Gastrointestinal Stromal Tumors: Whether Mutation Guided Diagnosis Matter

Abstract

Introduction: Gastrointestinal Stromal Tumor (GIST), now the most common mesenchymal tumor of the Gastrointestinal Tract (GIT), spans a clinical spectrum from benign to malignant. It has been frequently studied, especially with regard to its successful targeted therapy using imatinib mesylate. Approximately 70-80% of GISTs have gain of function mutation of the KIT gene. The aim of the study is to describe spectrum of clinical presentation and histomorphologic characteristics in classic GIST with CD117 immunostaining in a tertiary care hospital from north east India. Design: This is a descriptive cross sectional study of cases encountered over one-year period. Cases included after histomorphology and immunohistochemistry staining with CD117. Results: A total of 10 cases of GIST like histomorphology were studied and 6 were confirmed as GIST and included in the study. Four were males and two females with age ranged from 32 to 55 years. The cases had variable clinical presentations with abdominal pain and lump, melena and bleeding per rectum. Two of the cases were located in the stomach, one in the duodenum involving the periampullary area, one each in the ileocaecal region, transverse colon and rectum. Most of the cases grossly presented as a polypoidal growth. Four of the cases showed typical spindle cell morphology composed of interlacing bundles of uniform spindle shaped cells. One had a mixed morphology with features of both spindle cell and epithelioid pattern and one case mostly epithelioid type. Two cases showed intense immunoreactivity for CD117 in 90% of the tumour cells, three cases showed immunoreactivity for CD117 in 70-80% and in one case 50%. The management by surgical resections followed by 6 months imatinib mesylate treatment of 5 cases in the study had been showing good response for last two years. Conclusion: The molecular phenotype is an important consideration in the treatment of patients from prognostic point of view. Those with mutations in KIT or PDGFRA often respond to the tyrosine kinase inhibitor imatinib in contrast, tumors without these mutations are generally resistant. So a uniform category of cases with cKIT mutation may be helpful to study treatment outcome besides standard predictor of biologic behavior. It would be interesting to see whether mutation guided diagnosis has any bigger role in prognosis of classic GIST in future studies involving larger sample size.