Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumorsusing morphology, immunocytochemistry, and mutational analysis of c-kit

BACKGROUND. Differentiating gastrointestinal stromal tumors (GISTs) from ot her intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are im munophenotypically and genetically distinct. GISTs exhibit consistent immun ohistochemical ex pression of CD-117 (KIT) and often express activating mut ations of this protooncogene. The aim of the current study was to employ im munocytochemistry and mutational analysis of the c-kit gene to aid in the d iagnosis of GISTs on FNAB. METHODS. Five endoscopic ultrasound-guided FNABs of gastrointestinal spindl e cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemi cal stains was performed on each cellblock including CD-117 (KIT), smooth m uscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracte d, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by po lymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Dire ct sequencing of amplicons identified the mutations. RESULTS. Five patients were diagnosed with GISTs based on morphology and im muno cyto chemical positivity for CD-117 and CD34. PCR analysis of c-kit ex on 11 revealed three cases with novel-sized PCR bands in addition to the ex pected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exo n 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 o f c-kit were found in the remaining case. CONCLUSIONS. Ancillary techniques such as immuno cyto chemistry and c-kit g ene mutational analysis may aid in the diagnosis of GISTs on FNABs. (C) 200 1 American Cancer Society.