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Zorluk: OrtaPathology and Biopsy Interpretation

A 58-year-old man undergoes an upper gastrointestinal endoscopy for evaluation of progressive early satiety, postprandial nausea, and a 9-kg (20-lb) weight loss over the past 4 months. During the procedure, the endoscopist notes a diffusely thickened, rigid gastric body and antrum with poor distensibility upon air insufflation. No discrete exophytic mass or large ulcer is visualized. Multiple deep mucosal biopsies are obtained. Which of the following histopathologic and immunohistochemical findings are characteristic of this patient's most likely diagnosis? (Select all that apply)

  1. Presence of discohesive cells with abundant intracytoplasmic mucin displacing the nucleusCevap
  2. Loss of E-cadherin expression on immunohistochemical stainingCevap
  3. C
    Formation of distinct neoplastic glandular structures with cellular stratification
  4. D
    Strong, uniform membranous overexpression of HER2/neu protein
  5. E
    Prominent background of chronic atrophic gastritis with intestinal metaplasia

Cevap

Presence of discohesive cells with abundant intracytoplasmic mucin displacing the nucleus AND Loss of E-cadherin expression on immunohistochemical staining
The patient's endoscopic presentation of a thickened, rigid stomach with poor distensibility is classic for linitis plastica, which is strongly associated with diffuse-type gastric adenocarcinoma. On biopsy, this malignancy is characterized by the presence of signet-ring cells—discohesive cells with abundant intracytoplasmic mucin that displaces the nucleus to the periphery. Immunohistochemically, these tumors characteristically show a loss of E-cadherin expression, a cell adhesion molecule, which explains their discohesive and infiltrative growth pattern. This loss of adhesion is often driven by mutations in the CDH1 gene.

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1
Identify the clinical presentation and endoscopic findings.
The patient has symptoms of gastric malignancy with endoscopy showing a diffusely thickened, rigid stomach with poor distensibility.
This macroscopic appearance is classic for 'linitis plastica', which strongly points toward a specific subtype of gastric cancer.
2
Correlate the gross endoscopic appearance with the histopathologic subtype.
Linitis plastica is caused by diffuse-type gastric adenocarcinoma, which infiltrates the gastric wall extensively without necessarily forming a discrete mass.
Differentiating between diffuse and intestinal types of gastric adenocarcinoma is crucial for understanding the pathogenesis and interpreting the biopsy.
3
Determine the characteristic histopathologic and immunohistochemical features of diffuse-type gastric adenocarcinoma.
It is characterized by signet-ring cells (mucin-filled cells with peripheral nuclei) and a loss of E-cadherin expression (often due to CDH1 mutations).
These specific microscopic and molecular features confirm the diagnosis and explain the tumor's infiltrative, discohesive behavior.

Anahtar Kavram

Diffuse-type gastric adenocarcinoma presents as linitis plastica and is characterized histologically by discohesive signet-ring cells lacking E-cadherin expression.
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