SDH-deficient gastrointestinal stromal tumor.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They are most commonly found in the stomach, but can also occur in the small intestine, colon, rectum, and esophagus. They are believed to be derived from the interstitial cells of Cajal and may exhibit a spindle cell, epithelioid, or mixed morphology.
The vast majority of GISTs characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. A small proportion (10-15%) of GISTs lack either the KIT or PDGFRA mutations and are thus considered wild-type GISTs. Of these wild-type GISTs, approximately half are characterized as succinate dehydrogenase (SDH) deficient GISTs.
SDH deficient GISTs occur primarily in the stomach of children and young adults, and are more common in females (2:1). Histologically they typically have an epithelioid or mixed morphology with a plexiform growth pattern and a multinodular appearance of neoplastic cells separated by dividing fibrous bands. Multifocality, lymphovascular invasion, and lymph node metastases are more typically observed in this subtype of GISTs. These GISTs typically have an indolent behavior. Immunohistochemical stains are positive for CD117 and DOG1, while negative for SDH immunostains. The lack of oncogenic activating tyrosine kinase mutations in SDH-deficient GISTs makes it resistant to tyrosine kinase inhibitors. Therefore, these tumors are typically removed surgically.
The vast majority of GISTs are sporadic tumors. Rarely, however, GISTs are found in association with defined syndromes, as is the case with Carney’s triad and Carney-Stratakis syndrome. Patients with Carney’s triad will exhibit gastric GISTs, paragangliomas, and pulmonary chondromas. These GISTs are wild-type, without KIT or PDGFRA mutations, and variable loss of expression of SDHB. In comparison, Carney-Stratakis syndrome includes the development of gastric GISTs and paragangliomas, without pulmonary chondromas. Carney’s triad typically occurs in female children and young adults and is non-heritable, while Carney-Stratakis syndrome is an autosomal dominant syndrome found in both men and women.
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