Keratin-positive Gastrointestinal Stromal Tumor of the Stomach Mimicking Gastric Carcinoma: Diagnosis Confirmed by c-kit Mutation Analysis

Abstract

In routine practice, gastrointestinal stromal tumor (GIST) can usually be identified with relative ease on the basis of a rather simple immunohistochemical panel besides its characteristic morphology. Still, serious differential diagnostic problems may arise because of the heterogeneity of these tumors in both morphologic appearance and clinical behavior. In our case, we present a metastatic, ulcerative, hemorrhagic GIST with epithelioid appearance, which displayed diffuse pan cytokeratin (AE1/AE3) positivity beside CD117 expression. As carcinomas may also be CD117-positive, definitive diagnosis was confirmed by the detection of a hexanucleotide deletion in the exon 11 of c-kit. This case demonstrates that although gastric carcinoma more commonly ulcerates or causes hemorrhage than GIST, keratin-positive GIST should also be considered from a differential diagnostic point of view. In these cases, c-kit mutation analysis may be necessary.

Gastrointestinal stromal tumours can express CD10 and epithelial membrane antigen but not oestrogen receptor or HMB45

“…The fact that GISTs may demonstrate focal EMA immunopositivity is consistent with these neoplasms potentially showing expression of other epithelial markers, e.g. cytokeratins 9–12 . GISTs may demonstrate CD99 immunopositivity, 8 whereas synovial sarcoma can show both CD117 and DOG1 immunopositivity 4,5 .…”

“…Immunohistochemical markers, which are often expressed by synovial sarcomas, include CD99, epithelial membrane antigen (EMA) and cytokeratins 7 . It is well documented that GISTs can express CD99 8 and/or cytokeratins (cytokeratin cocktails or specific cytokeratin subtypes) 9–12 . By contrast, while there have been a few case reports of GISTs being found to be EMA immunonegative, 10,11,13 we are unaware of any formal studies of whether this neoplasm can express EMA.…”

Cytokeratin-Positive Gastrointestinal Stromal Tumor of Biphasic Morphology: A Case Report

“…If spindle-cell components or epithelioid cells with unusual morphology and immunophenotype are present, other potential diagnoses should be considered, and additional ancillary tests are needed to make an accurate diagnosis. Several reports have demonstrated that GIST may have CK-positivity with variable intensities and patterns[2-6]. CK expression in GIST using monoclonal CK antibodies, such as CK18 or CK8, has been evaluated in several studies, and these studies support the conclusion that CK-immunoreactivity is more frequently noted in the epithelioid area than in the spindle-cell area (Table 1).…”

“…A definitive diagnosis of GIST is important to ensure administration of effective drugs, such as imatinib mesylate, and immmunohistochemical staining for c-Kit or DOG1 is useful for the diagnosis. According to previous studies, cytokeratin (CK) expression is a rare event in GISTs[2-6], so they can easily be misdiagnosed as other epithelial or epithelioid mesenchymal tumors. In such cases, a diagnosis of GIST can be made when DOG1 immunoreactivity or mutation of KIT or PDGFRA are observed.…”

c-kit (CD117) Expression in Human Tumors and its Prognostic Value: An Immunohistochemical Analysis

“…DOG1 was highly specific for GIST, but exceptional DOG1-positive other mesenchymal tumors were found [15]. Further, keratin-positive GIST should also be considered as GIST can be positive for both KIT and cytokeratin [16]. In these cases, c-kit mutation analysis can be helpful.…”