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)
- Presence of discohesive cells with abundant intracytoplasmic mucin displacing the nucleusAnswer
- Loss of E-cadherin expression on immunohistochemical stainingAnswer
- CFormation of distinct neoplastic glandular structures with cellular stratification
- DStrong, uniform membranous overexpression of HER2/neu protein
- EProminent background of chronic atrophic gastritis with intestinal metaplasia
Answer
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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Key Concept
Diffuse-type gastric adenocarcinoma presents as linitis plastica and is characterized histologically by discohesive signet-ring cells lacking E-cadherin expression.