Thus tumors arising in the stomach were thought initially to represent a uniform disease entity but later studies have demonstrated significant differences regarding their localization in the stomach (gastroesophageal junction and body versus distal antrum) [7], histology (pure spindled versus mixed/ selleck chemicals 17-DMAG epithelioid) and molecular profile (KIT deletions versus point mutations versus PDGFRA mutations) [32], patient age (pediatric versus elderly) and occurrence in syndromic settings (Carney triad, NF1 versus sporadic) [33,34]. In brief, four major disease categories seem to exist: 1) KIT mutated GISTs arising at different anatomic sites seem to represent the bulk of the disease and most publications on GISTs actually describe this subgroup [1], 2) PDGFRA-mutants generally arise as epithelioid gastric tumors and may grow to a huge size, still possessing a favorable outcome [35,36].

3) Pediatric-type (Carney-type) GISTs whether developing in pediatric or adult patients, irrespective of presence or absence of features of the Carney-triad seem to represent a clinicopathologically and molecu-larly distinct disorder [34,37,38], and 4) NF-1 associated GISTs which lack kinase mutations and tend to follow a more favorable clinical course [33]. These four major subgroups of GISTs differ not only in their histological appearance and clinical features but also in their prognosis, route of tumor spread and overall survival. Pediatric GISTs and GISTs in young adults and the problem in the light of the TNM system GISTs generally occur beyond the age of 50.

However, <10% of reported GISTs affected patients who were <40 yrs of age at first diagnosis [7]. Review of the recent literature and our data indicates that GISTs in this age group are most commonly of the pediatric-wild-type GIST, tumors that closely resemble the ��gastric stromal sarcoma�� in patients with the Carney triad [34]. These tumors differ in many aspects from their adult counterparts. Regarding their biological behavior, pediatric GISTs in the setting of the Carney triad showed inconsistent risk stratification. In particular, the risk group showed no correlation with disease outcome and development of recurrence or metastasis [34,37]. Notably, 3 of 6 patients who died of Carney triad GISTs had low risk tumors compared to 2 with high risk tumors [34].

Likewise, metastasis occurred in 23% of very low/low risk pediatric and young adult GIST patients reported in the series by Miettinen et al [37]. This contrasts strikingly with a frequency of only 2.5 % metastatic disease in comparable risk groups in adult gastric GISTs reported by the same authors Dacomitinib [7]. Furthermore, pediatric and Carney-triad GISTs showed a high rate of regional lymph node metastasis approaching 29% [34,38] compared to a nodal frequency of -2% in GIST in general [1,7,15].