Gastrointestinal stromal tumor and other primary metachronous or synchronous neoplasms as a suspicion criterion for syndromic setting

Abstract

Abstract.Gastrointestinal stromal tumors (GISTs) may be sporadic or inherited. Although KIT and PDGFRA activating mutations are the oncogenic mechanisms in most sporadic and inherited GISTs, a small subset of GISTs are negative for both. Besides the classical Familial GIST Syndrome, GIST can occur as part of multi-neoplastic disease. The present study was designed to analyze the synchronous and metachronous tumors developed among GIST patients assessed by our institution for GIST Syndrome setting recognition. Patients (n=141) with primary GIST (77 men and 64 women) were recruited between 1988 and 2007 and their clinical and pathological records were reviewed. Mutation analysis of KIT, PDGFRA, NF1 and MMR genes was performed on somatic and peripheral blood DNA. GISTs occurred associated with other primary malignancies in 46 of 141 (32.6%) patients. The most common neoplasms were gastrointestinal and genitourinary. A novel exon 6 germline large deletion of NF1 was identified in the NF1/ GIST kindred. The development of GIST associated with other neoplasms is common and diagnosis of peculiar benign associated-neoplasms warrants the search for familial cancer susceptibility. In particular, syndromic or familial settings have to be suspected in the presence of neurofibroma or lung chordoma in C-KIT and PDGFRA negative GIST patients.

Synchronous Gastrointestinal Stromal Tumor and Primary Lung Adenocarcinoma

“…The synchronous occurrence of GIST and other primary gastrointestinal malignancies has been reported previously (3)(4)(5)(6)(7)(8)(9)(10). However, the synchronous existence of lung cancer and GIST seems to be extremely rare (7)(8)(9)(10). We experienced a case of advanced stage lung adenocarcinoma associated with intestinal GIST.…”

“…Synchronous and asynchronous cases of GIST and other malignancies have been studied in several series (3)(4)(5)(6)(7)(8)(9). Based on these reports, GIST associated with other primary malignancies occurs at incidence rates ranging from 2.9% to 32.6%.…”

Late recurrences of gastrointestinal stromal tumours (GISTs) after 5 years of follow-up

“…It is likely that the association of GIST with other malignancies may be related to syndromic diseases [33]. Therefore, even if the risk of second primary GIST may be a rare event compared to other malignancies, a prolonged follow-up may be useful not only for the detection of late recurrent cancer, but also for the early diagnosis of other metachronous cancers.…”

Genetics of Gastrointestinal Stromal Tumors

“…27,28 Since their original description by Nishida and colleagues, 29 an additional 27 families with familial GIST have been identified. 27,30 These mutations are identical to those found in sporadic tumors, and are inherited in an autosomal dominant pattern.…”