mens that showed no other significant abnormalities. The cyto-
logic atypias were characterized by the presence of clusters of
transitional epithelial cells with smooth borders and 5 to 150
cells per cluster. They were often papillary in shape (Figs 15.17
and 15.18). Nuclei were centrally located, of normal size and
shape, and surrounded by an even rim of cytoplasm. The tran-
sitional cells considered suspicious of carcinoma and, in one
of the series, caused a false-positive cytologic diagnosis in 4%
of the patients were arranged in irregular clusters with ragged
borders. The nuclear morphology was abnormal, with nuclear
pleomorphism and variable staining. Some nuclei were large,
with prominent nucleoli and a coarse granular chromatin, and
others were dark and dense. Occasional mitoses were seen.
Key features associated with calculi
• Clusters of urothelial cells with smooth borders;
• Papillary groups, occasional ragged borders;
• Centrally placed nuclei;
• Dark and dense chromatin; and
• Normal nuclear size and shape.
The cytologic appearance of these abnormal cells includes
some criteria of malignancy. Although it is not possible to distin-
guish individual cells or a few cell clusters from those exfoliated
from malignant tumors, knowledge of the clinical history and
the radiologic findings is helpful. The fact that urine specimens
from patients with tumors almost invariably contain numerous
malignant cells, including many more single malignant cells and,
in papillary tumors, cell clusters, should also aid in avoiding a
false-positive diagnosis. Furthermore, more than half of urine
specimens from patients with calculi show no significant epithe-
lial abnormalities at all, and the only finding may be hematuria.
If abnormalities exist, they involve relatively few cells, and in a
majority of cases, the clusters are smooth bordered (see Fig. 15.18)
and the individual transitional cells may vary in size but are well
differentiated, as noted previously. The urine of some patients
with calculi contains increased numbers of large but cytologically
benign-appearing multinucleated superficial transitional cells. A
relation between calculi and cancer of the upper urogenital tract
has been suggested but has not been clearly established.
Fig. 15.17 Histology of urothelium in a calculus-containing kidney
with surface ulceration and shedding of papillary transitional cell cluster
(H&E x MP).
Most iatrogenic changes are related to treatment for cancer of
the urinary tract and are described in that section.
Hyperplasia, Atypia, and Dysplasia
Hyperplasia, atypia, and dysplasia are or may be precursors of
tumors of the urothelium and are described in that section.
Tumors of the Urinary Tract
Approximately 120,000 tumors of the urinary tract are newly
diagnosed in the United States annually, including 67,000 car-
cinomas of the urinary bladder.26 Between 75 and 85% of these
cases are superficial. The urothelial tumors may be papillary
or nonpapillary and invasive or in situ. Nonpapillary tumors
and at least the poorly differentiated papillary tumors arise
from areas of atypical urothelial proliferation. Mapping of the
urinary bladder in cystectomy specimens clearly demonstrates
the association of epithelial atypias and carcinoma in situ with
invasive nonpapillary carcinoma. Papillary and nonpapillary
tumors often coexist in the same patient, but the development
of well-differentiated papillary tumors from areas of epithelial
atypia is not as clearly demonstrable, and these tumors are often
surrounded by normal-appearing urothelium. Because of their
different biologic behavior and different cytologic presentation,
the papillary and nonpapillary tumors are discussed separately.
All tumors of the urothelium exfoliate readily into the urinary
stream. The great majority occur in the urinary bladder. Squa-
mous and glandular components may be present. The tumors
that arise below the surface epithelium, such as in the renal
parenchyma or in the prostate, are unlikely to exfoliate until
they have become large and disrupt the urothelial lining. Urine
cytology is rarely a means of primary diagnosis in these cases.
employed throughout the years. We will follow an adapted
version of the 2003 World Health Organization (WHO) clas-
sification of the urinary bladder tumors.27
Fig. 15.18 Urothelial cells in a papillary group from a patient with
calculus disease. Note smooth borders that suggest a benign process
(Papanicolaou x MP).