Urothelial carcinoma

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Urothelial carcinoma, also urothelial cell carcinoma, is a malignancy that arises the urothelium. Urothelial carcinoma is abbreviated UC and urothelial cell carcinoma is abbreviated UCC.

The article deals with flat invasive urothelial carcinoma. The direct precursor is dealth with in urothelial carcinoma in situ.

Papillary urothelial carcinomas are dealt with in low-grade papillary urothelial carcinoma and high-grade papillary urothelial carcinoma.

See urine cytology for the cytopathology.

General

  • These lesions lack papillae and are typical flat.
  • Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and renal cell carcinoma.

Microscopic

Features:

  • Nuclear pleomorphism - key feature.
    • Compare nuclei to one another.
  • Increased N/C ratio.
  • Lack of maturation to surface (important).
  • Cells become dyscohesive.
    • Mostly useless in my experience.

Invasion vs. in situ: Useful features - present in invasion:[1]

  • Thin-walled vessels.
  • Stromal reaction (hypercellularity).
  • Retraction artefact around the tumour cell nests.

Note:

  • The presence/absence of muscle should be commented on in biopsy specimens.
  • Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does not imply invasion deep to the muscularis propria.[2]

DDx:

Staging

  • T1 - lamina propria.
    • Several subdivisions of T1 exist:
      • T1a - superficial or in muscularis mucosae.
      • T1b - beyond muscularis mucosae - into submucosa.
  • T2 - muscularis propria.

Subtypes of urothelial carcinoma

There are numerous subtypes:[3]

Benign patterns - mnemonic Much GIN:

  • Microcystic.
  • Small tubular/glandular.
  • Inverted.
  • Nested.

Plasmacytoid urothelial cell carcinoma

Features:

  • Abundant gray cytoplasm, eccentric nucleus.

Images:

Nested urothelial cell carcinoma

  • AKA nested variant urothelial cell carcinoma.

Features:[4]

  • High density of well-circumscribed nests.
  • Mild-to-moderate nuclear atypia.
  • +/-Foci of unequivocal conventional urothelial carcinoma.
    • Focally solid or gland fusion.
    • Moderate-to-severe nuclear atypia +/- abundant mitoses.
  • +/-Extension into the muscularis propria.

DDx:

Images

  • Nested variant of urothelial carcinoma - intermed. mag. (WC/Nephron)

  • Nested variant of urothelial carcinoma - high mag. (WC/Nephron)

  • Nested variant of urothelial carcinoma - very high mag. (WC/Nephron)

www:

IHC

Features:

  • CK7 +ve CK20 +ve.
    • CK20 may be negative in over 50% of cases with metastases.[6]

UCC vs. prostate:

  • UCC: p63+, PSA-, PSAP-, CK7+, CK20+.
  • Prostate: p63-, PSA+, PSAP+, CK7-, CK20-.

UCC vs. RCC:

Staging - muscularis propria invasion versus muscularis mucosae invasion smoothelin stain:[8]

  • Muscularis propria - usu. strong. †
  • Muscularis mucosae - negative/weak. †

Note:

  • † Overlap between the patterns is described,[9] this limits the utility of the stain.

Molecular

Not used for diagnosis.

Changes:

  • 9p deletion -- site of CDKN2A[10] (AKA p16).
  • 17p deletion -- site of PT53 (AKA p53).

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High grade UC

URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT): 
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION AT LEAST INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.

Nested variant

 URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION OF BLADDER TUMOUR (TURBT):
- INVASIVE LOW-GRADE UROTHELIAL CARCINOMA, NESTED VARIANT.
- TUMOUR PRESENT AT EDGE OF TISSUE.
- NO MUSCULARIS PROPRIA IDENTIFIED.

See also

References

  1. ↑ Sternberg, SE. Histology for Pathologists. P.2047.
  2. ↑ Bochner, BH.; Nichols, PW.; Skinner, DG. (Mar 1995). "Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder.". Urology 45 (3): 528-31. doi:10.1016/S0090-4295(99)80030-2. PMID 7879346.
  3. ↑ URL: http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html. Accessed on: 19 August 2011.
  4. ↑ Talbert, ML.; Young, RH. (May 1989). "Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases.". Am J Surg Pathol 13 (5): 374-81. PMID 2712189.
  5. ↑ Terada, T. (Oct 2011). "Nested variant of urothelial carcinoma of the urinary bladder.". Rare Tumors 3 (4): e42. doi:10.4081/rt.2011.e42. PMC 3282447. PMID 22355497. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/.
  6. ↑ Jiang, J.; Ulbright, TM.; Younger, C.; Sanchez, K.; Bostwick, DG.; Koch, MO.; Eble, JN.; Cheng, L. (Jul 2001). "Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis.". Arch Pathol Lab Med 125 (7): 921-3. doi:10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2. PMID 11419977.
  7. ↑ Langner, C.; Ratschek, M.; Tsybrovskyy, O.; Schips, L.; Zigeuner, R. (Aug 2003). "P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors.". J Histochem Cytochem 51 (8): 1097-9. PMID 12871991.
  8. ↑ Paner, GP.; Shen, SS.; Lapetino, S.; Venkataraman, G.; Barkan, GA.; Quek, ML.; Ro, JY.; Amin, MB. (Jan 2009). "Diagnostic utility of antibody to smoothelin in the distinction of muscularis propria from muscularis mucosae of the urinary bladder: a potential ancillary tool in the pathologic staging of invasive urothelial carcinoma.". Am J Surg Pathol 33 (1): 91-8. doi:10.1097/PAS.0b013e3181804727. PMID 18936687.
  9. ↑ Miyamoto, H.; Sharma, RB.; Illei, PB.; Epstein, JI. (Mar 2010). "Pitfalls in the use of smoothelin to identify muscularis propria invasion by urothelial carcinoma.". Am J Surg Pathol 34 (3): 418-22. doi:10.1097/PAS.0b013e3181ce5066. PMID 20154589.
  10. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 600160
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