Fine Needle Aspiration Cytopathology: Bone and Soft Tissue
Moderator: Dr. William J. Frable
Section 2 -
The Value Of Fine Needle Aspiration Cytology In The Diagnostic Work-Up Of Spindle
Cell Lesions Of Soft Tissue
Dr. Henry K. Domanski
Fine needle aspiration cytology (FNAC) used as a primary examination method to obtain a morphologic
diagnosis, has been part of the diagnostic work-up of patients admitted to the Musculoskeletal Tumor
Center of the Lund University Hospital since 1972. The center has been responsible for the
evaluation and treatment of patients with musculoskeletal tumors in the Southern Health Care Region
comprising approximately 1.7 million inhabitants.
Compared to open biopsy, FNA is an outpatient procedure which is well tolerated by patients and has
negligible risks for serious complications. With thin needles it is easy to sample material from
different parts of large tumors, and thereby revealing possible tumor heterogeneity.While tumor tissue
architecture is better evaluated in surgical biopsies, it can also be evaluated in cell blocks prepared
from specimens obtained by FNA. Through rapid staining applied to aspiration smears it is possible to
assess FNA specimen adequacy while the patient waits. If necessary, additional aspirations can be
performed in order to obtain material for ancillary studies. One disadvantage of FNAC, however, is the
occasional difficulty in obtaining sufficient material for ancillary studies.
FNAC of Spindle Cell Lesions
Apart from classifications focused on clinical management and based on delineating subcategories of
therapeutic and prognostic importance, soft tissue lesions can be classified histogenetically based on
their presumed histogenesis or their differentiation towards a predominant cell type, typically on
cytoarchitectural features in FNA smears. The majority of soft
tissue tumors can be placed into one of the following five categories by the predominant cytologic
pattern: pleomorphic, spindle cell, myxoid, small round/ovoid cell and epithelioid cell.  The
spindle cell pattern is dominated by more or less atypical spindle cells with fusiform or ovoid nuclei
and elongated uni- or bipolar cytoplasm. Spindle cells in FNA smears occur frequently in sheets or
fascicles, but dissociated spindle cells can be also present. In addition
minor populations of larger rounded, polygonal or triangular cells with relatively abundant cytoplasm and
nuclei of variable size and shape may be present in some spindle cell lesions.
Common benign and intermediate tumors displaying a spindle cell pattern are nodular fasciitis (NF),
neurilemoma and desmoid fibromatosis while spindle cell lipoma (SCL) elastofibroma dorsi (EFD) and
solitary fibrous tumor (SFT) / hemangiopericytoma are less usual. Common spindle cell sarcomas include
leiomyosarcoma (LMS), malignant periphery nerve sheath tumor (MPNST) and synovial sarcoma while
dermatofibrosarcoma protuberans (DFSP), fibrosarcoma and low-grade fibromyxoid sarcoma (LGFMS) are
The mainstay of treatment for spindle cell sarcomas, similarly to other types of adult sarcomas, is
surgery, based largely on such factors as tumor size and location and proximity to vital structures
(vessels, nerves and bone) and to a lesser extent on histological type. Failure in diagnosing the exact
histological subtype of a soft tissue sarcoma does not always mean that correct therapy cannot be
initiated. Correct diagnosis of "sarcoma, NOS" is often sufficient for the planning of surgical
treatment. Knowledge of the histological subtype, however, is often necessary in establishing whether a
lesion is malignant or benign, and the grade of malignancy.
In addition different treatment options for some low grade and local aggressive/benign spindle cell
tumours require an exact histotype diagnosis. The histologic subtyping of spindle cell tumors in FNA
smears is more reliable when dealing with well differentiated tumors showing specific cytomorphologic
diagnostic and immunocytochemical criteria. Conversely, poorly differentiated spindle cell sarcomas can
represent a difficult diagnostic group, due to lack of distinctive morphological and immunocytochemical
criteria. In addition, relatively common spindle cell lesions of fibroblasic and myofibroblastic origin,
share a cytomorphologic and immunocytochemic profile both with each other and with other entities such as
smooth muscle and fibrohistiocytic neoplasms. 
Thus, some spindle cell tumors display diagnostic morphological features in FNA smears alone
, while many others require the use of ancillary techniques in addition to strict cytological
criteria and proper clinical information for a correct diagnosis.
Ancillary Techniques in the FNAC of Spindle Cell Lesions
Essentially the same ancillary techniques are used for cytological as for histopathological diagnosis.
Immunocytochemistry is the most important ancillary method used in the evaluation of FNA of spindle
cell tumors of soft tissue, but even other methods, such as cytogenetic and molecular biological
techniques as well as electron microscopy, can play an important role.
When evaluating aspirates from spindle cells tumors, expression of desmin and smooth muscle specific
actin is a very useful criterion for accurate diagnoses. Desmin shows a high specificity for muscle and
myofibroblastic tumors, and about 70 % of LMS express at least focal desmin positivity. Smooth muscle
specific actin (SMA) is often more sensitive than desmin but not so specific. S-100 protein is a very
useful marker in the examination of spindle cell tumors as all benign nerve sheath tumors are positive
for S-100. Expression of S-100 protein has low specificity, however, as many other tumors also show a
positive reaction; melanocytic tumors, chondrosarcoma, liposarcoma and sometimes synovial sarcoma.
Detection of epithelial membrane antigen (EMA) is often essential in the diagnosis of synovial
sarcomas, which in more than 90 % are positive for EMA. CD34 is also a useful marker in the examination
of spindle cell tumors. DFSP but also benign and border-line spindle cells tumors, such as SCL or
SFT/haemangiopericytoma, express strong positivity for CD34.
Experience has shown that routine karyotyping from solid soft tissue neoplasms is difficult. It is
not always possible to aspirate a sufficient number of tumor cells for successful culture. Molecular
biologic methods, requiring fewer cells, are more likely to succeed. Molecular biologic techniques such
as polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) have proved to be
suitable for fine needle aspirates, although a prerequisite is that the genes involved are characterized.
With regard to soft tissue spindle cell tumors, the major diagnostic use is in cases of suspected
synovial sarcoma. 
Summary of Clinical and Cytological Features in the Differential Diagnosis in the Spindle Cell Lesions/Tumors of Soft Tissue
|Diagnosis ||Clinical features ||Cytologic features|
||Predominantly a tumor of adults but can occur in children. Variable location and size. Can be cystic. Often painful at aspiration. Usually a long clinical history. ||Variable yield. Mixture of fascicles or dissociated spindled cells with moderate nuclear pleomorphism. Usually admixture of rounded/ovoid cells. Common features are variable cellularity in the fascicles with appearance similar to histological Antoni A and Antoni B features, elongated nuclei with pointed ends occasionally having a "fish-hook" appearance and a fibrillar background. Occasional palisading of nuclei. Rare Verocay bodies.|
|Nodular fascitis  ||A rapidly growing, occasionally tender mass showing a predilection for upper extremities in young adults. Usually superficial and less than 3.0 cm. Majority of NF regress spontaneously within 3-6 weeks. ||Rich yield. Moderate pleomorphic spindle, triangular or rounded cells. Nuclei have bland chromatin, often prominent nucleoli and occasional mitoses. Myxoid background and ganglion-like cells frequently present. Occasionally multinucleated cells or/and inflammatory cells. Late fasciitis often shows more uniform spindled cells than fasciitis in the growing phase.|
|Solitary fibrous tumor  (Extrapleural) ||Deep-seated soft tissue tumor of adults seen in various locations. Often slow- growing. ||Rich to moderate yield. Uniform spindle cells having scanty uni- or bipolar cytoplasm. Cells are dissociated or arranged in fascicles in a haphazard or, occasionally, a storiform pattern. Stripped nuclei and collagen matrix fragments in background.|
|Spindle cell lipoma  ||Small or medium-sized, subcutaneous mass, typically localized in the neck, back or shoulder of middle-aged men. Long clinical history. ||Variable yield. Strands of uniform spindled cells, adipose tissue and collagen bundles/fibers in variable proportions. Long, slender, acellular collagen fibers are common. Often a myxoid background with mast cells.|
|Desmoid fibromatosis  ||Infiltrative masses in the deep soft tissues. Usually in the proximal extremities or limb girdles of young adults. Often larger than 5.0 cm. ||Variable yield. Spindled cells, either dissociated or in clusters, with indistinct cytoplasm and cytoplasmic processes. Uniform, spindled or fusiform nuclei, sometimes with moderate anisokaryosis. Stripped nuclei and fragments of more or less cellular collagenous tissue common. Occasional striated-muscle "giant cells".|
|Elastofibroma dorsi  ||Typically located near the inferior margin of the scapula or between the scapula and the chest wall in elderly women. ||Poor to moderate yield. Mixture of uniform spindle cells, mature adipocytes and fragments of acellular collagen bundles and fibres in varying proportions. In alcohol fixed smears degenerated elastic fibres with linear ("braid-like"), globular and stellate appearances.|
||A rare soft tissue tumor, most often localized in the deep soft tissues and retroperitoneum. ||Variable yield. Irregular clusters of cohesive cells mixed with dispersed cells. Often stripped nuclei. Branching vessels are seen as stalks in the middle of cell clusters. Slightly atypical spindle cells with elongated cytoplasm. Synovial sarcoma with hemangiopericyte-like pattern must be excluded.|
||Can occur at almost any age and in any site. Often long clinical history. ||Rich yield. Mixture of tight sheets or clusters and dispersed small to medium sized, often bland-looking cells with spindle/ovoid or rounded nuclei and scanty unipolar or bipolar cytoplasm. Nucleoli are inconspicuous and chromatin finely granular. Capillary vessels within cell-clusters and mast cells usually present. Storiform pattern and a myxoid matrix may be seen. The infrequent subcutaneous monophasic synovial sarcoma can mimic DFSP.|
||Occur predominantly in adults. Most common locations: retroperitoneum and limbs, both subcutaneously and deeply seated. ||Moderate to rich yield. Tumor cell fascicles with an admixture of dispersed cells or stripped nuclei. Spindle cells with elongated, blunt-ended, segmented or fusiform nuclei and round/polygonal cells, often with rounded or indented nuclei. In high-grade LMS often pleomorphic, multinucleated cells and intranuclear vacuoles.|
|Malignant peripheral nerve sheath tumor
||Occur usually in adults, may occur in children Upper extremities, thigh, buttock and paraspinal tissues are common sites. ||Moderate to rich yield. Mixture of dispersed cells and cells in tight cluster or fascicles. Variably atypical spindle cells. Typically elongated nuclei with pointed ends. In high grade malignant MPNST marked pleomorphism. Variable diagnostic help with immunocytochemistry. Low grade variants difficult to diagnose correctly in FNA.|
||Occur usually in young and middle-aged adults. Slowly growing involving dermis, subcutis, rarely deep soft tissue in the trunk, abdomen, proximal extremities and head. ||Moderate to rich yield. Compact, thick clusters of spindle cells with an admixture of small sheets of spindle cells as well as numerous dissociated cells or naked nuclei. Relatively uniform spindle to oval nuclei with finely dispersed chromatin and inconspicuous nucleoli. Occasionally storiform pattern and spindle cells embedded in a collagenous/fibrillar matrix.|
|Adult fibrosarcoma ||Uncommon sarcoma arising in the deep soft tissues in extremities and head and neck region. ||Mixture of dispersed cells and cell clusters. Variably atypical spindle cells. Marked atypia in high grade malignant tumors. Insufficiently characterised in FNA.|
|Low grade Fibromyxoid sarcoma  ||Young adults but described in children. Uncommon sarcoma, typically in the extremities or trunk. ||Variable yield, variable prominent myxoid matrix. Slightly atypical spindly or ovoid cells. Difficult to distinguish from benign myxoid/spindle tumors such as soft tissue perineurioma. Insufficiently described in FNA.|
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