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

Rhonda K. Yantiss, Andrew Rosenberg, Lisa Sarran, Peter Besmer, Cristina R. Antonescu

Research output: Contribution to journalArticle

91 Citations (Scopus)

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 neurofibromatosis 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.

Original languageEnglish
Pages (from-to)475-484
Number of pages10
JournalModern Pathology
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

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Gastrointestinal Stromal Tumors
Neurofibromatosis 1
Platelet-Derived Growth Factor alpha Receptor
Exons
Neoplasms
Germ-Line Mutation
Polymerase Chain Reaction
Mutation
Neurofibromatoses
Desmin
S100 Proteins
Lost to Follow-Up
DNA
Receptor Protein-Tyrosine Kinases
Keratins
Point Mutation
Paraffin
Actins

Keywords

  • GIST
  • KIT
  • PDGFRA
  • VonRecklinghausen's disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Multiple gastrointestinal stromal tumors in type I neurofibromatosis : A pathologic and molecular study. / Yantiss, Rhonda K.; Rosenberg, Andrew; Sarran, Lisa; Besmer, Peter; Antonescu, Cristina R.

In: Modern Pathology, Vol. 18, No. 4, 01.04.2005, p. 475-484.

Research output: Contribution to journalArticle

Yantiss, Rhonda K. ; Rosenberg, Andrew ; Sarran, Lisa ; Besmer, Peter ; Antonescu, Cristina R. / Multiple gastrointestinal stromal tumors in type I neurofibromatosis : A pathologic and molecular study. In: Modern Pathology. 2005 ; Vol. 18, No. 4. pp. 475-484.
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