Definition/General
Introduction:
Gastric mucinous adenocarcinoma is a distinct variant of gastric adenocarcinoma
It is characterized by abundant extracellular mucin pools
The mucin comprises >50% of tumor volume
Also known as colloid carcinoma
It constitutes 2-6% of all gastric cancers.
Origin:
Originates from the gastric epithelial cells
Specifically from the mucin-producing goblet cells
The neoplastic transformation involves excessive mucin secretion
It leads to formation of large extracellular mucin lakes
This results in characteristic gelatinous appearance.
Classification:
Classified as a specific variant of adenocarcinoma in WHO classification
Forms part of intestinal-type gastric cancer according to Lauren classification
Better prognosis compared to signet ring cell carcinoma
Grading follows WHO criteria
Usually moderately differentiated.
Epidemiology:
Peak incidence in 6th-7th decades
Male predominance (M:F ratio 2:1)
More common in distal stomach
Associated with intestinal metaplasia
Environmental factors include H
pylori infection
Salt-preserved foods increase risk
Lower incidence in Indian population compared to conventional adenocarcinoma.
Clinical Features
Presentation:
Epigastric pain (most common symptom)
Palpable mass in advanced cases
Weight loss and anorexia
Gastric outlet obstruction due to antral location
Early satiety and bloating
Better clinical outcomes than other gastric cancers.
Symptoms:
Abdominal pain (80-90%)
Dyspepsia and indigestion
Nausea and vomiting
Weight loss (less severe than other types)
Gastrointestinal bleeding (uncommon)
Palpable abdominal mass in large tumors
Ascites in advanced peritoneal spread.
Risk Factors:
H
pylori infection
Chronic atrophic gastritis
Intestinal metaplasia
Dietary factors (high salt, nitrates)
Smoking and alcohol
Previous gastric surgery
Family history of gastric cancer.
Screening:
Upper endoscopy with biopsy
Chromoendoscopy for early detection
High-risk individual surveillance
Serum pepsinogen levels
H
pylori testing and eradication
Genetic counseling for familial cases.
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Gross Description
Appearance:
Gelatinous, mucoid mass with translucent appearance
Soft consistency compared to other gastric cancers
Cut surface shows abundant mucin
Well-circumscribed in many cases
Gray-white to yellow-tan coloration.
Characteristics:
Mucoid consistency on palpation
Gelatinous cut surface
Abundant clear to slightly turbid mucin
Soft texture that may fragment easily
May show areas of hemorrhage and necrosis.
Size Location:
Size ranges from 2-15 cm
Most common in gastric antrum (60-70%)
Body and fundus less commonly involved
Exophytic growth pattern common
May involve gastroesophageal junction.
Multifocality:
Usually unifocal
Lower metastatic potential compared to other gastric cancers
Lymph node involvement less common
Peritoneal seeding possible but less frequent
Local invasion into adjacent organs.
Microscopic Description
Histological Features:
Large pools of extracellular mucin (>50% of tumor)
Floating malignant cells within mucin lakes
Glandular structures preserved in many areas
Goblet cell differentiation
Variable cellular atypia
Desmoplastic stroma between mucin pools.
Cellular Characteristics:
Columnar epithelial cells with mucin secretion
Moderate nuclear pleomorphism
Prominent nucleoli in some cases
Intracytoplasmic mucin in addition to extracellular
Mitotic activity variable
PAS-positive mucin.
Architectural Patterns:
Glandular pattern with mucin lakes
Cribriform architecture in some areas
Papillary structures may be present
Infiltrating growth at periphery
Solid areas less common
Mucin dissection of stroma.
Grading Criteria:
Usually well to moderately differentiated
WHO Grade 2 in most cases
Nuclear pleomorphism mild to moderate
Glandular differentiation preserved
Mitotic count variable
Better differentiation than conventional adenocarcinoma.
Immunohistochemistry
Positive Markers:
CK20 (85-90%)
CDX2 (70-80%)
MUC2 (intestinal-type mucin)
CEA (cytoplasmic and luminal)
CK7 (variable, 30-50%)
Villin (intestinal differentiation).
Negative Markers:
CK5/6 and CK14
TTF1 and napsin A
PSA and PSAP
Hepatocyte markers
Neuroendocrine markers
Melanoma markers.
Diagnostic Utility:
CK20/CDX2 positivity supports intestinal phenotype
MUC2 expression indicates intestinal-type mucin
CEA pattern helps confirm adenocarcinoma
CK7 expression variable in gastric origin
Microsatellite instability testing important.
Molecular Subtypes:
Intestinal type in Lauren classification
Microsatellite stable or instable subtype
EBV-negative in most cases
Chromosomal instability subtype common
HER2 amplification possible.
Molecular/Genetic
Genetic Mutations:
APC mutations (40-50%)
TP53 mutations (35-45%)
KRAS mutations (20-30%)
PIK3CA mutations (15-25%)
SMAD4 mutations (10-15%)
BRAF mutations (5-10%).
Molecular Markers:
β-catenin nuclear localization
p53 overexpression
Ki-67 proliferation index (moderate)
HER2 amplification (10-15%)
MSI-H (microsatellite instability-high)
PD-L1 expression variable.
Prognostic Significance:
MSI-H status associated with better prognosis
HER2 amplification indicates targeted therapy eligibility
p53 mutation correlates with progression
KRAS mutation affects treatment response
Better overall survival than other gastric cancers.
Therapeutic Targets:
HER2 targeting (trastuzumab) in amplified cases
Immunotherapy for MSI-H tumors
Anti-VEGF therapy (bevacizumab, ramucirumab)
EGFR inhibitors in selected cases
Chemotherapy remains mainstay
Targeted therapy options expanding.
Differential Diagnosis
Similar Entities:
Mucinous adenocarcinoma from other GI sites
Metastatic mucinous carcinoma (ovarian, colorectal)
Signet ring cell carcinoma
Primary peritoneal carcinoma
Mucocele or mucinous cystadenoma.
Distinguishing Features:
Gastric mucinous: Gastric location and mucin pattern
Gastric: CK7 variable, CK20 positive pattern
Colorectal metastasis: CK7 negative, CK20 strongly positive
Ovarian metastasis: CK7 positive, gynecological markers
SRCC: Intracytoplasmic mucin predominant
SRCC: Individual cell infiltration.
Diagnostic Challenges:
Distinguishing primary vs metastatic mucinous carcinoma
Differentiating from mucinous cystadenoma
Sampling adequacy in mucinous tumors
Assessing depth of invasion
Determining site of origin in peritoneal disease.
Rare Variants:
Mucinous adenocarcinoma with signet ring features
Mucinous carcinoma with neuroendocrine differentiation
Mixed mucinous and conventional adenocarcinoma
Mucinous carcinoma with hepatoid features
Pseudomyxoma peritonei pattern.
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
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
Gastric Mucinous Adenocarcinoma
Classification
Lauren Classification: Intestinal type, WHO Grade: [grade]
Histological Features
Extracellular mucin comprises [percentage]% of tumor volume with floating malignant glands
Differentiation
[well/moderately/poorly] differentiated with glandular architecture
Extent
Invasion depth: [mucosa/submucosa/muscularis propria/serosa]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: CK20: [positive/negative], CDX2: [positive/negative], MUC2: [positive/negative]
MSI status: [MSI-H/MSS], HER2: [amplified/not amplified]
PAS stain: [positive/negative] for mucin
TNM Staging
pT[X] pN[X] pM[X] - Stage [stage]
Final Diagnosis
Gastric Mucinous Adenocarcinoma, Intestinal Type, WHO Grade [grade], Stage [stage]