Esophagus
Other malignancies
Gastrointestinal stromal tumor (GIST)

Author: Feriyl Bhaijee, M.D. (see Authors page)
Editor: Israh Akhtar, M.D.

Revised: 29 January 2018, last major update August 2013

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

PubMed Search: Gastrointestinal stromal tumor esophagus free full text[sb]

Cite this page: Bhaijee, F. Gastrointestinal stromal tumor (GIST). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/esophagusGIST.html. Accessed May 27th, 2018.
Definition / general
  • Mesenchymal tumor of digestive tract, likely originating from multipotential progenitors of interstitial cells of Cajal
Terminology
  • Microscopic GIST: sporadic interstitial cell of Cajal hyperplasia, seedling GIST, minimal GIST
Epidemiology
  • Very rare: < 3% of all GIST arise in esophagus
  • No gender predilection
  • Wide age range, average 50 - 60 years
  • May be incidental finding in patients undergoing resection of upper GI neoplasms (Can J Surg 2012;55:366)
Sites
  • Mid to lower esophagus
Etiology
  • Mostly sporadic
  • Higher incidence in patients with
    • Neurofibromatosis type I (NF1, von Recklinghausen disease)
    • Carneys triad
  • Familial GIST syndrome: rare, autosomal dominant genetic disorder, characterized by germline KIT or PDGFRA mutations, early onset of multiple GIST tumors, skin pigmentation abnormalities (Am J Surg Pathol 2013;37:898)
Clinical features
  • Esophageal mass, stricture, perforation
  • Dysphagia
  • Metastatic spread to liver and peritoneum
Diagnosis
  • Biopsy with immunohistochemical / molecular confirmation
Radiology description
  • CT / MRI: useful for preoperative and metastatic evaluation
  • PET: FDG avidity
    • Used to monitor response to tyrosine kinase inhibitor therapy
  • Barium studies: smooth intraluminal mass or large ulcerative mass extending intraluminally
  • Endoscopic ultrasound: enables image guided core needle biopsy or fine needle aspiration
Radiology images

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40 year old man with dysphagia

Enhancing chest CT

CT scan shows well circumscribed tumor

Prognostic factors
  • Risk stratification based on size and mitotic activity per 50 high power fields (HPF):
    • Low risk: < 5 cm and < 5/50 HPF
    • Intermediate risk: < 5 cm and 6 - 10/50 HPF OR 5 - 10 cm and < 5/50 HPF
    • High risk: > 5 cm and > 5/50 HPF OR > 10 cm and any mitotic rate OR any size and > 10/50 HPF

Risk category Tumor size Mitotic rate/50 HPF
Low < 5 cm < 5
Intermediate < 5 cm 6 - 10
Intermediate 5 - 10 cm < 5
High > 5 cm > 5
High > 10 cm Any mitotic rate
High Any size > 10
Case reports
Treatment
  • Surgical resection
  • Neoadjuvant small molecule tyrosine kinase inhibitors: imatinib mesylate (STI571, Gleevec), sunitinib maleate
Clinical images

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Endoscopic images

Gross description
  • Lobulated, well circumscribed mass with fleshy cut surfaces
  • Cystic degeneration, necrosis, hemorrhage common
  • Overlying esophageal mucosa may be ulcerated
Gross images

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19 cm tumor with cystic degeneration and necrosis

Multinodular,
well circumscribed
mass in posterior
mediastinum

Microscopic (histologic) description
  • Histologic heterogeneity:
    • Spindle cell type (70%): relatively uniform eosinophilic cells in short fascicles or whorls, indistinct cell borders, paranuclear cytoplasmic vacuoles, stromal lymphocytes and microcystic stromal degeneration (as in schwannoma), minimal collagen, delicate thin walled vessels, stromal hemorrhage
    • Epithelioid type (20%): rounded cells with variably eosinophilic or clear cytoplasm in nests or sheets, uniform round / ovoid nuclei with vesicular chromatin
    • Mixed type (10%): may have abrupt transition between spindle cell and epithelioid areas or complex comingling of both
  • Stromal skeinoid fibers (< 20%): hyaline or fibrillary brightly eosinophilic PAS+ structures, representing nodular tangles of collagen fibers; more common in small bowel GIST
  • Rarely: cytologic atypia, myxoid stroma
  • Variable mitotic activity
  • Microscopic GIST: < 1 cm, spindle cells with hyalinized stroma and variable calcification (Pathology 2008;40:9)
Microscopic (histologic) images

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Dense cellularity, mixture of epithelioid and spindled areas

Intramural nodule
and fascicular
arrangement of
spindle cells

H&E

Spindle cell proliferation

Moderate atypia, occasional mitotic figures


KIT

KIT / CD117

CD117 and desmin

CD117, CD34, SMA, S100

Cytology description
  • Cellular monomorphic proliferations of epithelioid or spindle cells
    • Round / oval nuclei, vesicular chromatin, fibrillary cytoplasm
  • Cohesive fragments with admixed delicate, thin walled vessels
  • Features of malignancy: cellular dyscohesion, nuclear pleomorphism, prominent nucleoli, increased mitotic activity, prominent necrosis
Cytology images

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Spindle cells with high cellularity

Epithelioid cells with round nuclei

Positive stains
Negative stains
Electron microscopy description
  • Relative lack of differentiation
    • Incomplete smooth muscle or neuroaxonal differentiation
    • No bundles of actin filaments (seen in true smooth muscle tumors)
Electron microscopy images

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Ultrastructural
demonstration of
cytoplasmic vesicles
in high risk GIST

Molecular / cytogenetics description
  • Mutually exclusive mutations of activating KIT (95%) or platelet derived growth factor alpha (PDGFRA) receptor tyrosine kinase (5%)
    • In frame deletions, point mutations, duplications, insertions
    • Most common: KIT juxtamembrane domain (exon 11) mutations
      • Confers better response to tyrosine kinase inhibitor therapy
Differential diagnosis