PUNLMP
- Orderly cellular arrangement with minimal architectural abnormalities and minimal nuclear atypia
- Unlikely to progress.
- May recur (20 %) as either PUNLMP or low grade urothelial cancer.
Low grade urothelial cancer
- Some cellular irregularity and nuclear differentiation and nuclear atypia
- 50 – 70 % recurrence
- 5 % progression
- Significantly different tumour behaviour between low grade and high grade – separate genetic pathways and essentially different diseases (although urothelial cancer is a field change disease, so low and high grade can co-exist and low grade patients may develop high grade at a later date).
High grade urothelial cancer
- 80 % recurrence
- 20 – 50 % progression
- Nuclear atypia, loss of polarity, multiple mitotic bodies, pleomorphic cells and loss of cohesion
Carcinoma in situ
- Flat high grade urothelial carcinoma confined to urothelium and above basement membrane.
- Significant loss of cohesion
- Loss of polarity, hyperchromatic nuclei, loss of umbrella cells, nuclear atypia.
- Behaves as high grade urothelial cancer.
- > 50 % progression and 80 % recurrence without treatment.
Prognostic factors:
- Grade is most important
- Stage
- CIS presence
- Size of tumour > 3 cm
- Multifocality
- Hydronephrosis
- Variant histology
- Prostatic urethral involvement
- Recurrence within one year
- LVI
Pathological variants
Squamous differentiation
- Treat as per urothelial carcinoma stage
- Any urothelial component should be treated as such
- May be more common in advanced disease – but stage for stage outcomes similar to TCC
Micropapillary
- 2 – 5 %
- Higher rates of progression in T1 disease
- Less responsive to BCG
- Understaging more common
Nested
- Rare 1 %
- Deceptively bland and may mimic benign lesions
- Presents at more advanced stage, higher rates of muscle invasion and metastasis
Plasmacytoid
- Characteristic spread with single file cell invasion – therefore malignant cells may be far visible macroscopic disease
- Higher positive margin rates
- Tends to present later and harbour poorer prognosis
Sarcomatoid
- Frequently presents at advanced stage with poorer prognosis stage for stage
- Worse overall survival than pure UC
- No benefit for chemotherapy
- Spindle cells
Small cell
- Rare, very aggressive
- High propensity for mets and haematogenous spread, including brain mets
- Chemotherapy is mainstay of treatment – cisplatin and etoposide
- Follow with local control – cystectomy or radiation.
- Sheets of infiltrative small blue cells
Squamous cell carcinoma (SCC)
- Related to chronic inflammation or recurrent infection – classically schistosomiasis
- < 5 % in non endemic areas
- Lower incidence of nodal and metastatic disease, but often seen initially at more advanced stages
- No consensus on neoadjuvant treatment – radical cystectomy is preferred treatment.
Adenocarcinoma
- May be primary, but may be metastatic or locally invasive from colon, prostate, cervix or endometrium
- Risk factors also – bladder exstrophy, bladder augmentation, schistosomiasis, chronic inflammation or infection, urachal remnants and possibly intestinal metaplasia / cystitis glandularis.
- Rule out colonic malignancy or other primary cancers – scopes, CEA
- Radical cystectomy is main treatment
Urachal adenocarcinoma
- Usually muscle invasive due to location and nature
- En bloc resection of bladder dome, urachus, +/- umbilicus
For any variant histology consider:
- Expert pathology review / MDT discussion
- Consider early cystectomy if not T2 (survival rates better)
- Adenocarcinoma – consider urachus or colon cancer
- Evidence for neoadjuvant chemo for urothelial variants not well established and consider upfront cystectomy
- If not for cystectomy, need early re-resection
