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Saturday 20 April 2013

urothelial cells; transitional epithelium



- Normal urothelium :

The normal urothelial lining varies in thickness from two layers to seven layers of cells, depending upon the degree of distension of the bladder. A surface umbrella cell layer can be seen. The urothelial lining in this image is 3 to 5 layers thick. Umbrella cell layer is prominent. The underlying lamina propria contains a rich capillary network.

The basal cells are separated from the underlying lamina propria by a thin basement membrane.

The lamina propria is a highly vascular zone consisting of capillaries, lymphatic channels, sensory nerves, and elastic fibers. The lamina propria also contains thin delicate bundles of smooth muscle known as muscularis mucosae which are usually associated with prominent medium-sized blood vessels.

Brunn nests represent a commonly encountered reactive change and consist of solid nests of urothelial cells within the lamina propria. Some nests may retain connection with the overlying urothelium, where as others appear free in the lamina propria. The most important differential diagnosis is with nested variant of urothelial carcinoma. Brunn nests are usually large, superficially located, regular in shape and spacing, and lack cytologic atypia.


- urothelium



Cytokeratins expressed by normal urothelium

- basal cells: CK5 , CK7 , CK8 , CK13 , CK17 , CK18 , CK19
- intermediate cells: CK7 , CK8 , CK13 , CK18 , 1CK9 , ( CK20 in a few cells)
- superficial "umbrella" cells: CK7 , CK8 , CK18 , CK19 , CK20

Occasional cells express CK4 , but the location is not agreed.
CK7 is homogenous in renal pelvis and ureters, heterogeneous in bladder.

By CKs

- CK8 - Cytokeratin 8: some antibodies (e.g. M20) detect CK8 uniformly throughout the normal urothelium and uniformly in all grades of transitional cell carcinoma. Others (e.g. LE41) detect CK8 superficially in normal urothelium and low grade non-invasive transitional cell carcinoma with increased reactivity in invasive transitional cell carcinoma, especially in cells bordering the stroma.

- CK13 - Cytokeratin 13 is retained in most G1 and G2 tumours, reduced to focal basal and suprabasal expression in superficial G3 tumours and lost entirely from muscle-invasive G3 tumours.

- CK14 - Cytokeratin 14 is not expressed in normal urothelium, but is expressed in transitional cell carcinomas with squamous differentiation and in some transitional cell carcinomas which lack overt squamous differentiation.

- CK17 - Cytokeratin 17 is expressed by basal cells only in normal epithelium. In G1 and G1/G2 transitional cell carcinomas, it is expressed by basal cells, and in some cases by suprabasal cells. In G2 and G2/G3 tumours, it is expressed uniformly by all cells. In anaplastic G3 tumours, it is reduced to focal expression: these foci are basal in Transitional cell carcinomas with squamous differentiation.

- CK18 - Cytokeratin 18: some antibodies (e.g. RCK 106 and CK18-2)detect CK18 uniformly throughout the normal urothelium and uniformly in all grades of transitional cell carcinoma Others (e.g. 2C8 and RGE53) detect CK18 superficially in normal urothelium and low grade non-invasive transitional cell carcinoma with increased reactivity in grade 3 Transitional cell carcinoma 2C8 shows increased reactivity especially in cells bordering the stroma1.

- CK20 - Cytokeratin 20 is restricted to umbrella cells and very occasional intermediate cells in normal urothelium. Retention of this normal pattern in low-grade transitional cell carcinomas is associated with non-recurrence and may define a "benign papilloma". Uniform positivity was associated with an increased risk of recurrence. Carcinoma in situ shows overexpression of CK204. Uniform positivity may also be an objective marker of dysplasia preceding the development of a transitional cell carcinoma. Squamous differentiation in a tumour is associated with reduction in cytokeratin 20 expression.


- Southgate, J., Harnden, P., Trejdosiewicz, L. K. Cytokeratin expression patterns in normal and malignant urothelium: a review of the biological and diagnostic implications. Histol Histopathol 1999;14:657-664.

- Harnden, P., Mahmood, N., Southgate, J. Expression of cytokeratin 20 redefines urothelial papillomas of the bladder. Lancet 1999;353:974-977.

- Harnden, P., Eardley, I., Joyce, A. D., Southgate, Cytokeratin 20 as an objective marker of urothelial dysplasia. J.Br J Urol 1996;78:870-875

- McKenney, J. K., Desai, S., Cohen, C., Amin, M. B. Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. Am J Surg Pathol 2001;25:1074-1078.