Fig. 15.29 Histology of carcinoma in situ of bladder involving nests of
von Brunn (H&E x MP).
Carcinom a in Situ
This diagnosis is made if the changes are cytologically those of
urothelial carcinoma, with nuclear enlargement, irregularity, hyper-
chromasia, and prominent mitotic activity (Fig. 15.29). It has been
proposed that only lesions with cells that contain nuclei larger than
80 pm2 should be classified as carcinoma in situ, and lesions with
smaller nuclei that are classified as low-grade carcinomas in situ by
some should be classified as mild, moderate, or severe dysplasia.36
This is a reasonable histologic classification that closely relates to
cytology because it is the lesions with greater nuclear size and pleo-
morphism that show particular lack of cellular cohesion and are
associated with extensive exfoliation and pseudocystitis.
The cytology of carcinoma in situ is characterized by the pres-
ence of numerous abnormal cells that are moderately larger than
normal transitional cells and have hyperchromatic, enlarged, and
irregularly outlined nuclei (Figs 15.30 and 15.31). The chroma-
tin is usually coarsely granular, and the nucleocytoplasmic ratio
is high. Large nucleoli are prominent. The pattern is relatively
monotonous, and bizarre and very pleomorphic cancer cells are
rare. Many of the cells exfoliate singly, but a few occur in small
fragments or clusters. In many cases there is no ulceration or
inflammation, and the background is usually clean. Some leuko-
cytes or red blood cells are present if the epithelium is denuded.
Because of the extensive exfoliation from these lesions, the cyto-
logic accuracy is high and a diagnosis can be made in most cases.
Key features of carcinoma in situ
• Numerous abnormal cells;
• Enlarged, hyperchromatic, and irregularly outlined
• Prominent nucleoli; and
• Clean background.
Urine samples from
tain abnormal cells, corresponding to the dysplastic changes
described.The exfoliation is less extensive, and fewer abnormal
cells are present. The nuclei are smaller, less pleomorphic, and
hyperchromatic, and the background is clean (Fig. 15.32). The
principal cytologic differential diagnosis includes the atypical
changes caused by inflammation, calculi, or instrumentation. In
Fig. 15.30 Urine specimen in the same case of carcinoma in situ of
bladder as Fig. 15.29. Many abnormal cells with enlarged, moderately
irregular nuclei are present. The chromatin is coarsely granular, and the
nucleocytoplasmic ratio is high (Papanicolaou x MP).
Fig. 15.31 Single abnormal urothelial cells with enlarged hyperchromatic
nuclei in urothelial carcinoma in situ of bladder (Papanicolaou x MP).
these cases and particularly in calculous disease, individual cells
may be impossible to differentiate from those exfoliated in severe
dysplasia or carcinoma in situ, but the cellularity is never as great
as in the latter conditions. As noted, this is because of lack of
cohesion of cells in areas of carcinoma in situ and, to a lesser
degree, dysplasias. This appears to be associated with the decrease
in numbers of desmosomes with increasing tumor grade.
Carcinoma in situ and urothelial dysplasia are conditions
most often found in middle-aged or elderly men. They occur
predominantly in the urinary bladder but may involve all other
portions of the urothelium and not infrequently extend into
prostatic ducts. The changes precede invasion but can involve
nests of Brunn (see Fig. 15.29).
invasive Nonpapillary Urothelial Carcinoma
The noninvasive phase of nonpapillary urothelial carcinoma is
flat, transitional cell carcinoma in situ as described previously.
Because the epithelium in carcinoma in situ is frequently not