Common Diagnostic Dilemmas in Bone and Soft Tissue Surgical Pathology
Scott Kilpatrick and Omar Sangueza
Due to their absolute rarity (< 1% of all malignant neoplasms), compounded by the realization that
a malignant diagnosis often leads to adverse consequences (i.e. amputation), the diagnosis of bone and
soft tissue tumors has always been difficult. Further apprehension may be related to the fact that many
sarcomas (and pseudosarcomas) affect children. In this brief presentation, we will present to you a
series of ten cases, illustrating important but often common differential diagnostic dilemmas, providing
practical guidelines for their resolution.
When possible, correlation with clinical and radiologic features cannot be over-emphasized. Some
neoplasms are virtually non-existent in children (e.g. liposarcoma) while others tend to be extremely
rare in adults (e.g. lipoblastoma). Radiographs, including computed tomography (CT) scans and magnetic
resonance imaging (MRI), provide information regarding anatomic location, size, and bony involvement,
homogeneity vs. heterogeneity, content, and relationships to neurovascular structures. Combining
clinical and radiographic information helps the pathologist provide a more accurate and definitive
It is our opinion that ancillary studies, such as immunohistochemistry, are useful diagnostic aids but
should never supplant thoughtful scrutiny of pertinent clinical and morphologic features. Following
intensive scientific investigation, the initial enthusiasm associated with the discovery of specific
immunohistochemical and molecular markers is virtually always replaced by a more realistic perspective.
The immunohistochemical marker CD99, initially reported as highly specific for Ewing's sarcoma, has now
been convincingly documented in most cases of mesenchymal chondrosarcoma, synovial sarcoma and a few
examples of small cell osteosarcoma, rhabdomyosarcoma and desmoplastic small round cell
Cytokeratin positivity is sometimes observed in rhabdomyosarcoma.
Desmin, an immunohistochemical marker usually associated with rhabdomyosarcoma, is often expressed by the
blastemal portion of Wilm's tumor.  Cytogenetic and molecular analyses have yielded similar
surprisingly nonspecific results. The most frequent Ewing's sarcoma translocation, t(11;22)(q24;q12)
with the EWS-FLI1 fusion product, has been reported in phenotypically classic examples of mesenchymal
chondrosarcoma, embryonal and alveolar rhabdomyosarcoma, polyphenotypic tumor of childhood, and
Both the EWS-FLI1 and the EWS-ERG fusion transcripts have been described
in cases of intra-abdominal desmoplastic small round cell tumor.
For these reasons,
immunohistochemical and molecular studies should be considered ancillary not definitive tests. The "gold
standard" for diagnosis remains light microscopy. This should not imply that knowledge and application
of these ancillary tests are not helpful for the pathologist faced with a challenging case, but such data
should only be interpreted with the complete knowledge of the pertinent clinical and microscopic
features. As summarized by Dehner, "…the gold standard for pathologic diagnosis is predicated on the
microscopic features of the tumor. Once the results of an ancillary method like immunohistochemistry
become disconnected from the clinical and pathologic findings, we find ourselves separated from the first
principles of diagnostic pathology that have served as one of the fundamental pillars in the practice of
- Stevenson AJ, Chatten J, Bertoni F, Miettinen M. CD99 (p30/32MIC2) neuroectodermal/Ewing's sarcoma antigen as an immunohistochemical marker: review of more than 600 tumors and the literature experience. Appl Immunohistochem 1994;2:231-240.
- Granter SR, Renshaw AA, Fletcher CD, et al. CD99 reactivity in mesenchymal chondrosarcoma. Hum Pathol 1996;27:1273-1276.
- Dei Tos AP, Wadden C, Calonje E, et al. Immunohistochemical demonstration of glycoprotein p30/32 MIC2 (CD99) in synovial sarcoma: a potential cause of diagnostic confusion. Appl Immunohistochem 1995;3:168-173.
- Dehner LP. On trial: a malignant small cell tumor in a child: four wrongs do not make a right. Am J Clin Pathol 1998;109:662-668.
- Miettinen M, Rapola J. Immunohistochemical spectrum of rhabdomyosarcoma and rhabdomyosarcoma-like tumors: expression of cytokeratin and the 68-kD neurofilament protein. Am J Surg Pathol 1989;13:120-132.
- Folpe AL, Patterson K, Gown AM. Antibodies to desmin identify the blastemal component of nephroblastoma. Mod Pathol 1997;10:895-900.
- Thorner P, Squire J, Chilton-McNeill S, et al. Is the EWS/FLI-1 fusion transcript specific for Ewing's sarcoma and peripheral primitive neuroectodermal tumor? A report of four cases showing this transcript in a wider range of tumor types. Am J Pathol 1996;148-1125-1138.
- Sorenson PHB, Shimada H, Liu XF, et al. Biphenotypic sarcomas with myogenic and neural differentiation express the Ewing's sarcoma EWS/FLI1 fusion gene. Cancer Res 1995;55:1385-1392.
- Burchill SA, Wheeldon J, Cullinane C, et al. EWS-FLI-1 fusion transcripts identified in patients with typical neuroblastoma. Eur J Cancer 1997;33:239-243.
- Sainati L, Scapinello A, Montaldi A, et al. A mesenchymal chondrosarcoma of a child with the reciprocal translocation (11;22)(q24;q12). Cancer Genet Cytogenet 1993;71:144-147.
- Ordi J, de Alava E, Torne A, et al. Intraabdominal desmoplastic small round cell tumor with the EWS/ERG fusion transcript. Am J Surg Pathol 1998;22:1026-1032.
- Katz Rl, Quezado M, Senderowicz AM, et al. An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript. Hum Pathol 1997;28:502-509.