lab Med. 1990;114:
705.
38. Kilpatrick SE, Mentzel T, Fletcher CDM. Leiomyoma of deep soft tissue:
© 2003 Lippincott Williams & Wilkins
Adv Anat Pathol • Volume 11, Number 1, January 2004
clinicopathologic analysis of a series. Am J Surg Pathol. 1994;18:576–
582.
39. Liu K, Layfield LJ. Cytomorphologic features of angiosarcoma on fine
needle aspiration biopsy. Acta Cytol. 1999;43:407–415.
40. Fletcher CD, Gustafson P, Rydholm A, et al. Clinicopathologic re-
evaluation of 100 malignant fibrous histiocytomas: prognostic relevance
of subclassification. J Clin Oncol. 2001;19:3045–3050.
41. Creager AJ, Pitman MB, Geisinger KR. Cytologic features of clear cell
sarcoma (malignant melanoma) of soft parts: a study of fine-needle aspi-
rates and exfoliative specimens. Am J Clin Pathol. 2002;117:217–224.
© 2003 Lippincott Williams & Wilkins
Fine Needle Biopsy of Soft Tissue Sarcomas
42. Kilpatrick SE, Garvin AJ. Recent advances in the diagnosis of pediatric
soft-tissue tumors. Med Pediatr Oncol. 1999;32:373–376.
43. Silverman JF, Gurley AM, Holbrook CT, et al. Pediatric fine-needle as-
piration biopsy. Am J Clin Pathol. 1991;95:653–659.
44. Layfield LJ, Liu K, Dodge RK. Logistic regression analysis of small round
cell neoplasms: a cytologic study. Diagn Cytopathol. 1999;20:271–277.
45. Jimenez RE, Folpe AL, Lapham RL, et al. Primary Ewing’s sar-
coma/primitive neuroectodermal tumor of the kidney: a clinicopathologic
and immunohistochemical analysis of 11 cases. Am J Surg Pathol. 2002;
26:320–327.
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