PART TWO
Diagnostic Cytology
Fig. 15.15 Polyomavirus infected cells with large intranuclear
homogeneous inclusions (Papanicolaou x HP).
The human papillomavirus is responsible for condylomatous
lesions in the lower urinary tract, but these lesions are gener-
ally confined to the urethra and the mucocutaneous regions of
the meatus and are readily accessible for biopsy and excision.
Koilocytosis and other morphologic changes characteristic of
this condition are described elsewhere.
Malacoplakia
Malacoplakia is a granulomatous disease of the bladder or upper
urinary tract. Multiple soft, nodular, often umbilicated yellow-
ish plaques appear in the mucosa and submucosa, frequently in
the region of the trigone. They may be mistaken for cancer clini-
cally and are associated with immunodeficiency states. Several
cases have been encountered in transplant recipients.
Histologically, the plaques are found to consist of epithelioid
histiocytes with a granular, acidophilic cytoplasm. Some of the
cells contain homogeneous or concentrically layered intracy-
toplasmic inclusions known as Michaelis-Gutmann bodies or
calcospherites. The inclusions are basophilic and periodic acid-
Schiff positive and stain for iron and calcium. They may rep-
resent the end result of bacterial degradation and degenerative
changes, and the process is regarded by some as a defect in the
host macrophage response to bacterial infection, usually Gram-
negative bacilli. The urine contains histiocytes of this type, often
with multiple granules in a foamy cytoplasm (Fig. 15.16). Some
may be found to contain the calcospherites that average 8 pm
in diameter. The condition is rare, and finding cells that are
diagnostic is exceptional.
Degenerative changes
Disintegration of the cytoplasm, pyknosis of the nuclei, and
karyolysis of the nuclei of scattered transitional cells may be seen
in urine from healthy individuals as well as in urine containing
malignant cells. Cells with an attached tag of partially preserved
cytoplasm were initially described by Papanicolaou and are
sometimes called comet or decoy cells. They may have some of
the characteristics of malignancy, and it is therefore important
that they be recognized for what they are.23 For the most part,
they contain round or oval nuclei that have a coarse chromatin
network or are opaque and hyperchromatic. Occasional cells are
binucleate. The smooth nuclear outline, evidence of cytoplasmic
Fig. 15.16 Histiocyte containing intracytoplasmic laminated inclusions
consistent with malakoplakia (H&E x HP).
degeneration, and the usually small number of these abnormal
cells in an often hypocellular urine specimen should prevent a
false-positive diagnosis. It should be noted that they are rare in
immediately fixed urine specimens.
Key features of degenerative changes
• Cytoplasmic degeneration;
• Round or oval nuclei, opaque chromatin;
• Karyopyknosis; and
• Karyolysis.
intracytoplasmic and intranuclear inclusions
Inclusions other than those caused by viruses may be present
in epithelial cells in urine. Some studies have concluded that
the presence of eosinophilic intracytoplasmic inclusion bod-
ies (EIBs) is not correlated with a specific disease and may be
a degenerative phenomenon (see Fig. 15.13). Other studies
indicate that many intracytoplasmic and intranuclear inclusion-
bearing cells are related to heavy metal toxicity or are related to
drugs or chemotherapy, microorganisms, metabolic disorders, or
immunologic alterations. It has been demonstrated by quantita-
tive studies that the EIBs are significantly associated with degen-
erative changes. Only rare cells with inclusion bodies have intact
nuclei. The inclusions are more common in women older than
50 years and in voided rather than catheterized specimens, fur-
ther indicating the possibility of degenerative change. Increased
numbers of EIBs have definitely been demonstrated, however, in
industrial workers exposed to lead, in immunosuppressed renal
transplant recipients; and in diverse disease processes, including
mucocutaneous lymph node syndrome (Kawasaki's disease).
cytologic changes Associated with calculi
Urinary tract calculi may be associated with cytologic changes
and atypias that are a major cause of false-positive cytologic
diagnoses. The changes are often due to uric acid calculi in the
upper urinary tract. If they are thought to be related to a mass
lesion in a renal pelvis or ureter, a false-positive diagnosis has at
times resulted in an unjustified nephrectomy. Two major studies
of this subject showed the results of cytologic examination of the
urine to be normal in 53 and 87% of the cases, respectively.24,25
Hematuria and leukocyturia were observed in many of the speci-
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