gastrointestinal stromal tumor (GIST)
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Introduction
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
- distribution
- behavior:
- GISTs of stomach considered to be malignant if > 5-10 cm, high mitotic index or metastasized.
- GISTs of small bowel considered to be malignant if > 2cm & any mitoses.
- most esophageal & colonic GISTs are malignant
Microscopic pathology
variable
- cellular spindle cell tumors with moderate to slight interstitial collagen
- may have nerve sheath tumor-like nuclear pallisading
- some have prominant perinuclear vacuolization
- epithelioid appearance - solid, myxoid, paraganglioma- or carcinoid- like clustering
- significant nuclear pleomorphism rare
- 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
- succinate dehydrogenase in tissue
- see ARUP consult[2]
Diagnostic procedures
Differential diagnosis
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]
- 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]
More general terms
Additional terms
- 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)
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/11213830
- ↑ 2.0 2.1 2.2 ARUP Consult: Gastrointestinal Stromal Tumors - GIST The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/gastrointestinal-stromal-tumors
- ↑ 3.0 3.1 3.2 3.3 Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018
- ↑ 4.0 4.1 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: https://www.ncbi.nlm.nih.gov/pubmed/22453568
- ↑ 5.0 5.1 5.2 5.3 5.4 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: https://www.ncbi.nlm.nih.gov/pubmed/29846513