"Pediatric-type" gastrointestinal stromal tumors in adults: distinctive histology predicts genotype and clinical behavior.

Gastrointestinal stromal tumors (GISTs) rarely affect children, mainly girls. Pediatric GISTs typically arise in the stomach as multifocal tumors with a multinodular growth pattern, epithelioid morphology, lymph node metastases, an absence of KIT and PDGFRA gene mutations, and indolent behavior. Occasional GISTs in adults show similar features. Such tumors are not widely recognized. GISTs with a multinodular growth pattern in patients over the age of 18 years were retrieved from surgical and consultation files. Hematoxylin and eosin-stained slides were reviewed, immunohistochemistry was performed, and KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12, 14, and 18) genes were screened for mutations. Clinical follow-up was obtained. Sixteen cases were identified, affecting 13 women and 3 men (median age, 31.5 y; range, 19 to 56 y), all in the stomach. The mean tumor size was 5.4 cm (range, 1.8 to 11 cm); 4 were multifocal. All tumors showed a multinodular or plexiform architecture and epithelioid (N=3) or mixed epithelioid and spindle cell (N=13) morphology. Five tumors had vascular invasion; 6 had focal necrosis. Mitotic activity ranged from 3 to 156/50 high-power fields (8 tumors had ≤5/50 high-power fields). Using Armed Forces Institute of Pathology risk stratification, categories for primary tumors were: none (N=2), very low risk (N=3), low risk (N=3), moderate risk (N=3), and high risk (N=5). By immunohistochemistry, all tumors were positive for KIT, 82% DOG1, 72% CD34, 18% caldesmon, 9% S-100, 8% smooth muscle actin, and 0% desmin. All tumors were wild type for KIT and PDGFRA in the exons that were screened. At primary resection, 9 patients (56%) had lymph node metastases and 3 patients had liver metastases. Follow-up ranged from 16 months to 16 years (median, 5 y). Two tumors recurred locally in the stomach and 7 patients developed subsequent metastases to the lymph nodes (N=5), liver (N=3), and peritoneum/omentum (N=3). Primary tumors from 7 patients with metastases were Armed Forces Institute of Pathology low risk, very low risk, or no risk of recurrence. None of the metastatic tumors responded to treatment with imatinib mesylate. One patient died of disseminated liver and intra-abdominal metastases and the remaining patients were alive at last follow-up. Gastric GISTs in adults with a multinodular or plexiform growth pattern and epithelioid or mixed morphology are similar to pediatric GISTs. Unlike conventional adult GISTs, this distinctive subset predominantly affects women, often metastasizes to lymph nodes, and lacks mutations in KIT and PDGFRA. Current risk assessment criteria do not reliably predict behavior for this group. Although metastases are common and most tumors are imatinib resistant, they pursue a relatively indolent clinical course. Recognition of "pediatric-type" GISTs in adults is critical for prognosis, appropriate therapy, and follow-up.