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

UMMS Affiliation

Department of Pathology

Publication Date


Document Type



Adult; Aged; Aged, 80 and over; Antigens, CD34; Base Sequence; DNA Mutational Analysis; DNA, Neoplasm; Fatal Outcome; Female; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; Male; Middle Aged; Mutation; Neurofibromatosis 1; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Vimentin


Life Sciences | Medicine and Health Sciences


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 neuro-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.

DOI of Published Version



Mod Pathol. 2005 Apr;18(4):475-84. Link to article on publisher's site

Journal/Book/Conference Title

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

Related Resources

Link to Article in PubMed

PubMed ID