Anatomical Pathology Interesting Case Conference

Microscopic Description:

The Tumor is characterized by closely irregularly packed bland confluent nests of poorly defined urothelial cells infiltrating the lamina propria and the muscularis propria.

Generally, there is no evidence of surface epithelial involvement(urothelium)

Presence of focal atypia (mild pleomorphism, slightly increased nuclear/cytoplasmic ratios, occasional prominent nucleoli, and rare mitotic figures)Atypia may become more prominent with a greater depth of invasion.

Deceptive benign appearance, should be ruled out as it can be mistaken for a benign bladder lesion called Von Brunn’s nests.

Discussion:

Von Brunn’s nests:

  • Regularly spaced large nests, that do not
  • The Central lumen is often formed, sometimes
  • Immunostaining has little affinity to MIB-1
  • Can present with focal atypia

Nested Variant Urothelial Carcinoma

  • Infiltrative pattern of irregular confluent variably sized nests into the lamina propria and muscularis propria. The urothelium is often spared.
  • The lumens and spaces are often empty however may present with necrotic debris or have PAS stainable material, the carcinoma cells forming and lining the spaces do not have secretory/glandular cytoplasmic differentiation.
  • Cytologically bland features include focal atypia, which if present in the muscularis propria excludes the possibility of a benign lesion.
  • Often involves the ureteric orifices

Cytogenetics and IHC

Molecular / cytogenetics:
  • Loss of p27. Has also been associated with increased progression and proliferation of the disease
  • (FOXA1+ / CK5/6-)
  • TERT promotor mutations
  •  
Positive Stains:
 
  • CK7, CK20, CK903, p63, Ki-67
Negative Stains:
  • P53, bcl-2  generally negative
  • Loss of p27  present in the deep component

Microscopic (histologic) description:

  • The Tumor is characterized by closely irregularly packed bland confluent nests of poorly defined urothelial cells infiltrating the lamina propria and the muscularis propria.
  • Generally, there is no evidence of surface epithelial involvement(urothelium)
  • Presence of focal atypia (mild pleomorphism, slightly increased nuclear/cytoplasmic ratios, occasional prominent nucleoli, and rare mitotic figures)Atypia may become more prominent with a greater depth of invasion.
  • Deceptive benign appearance, should be ruled out as it can be mistaken for a benign bladder lesion called Von Brunn’s nests.
References:

M. Brown, M. Tretiakova.  Bladder & urothelial tract Urothelial carcinoma – invasive Nested. https://www.pathologyoutlines.com/topic/bladdernested.html.  (October 4, 2023)

D. Dhall, H. Al-Ahmadie, S. Olgac, Nested variant of urothelial carcinoma. Arch Pathol Lab Med 131, 1725-1727 (2007).

O. Lin et al., Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. Mod Pathol 16, 1289-1298 (2003).

A. K. Venyo, Nested variant of urothelial carcinoma. Adv Urol 2014, 192720 (2014).

K. E. Volmar, T. Y. Chan, A. M. De Marzo, J. I. Epstein, Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. Am J Surg Pathol 27, 1243-1252 (2003).