Fig. 15.54 Irradiation changes in urothelial cells. Marked cellular
enlargement with nuclear and cytoplasmic vacuolization
(Papanicolaou x HP).
Fig. 15.55 Nuclear enlargement and prominent nucleolus and
bland chromatin in exfoliated cells from a patient who was treated with
methotrexate (Papanicolaou x HP).
and the degenerative changes associated with the cytologic effect
should permit correct interpretation. It must be noted, however,
that epithelial cancers and in particular transitional cell carci-
noma may develop in patients after treatment with cyclophos-
phamide, and the presence of cytologically malignant cells that
appear viable should therefore not be dismissed as being merely
secondary to chemotherapy.
In contrast to cyclophosphamide, triethylenethiophosphor-
amide (thiotepa) and mitomycin C are polyfunctional alkylating
agents used for treatment of superficial transitional cell carci-
noma of the bladder by intravesical installation. The changes
introduced by thiotepa mimic those of neoplastic cells but
differ in several respects.60 There is moderate hyperchromasia,
but the chromatin is often smudgy and lacks a sharply detailed
pattern. The nuclei become slightly or moderately enlarged and
are round or ovoid with smooth, thin chromatinic rims that
may be wrinkled. Large multinucleated cells are often present.
Small and sometimes multiple nucleoli occur. The cytoplasm
of these cells shows degenerative changes including vacuolation
and frayed borders (Fig. 15.55). If a transitional cell carcinoma
is present, it can be diagnosed before as well as after therapy,
and as after treatment with cylophosphamide, the presence of
preserved cells that show good criteria of malignancy indicates
neoplasia rather than reactive changes.
Mitomycin C is also used intravesically for the treatment of
superficial transitional cell carcinoma and is effective in one-
third to one-half of patients. Like thiotepa, mitomycin C acts to
abrade vesical mucosa of visible superficial tumors and may be
followed by nuclear and cytoplasmic changes similar to those
observed with thiotepa.61 They mimic neoplastic changes, but
degeneration is readily apparent. Cytologic examination of
urine is useful in the follow-up of patients so treated and per-
mits diagnosis of persistent in situ or high-grade transitional cell
Doxorubicin hydrochloride, epirubicin, interferon, and BCG
are also used for intravesical therapy. O f these, BCG appears to
be the most effective agent in reducing the recurrence rate.62 It
causes inflammation in the bladder, with granulomata in 24%
of the cases. Recurrence is often preceded by urothelial dysplasia,
which can be detected by cytologic follow-up examinations.63
Cytology of ileal Conduits
Ileal conduits or pouches are created at the time of cystectomy.
The ureters empty into the pouch, and examination of the urine
is a sensitive means of diagnosing additional or multicentric
carcinoma of the upper urinary tract.
The small intestinal mucosa of the pouch becomes flat-
tened after 2 years, but the epithelial cells remain columnar.64
The mucosal stroma invariably becomes chronically inflamed
and contains numerous macrophages and lymphocytes. The
cell turnover rate of the intestinal epithelium exceeds that of
the bladder, resulting in abundant exfoliation of intestinal-type
epithelial cells and histiocytes. Both single cells and clusters are
numerous. Most of the cells are rounded, with dark staining,
moderately irregular nuclei, and an amphophilic cytoplasm.
Nuclear pyknosis, karyorrhexis, and cytoplasmic inclusions are
common. The cytoplasm is often vacuolated. Red blood cells are
occasionally seen, and leukocytes are invariably present. Special
organisms such as
spp may be found.
Key features of ileal conduits urine
• Intestinal type epithelial cells;
• Rounded cells with vacuolated cytoplasm;
• Cytoplasmic inclusions are common;
• Dark, irregular nuclei;
• Karyorrhexis and karyopyknosis; and
spp may be present.
Malignant cells from recurrent or multicentric carcinoma can
be diagnosed in this background of normal or degenerating cells
if they are well preserved and viable. The nuclear hyperchroma-
sia in the ileal epithelial cells is due to degeneration and must
be differentiated from malignant changes.
Direct involvement of an ileal conduit with a recurrent transi-
tional cell carcinoma is relatively rare, but several cases of direct
neoplastic involvement of the ileal pouch have been reported
Renal Allograft Monitoring
Examination of urine to evaluate renal abnormalities preceded
the use of urine cytology for cancer diagnosis and is still an
important component of clinical microscopy. Renal tubular