Fig. 15.50 Moderately differentiated papillary urothelial carcinoma
of renal pelvis. Note vascular core of papillary group (Papanicolaou x MP).
bladder urine and could be mistakenly interpreted as carcinoma
of the upper urinary tract. Good cell preservation and adherence
to clear-cut nuclear criteria of malignancy are necessary to make
a positive diagnosis (Fig. 15.52).
As noted previously, urinary cytology is unsatisfactory as a means
of detecting renal cell carcinoma. Some researchers report a
positive diagnosis in more than 40% of patients with renal ade-
nocarcinoma,56 but the results obtained by most other laborato-
ries indicate a lesser sensitivity. If malignant cells are present in
advanced cases, they are usually large, with distinct nucleoli and
a clear or vacuolated cytoplasm (see Fig. 15.39). Granular eosi-
nophilic cells with pyknotic nuclei and distinct or ill-defined
cytoplasmic borders are also seen and are probably the result of
As described elsewhere, fine-needle aspiration of the prostate is a
recognized procedure for the diagnosis and classification of pro-
static adenocarcinoma. Cells characteristic of adenocarcinoma
may be present in voided urine spontaneously or after prostatic
massage, particularly if the carcinoma is high grade or advanced.
The sensitivity of urine cytology, however, is only approximately
20%,57 and this procedure is therefore not appropriate for the
early detection of prostatic carcinoma.
Instrumentation and catheterization of the ureters and renal pel-
ves are followed by reactive changes and produce large numbers
of superficial cells. Some of these may show reactive or atypical
changes and can be misinterpreted as dysplastic or malignant.
The major iatrogenic changes, however, are those that follow
treatment of cancer and transplant procedures with immuno-
suppression. Just as modern therapy of leukemias and malig-
nant lymphomas is effective but causes a host of significant early
and late pathologic changes, so does the therapy of tumors of
the urinary tract. Treatment of other sites, such as irradiation of
the rectum or systemic chemotherapy, similarly may cause sig-
nificant pathologic and cytologic changes of the urinary tract.
Fig. 15.51 Grade III urothelial carcinoma of ureter. Note enlarged
nuclei with coarse chromatin and nucleoli (Papanicolaou x MP).
Post-laser coagulation bladder or ureteral washings show a strik-
ing artifact of cellular spindling. The spindled cells occur sin-
gly, in loose clusters, and in lamellar stacks and have elongated
nuclei with dense chromatin and bipolar cytoplasm (Fig. 15.53).
The changes are a nonspecific epithelial response to heat. No
interpretation should be attempted during the immediate post-
Irradiation of the urinary bladder or other portions of the col-
lecting system initially causes mucosal congestion and localized
edema. This progresses to edema of the lamina propria with vas-
culitis, inflammatory changes, and ulceration. The epithelium
adjacent to the ulcers is often hyperplastic and may undergo
Cytologically, the urothelial cells exfoliating from this mucosa
have moderately irregular, enlarged, mildly to moderately hyper-
chromatic nuclei and sometimes multiple nucleoli. The cytoplasm
shows polychromasia, is often frothy, and contains fine-to-large
vacuoles. The most reliable criterion of radiation effect is the
marked cellular enlargement (Fig. 15.54). The cells measure up
to 2500 pm2, averaging approximately 900 pm2. Irradiated malig-
nant cells from transitional cell carcinomas show similar changes
but have a relatively scanty cytoplasm with enlarged, irregular,
and hyperchromatic nuclei. Irregular jagged macronucleoli are
sometimes present. The described irradiation changes appear at a
predictable dose level after approximately 2800 rad.59
Key features of irradiation changes
• Enlarged and frothy cytoplasm;
• Marked nuclear enlargement; and
• Hyperchromatic nuclei, multiple nucleoli.
Effects of Chemotherapy and immunotherapy
The bladder epithelium is affected by chemotherapeutic agents
that may be given systemically for the treatment of malignancies
of various organ systems and by alkylating agents administered