"Pediatric-Type" Gastrointestinal Stromal Tumors in Adults: Distinctive Histology Predicts Genotype and Clinical Behavior.
Tanya A Rege, Andrew J Wagner, Christopher L Corless, Jason L Hornick. Brigham and Women's Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA; Oregon Health and Science University, Portland
Background: Gastrointestinal stromal tumors (GISTs) rarely affect children, mainly girls. Pediatric GISTs typically arise in the stomach and show epithelioid morphology, multinodular architecture, lymph node metastases, an absence of KIT and PDGFRA mutations, and indolent behavior. Occasional GISTs in adults show similar features. Such tumors are not widely recognized.
Design: GISTs in patients >18 yrs with a multinodular growth pattern were retrieved from surgical and consult files. H&E slides were reviewed, immunohistochemistry (IHC) 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.
Results: 16 cases were identified, affecting 13 women and 3 men (mean age, 34 yr; range, 19-56 yr), all gastric. Mean tumor size was 5.4 cm (range, 1.8-11 cm); 4 were multifocal. All showed an infiltrative architecture and epithelioid (3) or mixed (13) morphology. Five tumors had vascular invasion; 6 focal necrosis. Mitoses ranged from 3-156 per 50 HPF (8 tumors had ≤5). Using AFIP risk stratification, categories were: none (2), very low (3), low (3), moderate (3), and high (5). By IHC, all tumors were positive for KIT, 82% DOG1, 72% CD34, 18% caldesmon, 9% S100, 8% SMA, and 0% desmin. All were wild-type for KIT and PDGFRA in the exons screened. At primary resection, 8 patients had lymph node and 3 liver metastases. Follow-up ranged from 16 mo – 16 yr (median, 5 yr). Only 3 of 11 patients treated with imatinib responded. Two tumors recurred locally, and 8 subsequently metastasized, to lymph nodes (5), liver (3), and peritoneum (3). Resected tumors from 3 patients who developed metastases were AFIP low or very low risk for recurrence. All patients are alive at last follow-up.
Conclusions: Gastric GISTs in adults with a multinodular/infiltrative 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 an indolent clinical course. Recognition of "pediatric-type" GISTs in adults is critical to guide mutational testing and appropriate therapy and follow-up.
Tuesday, March 1, 2011 11:30 AM
Platform Session: Section E, Tuesday Morning