Around 5 -10% of GIST lack driver mutations (KIT, PDGFR alpha) and are deficient in succinate dehydrogenase. Succinate Dehydrogenase deficient GISTs are unique in the fact that they occur predominantly in the younger population, are multifocal and generally resistant to imatinib. Surgery is a mainstay, but recurrence is common. Data regarding SDH deficient GIST from Indian subcontinent is very sparse.
This is a retrospective study of patients with SDH deficient GIST who presented to the sarcoma GIST/clinic in All India Institute of Medical Sciences, New Delhi, India from 2016-2022. 9 out of 120 GIST patients (7.5%) were SDH deficient. All patients were discussed in sarcoma/GIST tumor board and pathologies were re-reviewed by dedicated sarcoma/GIST pathologist. Data was collected retrospectively from prospectively maintained database.
There were 9 patients with median age of 48 years (range 15-63), of which there were 5 males (n=5, 55.5%). 8 patients (n=8, 88.8%) had primary in stomach, 1 had duodenal GIST. In stomach, body was the most common location (n=6,75%). 3 out of 9 patients (n=3, 33.3%) had multifocal disease. 8 out of 9 (88.8%) had metastasis at presentation. Most common site of metastasis was liver (7 out of 8, 87.5%) Lymph node involvement was present in 4 out of 9 patients (44.4%). One patient had classical Carneys triad at presentation. 8 out of 9 (88.8%) had epithelioid morphology and 1 (11.1%) had mixed epithelioid-spindle picture. 5 out of 9(55.5%) patients had germline SDH mutations. Out of 9 patients, 1 was put on observation post surgery and therapy was given for 8 patients(n=8,88.8%). None of the 8 patients responded to imatinib, 3 out of 5 patients (60%) had response with sunitinib, 3 were started on regorafenib out of which 1 had partial response and 1 patient had partial response with temozolamide. Median overall survival was NR- not reached (95% CI 12.96-NR).
Majority of patients with SDH deficient GIST had advanced disease and most of them were in stomach and had epithelioid morphology. We had male preponderance as compared to literature and higher age. Also there was poor response to first line tyrosine kinase inhibitors like imatinib. Based upon this data we have incorporated SDH IHC upfront in all cases similar to CAP guidelines.
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All authors have declared no conflicts of interest.