A Duodenal SDH-Deficient Gastrointestinal Stromal Tumor in a Patient With a Germline SDHB Mutation.
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract arising from the interstitial cells of Cajal. Succinate dehydrogenase (SDH)-deficient GISTs are a unique class of GIST defined by loss of immunohistochemical expression of SDHB, indicating dysfunction of the mitochondrial complex 2; lack of driver mutations in KIT and PDGFRA; and distinctive morphologic features and natural history. To date, all reported SDH-deficient GISTs have arisen in the stomach. We report an SDH-deficient GIST arising in the gastrointestinal tract outside the stomach.



A 29-year-old man with a germline SDHB mutation (p.Arg90*) presented with acute upper gastrointestinal hemorrhage. Endoscopy identified a lesion in the second part of the duodenum, close to the distal common bile duct, consistent with a GIST. Endoscopic ultrasonography and magnetic resonance imaging did not demonstrate metastatic or nodal disease. Open transduodenal excision was performed to remove the tumor. Histologic evaluation confirmed the clinical diagnosis of a GIST, with positive staining for DOG1 and KIT. The mitotic count was low (1 per 50 high-power fields). Immunohistochemistry for SDHB was negative in the presence of an internal control. SDHA expression was retained. No somatic mutations were identified in KIT (exons 9, 11, 13, and 17) or PDGFRA (exons 12, 14, and 18). The germline SDHB mutation and loss of heterozygosity were confirmed on molecular testing of the tumor.



We describe an SDH-deficient GIST occurring outside of the stomach. This case indicates that SDH-deficient GISTs may also arise in the small intestine.
Department of Endocrinology, Waikato Hospital, Hamilton 3240, New Zealand.|Waikato Clinical Campus, University of Auckland, Hamilton 3240, New Zealand.
Marianne S
MS
Elston
Department of Endocrinology, Waikato Hospital, Hamilton 3240, New Zealand.
Shekhar
S
Sehgal
Department of Anatomical Pathology, Waikato Hospital, Hamilton 3240, New Zealand.
Michael
M
Dray
Department of Gastroenterology, Waikato Hospital, Hamilton 3240, New Zealand.
Elizabeth
E
Phillips
Waikato Clinical Campus, University of Auckland, Hamilton 3240, New Zealand.
John V
JV
Conaglen
Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, St Leonards 2065, Australia.|Department of Medicine, University of Sydney, Sydney 2006, Australia.
Roderick J
RJ
Clifton-Bligh
Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards 2065, Australia.|Sydney Medical School, University of Sydney, Sydney 2006, Australia.
Anthony J
AJ
Gill
D000328:Adult; D000075369:Anoctamin-1; D018118:Chloride Channels / Q000378:metabolism; D004378:Duodenal Diseases / Q000209:etiology; D004379:Duodenal Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D046152:Gastrointestinal Stromal Tumors / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics* / Q000378:metabolism
C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha