Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1510475 (diverticular disease)
 2,138 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder. We report the second family to date with a germline point mutation in exon 17 of the KIT gene that leads to substitution of aspartic acid at position 820 with tyrosine (D820Y). One or more GISTs was documented in three generations of this kindred, and there was associated hyperplasia of the interstitial cells of Cajal (ICC). One affected family member complained of dysphagia and another suffered small intestinal diverticulosis with perforation, which may represent additional consequences of ICC hyperplasia. Diffuse and nodular ICC hyperplasia associated with the latter family member's small intestinal diverticulosis is illustrated, providing supportive functional and morphologic evidence for the ICC being the cell of origin of GISTs. Skin hyperpigmentation was not observed. Analysis of a 17-cm malignant GIST in the index patient revealed that it was hemi/homozygous for the germline D820Y mutation, indicating loss of the remaining wild-type KIT allele with tumor progression. Two smaller lesions from this patient were heterozygous for the mutation. This phenomenon has been observed in up to 8% of sporadic malignant GISTs but has not been documented in familial disease.
 ...
PMID:Gastrointestinal stromal tumors: insights from a new familial GIST kindred with unusual genetic and pathologic features. 1632 43

Microscopic gastrointestinal stromal tumors (GISTs) (synonyms: sporadic interstitial cell of Cajal hyperplasia, seedling GISTs, minimal GISTs) are common incidental findings in gastroesophageal resections (9% to 35%). To our knowledge, their frequency, clinicopathologic features, and molecular pathogenesis from nongastroesophageal sites have so far not been sufficiently analyzed. We studied 19 lesions from distal esophagus (n=8), gastroesophageal junction (n=2), sigmoid colon (n=5), and vermiform appendix, cecum, rectum, and small intestine (1 each). Microscopic GISTs were detected in 0.2%, 0.1%, and 0.01% of routinely processed resection specimens from sigmoid colon, vermiform appendix, and rectum, respectively. Patients were 11 men and 8 women with a mean age of 66 years (range, 57 to 86 y). Thirteen patients had GI cancers and 5 had diverticular disease. None has a family history of GIST or features of neurofibromatosis 1. Lesions were 0.5 to 4 mm in size (mean, 1.12 mm), were all spindled and had noncircumscribed infiltrating borders. All arose in the muscularis propria and 2 were predominantly subserosal. Immunohistochemistry revealed a CD117/CD34/smooth muscle actin-negative phenotype in 18/19 lesions. Three KIT exon 11 mutations (2 point mutations and 1 deletion, all involving W557) were detected in 3/12 lesions with successful molecular analysis. In conclusion, incidental microscopic GISTs are uncommon in intestinal resections (< or =0.1%), contrasting with their gastroesophageal counterparts (> or =9%). Somatic KIT mutations are early initiating molecular events in a subset of them. The remarkable variation in the incidence of microscopic GISTs at different GI sites suggests an origin from heterogeneous subsets of interstitial cells of Cajal with varying potentials for neoplastic transformation.
 ...
PMID:Microscopic gastrointestinal stromal tumors in esophageal and intestinal surgical resection specimens: a clinicopathologic, immunohistochemical, and molecular study of 19 lesions. 1840 93