Urothelial (Transitional Cell) Carcinoma In Situ (including flat hyperplasia and dysplasia)
Definition
- Flat non-invasive high grade urothelial neoplasm
Alternate/Historical Names
- The term Urothelial is preferred over Transitional as is is more specific and includes neoplasms with non-transitional differentiation arising in urothelium
- High grade and severe dysplasia as well as some moderate dysplasia are included in carcinoma in situ
- (While non-invasive papillary urothelial neoplasms are technically also in situ, they are not referred to as carcinoma in situ)
Diagnostic Criteria
- The only clearly significant and reproducible distinction is between carcinoma in situ (CIS) and lesions that fall short of malignancy
- Essentially, all lesions short of CIS, except perhaps flat hyperplasia, require clinical followup, while CIS justifies intravesical chemotherapy or cystectomy
- The following non-malignant atypical lesions have been described
- Flat urothelial hyperplasia
- Reserved only for markedly thickened urothelium
- Normal urothelium is 2-4 cells thick when distended, 4-7 if contracted
- May be seen adjacent to papillary neoplasms
- No clinical significance has been shown for isolated hyperplasia
- Reserved only for markedly thickened urothelium
- Reactive atypia is non-neoplastic
- Acute or chronic inflammation
- Retention of polarity and orderly maturation
- Uniform nuclear enlargement
- Uniform single central nucleolus
- Fine or vesicular chromatin
- Mtotic figures may be present but not atypical
- No progression to neoplasm but inflammation may coexist with neoplasm
-
Dysplasia (low grade intra-urothelial neoplasm)
- Significant atypia but falling short of CIS
- Nuclear membrane irregularities
- Dense, clumped chromatin
- Nuclei may be 2x size of lymphocytes but few reach 5x size of lymphocytes
- Loss of polarity
- Lack of significant inflammation
- Frequently seen adjacent to carcinoma
- This diagnosis should be made with great caution in the absence of a conconcurrent or prior urothelial neoplasm
- This restriction severely limits the utility of this diagnosis
- Significant atypia but falling short of CIS
- Atypia of unknown significance
- Features compatible with dysplasia (above) but in the presence of significant inflammation or lacking a history of urothelial neoplasm
- Flat urothelial hyperplasia
- Carcinoma in situ (high grade intraurothelial neoplasm)
- Cytologically malignant cells
- Features that if papillary would be diagnosed as high grade urothelial neoplasm
- Large irregular hyperchromatic nuclei
- Nuclear membrane irregularities
- Dense, clumped chromatin
- ≥25% of nuclei should be large enough to contain ≥5 lymphocyte nuclei
- Mitotic figures are frequently seen and may be atypical
- Loss of polarity and disordered maturation
- Other features may be helpful but not required:
- Full thickness atypia
- High nuclear:cytoplasmic ratio
- Loss of umbrella cell layer
- Loss of intercellular cohesion may lead to sloughing and denudation
- This should always prompt close examination
- Cytologic atypia as above is still required
- Sloughing may also be seen with inflammatory processes
- Correlation with bladder wash cytology is very important
- It is unusual for a biopsy to be positive when the concurrent bladder wash is negative
- Extra caution should be used in such cases
- Sampling error may explain the converse situation, when the biopsy is negative with a positive cytology study
- It may be useful to explain this in the pathology biopsy report
- It is unusual for a biopsy to be positive when the concurrent bladder wash is negative
- Carcinoma in situ is by definition high grade, thus grading is not necessary
- There is no such thing as low grade CIS
- Various patterns may be seen
(described in Amin & McKenney)
- Large cell pleomorphic (usual pattern)
- Large cell monomorphic
- Nucleli uniformly large and atypical
- May be deceptive due to lack of pleomorphism
- Small cell
- Same large uniformly atypical nuclei but scant cytoplasm
- Clinging/discohesive
with shedding
- Few cells may be left attached for diagnosis
- Requires same cytologic features of malignancy
- Correlation with bladder wash cytology is especially important
- Inflammation may also lead to discohesion and shedding
- Few cells may be left attached for diagnosis
- Pagetoid cancerization
- Undermining cancerization
- Glandular differentiation may rarely be seen
- These types do not need to be reported
- Their recognition may aid in diagnosis
- Cytologically malignant cells
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting/updates: 10/20/12
