Small intestine & ampulla

Other malignancies

GIST


Editorial Board Member: Aaron R. Huber, D.O.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Tom Liang, M.D.
Shefali Chopra, M.D.

Last author update: 24 June 2021
Last staff update: 22 July 2021

Copyright: 2003-2023, PathologyOutlines.com, Inc.

PubMed Search: Gastrointestinal stromal tumor [TI] review [PT] "last 5 years" [DP]

Tom Liang, M.D.
Shefali Chopra, M.D.
Page views in 2022: 11,875
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Cite this page: Liang T, Chopra S. GIST. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/smallbowelGIST.html. Accessed February 3rd, 2023.
Definition / general
  • Most common mesenchymal tumor of the gastrointestinal (GI) tract
  • Derived from interstitial cells of Cajal
Essential features
  • Small bowel is second most common site of GISTs (stomach is first)
  • NF1 and BRAF mutated GISTs are more common in small bowel versus other sites
  • Prognosis depends on size, mitotic rate and location
Terminology
  • Gastrointestinal stromal tumor (GIST)
ICD coding
    • ICD-10: C49.A3 - gastrointestinal stromal tumor of small intestine
    • ICD-11: 2B5B&XH9HQ1 - gastrointestinal stromal tumor
    • ICD-O: 8936/3 - gastrointestinal stromal tumor, malignant
Epidemiology
  • M:F = 1
  • Median age is 60 - 65 years; rare in children and young adults
  • May present in younger patients in neurofibromatosis type 1 (NF1) lesions (mean age 49 years), Carney triad (childhood), familial (middle age)
  • Annual incidence of GIST is between 11 and 14.5 cases per million (Int J Cancer 2005;117:289, Cancer 2005;103:821)
  • GISTs account for 1 - 3% of all GI neoplasms
Sites
  • Occurs anywhere in tubular GI tract
  • Small bowel is second most common site
  • Stomach (60%) > jejunum and ileum (30%) > duodenum (4 - 5%) > rectum (4%) > colon and appendix (1 - 2%) > esophagus (< 1%) (Semin Diagn Pathol 2006;23:70)
  • Extraintestinal GISTs occur in mesentery, omentum, retroperitoneum (Am J Surg Pathol 2005;29:52, Mod Pathol 2000;13:577)
    • May represent a metastasis from an unrecognized primary or a detached mass from the GI tract
Pathophysiology
  • Sporadic - vast majority
  • Sporadic tumor syndrome (nonhereditary)
    • Carney triad (GIST, paraganglioma, pulmonary chondroma)
      • SDH deficient but lacking SDH germline mutations
  • Autosomal dominant hereditary syndromes (5 - 10% of all GISTs)
    • Neurofibromatosis type 1 (NF1) - commonly small bowel and often multifocal
    • Germline KIT mutations
    • Germline PDGFRA mutations
    • Carney-Stratakis syndrome
Etiology
  • Unknown, most cases are sporadic
  • Small subset of cases can be familial (see Pathophysiology)
Diagrams / tables

Images hosted on other servers:

Guidelines for risk assessment of primary GIST

Clinical features
  • Vague abdominal pain
  • Symptoms related to mucosal ulceration, including bleeding (47%) (Ther Clin Risk Manag 2018;14:1467)
  • Abdominal mass
  • Smaller GISTs are discovered incidentally
  • NF1 associated GISTs (Am J Surg Pathol 2006;30:90)
    • Patients are more likely to develop multiple independent GISTs
    • NF1 tumors have a strong predilection to arise in small bowel
    • While NF1 associated GISTs have been estimated to account for only about 1 - 2% of tumors from all anatomic sites, they make up ~4 - 6% of small intestinal GISTs
Diagnosis
  • Double balloon enteroscopy (89%), CT angiography (71%) and CT (55%) are best imaging modalities (Ther Clin Risk Manag 2018;14:1467)
  • Endoscopy with biopsy or fine needle aspiration
Radiology description
  • Radiologic findings are variable, depending on size and time of presentation
  • CT usually shows a solid, heterogeneous mass (reflecting the presence of hemorrhage or cystic degeneration)
  • Endoscopic ultrasound reveals a hypoechoic solid mass
  • References: Front Oncol 2021;11:582847, Front Oncol 2021;11:631927
Radiology images

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Duodenal GIST

Jejunal GIST

Ileoileal intussusception - small bowel GIST

Prognostic factors
  • Prognosis depends on site, size, mitotic activity, molecular profile (Semin Diagn Pathol 2006;23:70)
  • Small bowel GISTs are more likely to be malignant (35 - 40%) compared with gastric GISTs (25%) (Am J Surg Pathol 2006;30:477, Am J Surg Pathol 2005;29:52)
  • NF1 mutated GISTs are usually grossly small and mitotically inactive, much like spontaneous low grade GISTs of the small intestine
    • Their histologically benign appearance is reflected in their commonly nonaggressive clinical behavior
    • NF1 associated tumors that do manifest as clinically malignant disease are generally bigger (> 5 cm in greatest dimension) and more proliferative (> 5 mitoses/5 mm2), adhering to the risk stratification provided by standard staging criteria
Case reports
Treatment
  • Most GISTs are treated with surgical resection
  • Imatinib mesylate (Gleevec): tyrosine kinase inhibitor of KIT and PDGFRα
    • Metastatic / recurrent / high risk GIST
  • Sunitinib malate (Sutent): a tyrosine kinase inhibitor of KIT, PDGFRα, VEGFR
    • Used in imatinib resistant GIST
  • NF1 mutated GISTs - surgery is treatment of choice as these tumors do not respond to imatinib
  • BRAF mutated GISTs do not respond to imatinib and BRAF inhibitors are used for therapy if indicated
  • References: Am J Surg Pathol 2015;39:922, Surg Clin North Am 2017;97:437
Clinical images

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Small bowel GIST

Endoscopy of ulcerated mass

Gross description
  • Well circumscribed masses of various sizes
  • Cut surface may show hemorrhage, cystic change or necrosis
  • Usually centered in the muscularis propria
  • Small bowel GISTs more frequently present as external masses
  • Reference: Am J Surg Pathol 2009;33:1267
Gross images

Contributed by Shefali Chopra, M.D.
Adherent small bowel

Adherent small bowel

Hemorrhage & cystic change

Hemorrhage & cystic change



Frozen section description
  • Spindle cell neoplasm
Microscopic (histologic) description
  • 3 morphologic types: spindle (70%), epithelioid (20%), mixed (10%)
  • Monotonous, bland cells with spindled or epithelioid cytoarchitecture, lightly eosinophilic to pale cytoplasm and vesicular chromatin residing within uniformly ovoid or round nuclei
  • In spindle cell GISTs, the pink cytoplasm often has a fibrillary texture with indistinct cell borders
  • Can show a degree of nuclear palisading reminiscent of schwannoma
  • Small intestinal GISTs are most often spindled
    • Epithelioid morphology in small intestinal GIST portends malignant behavior, in contrast to the stomach, where epithelioid morphology is not a significant prognostic feature
  • Small intestine GISTs more commonly feature skeinoid fibers, stromal PAS positive globules of curved collagen fibrils, which, when present in a small intestinal tumor, correlate with less malignant clinical behavior
  • Treated tumors can display a widely variable histomorphology that may significantly differ from treatment naive tumors
    • Tumor may be necrotic or hypocellular; the stromal component, which may be hyalinized or calcified, becomes prominent
    • Cytomorphology of the tumor cells can change, usually adopting a more epithelioid and even anaplastic or sarcomatoid appearance
  • Histologic grade
    • G1: low grade, mitoses < 5/5 mm2
    • G2: High grade, mitoses > 5/5 mm2
  • References: Am J Surg Pathol 2017;41:577, Arch Pathol Lab Med 2020;144:655
Microscopic (histologic) images

Contributed by Shefali Chopra, M.D.
Relation to overlying mucosa

Relation to overlying mucosa

Skeinoid fibers

Skeinoid fibers

Spindle cell morphology

Spindle cell morphology

Therapy effect

Therapy effect

CD117

CD117

DOG1

DOG1

Virtual slides

Images hosted on other servers:

Duodenal GIST

Cytology description
  • Bland spindle and sometimes epithelioid cells
  • EUS-FNA with IHC staining of cell block can lead to diagnosis
    • If not enough material and large tumor size, there might not be enough for genotyping to guide neoadjuvant therapy
  • Without enough tissue to perform immunohistochemical stains, it might be hard to get to a definitive diagnosis
  • Reference: Diagn Cytopathol 2021 May 18 [Epub ahead of print]
Cytology images

Contributed by Shefali Chopra, M.D.
Diff-Quik, spindle cells

Diff-Quik, spindle cells

Pap, spindle cells

Pap, spindle cells

Cell block, spindle cells

Cell block, spindle cells

Negative stains
Molecular / cytogenetics description
Molecular / cytogenetics images

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KIT mutations

Videos

Small bowel GIST

Sample pathology report
  • Duodenum, resection:
    • Gastrointestinal stromal tumor (GIST), spindle cell type, 3.0 cm, grade 1 (see synoptic report for risk stratification as well as biomarker report)
Differential diagnosis
Board review style question #1

Which of the following is true regarding gastrointestinal stromal tumors in NF1 patients?

  1. Always associated with KIT mutation
  2. Epithelioid in morphology with loss of SDHB immunostaining by immunohistochemistry
  3. More aggressive than sporadic GISTs and present with metastasis
  4. Tumor can be multiple, is spindle cell in morphology, located in small intestine and indolent in behavior
Board review style answer #1
D. Tumor can be multiple, is spindle cell in morphology, located in small intestine and indolent in behavior

Comment Here

Reference: Gastrointestinal stromal tumor (GIST)
Board review style question #2
Besides KIT and PDGFRa mutations, what other mutations can be seen more commonly in small intestinal GISTs?

  1. BRAF
  2. IDH
  3. KRAS
  4. SDH
Board review style answer #2
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