CASE REPORT Simultaneous KIT mutation and succinate dehydrogenase (SDH) deficiency in a patient with a gastrointestinal stromal tumour and Carney-Stratakis syndrome: a case report Maria Jove, Jaume Mora, 1 Xavier Sanjuan, 2 Eva Rodriguez, 1 Mercedes Robledo, 3 Leandre Farran 4 & Xavier Garcia del Muro Department of Medical Oncology, Institut Catala d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain, 1 Department of Pediatric Oncology, Hospital Sant Joan de Deu (HSJD), Barcelona, Spain, 2 Department of Pathology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain, 3 Hereditary Endocrine Cancer, Group Leader, Human Cancer Genetics Programme, Spanish National Cancer Centre (CNIO), Madrid, Spain, and 4 Department of Surgery, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain Jove M, Mora J, Sanjuan X, Rodriguez E, Robledo M, Farran L, Garcia del Muro X (2014) Histopathology 65, 712–717 Simultaneous KIT mutation and succinate dehydrogenase (SDH) deficiency in a patient with a gastrointestinal stromal tumour and Carney-Stratakis syndrome: a case report Keywords: carney-stratakis syndrome, gastrointestinal stromal tumour, succinate dehydrogenase gene Introduction Gastrointestinal stromal tumours (GISTs) have recently been classified in two subgroups as positive or negative for succinate dehydrogenase (SDH) B immunohistochemistry (IHC). 1,2 The SDH is an enzyme, located in the mitochondrial inner mem- brane. It is composed of four subunits: SDH flavopro- tein (SDHA), SDH iron-sulfur protein (SDHB) and SDH membrane proteins (SDHC and SDHD). SDH catalyses the oxidation of succinate to fumarate in the citric acid cycle of the electron transport chain. 3–5 SDHB immunohistochemistry is a marker of the integrity of the mitochondrial complex 2; thus, when the mitochondrial complex 2 is disrupted (for what- ever reason), SDHB staining is negative. 2 SDHB-positive GISTs are classic GISTs encountered in adults with mutually exclusive mutations 6 in the KIT (60–80%) and PDGFRA (5–10%) genes, neurofi- bromatosis 1 or germline KIT/PDGFRA mutations. These GISTs are characterized by their location in the gastrointestinal tract, a predominantly spindle-cell morphology and good response to imatinib. More fre- quent in women, children and young adults are SDHB-negative GIST, usually called SDH-deficient GISTs, which are characterized by no mutations in KIT or PDGFRA, a predominantly epithelioid cell morphology, a poor response to imatinib and possible association with Carney Triad and Carney-Stratakis syndrome (germline SDH mutation). 1,2 Carney’s triad (CT), which mostly affects women, was described in 1977 as a non-familial condition featuring multifocal epithelioid GISTs, paraganglioma and pulmonary chondroma. 7 Patients with CT may also develop pheochromocytoma, esophageal leiomy- oma and other hamartomatous lesions. 8,9 Molecular genetic studies have failed to uncover specific altera- tions other than recurrent changes in chromosome 1. 4,10,11 Negative immunohistochemistry staining for SDHB suggests that Carney’s triad may be due to mitochondrial complex 2 abnormalities. 1,2 No SDH mutations have been found in patients with CT 1,2 Address for correspondence: M Jove, Avinguda Gran Via de L’Hospitalet, 199-203, 08908 L’Hospitalet de Llobregat, Barcelona, Spain. e-mail: mjovecas@gmail.com / mjove@iconcologia.net © 2014 John Wiley & Sons Ltd. Histopathology 2014, 65, 712–717. DOI: 10.1111/his.12506