Tumors of Urinary Bladder and Urothelial Tract

Tumors of Urinary Bladder and Urothelial Tract

• The WHO 2022 classification of urinary and male genital tumors (5th edition) is organized by tumor lineage.
• Urothelial tumors are a key category.
• Squamous cell neoplasms are another key category.
• Glandular neoplasms are also a key category.
• Urachal and diverticular neoplasms are another category.
• Urethral neoplasms are a category.
• Tumors of the Müllerian type are a category.

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

Clinical Features

• Clinical: Painless hematuria is a common symptom.
• Affected individuals are typically aged 50-70, with men three times more likely to be affected than women.
• Risk factors: Smoking, industrial solvents, hydrocarbons, dyes, Cystitis, Schistosomiasis, and drugs like Cyclophosphamide.

Clinical (Continued)

• Clinical: High recurrence rate is common.
• Clinical: Fatal cases frequently involve ureteric obstruction.
• Clinical: Overall 5-year survival is 57%.
• Clinical: Five-year survival for ureteric carcinoma is 10%.

Urothelial Papilloma - Morphology

• Morphology: Solitary, exophytic, with thin fibrovascular cores lined by normal urothelium (4-7 layers, normal thickness) without cytologic atypia.
• Morphology: Non-branching, non-fused papillae, sometimes with ballooning of umbrella cells.

Other High Yield Points

• Benign: Age range: 8-87 years, majority in the 5th decade, more common in males.
• Benign: Locations: Trigone, other areas; Size: 2–3 cm typically.
• Pathogenesis: HRAS, KRAS mutations are often involved.
• Gross: Polypoid/papillary is a common appearance.
• Differential Diagnosis: Polypoid/papillary cystitis (broad edematous core, inflammation) may overlap.
• IHC: Positive for CD44 (basal cells) and CK20 (umbrella cells), like normal urothelium.

Inverted Urothelial Papilloma - Morphology

• Morphology: Inverted/endophytic pattern, anastomosing and proliferating cords of urothelial cells.
• Morphology: Cells maintain polarity, palisaded basal cells border cords, surrounding central streaming urothelial cells, and normal thickness.
• Morphology: No atypia is present.

Other High Yield Points (Continued)

• Benign: Age range: any age.
• Location: Bladder neck, trigone, renal pelvis, ureter, urethra,
• Gross: Polypoid
• Pathogenesis: Mutations in HRAS and KRAS genes.
• Differential Diagnosis: Other inverted papillary tumors such as LGPUC, HGPUC, invasive urothelial carcinoma.
• IHC: Positive for CD44 (basal cells). Negative for CK20, p53.

Papillary Urothelial Neoplasm of Low Malignant Potential - Morphology

• Morphology: Papillary architecture, fibrovascular cores lined by thickened urothelium.
• Morphology: Mild cytologic atypia (monotonous appearing cells with mild nuclear enlargement).
• Morphology: Not appreciable at low magnification of the tissue.
• Morphology: No marked cytologic atypia is easily appreciated at low magnification.

Other High Yield Points (Continued)

• Age group: 6th-7th decades, more frequent in males than females.
• Pathogenesis: Some cases with TERT promoter and FGFR3 mutations may be involved; not fully known.
• Cystoscopy: Papillary lesion, small and solitary.
• Gross: Papillary lesion.
• IHC: Not useful for diagnosis.

Non-Invasive Papillary Urothelial Carcinoma, Low-Grade - Morphology

• Morphology: Papillary architecture, fibrovascular cores lined by urothelial cells of variable thickness
• Morphology: With or without mild cytologic atypia (mild nuclear enlargement, hyperchromasia, and size variation), with a mild loss of polarity
• Morphology: Not appreciable at low magnification
• Morphology: No marked cytologic atypia appreciated at low magnification
• Morphology: Mitosis mostly basal
• Morphology: Inverted variant with an inverted growth pattern.

Other High Yield Points (Continued)

• Risk factors: Smoking and chemical exposure.
• Pathogenesis: FGFR3 alterations and TERT promoter mutations may be involved.
• Cystoscopy/Gross: Exophytic papillary tumor, single or multiple, variable size. It's less translucent than LG.
• Prognosis: Frequent recurrence (50%), rare progression to invasive urothelial carcinoma.
• IHC: Not useful.

Non-Invasive Papillary Urothelial Carcinoma, High Grade-Morphology

• Morphology: Papillary architecture, fibrovascular cores lined by urothelial cells.
• Morphology: Marked cytologic atypia including nuclear enlargement, hyperchromasia, prominent nucleoli, and irregular contours.
• Morphology: Loss of polarity/disordered architecture; easily appreciable at low power.
• Morphology: Frequent mitosis, including atypical forms.
• Morphology: More complex and fused papillae compared to LGPUC.
• Morphology: High grade features in at least 5% of total tumor.
• Morphology: Inverted variants with inverted growth pattern.

Other High Yield Points (Continued)

• Mean age: 70 years, more frequent in males than females (3:1).
• Risk factors: Smoking and chemical exposure.
• Pathogenesis: TERT promoter mutations, FGFR3 alterations, and p53 mutations
• Cystoscopy: Exophytic papillary tumor, single or multiple, variable in size, less translucent than LG.
• Prognosis: Frequent recurrence (60%), progression to invasive urothelial carcinoma (25%).
• IHC: CK20 (full thickness), increased Ki67; Negative CD44

Urothelial Carcinoma In Situ - Morphology

• Morphology: Flat lesion with variable thickness; markedly atypical urothelial cells.
• Morphology: Disordered architecture/loss of polarity.
• Morphology: No papillary architecture.
• Morphology: Variants include: Pagetoid (single cells), clinging (mostly denuded).
• Morphology: Glandular variants also exist.

Other High Yield Points (Continued)

• Affects elderly: Affects older patients.
• Pathogenesis: TERT promoter and p53, DNA damage genes, PI3K and MAPK pathways are involved.
• Cystoscopy: Erythematous mucosal patches, difficulty in identification. It can be multifocal.
• Prognosis: Frequent recurrence and progression to invasive urothelial carcinoma is common.
• Differential Diagnosis: Urothelial dysplasia (cytologic atypia of a neoplastic process).
• FISH: Urovision chromosomes 3, 7, 17, 9p21 are involved.
• IHC: Not necessary in classic cases.
• IHC Positive: CK20 (full thickness), p53, increased Ki67
• IHC Negative: CD44 (or decreased)

Invasive Urothelial Carcinoma, Conventional Type - Morphology

• Morphology: Nests, sheets, cords, or single cells that invade lamina propria and beyond.
• Morphology: Mixed architectural patterns; variation in appearance.

Other High Yield Points (Continued)

• Age: Seventh decade or later commonly, 4 males for every 1 female
• Locations: Urinary bladder, upper urinary 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

Pure Squamous Cell Carcinoma of Urinary Bladder - Morphology

• Morphology: Pure squamous morphology (100%) with the presence of intercellular bridges, keratin pearls, and keratinized cells.
• Morphology: Should not contain conventional UC (urothelial cell carcinoma).

Other High Yield Points (Continued)

• Risk factors: Indwelling catheter (>10 years), bladder stones, smoking, Schistosoma haematobium infection.
• Pathogenesis: Chronic inflammation, loss of chromosomes 17q and 18p in cases associated with Schistosoma.
• Gross: Large, solid, polypoid, nodular, or ulcerated.
• Prognosis: Worse than conventional types
• IHC Positive: CK5, CK6, p63, desmoglein 3
• IHC negative: Uroplakins.

Adenocarcinoma, NOS of Urinary Bladder - Morphology

• Morphology: Pure (100%) adenocarcinoma morphology.
• Morphology: Various patterns may be seen, including enteric/colonic type, mucinous, signet ring cell, or mixed.
• Morphology: Should not contain conventional UC.

Other High Yield Points (Continued)

• Occurrence: Rare (2%), peak in the 7th decade.
• Locations: Urinary Bladder, renal pelvis, ureter.
• Pathogenesis: Unknown; chronic irritation is suspected
• Gross: Single, sessile, nodular, ulcerated
• IHC Positive: CK20, CDX2, Villin, (+/-) CK7, nuclear beta-catenin
• IHC Negative: GATA3 (can be positive, sometimes)

Urothelial Carcinoma of Ureter and Renal Pelvis - Description

• Urothelial carcinoma of the ureter and renal pelvis are variations in disease location.

Conclusion- Summary of Urothelial Tumors

• 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