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Stomach

Stromal/other tumors

Gastrointestinal stromal tumor (GIST)

Reviewers: Elliot Weisenberg, M.D. (see Reviewers page)
Revised: 13 October 2012, last major update July 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● 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
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● 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
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● 69 year old man with malignant GIST with secondary amyloidosis (Arch Pathol Lab Med 2003;127:470)
● 73 year old woman with multiple GIST tumors, carcinoid tumor and lipoma (Arch Pathol Lab Med 2001;125:318)

Treatment
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● Specific targetted 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 targetted therapy
● Complete surgical excision is usually recommended for incompletely resected tumors, metastatic disease, or high risk tumors

Micro description
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● 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

Micro images
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Benign spindle cell gastric stromal tumor


Malignant spindle cell gastric stromal tumor


Benign epithelioid gastric stromal tumor


Malignant epithelioid gastric stromal tumor


Simultaneous stomach GIST and adenocarcinoma/carcinoid


GIST tumor/carcinoid tumor

   
CD117

Positive stains
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● CD117/c-kit, CD34; also DOG1, vimentin

Molecular features
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● 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;35:1721), including GISTs associated with Carney-Stratakis syndrome (GIST and paraganglioma) and famial paraganglioma syndromes

Additional references
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● Am J Surg Pathol 2002;26:705, Am J Surg Pathol 1999;23:82, Hum Pathol 2002;33:669
● Hum Pathol 2002;33:459, Hum Pathol 2002;33:478, Mod Pathol 2003;16:366

End of Stomach > Stromal/other tumors > Gastrointestinal stromal tumor (GIST)

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