title: Additional Primary Malignancies in Patients with Gastrointestinal Stromal Tumor (GIST): A Clinicopathologic Study of 260 Patients with Molecular Analysis and Review of the Literature.
abstract: BACKGROUND
  The incidence of other primary neoplasms in gastrointestinal stromal tumor (GIST) patients is relatively high. Our aim was to better characterize the clinicopathologic and molecular relationships in a cohort of GIST patients.
  
  
  METHODS
  All GIST patients with tumor samples sent for molecular testing were identified via electronic medical records. Clinicopathologic characteristics of GIST and additional primary malignancies were analyzed.
  
  
  RESULTS
  Of 260 patients, 50 (19 %) had at least one additional primary malignancy. In 33 patients, separate primary neoplasms predated their GIST diagnosis and most commonly included: prostate (n = 9), breast (n = 8), and hematologic (n = 5). Renal (n = 4) and hematologic (n = 3) malignancies were the most frequent cancers identified after GIST diagnosis. The majority (8 of 12, 66 %) of malignancies diagnosed after GIST were found incidentally. Patients who developed other malignancies after GIST more often had KIT exon 11 mutations (100 vs. 66 %, P = 0.01). In comparison to patients with only GIST, patients with a second primary neoplasm of any chronology had GISTs with increased mitotic rate (≥5 per 50 high-power fields) (P = 0.0006). Literature review revealed colorectal cancer, gastric, prostate, renal, leukemia, and desmoid-type fibromatosis as the most common secondary neoplasms.
  
  
  CONCLUSIONS
  Nineteen percent of GIST patients develop other malignancies. This is the first report to describe a relationship between additional primary malignancy and both mutation and mitotic rate of GIST. Although the basis of these relationships remains to be investigated, caution in the clinical management of GIST patients with additional lesions is warranted.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, hechtmaj@mskcc.org.
authors.forename: Jaclyn Frances
authors.initials: JF
authors.lastname: Hechtman
authors.forename: Ronald
authors.initials: R
authors.lastname: DeMatteo
authors.forename: Khedoudja
authors.initials: K
authors.lastname: Nafa
authors.forename: Ping
authors.initials: P
authors.lastname: Chi
authors.forename: Maria E
authors.initials: ME
authors.lastname: Arcila
authors.forename: Snjezana
authors.initials: S
authors.lastname: Dogan
authors.forename: Alifya
authors.initials: A
authors.lastname: Oultache
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Meera
authors.initials: M
authors.lastname: Hameed
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D054643:INDEL Mutation; D015994:Incidence; D033162:Incidental Findings; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics / Q000628:therapy; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha