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gastrointestinal stromal tumor (GIST)

CD117 (c-kit) positive (immunocytochemistry) mesenchymal spindle cell or epithelioid neoplasm primary to GI tract. Gastrointestinal autonomic nerve tumors (GANTs) may represent a subset. Epidemiology: - most common mesenchymal neoplasm of digestive tract. - most (70-80%) are benign. - typically older individuals (over 50 yrs, rare before 40 yrs.) Pathology: 1) distribution a) stomach 60-70% b) small intestine 20-25% c) colon & rectum 5% d) esophagus < 5% e) occasionally omentum or mesentery 2) behavior: a) GISTs of stomach considered to be malignant if > 5-10 cm, high mitotic index or metastasized. b) GISTs of small bowel considered to be malignant if > 2cm & any mitoses. c) most esophageal & colonic GISTs are malignant Microscopic pathology: variable 1) cellular spindle cell tumors with moderate to slight interstitial collagen 2) may have nerve sheath tumor-like nuclear pallisading 3) some have prominant perinuclear vacuolization 4) epithelioid appearance - solid, myxoid, paraganglioma- or carcinoid- like clustering 5) significant nuclear pleomorphism rare 6) mitotic figures & malignancy - mitotic index is a marker of recurrence risk after resection Immunophenotype: - CD117 (c-kit): most are strongly & uniformly +, - gain of function mutations of kit proto-oncogene have been found, more commonly in malignant GISTs. - CD34: ~70% + - smooth muscle actin: 20-30% + - S100 protein: 10% + - desmin: < 5% + Laboratory: - mutational analysis for GISTs >= 2 cm & rectal GISTs - KIT gene exon 9 mutation - PDGFRA D842V-mutation - NF1 gene mutation - succinate dehydrogenase in tissue - see ARUP consult [2] Special laboratory: - endoscopic ultrasound - observation for esophagus, gastric or duodenal GISTs <2 cm - excisional biopsy for GISTs >= 2 cm [5] - high-risk features include size > 2 cm, lobulated or irregular borders, invasion into adjacent structures, & heterogeneity Differential diagnosis: - leiomyoma - leiomyosarcoma - nerve sheath tumor Management: - surgical resection for localized disease [3] - without dissection of clinically negative lymph nodes - adjunctive chemotherapy with imatinib for 3 years for high-risk tumors [3] - metastatic disease is treated with imatinib [3] - 3 years of therapy improves survival relative to 1 year [4] - GISTs with PDGFRA D842V-mutation should not be treated with adjuvant imatinib [5] - standard treatment of patients with KIT gene exon 9 mutation is 800 mg daily of imatinib. - avoid adjuvant chemotherapy in NF1 gene mutation positive & succinate dehydrogenase in tissue negative GISTs [5] - sunitinib for imatinib failure [2] - regorafenib 160 mg daily for 3 of 4 weeks for imatinib & sunitinib failure [5]

Interactions

disease interactions

Related

c-kit protein; mast/stem cell growth factor receptor; SCFR; proto-oncogene tyrosine-protein kinase Kit; c-kit; CD117 (KIT) CD34; hematopoietic progenitor cell antigen CD34 (CD34)

General

gastrointestinal (GI) cancer soft tissue sarcoma (STS)

Properties

GENETIC-ABNORMALITY: mutation LOCUS: human chromosome-4 Q12 ABERRANT-GENE: kit proto-oncogene

References

  1. Miettinen M, Lasota J Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 2001 Jan;438(1):1-12 PMID: 11213830
  2. ARUP Consult: Gastrointestinal Stromal Tumors - GIST The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/gastrointestinal-stromal-tumors
  3. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018
  4. Joensuu H1, Eriksson M, Sundby Hall et al One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012 Mar 28;307(12):1265-72 PMID: 22453568
  5. Casali PG, Abecassis N, Bauer S et al Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 May 28. PMID: 29846513

Databases & Images

OMIM correlations MORBIDMAP 164920 images related to gastrointestinal stromal tumor