Tumors of Urinary Bladder & Urothelial Tract PDF

Tumors of Urinary Bladder and urothelial tract Prof. Nazik Elmalaika O.S. Husain, MBBS, MD, MSc, MHPE, PhD. Pathology Department, FMHS, Omdurman Islamic University, Sudan. The WHO 2022 classification of urinary and male genital tumors (5th edition)...

Tumors of Urinary Bladder and urothelial tract Prof. Nazik Elmalaika O.S. Husain, MBBS, MD, MSc, MHPE, PhD. Pathology Department, FMHS, Omdurman Islamic University, Sudan. The WHO 2022 classification of urinary and male genital tumors (5th edition) Is organized based on tumor lineage: 1. Urothelial tumors, 2. Squamous cell neoplasm, and 3. Glandular neoplasms. 4. Urachal and diverticular neoplasms 5. Urethral neoplasms 6. Tumors of the Müllerian type.  Objectives UROTHELIAL TUMORS Urothelial Papilloma Inverted Urothelial Papilloma Papillary Urothelial Neoplasm of Low Malignant Potential. Non-invasive Papillary Urothelial Carcinoma, Low-grade. Non-invasive Papillary Urothelial Carcinoma, High-grade. Urothelial Carcinoma In-situ. Invasive Urothelial Carcinoma, Conventional Type. PURE SQUAMOUS CELL CARCINOMA OF URINARY BLADDER. ADENOCARCINOMA, NOS OF URINARY BLADDER. Tumors of Urinary Bladder and urothelial tract Clinical: – Painless hematuria – 50-70 year, men 3x>women – Risk factors Smoking Industrial solvents, hydrocarbons, dyes Cystitis Schistosomiasis Drugs: Cyclophosphamide. Tumors of Urinary Bladder and urothelial tract Clinical: – High recurrence rate – Fatal by ureteric obstruction – Overall survival 5y: 57% – Ureteric carcinoma 5y survival: 10%.  UROTHELIAL PAPILLOMA MORPHOLOGY Solitary, exophytic, thin fibrovascular cores lined by normal urothelium (4-7 layers, normal thickness) without cytologic atypia. Non-branching, non-fused papillae; +/- ballooning of umbrella cells.  OTHER HIGH YIELD POINTS Benign, age range: 8-87 years, majority 5th decade, M>F Locations: Trigone, other; Size: 2-3 cm Pathogenesis: HRAS, KRAS mutations Gross: Polypoid/papillary DD: Polypoid/papillary cystitis (broad edematous core, inflammation) IHC: Positive: CD44 (basal cells), Ck20 (umbrella cells) like normal urothelium. UROTHELIAL PAPILLOMA  INVERTED UROTHELIAL PAPILLOMA MORPHOLOGY Inverted/endophytic pattern, anastomosing and proliferating cords of urothelial cells with maintained polarity, palisaded basal cells at the periphery of cords surrounding central streaming urothelial cells, and normal thickness. No atypia.  OTHER HIGH YIELD POINTS Benign, age group: any age Locations: Bladder neck, trigone, followed by renal pelvis, ureter, urethra; Gross: Polypoid Pathogenesis: HRAS, KRAS mutations Differential diagnosis: Other inverted papillary tumors like LGPUC, HGPUC, invasive urothelial ca. IHC: Positive: CD44 (basal cells); Negative: CK20, p53.  INVERTED UROTHELIAL PAPILLOMA Inverted/endophytic pattern, Palisaded basal cells at the periphery anastomosing and of cords. proliferating cords of urothelial cells.  PAPILLARY UROTHELIAL NEOPLASM OF LOW MALIGNANT POTENTIAL MORPHOLOGY Papillary architecture, fibrovascular cores lined by thickened urothelium with mild cytologic atypia (monotonous appearing cells with mild nuclear enlargement); not appreciable at low magnification. No marked cytologic atypia (easily appreciated at low  OTHER HIGH YIELD POINTS Age group: 6th to 7th decade, M>F, Without a history of urothelial carcinoma Pathogenesis: Not known, some cases with TERT promoter and FGFR3 mutations. Cystoscopy: Papillary lesion, small, single. Gross: Papillary lesion; IHC: Not useful. PAPILLARY UROTHELIAL NEOPLASM OF LOW MALIGNANT POTENTIAL: Fibrovascular cores lined by thickened urothelium with mild cytologic atypia.  NON-INVASIVE PAPILLARY UROTHELIAL CARCINOMA, LOW-GRADE MORPHOLOGY Papillary architecture, fibrovascular cores lined by urothelial cells of variably increased thickness with or without mild cytologic atypia (mild nuclear enlargement, hyperchromasia, and size variation), mild loss of polarity, not appreciable at low magnification. No marked cytologic atypia (easily appreciated at low magnification) Mitosis mostly basal. Inverted variant with an inverted growth pattern.  OTHER HIGH YIELD POINTS Age group: >60 years, M>F; Risk factors: Smoking, chemical exposure. Pathogenesis: FGFR3 alterations, TERT promoter mutations. Cystoscopy/gross: Exophytic papillary tumor, single or multiple, variable size. Prognosis: Frequent recurrence (50%), rare progression to invasive urothelial carcinoma. IHC: Not useful. NON-INVASIVE PAPILLARY UROTHELIAL CARCINOMA, LOW- GRADE: Papillary architecture, fibrovascular cores lined by urothelial cells of variably increased thickness with or without mild cytologic atypia.  NON-INVASIVE PAPILLARY UROTHELIAL CARCINOMA, HIGH-GRADE MORPHOLOGY Papillary architecture, fibrovascular cores lined by urothelial cells of variably increased thickness with marked cytologic atypia (marked nuclear enlargement, hyperchromasia, prominent nucleoli, irregular contours, and size variation), loss of polarity/disordered architecture, easily appreciable at low magnification Frequent mitosis, including atypical forms. More complex and fused papillae compared to LGPUC. High grade features present in at least 5% of total tumor. Inverted variant with an inverted growth pattern.  OTHER HIGH YIELD POINTS Mean age: 70 years, 3M:1F Risk factors: Smoking, chemical exposure Pathogenesis: TERT promoter mutations, FGFR3 alterations, p53 mutations, p16 loss (chromosome 9p). Cystoscopy: Exophytic papillary tumor, single or multiple, variable size, less translucent than LG. Prognosis: Frequent recurrence (60%), progression to invasive urothelial carcinoma (25%). IHC: Positive: CK20 (full thickness), increased Ki67; Negative: CD44. Non-invasive papillary urothelial carcinoma, high-grade Non-invasive papillary urothelial carcinoma, high-grade  UROTHELIAL CARCINOMA IN-SITU MORPHOLOGY Flat lesion of variable thickness, markedly atypical urothelial cells, disordered architecture/loss of polarity. No papillary architecture. Variants: Pagetoid (single cells growing in a pagetoid manner), clinging (mostly denuded with few attached malignant cells), glandular. UROTHELIAL CARCINOMA IN-SITU: Flat lesion of variable thickness, markedly atypical urothelial cells. UROTHELIAL CARCINOMA IN-SITU: Flat lesion of variable thickness, markedly atypical urothelial cells.  OTHER HIGH YIELD POINTS Affects elderly patients Pathogenesis: TERT promoter alterations, p53, DNA damage repair genes, PI3K and MAPK pathways Cystoscopy: Erythematous mucosal patches, difficult to identify, can be multifocal Prognosis: Frequent recurrence and progression to invasive urothelial carcinoma.  OTHER HIGH YIELD POINTS Differential diagnosis: Urothelial dysplasia (cytologic atypia of a neoplastic process but falls short of a diagnosis of CIS) FISH: UroVision chromosomes 3,7,17, 9p21 IHC: Not necessary in classic cases Positive: CK20 (full thickness), p53, increased Ki67 Negative: CD44 (or decreased). UROTHELIAL CARCINOMA IN-SITU: Positive: CK20 (full thickness), p53, increased Ki67. INVASIVE UROTHELIAL CARCINOMA, CONVENTIONAL TYPE MORPHOLOGY Nests, sheets, cords, or single cells invading lamina propria and beyond. Mixed architectural patterns.  OTHER HIGH YIELD POINTS Seventh decade or later, 4M:1F Locations: urinary bladder, 10% upper tract (renal pelvis, ureter). Risk factors: Smoking, radiation, chemicals-benzidine dyes, opiates, high socioeconomic status. Pathogenesis: TERT promoter mutations, TP53 mutations, others. Gross: Sessile, ulcerated, polypoid, or papillary. IHC: Positive: GATA3, HMWCK, CK7, CK20, P63, uroplakin, Negative: PAX8.  INVASIVE UROTHELIAL CARCINOMA, CONVENTIONAL TYPE: Nests, sheets, cords, or single cells invading lamina propria and beyond.  PURE SQUAMOUS CELL CARCINOMA OF URINARY BLADDER MORPHOLOGY Pure (100%) squamous morphology with the presence of intercellular bridges, keratin pearls, and keratinized cells. Should not contain conventional UC.  OTHER HIGH YIELD POINTS Risk factors: Indwelling catheter >10 years, bladder stones, smoking, Schistosoma haematobium infection (Egypt, Sudan). Pathogenesis: Chronic inflammation, loss of chromosome 17q and18p in Schistosoma associated cases. Gross: Large tumors, solid, polypoid, nodular, or ulcerated. Prognosis: Worse than conventional. IHC: Positive: CK5, CK6, p63, desmoglein3; Negative: Uroplakins. PURE SQUAMOUS CELL CARCINOMA OF URINARY BLADDER PURE SQUAMOUS CELL CARCINOMA OF URINARY BLADDER PURE SQUAMOUS CELL CARCINOMA OF URINARY BLADDER  ADENOCARCINOMA, NOS OF URINARY BLADDER MORPHOLOGY Pure (100%) adenocarcinoma morphology. Various patterns: enteric/colonic type, mucinous, signet ring cell, or mixed. Should not contain conventional UC.  OTHER HIGH YIELD POINTS Rare, 2%, Peak age: 7th decade. Locations: urinary bladder, renal pelvis urethra. Pathogenesis: Unknown, chronic irritation. Gross: Single, sessile, nodular, ulcerated. IHC: Positive: CK20, CDX2, Villin, +/- CK7, Nuclear beta- catenin. Negative: GATA3 (can be + in some cases). ADENOCARCINOMA, NOS OF URINARY BLADDER Enteric/colonic type Signet ring cell type Urothelial carcinoma of the ureter Urothelial carcinoma of the renal pelvis.  Conclusion UROTHELIAL TUMORS Urothelial Papilloma Inverted Urothelial Papilloma Papillary Urothelial Neoplasm of Low Malignant Potential. Non-invasive Papillary Urothelial Carcinoma, Low-grade. Non-invasive Papillary Urothelial Carcinoma, High-grade. Urothelial Carcinoma In-situ. Invasive Urothelial Carcinoma, Conventional Type. PURE SQUAMOUS CELL CARCINOMA OF URINARY BLADDER. ADENOCARCINOMA, NOS OF URINARY BLADDER. THANKS