PART TWO
Diagnostic Cytology
Fig. 15.19 A delicate vascularized stalk is covered by five to seven layers
of well-differentiated urothelial cells as seen in the histology of papilloma
(H&E x MP).
Fig. 15.20 Large epithelial fragment in catheterized urine from a
patient with bladder papilloma. Note somewhat angular and slightly
hyperchromatic but uniform nuclei (Papanicolaou x MP).
Papillary Tumors
Papilloma
Papillomas of the urinary bladder are uncommon benign papil-
lary tumors with thin fibrovascular cores covered by cytologically
normal or nearly normal urothelium that is less than seven layers
thick (Fig. 15.19). The tumors are small, may be multiple, and
arise in areas of the urothelium that, like the tumors themselves,
usually show no significant cytologic atypia. Inverted transi-
tional cell papillomas or brunnian adenomas are another vari-
ant of benign urothelial tumors composed of well-differentiated
transitional epithelial cells. These tumors occur mainly in elderly
men and are located in the trigone, bladder neck, or prostatic ure-
thra. They are composed of invaginated urothelium resembling
that of the nests of Brunn and are covered by layers of benign
urothelium on the surface. Because of the small size of transi-
tional papillomas and the good cohesion of the nearly normal
cells, exfoliation is scant. Although clusters of urothelial cells may
be more abundant, a cytologic diagnosis is rarely, if ever, possible.
The same is true for the inverted papillomas covered by normal
urothelium. These tumors can be effectively treated by transure-
thral resection and recur infrequently. If cytologically malignant
cells are found in their presence, they invariably exfoliated from
areas of dysplasia or carcinoma in situ that may coexist. Because
of the good differentiation and minimal deviation from normal
of the epithelial cells of papillomas, there are no specific findings
that permit a cytologic diagnosis. The specimens from patients
with papillomas, nevertheless, are often not normal.28 The exfoli-
ated epithelium is abundant in approximately one-third of such
cases (Fig. 15.20), and few specimens are scantily cellular. How-
ever, in one-half of 50 cases, the overall cellularity was similar to
that of cases without tumors. Red blood cells are present slightly
more frequently in patients with papilloma than in other uro-
logic patients. The most common abnormality in papillomas
is the presence of elongated epithelial cells. These must be dis-
tinguished from the elongated smooth muscle cells sometimes
found in catheterized urine specimens or in voided urine after
manipulation. Smaller round or slightly elongated epithelial cells
tend to be loosely clustered, but the elongated cells are usually
single. The nuclei of the exfoliated cells are minimally or not at
all abnormal, and any significant deviation from normal relates
to the cell shape. The minimal cytologic abnormalities present are
within the range of atypia that may be induced by inflammatory
or irritative processes. The cytologic findings may be described as
consistent with or suggestive of papilloma, particularly if the clin-
ical history or review of slide material indicates that the patient
had such tumors in the past, but a definite cytologic diagnosis
cannot be made.
Key features of papilloma
• Loose clusters and single cells;
• Small, round, or elongate cells; and
• Minimal cytologic atypia.
Papillary tumors include noninvasive and invasive papil-
lary tumors that resemble papillomas but are characterized by
a thicker (more than seven cell layers) urothelium, slight abnor-
mality in the architecture with occasional broader papillae, and
greater cytologic atypia than is seen in papillomas (Fig. 15.21).
The moderately differentiated (grade II) tumors have even
broader and blunter papillae, usually infiltrate the submucosa,
have nuclei that are larger and slightly pleomorphic, show
increased mitotic activity, are hyperchromatic, and may be aneu-
ploid (Fig. 15.22). Most pathologic classifications use only three
grades, and if not, grades III and IV should be combined in the
assessment of the biologic potential. These higher grade tumors
are invariably invasive and often extend into the muscle layer.
Only surface portions may retain a papillary configuration, and
the papillary processes are markedly blunted. The nuclei are even
larger and more pleomorphic, and the nucleocytoplasmic ratio
is high. Mitoses are frequent, and bizarre cell forms are present.
Squamous and, less commonly, glandular neoplastic compo-
nents may be present in a few of the high-grade papillary tumors,
but less commonly so than in nonpapillary carcinomas.
The cytologic findings in urine depend on the grade of the
tumor, and conversely, the grade can be predicted based on the
cytologic findings. Because the grade is also clearly associated
with the depth of invasion, the cytologic findings may provide
information about the probable stage of the tumor.
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