Definition/General
Introduction:
Gastric adenosquamous carcinoma is a rare variant of gastric carcinoma
It contains both adenocarcinomatous and squamous cell components
Both components must be malignant for diagnosis
It constitutes <1% of all gastric cancers
Also termed adenoacanthoma in some classifications.
Origin:
Originates from gastric epithelial cells with biphenotypic differentiation
May arise from gastric stem cells with dual differentiation potential
Can develop from metaplastic transformation of gastric mucosa
Squamous metaplasia followed by malignant transformation
Results in collision tumor appearance.
Classification:
Classified as mixed carcinoma in WHO classification
Both components must constitute >25% each of tumor volume
Distinguished from adenocarcinoma with squamous metaplasia
Graded based on highest grade component
Usually high-grade malignancy.
Epidemiology:
Peak incidence in 6th-7th decades
Male predominance (M:F ratio 3:1)
More common in Japanese population
Associated with chronic gastritis
Risk factors similar to conventional gastric adenocarcinoma
Extremely rare in Indian population.
Clinical Features
Presentation:
Aggressive clinical course
Epigastric pain and discomfort
Rapid tumor growth
Weight loss and anorexia
Dysphagia if proximal location
Palpable mass in advanced cases
Poorer prognosis than conventional adenocarcinoma.
Symptoms:
Abdominal pain (90-95%)
Severe weight loss
Nausea and vomiting
Hematemesis and melena
Dysphagia and odynophagia
Early satiety
Systemic symptoms of malignancy.
Risk Factors:
H
pylori infection
Chronic atrophic gastritis
Smoking and alcohol consumption
Dietary carcinogens
Previous gastric surgery
Genetic predisposition
Environmental toxin exposure.
Screening:
Upper endoscopy with multiple biopsies
Enhanced imaging for staging
High-risk individual surveillance
Molecular profiling for targeted therapy
Genetic counseling if familial
Multidisciplinary evaluation.
Master Adenosquamous Carcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Large, ulcerated mass with irregular borders
Fungating growth pattern common
Cut surface shows heterogeneous appearance
Areas of necrosis and hemorrhage
Firm consistency due to squamous component.
Characteristics:
Gray-white cut surface with areas of yellow necrosis
Hemorrhagic areas common
Firm to hard consistency
Infiltrative margins
May show cystic degeneration.
Size Location:
Size typically 5-15 cm
Most common in gastric antrum
May involve multiple sites
Transmural invasion common at presentation
Extension to adjacent organs.
Multifocality:
Usually unifocal
High metastatic potential
Lymph node involvement common
Peritoneal seeding frequent
Liver metastases in advanced cases
Local invasion into pancreas and colon.
Microscopic Description
Histological Features:
Admixture of adenocarcinoma and squamous cell carcinoma
Each component >25% of tumor
Glandular structures adjacent to squamous areas
Keratinization in squamous component
High-grade nuclear atypia
Extensive necrosis common.
Cellular Characteristics:
Adenocarcinomatous areas show columnar cells with mucin production
Squamous areas show polygonal cells with intercellular bridges
Severe nuclear pleomorphism
High mitotic activity
Keratin pearl formation
Prominent nucleoli.
Architectural Patterns:
Glandular pattern in adenocarcinomatous areas
Solid nests of squamous cells
Transition zones between components
Infiltrative growth pattern
Desmoplastic stroma
Extensive lymphovascular invasion.
Grading Criteria:
High-grade malignancy by definition
WHO Grade 3 (poorly differentiated)
Graded by worst component
High nuclear grade
High mitotic count
Extensive necrosis and invasion.
Immunohistochemistry
Positive Markers:
CK7 (glandular component)
CK5/6 (squamous component)
p63 (squamous nuclei)
CEA (glandular component)
CK20 (variable in glandular)
p40 (squamous component).
Negative Markers:
TTF1 (both components)
CDX2 (usually negative)
PSA and PSAP
Hepatocyte markers
Neuroendocrine markers
Melanoma markers.
Diagnostic Utility:
p63/p40 positivity confirms squamous differentiation
CK5/6 expression in squamous areas
CEA pattern helps identify glandular component
Dual staining demonstrates biphasic nature
TTF1 negativity excludes lung primary.
Molecular Subtypes:
Mixed histologic subtype
Chromosomal instability pattern common
TP53 mutations frequent
EBV-negative subtype
Microsatellite stable in most cases.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (70-80%)
PIK3CA mutations (30-40%)
KRAS mutations (20-25%)
CDKN2A deletions (25-30%)
SMAD4 mutations (15-20%)
APC mutations (10-15%).
Molecular Markers:
p53 overexpression (most cases)
High Ki-67 index
EGFR overexpression
Loss of p16 expression
β-catenin dysregulation
HER2 amplification rare.
Prognostic Significance:
TP53 mutation associated with poor prognosis
High proliferation index indicates aggressive behavior
EGFR overexpression correlates with invasion
Poor overall survival compared to conventional adenocarcinoma
Early metastasis common.
Therapeutic Targets:
Limited targeted options
EGFR inhibitors under investigation
PI3K/AKT pathway targeting
Combination chemotherapy preferred
Radiation therapy for squamous component
Immunotherapy potential.
Differential Diagnosis
Similar Entities:
Adenocarcinoma with squamous metaplasia
Collision tumor
Metastatic adenosquamous carcinoma
Primary squamous cell carcinoma
Undifferentiated carcinoma.
Distinguishing Features:
True adenosquamous: Both components malignant
True adenosquamous: >25% each component
Metaplasia: Benign squamous component
Collision: Sharp interface between tumors
SCC: Pure squamous differentiation
Metastatic: History of primary elsewhere.
Diagnostic Challenges:
Distinguishing from squamous metaplasia
Quantifying component percentages
Excluding metastatic disease
Adequate sampling requirements
Site of origin determination
Assessment of malignant nature of both components.
Rare Variants:
Adenosquamous carcinoma with neuroendocrine features
Sarcomatoid variant
Basaloid adenosquamous carcinoma
Mucoepidermoid-like variant
Spindle cell adenosquamous carcinoma.
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 Adenosquamous Carcinoma
Tumor Components
Adenocarcinomatous component: [X]%, Squamous cell component: [X]%
Histological Features
Biphasic tumor with malignant glandular and squamous components
Differentiation
Adenocarcinoma: [grade], Squamous carcinoma: [grade], Overall grade: [grade]
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: p63: [positive/negative] in squamous component, CEA: [positive/negative] in glandular component
Molecular: TP53: [mutated/wild-type]
CK5/6: [positive/negative] in squamous areas
TNM Staging
pT[X] pN[X] pM[X] - Stage [stage]
Final Diagnosis
Gastric Adenosquamous Carcinoma, WHO Grade [grade], Stage [stage]