Clinical History
A 28-year-old man presented with a soft tissue mass in the right
supraclavicular region. Clinically, this was felt to be a hematoma. Radiographically, three was no
involvement of bone. A fine needle aspiration biopsy was performed. Most of the material was submitted
for cytologic examination including cell block with immunocytochemistry; an aliquot was sent to
cytogenetics (Figures A,B,C).
Case 5 - Figure A - This smear is moderately to highly cellular and characterized by aggregated and dispersed small homogeneous cells. The smear background is devoid of fibrillary matrix, lymphoglandular bodies, and necrotic material (Diff-Quik stain, low power).
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Case 5 - Figure B - This cohesive cluster manifests no evidence of an organoid arrangement or nuclear molding. The larger cells have small solitary ovoid nuclei with delicate membranes, finely reticulated and evenly dispersed chromatin, absence of nucleoli, and extremely high nuclear-to-cytoplasmic ratios. Where visible, the cytoplasm is faintly basophilic (Diff-Quik stain, high power).
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Case 5 - Figure C - The small cells are strikingly homogenous in appearance. Each possesses a solitary, slightly ovoid nucleus with a delicate membrane, fine, even, dark chromatin, and rare minute nucleoli. Cytoplasm is barely visible (Papanicolaou stain, high power).
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Cytologic Findings
The smears were moderately to highly cellular
containing numerous small uniform-appearing neoplastic cells. Even at the scanning lens view, the
monotony of the cells was readily apparent. The cells were individually dispersed and present in
aggregates which showed true intercellular cohesion. The aggregates varied in size and contour but
demonstrated no distinct organoid arrangement. The smear background was distinctly clean (lacked
necrotic debris) and was devoid of lymphoglandular bodies and matrix material. The individual neoplastic
cells had extremely high N/C ratios. The cells were mononuclear possessing a single round nucleus with a
smooth but distinct membrane, fine and evenly dispersed darkly stained chromatin, and occasionally one or
two minute nucleoli. In most cells, cytoplasm was not readily apparent. In a minority of the neoplastic
elements, cytoplasmic blebs or rims were recognized. Specifically, no well formed rosettes were seen.
Scattered among these neoplastic cells were smaller cells with round or ovoid nuclei and
pyknotic-appearing chromatin. That is, it was very darkly stained and structureless. In such elements,
cytoplasm was not apparent. Although present, mitotic figures were relatively infrequent. Binucleation
was never seen. The cell block, although not abundant, demonstrated a diffuse, sheet-like growth pattern
of small homogeneous round cells.
Ancillary Diagnostic Results
By immunocytochemistry, there was a diffuse
and intense membranous staining of the neoplastic cells by CD99. Although weak, some of the neoplastic
cells also demonstrated immunoreactivity for bcl-2. The neoplastic cells were nonreactive for
pancytokeratin (AE1/AE3) and for cytokeratin 7. Cytogenetics revealed the following karyotype: 48, XY,
+8, (t11;22)(q24;q12), +12.
Discussion
The cytologic diagnosis in this case was primary soft
tissue (extraskeletal) Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET). This diagnosis was
based on a combination of the clinical picture, the routine light microscopy, and the results of the
ancillary diagnostic tests.
By immunocytochemistry, ES/PNET is almost uniformly diffusely and intensely positive for CD99 with a
membranous pattern. The latter is the protein product of the MIC2 gene. Although certainly not
specific, it is classically present in this family of tumors. A minority of these neoplasms may show
focal reactivity for low molecular weight cytokeratins, but they are almost always negative for
cytokeratin 7 (and cytokeratin 19). Over 90% of the neoplasms in this family are characterized by a
reciprocal translocation involving the EWS gene on chromosome 22q12 and the ETS-associated genes, most
frequently FLI1, on chromosome 11q24.
It is difficult to render a completely specific diagnosis of primary soft tissue ES/PNET based solely
on light microscopy. However, the use of ancillary diagnostic studies including immunocytochemistry and
especially cytogenetics have made a profound inroad in our ability to render absolutely specific
interpretations.
The differential diagnosis includes a number of other neoplasms which fall under the rubric of
malignant small round cell tumors. As this was a primary soft tissue neoplasm, most of the other
entities are even rarer than an extraskeletal ES/PNET. One must consider an extranodal nonHodgkin's
lymphoma. We excluded this based on the routine light microscopy. The presence of true intercellular
cohesion would not be expected in a malignant lymphoma. Furthermore, lymphoglandular bodies were
distinctly lacking in the smears. A major consideration for us was poorly differentiated synovial
sarcoma. These neoplastic cells may be positive for CD99 and bcl-2. However, they usually also express
pancytokeratin and cytokeratin 7. The nonreactivity of the latter to antibodies is strong evidence
against synovial sarcoma, as was the cytogenetic findings. The absence of osteoid in the smears was
evidence against a primary soft tissue small cell osteosarcoma. Furthermore, these neoplasms are only
rarely positive for CD99 and almost never show the same karyotypic abnormality. An extremely rare entity
in the differential diagnosis is a primary soft tissue desmoplastic small round cell tumor. Although
superficially similar, their karyotypic abnormality differs by the involved locus on chromosome 11
(Wilms' tumor gene). Finally, we considered the possibility of a primary soft tissue mesenchymal
chondrosarcoma. As stated by Weiss and Goldblum, mesenchymal chondrosarcomas may actually be part of the
ET/PNET family. Furthermore, chondroid matrix was distinctly lacking in the cytologic preparation.
References
- Weiss SW, Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors, 4th ed. Mosby, St. Louis, 2001. pp. 1289-1308.
- Geisinger KR, et al. Modern Cytopathology. Churchill Livingstone, Philadelphia, 2004. pp. 839-844 and 858-859.
