PART TWO
Diagnostic Cytology
SOFT TISSUE TUMORS
Introduction
Fine-needle aspiration biopsy (FNAB) of mesenchymal lesions
is still controversial. It is not as widely accepted as FNAB of
solid organs. One of the possible reasons for the low acceptance
might be the inexperience of most cytopathologists as soft tissue
neoplasms are relatively uncommon. Sarcomas represent less
than 1% of all malignancies and mostly are treated in tertiary
care centers. There is also a generalized perception that FNAB
of mesenchymal lesions does not provide enough information
for treatment. Despite all criticisms and limitations of FNAB in
the evaluation of mesenchymal neoplasms, it is important to
know the cytological features of mesenchymal neoplasms. It is
important to distinguish primary mesenchymal neoplasms from
metastatic epithelial or melanocytic neoplasms involving the
bone and soft tissue. Similarly, metastatic mesenchymal lesions
should be distinguished from primary or metastatic epithelial
lesions in the lung.
Morphologic Approach to Soft Tissue Lesions
A multidisciplinary approach is essential in the evaluation of
FNAB of mesenchymal neoplasms. Clinicoradiological informa-
tion such as patient age, tumor size, anatomic location, border
characteristics, and vascularization are all useful features to lead
to the correct differential diagnoses. Clinical history has a major
impact on the diagnostic accuracy of mesenchymal neoplasms,
particularly in bone lesions.1,2 The patient's age is important as in
any FNAB. In the particular case of round cell mesenchymal neo-
plasms, it is important to make use of the appropriate ancillary
studies. For instance, the differential diagnoses of a round cell
neoplasm in a child should include markers to rule out Ewing
sarcoma, rhabdomyosarcoma, and lymphoma, whereas a round
cell tumor in an older adult should include markers for round
cell liposarcoma. The site of the tumor may aid in determining
the nature of the lesion, since some lesions such as epithelioid
sarcoma are much more common in the extremities than well
differentiated liposarcomas, which are more commonly present
in the retroperitoneum. A definite cytological diagnosis must be
based on a combination of the cytological findings (i.e. adequate
specimen, cytomorphology) and results of ancillary studies
(immunohistochemistry, flow cytometry, cytogenetic analysis,
electron microscopy), along with the clinical and/or radiographic
data. An interesting prospect is the development of fluorescent in
situ hybridization (FISH) tests that can be applied to cytology
material. FISH probes targeted against specific translocations can
prove very useful in evaluating sarcomas with recurrent translo-
cations. Early studies has shown good results in evaluating cases
of synovial sarcoma, Ewing sarcoma, and rhabdomyosarcoma.3
Close interaction between the clinician and cytopathologist is
also an essential component to the success of FNAB in the work-
up of soft tissue sarcomas. The accuracy of FNAB to subtype previ-
ously undiagnosed soft tissue sarcomas varies from 21 to 76%.4-8
It is largely dependent on the experience of the cytopathologist.
In one of the largest series, FNAB of soft tissue lesions proved to
be more accurate in the histological subtyping of cases of pediat-
ric sarcomas (92%) than in that for adult sarcomas (52%).1
Most authors recommend dividing mesenchymal lesions into
five major cytomorphologic subtypes based on the predominant
morphology: myxoid, spindle cell, round cell, pleomorphic,
and polygonal/epithelioid cells.6,9,10 These cytomorphologic
subtypes are not mutually exclusive and some overlapping can
be seen. For instance, a myxoid fibrosarcoma can be included
in either myxoid or spindle cell category. Similarly, some of
the pleomorphic tumors might have overlapping features with
polygonal/epithelioid lesions.
Grade
The histological subclassification of soft tissue tumors according
to cell lineage can be very difficult, particularly in the absence of
abundant material for ancillary studies. Fortunately, histological
grading is more important for the clinical management than for
histological subclassification according to cell lineage. Histolog-
ical grading of soft tissue sarcomas has been reported as one of
the most important criteria for predicting metastases.11
The clini-
cal management of most sarcomas, except pediatric small round
cell tumors, is based mainly on anatomic location and stage, in
which histological grade is part of the stage criteria.1,6,12 The most
commonly used histological grading systems are that proposed
by Costa et al. from the National Cancer Institute (NCI) and that
by Guillou et al. from the Fédération Nationale des Centers de
Lutte Contré le Cancer (FNCLCC).13,14 A two-tier system (low- or
high-grade lesion) is favored in cytology specimens over a three-
tier system (grades 1-3), because the latter shows only moderate
correlation between the histological and cytology grade.15,16
The ability to accurately grade soft tissue lesions is very
dependent on cellular morphology. Cases classified as pleomor-
phic, epithelioid, and round cell are mostly high-grade lesions. For
instance, mesenchymal neoplasms with epithelioid morphology
are represented mostly by high-grade mesenchymal neoplasms
such as epithelioid leiomyosarcomas, epithelioid angiosarcomas,
and epithelioid gastrointestinal stromal tumor. Spindle cell lesions,
conversely, can be difficult cases to be graded on FNAB material as
the distinction of nonneoplastic spindle cell proliferations from
low-grade spindle cell neoplasms can be challenging.10,15,17 Fibrillar
ground substance, nuclei with neural (wavy) appearance, and clus-
ters with a tissue culture appearance are features suggestive of low-
grade spindle cell lesions. Benign or low-grade spindle cell lesions
in the retroperitoneum and thorax are usually associated with low
cellularity, fine chromatin pattern, and absence of macronucleoli.18
The criteria mostly associated with high-grade spindle cell lesions
are cellular atypia and/or pleomorphism.16,18 Other helpful criteria
are identification of features suggestive of specific sarcomas, such
as nuclei with fish hook appearance in leiomyosarcomas and intra-
cytoplasmic iron deposits in angiosarcomas.19 Myxoid lesions can
also be difficult to classify due to sampling issues or lack of marked
cellular atypia in some high-grade myxoid lesions.
Adipocytic Tumors
A lesion is considered to be of adipose tissue origin when at least
some of the neoplastic cells demonstrate fatty differentiation,
which can be manifested by clear vacuolated cytoplasm resulting
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