Stomach
Stromal / other tumors
Gastrointestinal stromal tumor (GIST)

Author: Elliot Weisenberg, M.D.

Revised: 14 June 2018, last major update July 2012

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Gastrointestinal stromal tumor [title](GIST[title]) stomach
Cite this page: Weisenberg, E. Gastrointestinal stromal tumor (GIST). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stomachGIST.html. Accessed June 18th, 2018.
Definition / general
  • Most common mesenchymal tumor of gastrointestinal tract; arises from or is differentiated towards interstitial cell of Cajal, involved in gut pacemaker activity to regulate peristalsis; usually due to activating mutation of c-kit
  • 25% are clinically malignant
Clinical features
  • 2 - 3% of gastric malignancies
  • Usually older adults, median age 60 - 65 years; 1% occur in children
  • Male = female incidence
  • Symptoms: abdominal pain, gastric outlet obstruction, mass effect, melena; may be asymptomatic
  • 95% sporadic, associated with neurofibromatosis type 1, Carney's triad (gastric GIST, paraganglioma, pulmonary chondroma), familial GIST syndrome, Carney-Stratakis syndrome (Am J Med Genet 2002;108:132)
  • Sites: stomach (60%), jejunum and ileum (30%), duodenum (5%), colorectum (5%), rarely esophagus, appendix, retroperitoneum, abdomen (extra GI stromal tumors)
  • Prognosis based on size and mitotic count (see GIST staging)
  • Rarely simultaneous stomach GIST and adenocarcinoma / carcinoid (Arch Pathol Lab Med 2000;124:682)
Case reports
Treatment
  • Specific targeted therapy (imatinib mesylate, sunitinib malate) is effective in most cases with kit mutations and many with PDFRA mutations; inactivates the ability of kit to perform intracellular signalling
  • Mutational analysis may provide helpful data in planning therapy because different mutations of kit and PDGFA may affect prognosis and response to therapy
  • Tumors lacking kit or PDGRA mutations likely will not respond to targeted therapy
  • Complete surgical excision is usually recommended for incompletely resected tumors, metastatic disease or high risk tumors
Microscopic (histologic) description
  • 4 main types: benign cellular spindle cell tumor, spindle cell sarcoma, benign epithelioid gastric stomal tumor, malignant epithelioid gastric stromal tumor; also mixed patterns

  • Benign cellular spindle cell tumor:
    • Cellular proliferation of bland spindle cells with pale to eosinophilic fibrillar cytoplasm
    • Cells in whorls or short intersecting fascicles, with frequent and prominent nuclear pallisading, numerous perinuclear vacuoles that indent nucleus, often extensive stromal hyalinization
    • Minimal pleomorphism; < 2 mitotic figures / 50 HPFs

  • Benign epithelioid gastric stromal tumor:
    • Predominantly sheets of epithelioid cells, often with a condensed rim of eosinophilic cytoplasm adjacent to nucleus and peripheral cytoplasmic clearing
    • Well defined cell membranes, round nuclei with small nucleoli
    • Also scattered bizarre or multinucleated cells
    • Epithelioid cells often mixed with plump spindle cells of similar size and nuclear characteristics
    • Frequent stromal liquefaction or hyalinization
    • Only rare mitotic figures

  • Benign mixed cell pattern: Mixture of above two patterns

  • Spindle cell sarcoma: Larger and more cellular than cellular spindle cell tumors, generally cells have less cytoplasm, more nuclear variability, tumor necrosis is often present, mitotic figures generally numerous

  • Malignant gastric epithelioid stromal tumor:
    • Higher N / C ratio than benign epithelioid gastric stomal tumor with more hyperchromatic nuclei, generally more cellular, but cellularity may be variable with sheet like areas and areas with a prominent mucopolysaccharide rich stroma, usually more monotonous than benign epithelioid pattern
    • Mitotic activity present, but may be variable
    • Benign and mixed patterns may be present in same tumor; extensive sampling recommended
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Andrey Bychkov, M.D., Ph.D., Kameda Medical Center

Spindle cells

Benign GIST

CD34

C-kit



Images hosted on other servers:



Contributed by: Dr. Saroona Haroon, The Aga Khan University Hospital (Pakistan)


GIST tumor / carcinoid tumor

   

Simultaneous stomach
GIST and adenocarcinoma
/ carcinoid


Positive stains
Molecular / cytogenetics description
  • 85% have c-kit activating mutations; less commonly, activating mutations of platelet derived growth factor alpha (PDGFA) which is closely homologous to kit; these tumors often have epithelioid morphology
  • 10 - 15% of GISTs lack kit or PDGRA mutations, these include pediatric GISTs, GISTs associated with neurofibromatosis type 1 and sporatic wild type GISTs
  • Rare tumors have BRAF mutations
  • Rare tumors have loss of function mutations of the succinate dehydrogenase complex (Am J Surg Pathol 2011;35:1712), including GISTs associated with Carney-Stratakis syndrome (GIST and paraganglioma) and famial paraganglioma syndromes