Bone Neoplasms ; Humans ; Ilium ; Paraganglioma ; Sacrum

Hemangiopericytoma ; pathology ; Humans ; Meningeal Neoplasms ; pathology ; Tomography, X-Ray Computed

Humans ; Kidney ; pathology ; Kidney Neoplasms ; pathology ; Neuroectodermal Tumors, Primitive ; pathology

OBJECTIVETo study the clinicopathologic features, diagnosis and differential diagnosis of succinate dehydrogenase (SDH) deficient gastrointestinal stromal tumors (GISTs) as a unique tumor subtype.

METHODSSDHB and SDHA immunohistochemistry was performed in 120 gastric GISTs, in addition to CD117, DOG-1, CD34, smooth muscle actin (SMA), desmin, S-100 protein, cytokeratin (CK) and Ki-67. Subset of the cases was further evaluated for the presence of mutations in CKIT exons 9, 11, 13 and 17 mutations and platelet derived growth factor receptor alpha(PDGFRA) exons 12 and 18.

RESULTSEight of 120 (6.6%) GIST cases were found SDH-deficient including 3 male and 5 female patients (median age of 36.2 years; ranging 16 to 65 years of age). The tumors involved antrum (6 cases), lesser curvature (1 case) and fundus (1 case). Macroscopically, the dominant tumor masses varied from 3 to 10 cm in diameter with a multinodular or plexiform pattern involving the gastric wall. Microscopically,tumor cells had predominantly epithelioid morphology, with occasional mixed spindle cell nodules. Lymphovascular invasion was identified in 5 cases. Immunohistochemistry for SDHB was negative in all 8 cases, and SDHA was negative in 5 cases. All 8 SDHB negative cases also expressed CD117, DOG-1 and CD34, but were negative for SMA, desmin, S-100 and CK. All 8 cases were found to have wild-type CKIT and PDGFRA genes. Available clinical follow-up were obtained in 7 cases, ranging from 2 to 60 months (median follow-up 23.3 months), and all patient were alive. Three cases were found to have liver metastases at their first diagnosis, and one developed omental and mesenteric metastases in 17 months.

CONCLUSIONSSDH-deficient GIST is a distinct subtype of GIST, with a predilection to occur in young and female patients. Characteristic pathological findings include multinodular gastric wall involvement, epithelioid cell morphology, frequently lymphovascular invasion with occasional lymph node and liver metastases, but an overall indolent clinical behavior. Immunohistochemistry for SDHB is required for the diagnosis.

Adolescent ; Adult ; Aged ; DNA Mutational Analysis ; Exons ; Female ; Gastrointestinal Neoplasms ; enzymology ; genetics ; Gastrointestinal Stromal Tumors ; enzymology ; genetics ; Genotype ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mutation ; Succinate Dehydrogenase ; deficiency ; genetics ; Young Adult