Succinate dehydrogenase deficient GIST: Case series and review of literature from a tertiary care center in India

Background: Succinate dehydrogenase (SDH) deficient gastrointestinal stromal tumor (GIST) is the most common type of wild type GIST characterized by lack of mutations in proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDFGR alpha) pathways. It has a unique predilection for females and young adults, with a relatively indolent prognosis and varied treatment modalities. Data regarding SDH GIST from the Indian subcontinent is sparse. Materials and Methods: This is a retrospective study of patients with SDH deficient GIST, who presented to the GIST clinic in a tertiary care center in India from 2016–2022. 9 out of 120 GIST patients were SDH deficient. All patients were discussed in GIST tumor board and pathologies were re-reviewed by a dedicated GIST pathologist. Data was collected retrospectively from prospectively maintained database. Results: There were nine patients with median age of 48 years (range 15–63), of which there were 5 males ( n = 5, 55.5%). Eight patients ( n = 8, 88.8%) had primary in stomach, one 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 nine patients, one was put on observation post surgery and therapy was given for eight patients ( n = 8,88.8%). Response to imatinib was very poor, 3 out of 5 patients (60%) had response with sunitinib, three were started on regorafenib out of which one had partial response and one patient had partial response with temozolomide. Median overall survival was NR- not reached (95% CI 12.96-NR). Conclusion: SDH deficient GIST is a unique subtype of gastrointestinal stromal tumor with distinct clinic-pathological features, diagnostic modalities, therapeutic strategies, and genetic implications as compared to C-kit/PDGFR-alpha mutated GIST.