Definition/General
Introduction:
Menetrier disease is a rare gastropathy characterized by giant rugal folds and protein-losing gastropathy
It involves massive foveolar hyperplasia
It causes hypoproteinemia due to protein loss
It has increased risk of gastric adenocarcinoma.
Origin:
Results from overexpression of TGF-α (transforming growth factor-alpha)
Leads to EGFR stimulation and cellular proliferation
Causes foveolar hyperplasia and mucin hypersecretion
Associated with loss of parietal cells
May be associated with CMV infection in children.
Classification:
Adult form: chronic progressive disease
Pediatric form: self-limited, often CMV-associated
Localized form: segmental involvement
Diffuse form: pan-gastric involvement
Associated with protein-losing gastropathy.
Epidemiology:
Very rare disease (<1 case per 1 million)
Male predominance (3:1 ratio)
Peak incidence: 30-60 years
Pediatric cases: associated with CMV infection
Higher reported incidence in Japan and Western countries.
Clinical Features
Presentation:
Protein-losing gastropathy (hypoproteinemia, edema)
Epigastric pain
Nausea and vomiting
Peripheral edema and ascites
Iron deficiency anemia
Weight loss and malnutrition.
Symptoms:
Abdominal pain (epigastric)
Peripheral edema (protein loss)
Diarrhea and malabsorption
Early satiety and bloating
Fatigue and weakness
Pleural effusion (severe protein loss).
Risk Factors:
Male sex (3:1 predominance)
Middle age (30-60 years)
CMV infection (pediatric cases)
H
pylori infection (controversial association)
TGF-α overexpression.
Screening:
Upper endoscopy (giant rugal folds)
Serum protein levels (albumin <2.5 g/dL)
Fecal α1-antitrypsin (protein loss)
CT/MRI abdomen
Endoscopic ultrasound.
Master Menetrier Disease Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Giant rugal folds (>10mm thickness)
Cerebriform pattern
Corpus and fundus involvement predominantly
Antral sparing (characteristic)
Mucosal surface appears mamillated
Folds are soft and pliable.
Characteristics:
Marked fold enlargement in body and fundus
Antral preservation (pathognomonic)
Cobblestone appearance
Mucosal surface irregularity
Preserved gastric peristalsis
No ulceration typically.
Size Location:
Corpus-fundus involvement (90% cases)
Antral sparing (characteristic feature)
Greater curvature predominance
Fold thickness: >10mm (vs
normal 2-3mm)
Diffuse involvement pattern.
Multifocality:
Diffuse involvement of body and fundus
Sharp demarcation at antro-corporal junction
Symmetric distribution
Progressive enlargement over time
Concurrent duodenal involvement rare.
Microscopic Description
Histological Features:
Massive foveolar hyperplasia (characteristic)
Cystic dilatation of surface epithelium
Loss of parietal and chief cells
Replacement by mucin-producing cells
Minimal inflammatory infiltrate
Submucosal edema.
Cellular Characteristics:
Hyperplastic mucin-producing cells
Enlarged surface epithelial cells
Mucin-filled cytoplasm
Minimal atypia
Increased mitotic activity
Loss of specialized cell types.
Architectural Patterns:
Elongated and tortuous foveolae
Cystic gland dilatation
Loss of oxyntic glands
Pseudopyloric metaplasia
Submucosal vascular congestion
Intact basement membrane.
Grading Criteria:
Foveolar hyperplasia: mild, moderate, severe
Glandular loss: percentage of oxyntic glands lost
Cystic dilatation: extent and severity
Inflammation grade: usually minimal.
Immunohistochemistry
Positive Markers:
MUC5AC (surface mucin, markedly increased)
TGF-α (overexpressed)
EGFR (epidermal growth factor receptor)
Ki-67 (increased proliferation)
PAS stain (mucin demonstration).
Negative Markers:
H+/K+-ATPase (parietal cell loss)
Pepsinogen I (chief cell loss)
MUC6 (pyloric gland mucin, decreased)
Chromogranin A (neuroendocrine cells, decreased).
Diagnostic Utility:
Demonstrates TGF-α overexpression (pathogenic mechanism)
Shows loss of specialized cells
Confirms mucin hypersecretion
Assesses proliferative activity
Excludes malignancy.
Molecular Subtypes:
Adult form: TGF-α overexpression, chronic course
Pediatric form: CMV-associated, self-limited
Localized form: segmental TGF-α expression
Diffuse form: pan-gastric involvement.
Molecular/Genetic
Genetic Mutations:
TGF-α gene overexpression (key pathogenic event)
EGFR pathway activation
Loss of gastrin expression
Cyclin D1 overexpression
Growth factor pathway dysregulation.
Molecular Markers:
Elevated TGF-α (tissue and serum)
EGFR overexpression
Decreased gastrin
Low pepsinogen I/II ratio
Increased mucin production.
Prognostic Significance:
Adult form: chronic progressive course
Protein loss severity: determines prognosis
Malignant transformation risk: 5-10% cases
Pediatric form: excellent prognosis with CMV treatment.
Therapeutic Targets:
EGFR inhibitors: cetuximab (experimental)
Octreotide (protein loss control)
Nutritional support
Gastrectomy (severe cases)
Antiviral therapy (CMV-associated).
Differential Diagnosis
Similar Entities:
Hypertrophic gastritis
Gastric adenocarcinoma (linitis plastica)
Lymphoma
Zollinger-Ellison syndrome
Gastric varices
Inflammatory pseudotumor.
Distinguishing Features:
Menetrier: antral sparing, foveolar hyperplasia, protein loss
Hypertrophic gastritis: inflammatory infiltrate
Cancer: malignant cells, transmural involvement
Lymphoma: lymphoid cells, systemic involvement.
Diagnostic Challenges:
Distinguishing from hypertrophic gastritis
Excluding underlying malignancy
Confirming protein-losing gastropathy
Adequate tissue sampling
Long-term cancer surveillance.
Rare Variants:
Pediatric CMV-associated form
Localized Menetrier disease
Association with neoplasms
Familial cases (very rare)
Drug-induced forms.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Gastric biopsy from [corpus/fundus], [number] fragments
Diagnosis
Menetrier disease (hypertrophic gastropathy)
Foveolar Changes
Massive foveolar hyperplasia with cystic dilatation
Specialized Cells
Loss of parietal and chief cells with replacement by mucin-producing cells
Inflammation
Minimal chronic inflammation
Dysplasia
No dysplasia or malignancy identified
Special Studies
PAS stain: strongly positive for mucin
MUC5AC: markedly increased, H+/K+-ATPase: decreased
TGF-α: [if performed] overexpressed
Recommendations
Clinical correlation with protein levels, surveillance for malignancy
Final Diagnosis
Menetrier disease with massive foveolar hyperplasia and protein-losing gastropathy