Urinary Tract
Fig. 15.13 Intracytoplasmic inclusions are present in degenerating
urothelial cells in cystitis (Papanicolaou stain x HP).
necrotic debris, histiocytes, degenerative changes in urothelial
cells, urothelial hyperplasia, and often reactive urothelial aty-
pia (Fig. 15.13) . Slightly greater irregularity of the cell outlines
and increased percentage of cells that contain generally small
nucleoli with occasional coarsely granular nucleoplasm are
noted. Red blood cells are invariably present. The transitional
cells are increased in number and are often obscured by the
inflammatory cell population. The nuclei tend to be moder-
ately enlarged, to an average nuclear diameter of 8 to 10 pm.
They often contain clear zones or chromatin "bars" and may
contain nucleoli. The cellular outline is usually hazy. Degen-
erated cells may be large and may have a clear or vacuolated
cytoplasm that contains collections of polymorphonuclear
leukocytes. Sizable clusters of partially necrotic cells may be
present. The coarsely granular pattern of malignant urothelial
cells or macronucleoli is not seen. A very dense, cellular inflam-
matory exudate associated with hyperplastic or degenerating
urothelial cells or partially necrotic cell clusters without the
nuclear characteristic of malignancy or severe dysplasia is of
infectious or inflammatory origin. Even extensively ulcerated
and necrotic transitional cell carcinomas of the urinary bladder
invariably exfoliate unequivocally malignant cells and a greater
amount of necrotic material and relatively fewer leukocytes
than is the case in cystitis.
Key features of cystitis
• Polymorphonuclear leukocytes;
• Necrotic debris;
• Histiocytes;
• Degenerative changes; and
• Reactive urothelial atypia.
Virus infections
A number of virus infections cause morphologically characteris-
tic changes in renal cells and in urothelium. Cytomegalic inclu-
sion disease is caused by cytomegalovirus (CMV), a member of
the herpes virus group. It is spread by intrauterine or perina-
tal transmission to the fetus by an infected mother, sexually or
through blood products. Young children and patients who are
immunosuppressed because of cancer or acquired immunodefi-
ciency syndrome (AIDS) or who suffer from immunosuppression
Fig. 15.14 CMV-infected cells with large eosinophilic intranuclear
inclusions surrounded by clear halos (Papanicolaou x MP).
associated with transplants are at risk. The renal tubular epi-
thelium is frequently involved, and the disease is seen in renal
transplant recipients. The affected cells are enlarged and contain
large basophilic or eosinophilic single nuclear inclusions sur-
rounded by clear halos. The inclusions are sharply demar-
cated from the nuclear membrane. Remnants of chromatin are
condensed peripherally (Fig. 15.14).
Herpes virus isolation from human bladder urine has been
described by Masukawa et al.19 The viral cytopathic changes are
the same as in other body sites. Urothelial cells are multinucle-
ated, with smudgy chromatin, nuclear molding, or eosinophilic
inclusion bodies surrounded by halos.
Papovaviruses are divided into two groups: papillomaviruses
and polyomaviruses. Polyomavirus is of particular importance in
urine cytology because active infection is often localized to the
brain and urinary tract. Urinary excretion of viruses in pregnant
women has been reported, showing that the fetus is at risk of
infection.20 Like CMV, the virus also infects or is reactivated if
the host's immunity is impaired by immunosuppressive drugs
such as those given to renal allograft recipients or by AIDS or
cancer. Polyomavirus is emerging as a major cause of allograft
dysfunction and loss. The BKV genotype in urine and serum is
significantly related to a high frequency and high number of
virus-infected cells, also known as decoy cells.21 More frequently,
however, the virus is found in patients with other types of uri-
nary tract infection, hematuria, or prostatic hypertrophy, report-
edly in 0.3-1.2% of urine specimens in these cases. There are
usually no sequelae of the infection.22 The virus is readily rec-
ognized morphologically in cells exfoliated in the urinary tract,
and the principal differential diagnosis is with CMV. The inclu-
sion-bearing cells are even larger than those infected with CMV
and contain dense, basophilic, homogeneous nuclear inclusion
bodies (Fig. 15.15). Usually, only a rim of chromatin is seen at the
edges of the inclusion, beneath thickened nuclear membranes. In
contrast to CMV-infected cells, in which the virus inclusions are
surrounded by a clear zone, the basophilic homogeneous inclusion
in a polyomavirus-infected cell often completely fills the enlarged
nucleus. If a clear halo remains, it is sharply distinguished from
the thickened nuclear membrane. Electron-microscopic examina-
tion shows the virus particles to be unencapsulated, in contrast to
the encapsulation observed in CMV. Immunoperoxidase proce-
dures with simian virus 40 antiserum have been successfully used
to confirm infection by polyomavirus.
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