Definition/General
Introduction:
Adenocarcinoma in urine cytology may represent primary bladder adenocarcinoma or metastatic adenocarcinoma from other organs
Primary bladder adenocarcinoma is rare, comprising 1-2% of all bladder cancers
Cytological recognition requires identification of glandular architecture and mucin production
Distinction between primary and metastatic disease is crucial for appropriate patient management.
Origin:
Primary bladder adenocarcinoma arises from metaplastic glandular epithelium or remnants of embryonic structures
Urachal adenocarcinoma develops from urachal remnants at the dome/anterior wall
Primary vesical adenocarcinoma arises from the bladder mucosa
Metastatic adenocarcinoma commonly originates from prostate, gynecological organs, gastrointestinal tract, or breast.
Classification:
Primary bladder adenocarcinomas include urachal adenocarcinoma, primary vesical adenocarcinoma, and adenocarcinoma arising in exstrophy
Urachal types include mucinous, enteric, signet-ring cell, and mixed subtypes
Primary vesical adenocarcinomas are classified as adenocarcinoma NOS or specific subtypes
Metastatic adenocarcinomas are classified by primary site of origin.
Epidemiology:
Primary bladder adenocarcinoma shows slight male predominance (1.5:1 ratio)
Peak incidence in 6th-7th decades for primary vesical type
Urachal adenocarcinoma typically affects younger patients (4th-5th decades)
Geographic variation exists with higher incidence in areas with schistosomiasis
Metastatic adenocarcinoma to bladder is more common than primary forms.
Clinical Features
Presentation:
Gross hematuria is the most common presenting symptom (70-80% of cases)
Irritative voiding symptoms including dysuria, frequency, and urgency
Suprapubic pain and discomfort, particularly with urachal tumors
Mucosuria may be reported in mucinous adenocarcinomas
Constitutional symptoms in advanced cases or when part of systemic metastatic disease.
Symptoms:
Intermittent gross hematuria with mucoid appearance in some cases
Chronic suprapubic pain especially with urachal adenocarcinomas
Voiding dysfunction and incomplete bladder emptying
Recurrent urinary tract infections due to tumor obstruction
Weight loss and fatigue in advanced cases or systemic disease.
Risk Factors:
Urachal remnants predispose to urachal adenocarcinoma development
Exstrophy-epispadias complex increases adenocarcinoma risk
Chronic cystitis and inflammation may contribute to metaplastic changes
History of primary adenocarcinoma elsewhere increases metastatic risk
Endometriosis of bladder may rarely undergo malignant transformation.
Screening:
No routine screening recommended for primary bladder adenocarcinoma
Surveillance of high-risk patients with urachal remnants or exstrophy
Follow-up of patients with history of adenocarcinoma elsewhere
Investigation of persistent hematuria in appropriate clinical context
Monitoring of endometriosis patients for malignant transformation.
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Gross Description
Appearance:
Urine specimens may appear cloudy or mucoid due to mucin secretion
Gross hematuria ranging from pink-tinged to frank bleeding
Viscous consistency in mucinous adenocarcinomas
May contain visible tissue fragments or mucoid material
Clear appearance may be seen in non-mucinous types.
Characteristics:
High cellularity with increased cellular debris and mucin
Three-dimensional tissue fragments may be visible macroscopically
Mixed inflammatory infiltrate in the background
Specimens may show contamination with prostatic or gynecological cells
Bacterial overgrowth may complicate interpretation.
Microscopic Description
Immunohistochemistry
Positive Markers:
CK7 positive in most primary vesical adenocarcinomas
CK20 may be positive, particularly in enteric-type adenocarcinomas
CEA (carcinoembryonic antigen) frequently positive
CA 125 may be positive in primary adenocarcinomas
CDX-2 positive in enteric-type adenocarcinomas.
Negative Markers:
GATA3 typically negative, distinguishing from urothelial carcinoma
p63 negative in pure adenocarcinomas
TTF-1 negative except in lung primaries
PSA negative except in prostatic adenocarcinoma
ER/PR negative except in gynecological primaries.
Diagnostic Utility:
Immunocytochemistry essential for distinguishing primary from metastatic adenocarcinoma
Tissue-specific markers help identify primary site in metastatic cases
PSA and PSAP identify prostatic origin
ER, PR, and mammoglobin suggest breast origin
CDX-2 and CK20 pattern suggests gastrointestinal origin.
Molecular/Genetic
Genetic Mutations:
KRAS mutations common in enteric-type urachal adenocarcinomas (40-60%)
TP53 mutations present in 30-50% of primary bladder adenocarcinomas
GNAS mutations found in some mucinous adenocarcinomas
PIK3CA mutations present in 10-20% of cases
SMAD4 deletions may be present in pancreaticobiliary-type tumors.
Molecular Markers:
p53 overexpression correlates with TP53 mutations and poor prognosis
Ki-67 proliferation index elevated in high-grade lesions
β-catenin mutations may be present in some cases
MLH1/MSH2 loss suggests microsatellite instability
HER2 amplification rare but therapeutically relevant.
Prognostic Significance:
TP53 mutations associated with aggressive behavior and poor prognosis
KRAS mutations may predict resistance to EGFR-targeted therapy
Microsatellite instability predicts response to immunotherapy
Stage at diagnosis remains most important prognostic factor
Primary vs metastatic status significantly impacts treatment and prognosis.
Therapeutic Targets:
HER2-targeted therapy for amplified cases
EGFR inhibitors for KRAS wild-type tumors
Immunotherapy for microsatellite instable tumors
Targeted therapy based on primary site in metastatic cases
Anti-angiogenic therapy may be beneficial in advanced cases.
Differential Diagnosis
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
Urine cytology specimen, [collection method], adequate cellularity
Specimen Adequacy
Adequate: Sufficient cellular material with preserved morphology
Background
[Clean/inflammatory/mucinous] background with [characteristics]
Microscopic Findings
Malignant cells with glandular architecture and [specific features]. Nuclear pleomorphism and [cytoplasmic characteristics] identified.
Architectural Features
Glandular formations with [acinar/tubular/papillary] pattern. [Mucin production/signet-ring morphology] noted.
Cytological Diagnosis
Malignant cells consistent with adenocarcinoma
Classification
[Primary bladder/metastatic] adenocarcinoma, [subtype if determinable]
Immunocytochemistry
Panel performed for primary site determination: [specific markers and results]
Recommendations
Cystoscopy and tissue biopsy for confirmation. Clinical correlation and imaging to exclude metastatic disease.