Gastric Stromal Tumors in Carney Triad Are Different Clinically, Pathologically, and Behaviorally From Sporadic Gastric Gastrointestinal Stromal Tumors: Findings in 104 Cases

Abstract

Carney triad, as originally described in 1977, was the association of 3 tumors: gastric epithelioid leiomyosarcoma [later renamed gastrointestinal stromal tumor (GIST)], extra-adrenal paraganglioma, and pulmonary chondroma. The disorder affected mostly young women and was not familial. We studied the clinical and pathologic features of the gastric neoplasm in 104 patients with the syndrome. Most (88%) were young women (mean age, 22 y), and the usual presentation was gastric bleeding. The tumors, commonly antral-based (61%), were multifocal, and ranged from 0.2 to 18.0 cm in dimension. Most (86%) featured round and polygonal (epithelioid) cells. Metastasis occurred in 49 patients (47%): to gastric lymph nodes (29%), liver (25%), and peritoneum (13%). Immunopositivity was detected in the tumors tested as follows: KIT, 100%; CD34, 75%; PKCy, 21%; PDGFRA, 90%; and smooth muscle actin, 6%. Fourteen patients (13%) died of metastatic GIST at a mean age of 45 years (range, 30 to 69 y). Estimated 10 and 40-year survivals were 100% and 73%, respectively. Median survival time was 26.5 years (range, 16 to 60 y). There was no correlation between the National Institutes of Health tumor risk classification and the tumor behavior. Compared with sporadic gastric GISTs, the gastric stromal tumor in Carney triad showed distinctive features: female predilection, young patient age, epithelioid cell predominance, multifocality, frequent lymph node metastasis, serial tumor occurrence, and unpredictable behavior. Thus, the Carney triad gastric stromal tumor is different clinically, pathologically, and behaviorally from sporadic gastric GIST.

Succinate dehydrogenase-deficient GISTs are characterized by IGF1R overexpression

“…3,4,6,7,9 In this study we demonstrate that IGF1R is overexpressed in 100% of SDH-deficient GISTs (10 of 10 patients) but never in non-SDH deficient GISTs (0 of 41 patients). That is, it appears that IGF1R overexpression is yet another of the characteristic features of SDH-deficient GISTs.…”

“…4 The combined results of several studies have demonstrated that SDH-deficient GISTs are characterized by an exclusively gastric location, female preponderance, young age of onset and unique histological features, including a predominantly epithelioid morphology often with a plexiform growth pattern, a tendency to be associated with multifocal or metachronous disease and consistent primary resistance to imatinib therapy. [3][4][5][6][7][8][9] Unlike other GISTs, the prognosis of SDH-deficient GISTs cannot be predicted by size or mitotic rate, but when metastases do occur, they may be strikingly indolent, often with relatively stable disease over years to decades. 3,4,6,7,9 The great majority of pediatric GISTs and all the GISTs that occur in Carney Triad (the non-familial association of gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma) and Carney-Stratakis Syndrome (the familial association of GIST and paraganglioma) represent specific examples of SDHdeficient GISTs.…”

“…[3][4][5][6][7][8][9] Unlike other GISTs, the prognosis of SDH-deficient GISTs cannot be predicted by size or mitotic rate, but when metastases do occur, they may be strikingly indolent, often with relatively stable disease over years to decades. 3,4,6,7,9 The great majority of pediatric GISTs and all the GISTs that occur in Carney Triad (the non-familial association of gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma) and Carney-Stratakis Syndrome (the familial association of GIST and paraganglioma) represent specific examples of SDHdeficient GISTs. [3][4][5]7,8 Importantly SDH-deficient GISTs also account for between 5 (ref.…”

Gastrointestinal Stromal Tumors

“…Similar clinicopathologic features have also been observed in Carney triad GISTs, a subgroup of SDH-deficient GISTs. 86 Pathologically, SDH-deficient GISTs are notable for characteristic morphology: they have epithelioid cytology and multinodular gastric intramural involvement and a tendency for lymphovascular invasion and lymph node metastases. Notably, neither of the latter features are adverse prognostic factors.…”

“…Notably, neither of the latter features are adverse prognostic factors. 78,79,86 Optimal treatment for SDH-deficient GISTs remains to be determined. However, these tumors do not show a similar imatinib response as generally observed with KIT-mutant GISTs.…”