urothelial carcinoma


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  • Clinical

    • risk factors: smoking, aniline dyes, arsenic

  • Types

    • invasive: lamina propria invasion
    • non invasive: no invasion, confined to urothelium
      • male > female (3:1)
      • mean age 69
      • site: posterior or lateral walls close to ureter orifice (70%)
    • papillary: usually T1 tumors
    • non papillary: usually T2+ tumors, high grade
    • low grade (occasional mitosis)
    • high grade features
      • frequent mitosis, esp high up in epithelium
      • fusion of papillary stalks
      • architecture distortion
      • cytologic atypia, pleomorphism
      • lack polarity, maturation

  • Histology

    • architecture: papillae can be fused, branched, or lost all together
    • polarity loss: focal to complete
    • mitosis not confined to basal layer
    • nuclear enlargement with variation in size and shape
    • chromatin is more clumpy

  • Invasion

    • irregular nests
    • basement membrane disruption
    • tentacle projections
    • single cells
    • +/- stromal response: desmoplasia, inflammation
    • pitfalls: Brunn nests, muscularis mucosae, lamina propria fat, microcystic variant (invasive), nested variant (invasive)

  • Variants

    • with squamous differentiation (21%, most common)
      • give percentage of squamous component
      • can have basaloid or clear cell features
      • stains: CK14+
    • UC with glandular differentiation
      • 6%
      • true glands: don't count cytoplasmic mucin without glandular structure or necrosis pseudoglands
      • structures: tubules, enteric glands with mucin, colloid mucinous (nests of cells floating in mucin)
      • give percentage of glandular component
      • stains: MUC5
    • with trophoblastic differentiation: syncytiotrophoblasts
    • nested (rare, aggressive, but benign looking)
      • architecture looks like benign von Brunn nests
      • but contains foci of anaplastic cells
    • microcystic
    • micropapillary
      • muscularis invasion (needs biopsy with muscularis)
      • stains: EMA, CK7, CK20
    • lymphoepithelioma-like
      • epithelial: undifferentiated, pleomorphic, CK+
      • lymphoid stroma
    • lymphoma-like and plasmacytoid: looks hematopoietic, but CK+ and lymphoid negative
    • sarcomatoid +/- heterologous elements
    • giant cell
    • clear cell
    • lipid cell: cells distended with fat, mimicks signet ring cells
    • undifferentiated

  • Stains

    • positive: CK7 (100%), CK20(67%), p63 (81-92%), GATA3 (67-90%)
    • uroplakin most specific, but not sensitive
    • high grade can lose CK7 and 20
    • if uncertain muscularis propria invasion, order SMA
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