A CD117 and CD34 immunoreactive sarcoma masquerading as a gastrointestinal stromal tumor: diagnostic pitfalls of ancillary studies in sarcoma.

Departments of Pathology and Cell Biology at The University of South Florida College of Medicine, Tampa, Florida, USA.
Cancer control: journal of the Moffitt Cancer Center (Impact Factor: 3.59). 07/2011; 18(3):152-9.
Source: PubMed

ABSTRACT The immunohistochemical hallmarks of gastrointestinal stromal tumors (GISTs) are positivity for CD117 (c-kit) and CD34; however, CD117 is not specific for GISTs, and the list of CD117+ tumors/tissues is increasing. Also, MDM2 is known to be amplified in several types of mesenchymal tumors, including liposarcoma.
We report a spindle cell sarcoma arising in the mediastinum that morphologically and immunohistochemically mimicked GIST to illustrate the potential diagnostic pitfalls of ancillary studies in sarcoma and their appropriate use in conjunction with clinical content. Clinical information was obtained from electronic medical databases. Cytological, histological, and ancillary studies were retrieved from the archives of the Department of Anatomic Pathology at Moffitt Cancer Center. Literature of the last 20 years was reviewed. The role of biomarkers and their molecular testing in the prognosis and prediction of GIST is also discussed.
A 75-year-old woman with a history of well-differentiated liposarcoma of the trunk/inguinal canal 5 years earlier developed a 5.5-cm heterogeneously enhancing mediastinal mass by computed tomography. Fine-needle aspiration biopsy revealed spindle cells with moderate pleomorphism and immunohistochemically reactive to CD117 and CD34 suggestive of GIST, but the clinical picture was unusual for GIST. Mutational analyses for KIT and platelet-derived growth factor receptor alpha (PDGFRα) were negative; DOG1 was not immunoactive, and this was believed to rule out GIST. An additional study of MDM2 by fluorescent in situ hybridization was positive, suggesting that this tumor was a dedifferentiated liposarcoma vs a spindle cell sarcoma not otherwise specified.
CD117+/CD34+ sarcoma is not diagnostic for GIST. KIT and PDGFRα mutational analyses are important in confirming a diagnosis of GIST and predicting its response to imatinib therapy. MDM2+ sarcoma is not diagnostic for liposarcoma. Although MDM2 is almost always positive in well-differentiated liposarcoma, which is useful in differentiating benign from atypical/well-differentiated lipomatous tumor, it should not be used in differentiating liposarcoma from other sarcomas.

  • Journal of Gastrointestinal Cancer 03/2014; DOI:10.1007/s12029-014-9596-9
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction. Soft tissue tumour pathology is a highly specialised area of surgical pathology, but soft tissue neoplasms can occur at virtually all sites and are therefore encountered by a wide population of surgical pathologists. Potential sarcomas require referral to specialist centres for review by pathologists who see a large number of soft tissue lesions and where appropriate ancillary investigations can be performed. We have previously assessed the types of diagnostic discrepancies between referring and final diagnosis for soft tissue lesions referred to our tertiary centre. We now reaudit this 6 years later, assessing changes in discrepancy patterns, particularly in relation to the now widespread use of ancillary molecular diagnostic techniques which were not prevalent in our original study. Materials and Methods. We compared the sarcoma unit's histopathology reports with referring reports on 348 specimens from 286 patients with suspected or proven soft tissue tumours in a one-year period. Results. Diagnostic agreement was seen in 250 cases (71.8%), with 57 (16.4%) major and 41 (11.8%) minor discrepancies. There were 23 cases of benign/malignant discrepancies (23.5% of all discrepancies). 50 ancillary molecular tests were performed, 33 for aiding diagnosis and 17 mutational analyses for gastrointestinal stromal tumour to guide therapy. Findings from ancillary techniques contributed to 3 major and 4 minor discrepancies. While the results were broadly similar to those of the previous study, there was an increase in frequency of major discrepancies. Conclusion. Six years following our previous study and notably now in an era of widespread ancillary molecular diagnosis, the overall discrepancy rate between referral and tertiary centre diagnosis remains similar, but there is an increase in frequency of major discrepancies likely to alter patient management. A possible reason for the increase in major discrepancies is the increasing lack of exposure to soft tissue cases in nonspecialist centres in a time of subspecialisation. The findings support the national guidelines in which all suspected soft tissue tumour pathology specimens should be referred to a specialist sarcoma unit.
    Sarcoma 08/2014; 2014:686902. DOI:10.1155/2014/686902
    This article is viewable in ResearchGate's enriched format
  • Source
    Acta Medica Mediterranea 01/2013; 29(2):219-225. · 1.05 Impact Factor

Full-text (2 Sources)

Available from
Aug 19, 2014