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%; PKCtheta, 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.

FIGURE 1

Gross appearance of gastric stromal tumors. Tumors from the same patient at primary surgery. A, The serosal surface showed a series of juxtaposed generally hemispherical tumors high on the posterior wall and in its midportion. B, The opened stomach revealed sessile polypoid tumors high on the anterior and posterior walls, several with ulceration (arrow). C, The cut surface of the tumors showed a confluent mass of yellow and flesh-colored tumors, some with internal lobulation and areas of hemorrhage.

FIGURE 2

Panoramic and low-power microscopic appearance of gastric stromal tumors. A, The partly encapsulated, patternless tumor occupied the submucosa and the muscularis propria, in which residual bands of smooth muscle were preserved. The lesion penetrated into the mucosa and externally formed a small serosal expansion. The overlying mucosa showed patchy edema, foveolar hyperplasia, and vascular ectasia (arrow). B, A coarsely lobulated tumor with residual smooth muscle bands and a nodular pattern expanded the submucosa. Superficially, it was circumscribed and still confined within the muscularis propria. A mucosal lymphoid aggregate was present (arrow).

FIGURE 3

Cytology of gastric stromal tumors. A, Patternless sheet of poorly outlined polygonal, epithelioid cells with eosinophilic cytoplasm, and polygonal, irregular, crinkled nuclei. The nucleoli are small. B, Spindle cells with elongated nuclei and eosinophilic cytoplasm arranged in interlacing fascicles. C, Dis-cohesive polygonal cells with eccentric nucleus or nuclei have a plasmacytoid appearance. The cytoplasm is homogeneous and acidophilic and features an occasional vacuole. D, Enlarged multinucleated epithelioid cells have eosinophilic cytoplasm. Mitotic figures are present (arrows).

FIGURE 4

Immunostaining of gastric stromal tumors. A, Membranous and diffuse KIT positivity. B, Diffuse strong CD34 positivity. C, Strong diffuse staining for PKCy. D, Weak staining for PDGFRA.

FIGURE 5

Lymph node with gastric stromal tumor metastasis.

FIGURE 6

Gastric mucosal lesions in cases of gastric stromal tumor. A, Two small sessile polyps are in the gastric cardia (arrows). B, Cystic fundic gland polyp featured proliferated fundic glands, several of which are dilated. C, Proliferated foveolar cells created a hyperplastic mucosal polyp. D, Lymphoid aggregates extended into and through the thickened muscularis mucosa covering a circumscribed stromal tumor.