Urothelial Transitional Cell Carcinoma

Histological grade is one of the most important prognostic factors in bladder Ca.

The 1973 WHO classification:

Papilloma

Grade I  – Minimal architectural abnormality and cytological atypia. Greater than 7 urothelial cells thick, predilection for ureteric orifices. Increased risk of local recurrence, progression & death from bladder cancer.

Grade II – Moderate architectural abnormality and cytological atypia. Significantly worse risk than grade I with recurrence risk of 45-67%, invasion in 20% & cancer specific death in 13-20% post surgical treatment (in pTa).

Grade III  – Florid architectural abnormality and cytological atypia. Further increased risk of recurrence of 65-85%, invasion in 20-50% & cancer specific death in upto 35% post surgical treatment (in pTa).

Architectural Abnormality:

  • Increased cellularity
  • Loss of polarity
  • Loss of maturation
  • Nuclear crowding
  • Discohesive

Cytological Atypia

  • Enlarged nuclei
  • Irregularly shaped nuclei
  • Pleomorphism
  • Coarse chromatin
  • Atypical and prominent mitoses
  • Prominent nucleoli

1998 ISUP & 2004 WHO Classification

Designated Papilloma

Papillary urothelial neoplasm of low malignant potential – Corresponds to previous Grade I and therefore there is an increased risk of recurrence, progression and cancer related death.

Low grade urothelial carcinoma – Corresponds to Grade II.

High grade urothelial carcinoma – More atypical Grade II and all previous Grade III.

Tumour Heterogeneity

Papillary urothelial tumours can often show more than one grade of tumour. When describing the grade it may be worth describing the different grades and for this the 1973 classification is helpful. The highest grade should be noted. It appears prognostic accuracy is improved when tumour heterogeneity is taken into account.

Staging

Tx tumour cannot be assessed
T0 no evidence of tumour
Ta non-invasive papillary carcinoma
Tis carcinoma in situ
T1 invades lamina propria
T2 invades muscularis propria (detrusor)
T2a Tumour invades superficial muscle
T2b Tumour invades deep muscle
T3 invades perivesical tissue
T3a microscopic
T3b macroscopic
T4 invades adjacent organs – prostate, uterus, vagina, pelvic wall & abdominal wall
T4a prostate, uterus, vagina
T4b pelvic wall and abdominal wall

Invasion into lamina propria (pT1)

Identification of invasion into the lamina propria can be challenging! Features that might help include:

  • High grade tumours are more likely to show invasion.
  • Assess the stromal- epithelial interface which should be smooth and have a regular basement membrane in the non-invasive.
  • Invasive tumours may show a ragged, irregular edge.
  • Look for individual tumour cells (AE1/3 may be helpful)
  • Paradoxical differentiation – where invasive tumour cells may appear more eosinophilic compared to the overlying non-invasive area.
  • Stromal response showing inflammatory, myxoid or fibrous change.

Pitfalls in the diagnosis of pT1:

  • Tangential sectioning & poor orientation
  • Obscuring inflammation
  • Thermal injury
  • Urothelial carcinoma in situ involving von Brunn’s nests
  • Muscle invasion indeterminate for type of muscle (muscularis propria vs muscularis mucosae)
  • Variants of urothelial carcinoma with deceptively bland cytology
  • Pseudoinvasive nests of benign proliferative lesions

Management:

G1/G2 follow up

G3 BCG treatment

pT2 cystectomy, surgeons want to know about presence of deep muscle in the biopsy

Reference:

Boswick & Cheng. Urologic Surgical Pathology. 2nd ed.

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