BLADDER HISTOPATHOLOGYDr Dinah Parums, Principal Histopathologist, April 2007
PATHOLOGICAL SIEVE• Infection• Neoplasia
– Benign– Malignant
• Primary• Secondary
• Vascular• Immunological• Trauma• Endocrine• Degenerative• Metabolic• Drugs/Toxins
Anatomy of the Bladder
Normal Bladder Urothelium – Transitional Epithelium
L – lumenEp – EpitheliumLP – Lamina Proprium
Normal Bladder Urothelium – Transitional Epithelium
Dysplastic Urothelium – Transitional Carcinoma In-Situ
Papillary Transitional Cell Carcinoma
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Bladder Cancer
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WHO 2003 Histological Classification of Tumors of the Urinary Bladder
Urothelial tumoursInfiltrating urothelial carcinoma
with squamous differentiation with glandular differentiation with squamous and glandular differentiation Nested variant Microcystic variant Micropapillary variant Lymphoepithelioma-like carcinoma Lymphoma-like variant Plasmacytoid variant Sarcomatoid (w./w.o heterologous elements) Giant cell variant Undifferentiated carcinoma Other variants
WHO 2003 Histological Classification of Tumors of the Urinary Bladder
(contd)
Non-invasive urothelial neoplasiasHyperplasia (flat and papillary)
Dysplasia (include normal urothelium and atypia)Urothelial papilloma Urothelial papilloma, inverted type Non-invasive papillary urothelial neoplasm of LMP Non-invasive papillary urothelial carcinoma (low grade) Non-invasive papillary urothelial carcinoma (high grade)
Squamous neoplasmsSquamous cell carcinoma
Verrucous squamous cell carcinoma Squamous cell papilloma
Glandular neoplasmsAdenocarcinoma
Urachal carcinoma Clear cell adenocarcinoma In situ adenocarcinoma Villous adenoma
WHO 2003 Histological Classification of Tumors of the Urinary Bladder
(contd)
Neuroendocrine tumoursSmall cell carcinoma
Paraganglioma Carcinoid
Mesenchymal and miscellaneous tumoursRhabdomyosarcoma
Leiomyosarcoma Angiosarcoma Osteosarcoma Malignant fibrous histiocytoma Leiomyoma Granular cell tumour Neurofibroma Haemangioma Malignant melanoma Lymphoma
Metastatic tumours and secondary extension
Bladder Cancer - Staging
Bladder Cancer - Staging2002 AJCC/UICC TNM Staging of Bladder Carcinoma
Primary Tumor (T)• TX - Primary tumor cannot be assessed• T0 - No evidence of primary tumor• Ta - Non-invasive papillary carcinoma• Tis - Carcinoma in situ : "flat tumor"• T1 - Tumor invades subepithelial connective tissue• T2 - Tumor invades muscle• pT2a - Tumor invades superficial muscle (inner half)• pT2b - Tumor invades deep muscle (outer half)• T3 - Tumor invades perivesical tissue• pT3a - microscopically• pT3b - macroscopically (extravesical mass)• T4 - Tumor invades any of the following : prostate, uterus, vagina, pelvic wall,
abdominal wall• T4a - Tumor invades prostate, uterus, vagina• T4b - Tumor invades pelvic wall, abdominal wall
Bladder Cancer – Staging (contd)2002 AJCC/UICC TNM Staging of Bladder Carcinoma
Regional Lymph Nodes (N)Regional lymph nodes are those within the true pelvis; all others are distant lymph nodes
• NX - Regional lymph nodes cannot be assessed
• N0 - No regional lymph node metastasis
• N1 - Metastasis in a single lymph node, 2 cm or less in greatest dimension
• N2 - Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension
• N3 - Metastasis in a lymph node, greater than 5 cm in greatest dimension
• Distant Metastasis (M)
• MX - Distant metastasis cannot be assessed
• M0 - No distant metastasis
• M1 - Distant metastasis
Bladder Cancer - Diagnosis
Bladder Cancer - Cytology
Immunohistochemistry in Bladder Cancer
Marker Positivity inUrothelial Carcinoma
High molecular weight cytokeratin(antibody 34bE12) 65%
p63 85%CK7 83-100%CK20 15-74%Thrombomodulin 69-91%Uroplakin III 57%
Of these markers, only Uroplakin III is specific for urothelial differentiation.