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Difficulty: MediumPathology and Biopsy Interpretation

A 68-year-old man comes to the physician due to a 3-month history of fatigue and intermittent black, tarry stools. He has no prior medical history and takes no medications. Vital signs are within normal limits. Physical examination reveals conjunctival pallor and mild epigastric tenderness. Laboratory testing shows a hemoglobin of 9.2 g/dL. Esophagogastroduodenoscopy reveals a 4.5-cm, smooth, submucosal mass in the body of the stomach with a small area of central ulceration. Endoscopic ultrasound-guided core needle biopsy of the lesion is performed. Histopathologic examination shows intersecting fascicles of spindle cells with elongated nuclei and eosinophilic cytoplasm. Immunohistochemical staining of the biopsy specimen is strongly positive for CD117 (c-KIT) and DOG1, and negative for desmin, S-100 protein, and smooth muscle actin. Based on these histopathologic and immunohistochemical findings, which of the following is the most likely diagnosis?

  1. Gastrointestinal stromal tumorAnswer
  2. B
    Leiomyosarcoma
  3. C
    Gastric schwannoma
  4. D
    Gastric adenocarcinoma
  5. E
    Primary gastric lymphoma

Answer

Gastrointestinal stromal tumor
The correct answer is gastrointestinal stromal tumor (GIST). The patient's presentation of a bleeding submucosal gastric mass is highly suspicious for a mesenchymal tumor. The biopsy showing spindle cells that strongly express CD117 (c-KIT) and DOG1 is the hallmark diagnostic finding for a GIST. These tumors arise from the interstitial cells of Cajal (the pacemaker cells of the gut). Identification is critical as it dictates targeted therapy, often involving tyrosine kinase inhibitors like imatinib for unresectable or high-risk disease.

Step-by-Step Solution

1
Analyze the endoscopic and gross morphological findings.
The lesion is a submucosal mass in the stomach, which narrows the differential diagnosis primarily to mesenchymal tumors (e.g., gastrointestinal stromal tumors, leiomyomas/leiomyosarcomas, schwannomas).
Submucosal tumors arise from layers deep to the mucosa, differentiating them from primary epithelial tumors like adenocarcinoma.
2
Evaluate the cellular morphology from the biopsy.
The presence of intersecting fascicles of spindle cells confirms a mesenchymal origin.
Spindle cells are characteristic of connective tissue, smooth muscle, and neural origin tumors.
3
Interpret the immunohistochemical (IHC) staining profile.
Positivity for CD117 (c-KIT) and DOG1, combined with negativity for desmin, smooth muscle actin, and S-100, definitively identifies the tumor.
CD117 and DOG1 are highly sensitive and specific markers for tumors arising from the interstitial cells of Cajal, separating them from smooth muscle and neural tumors.

Key Concept

Immunohistochemical differentiation of gastrointestinal mesenchymal tumors
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Topics

Pathology and Biopsy Interpretation

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