Diagnostic Cytology
Fig. 15.25 Urothelial cells that exfoliated from low-grade papillary
urothelial carcinoma of bladder. Slight nuclear pleomorphism and
hyperchromasia are seen with a coarse chromatin pattern in some cells
(Papanicolaou x MP).
Fig. 15.26 Voided urine from a patient with moderately differentiated
(grade II) papillary urothelial carcinoma of bladder. Many clustered
and some single abnormal urothelial cells with slightly enlarged, moderately
irregular, and hyperchromatic nuclei are present (Papanicolaou x MP).
Papillary Urothelial Carcinom a, Grade II
This is usually identifiable by cytologic examination. The urine
samples are even more cellular. The neoplastic cells show more
striking nuclear abnormalities and still are frequently arranged
in clusters (see Fig. 15.26). This considerable cellularity is due
to the enhanced exfoliation of the neoplastic cells. Table 15.1
lists the number of neoplastic cells present in different catego-
ries, ranging from normal to high-grade tumors. The nuclei
are larger, with a mean nuclear size of 78 pm2, compared with
54 pm2 in grade I transitional cell carcinomas, as shown in
Fig. 15.27. The mean nucleocytoplasmic ratio, which for normal
cells is 12 and for papillary carcinomas grade I approximately
37, is further increased to approximately 42.2 The importance of
the nucleocytoplasmic ratio has also been emphasized by Boon
and co-workers.30 More recent studies of low-grade transitional
cell carcinomas by Raab and associates were based on logistic
regression analysis and identified an increased nucleocytoplas-
mic ratio along with irregular nuclear borders and cytoplasmic
homogeneity as key criteria indicating malignancy.31
Key features of papillary urothelial carcinoma grade II
• Cellular samples;
• Striking nuclear abnormalities;
• Increased nucleocytoplasmic ratio; and
• Irregular nuclear borders.
Papillary Urothelial Carcinom a Grade III
These are characterized by highly cellular urine specimens. They
are similar to the urine specimens of high-grade nonpapillary
carcinomas but still contain somewhat larger numbers of cell
clusters and minute tissue fragments. The nuclei are more than
twice the size of normal nuclei (Fig. 15.27) and average 90
pm2. They have irregular nuclear outlines and a predominantly
coarsely granular chromatin pattern. Many contain one or more
large or irregularly outlined nucleoli. The degree of hyperchro-
masia is greater than that of non-neoplastic transitional cells
and of cells from well-differentiated transitional cell carcinomas.
This increase in nuclear size, ragged nuclear outlines, coarse
chromatin pattern, pleomorphism, and the great cellularity per-
mit a diagnosis in almost all cases (Fig. 15.28). Many of these
tumors are partially necrotic or ulcerated, and red blood cells,
leukocytes, and necrotic debris are present. Keratinizing malig-
nant squamous cells may also be seen if the tumor includes
squamoid zones; this is sometimes the predominant cell type.
Key features of urothelial carcinoma grade III
• Highly cellular specimens;
• Pleomorphic cells;
• Irregular nuclear outlines;
• Coarse chromatin pattern; and
• Large or irregular nucleoli.
The high-grade neoplasms are aggressive, whether they are
papillary, flat, or nodular, and account for more than 90% of
tumor-related deaths.
Urothelial Dysplasia and Carcinoma in Situ
It has long been recognized that carcinoma in situ of the urothe-
lium may precede, accompany, or follow invasive bladder can-
cer.32,33 The association of precancerous lesions with bladder
cancer has been well documented by mapping of the urothelium
by Koss and associates and by Farrow and colleagues.34,35 Carci-
noma in situ in turn is preceded or accompanied by less severe
changes, with urothelial abnormalities ranging from normal or
nearly normal to full-fledged carcinoma in situ. These changes
have been referred to as atypical hyperplasia or as dysplasia. The
lesions are not strictly comparable with dysplasia of the uterine
cervix or cervical intraepithelial neoplasia, but because dyspla-
sia is recognized as denoting a premalignant condition, it is the
preferred term for these alterations. The increased exfoliation
and at least focal denudation of the urothelium in carcinoma in
situ causes a pseudocystitis. This may become symptomatic, with
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