Fine‐needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c‐kit

BACKGROUND Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine‐needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical expression of CD‐117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c‐kit gene to aid in the diagnosis of GISTs on FNAB. METHODS Five endoscopic ultrasound‐guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998–1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD‐117 (KIT), smooth muscle actin (SMA), desmin, S‐100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c‐kit was performed by polymerase chain reaction (PCR) on CD‐117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations. RESULTS Five patients were diagnosed with GISTs based on morphology and immunocytochemical positivity for CD‐117 and CD34. PCR analysis of c‐kit exon 11 revealed three cases with novel‐sized PCR bands in addition to the expected wild‐type–sized PCR product. Amplicons from these cases contained an in‐frame deletion mutation. One of the two cases with wild‐type–;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c‐kit were found in the remaining case. CONCLUSIONS Ancillary techniques such as immunocytochemistry and c‐kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs. Cancer (Cancer Cytopathol) 2001;93:269–275. © 2001 American Cancer Society. Fine‐needle aspiration biopsy was found to be useful in the diagnosis of gastrointestinal stromal tumors using morphologic criteria and immunocytochemical positivity for CD‐117 and CD34. In addition, the cellular material obtained can be analyzed for c‐kit mutations, which may have prognostic implications.