Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study

Abstract

Multiple gastrointestinal stromal tumors typically occur in familial form associated with KIT receptor tyrosine kinase or platelet-derived growth factor receptor-alpha (PDGFRA) germline mutations, but may also develop in the setting of type 1 neurofibromatosis. The molecular abnormalities of gastrointestinal stromal tumors arising in neurofibromatosis have not been extensively studied. We identified three patients with type 1 neurȯ -fibromatosis and multiple small intestinal stromal tumors. Immunostains for CD117, CD34, desmin, actins, S-100 protein, and keratins were performed on all of the tumors. DNA was extracted from representative paraffin blocks from separate tumor nodules in each case and subjected to a nested polymerase chain reaction, using primers for KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18, followed by direct sequencing. The mean patient age was 56 years (range: 37-86 years, male/female ratio: 2/1). One patient had three tumors, one had five, and one had greater than 10 tumor nodules, all of which demonstrated histologic features characteristic of gastrointestinal stromal tumors and stained strongly for CD117 and CD34. One patient died of disease at 35 months, one was disease free at 12 months and one was lost to follow-up. DNA extracts from 10 gastrointestinal stromal tumors (three from each of two patients and four from one patient) were subjected to polymerase chain reactions and assessed for mutations. All of the tumors were wild type for KIT exons 9, 13, and 17 and PDGFRA exons 12 and 18. Three tumors from one patient had identical point mutations in KIT exon 11, whereas the other tumors were wild type at this locus. We conclude that, although most patients with type 1 neurofibromatosis and gastrointestinal stromal tumors do not have KIT or PDGFRA mutations, KIT germline mutations might be implicated in the pathogenesis of gastrointestinal stromal tumors in some patients.

Silent mutations in KIT and PDGFRA and coexpression of receptors with SCF and PDGFA in Merkel cell carcinoma: implications for tyrosine kinase-based tumorigenesis

“…The primer sequences, corresponding annealing temperatures and expected product sizes are listed in Table 2. 25,26 PCR was performed using 10 mM dNTP mix and Platinum Taq DNA Polymerase (Invitrogen Inc., Carlsbad, CA, USA). The PCR conditions are as follows: the samples were incubated for 4 min at 941C, followed by 35 cycles of 941C for 30 s, the relevant annealing temperature for 30 s, 721C for 30 s, and finally incubated at 721C for 30 min.…”

Tumeur stromale rectale : à propos d’une observation

“…La localisation rectale est extrêmement rare et représente uniquement 5% [1,2]. La survenue de GIST rectale est sporadique dans la grande majorité des cas, mais il existe quelques prédispositions familiales, telles la neurofibromatose de type I [3] et d'exceptionnelles formes familiales [4]. Les symptômes des GIST rectales sont très peu spécifiques, et ne diffèrent pas de ceux des autres tumeurs rectales [5,6].…”

GISTs múltiplos em neurofibromatose tipo 1: diagnóstico incidental em paciente com abdome agudo

“…O presente relato está em conformidade com outras publicações, que teem demonstrado que a associação de GIST e neurofibromatose tipo 1 não é casual 1,7,10,14,15 . Em particular, a faixa etária acometida pelos GISTs na neurofibromatose tipo 1 é menor do que em casos isolado5.…”

“…Uma apresentação característica é o achado de neurofibromas de pele disseminados pela superfície corporal. Os indivíduos portadores apresentam risco aumentado de desenvolver neoplasias malignas em geral, incluindo tumores carcinóides, feocromocitoma e GISTs 14 . Em uma série de necropsias em pacientes com neurofibromatose tipo 1, foi detectada a presença de GISTs incidentais em um terço dos indivíduos 5 .…”