Fig. 15.56 Urothelial carcinoma in an ileal conduit urine.
Note degenerating glandular cells, debris, and two tumor cells
(Papanicolaou x MP).
Fig. 15.57 Renal tubule cell cast in a case of allograft injury. The cast is
composed of collecting cells in a fibrinous protein matrix
(Papanicolaou x HP).
epithelial cells and renal tubular casts can be recognized in
routinely processed cytologic material. These elements exfoliate
in renal inflammatory or degenerative as well as in neoplastic
disease. Renal epithelial fragments must be differentiated from
urothelial cells as well as from renal casts. They are defined as
structures containing at least three cells of collecting duct origin
(Fig. 15.57). They may encase casts, have a honeycomb arrange-
ment, or be attached to a cast. The cytoplasm may be pigmented
and may contain crystals or lipid vacuoles.
Urine cytology has become an important means of moni-
toring for acute allograft rejection. Renal transplantation is
the accepted therapy for end-stage renal failure, and cytologic
examination of urine has been performed since this procedure
was developed.66,67 The most common complications are acute
allograft rejection and CMV infection. Both can be diagnosed
and monitored by cytologic examination.
During the first postoperative hours, macrohematuria is
observed; it is reduced to microhematuria during the following
days and usually ceases after 10 days. Some casts, oxalate crys-
tals, and slightly increased numbers of polymorphonuclear leu-
kocytes are found during the first 3 days. Macrophages are more
frequent than urothelial cells, and lymphocytes and degenerated
renal tubular cells are common. If there are no further complica-
tions, the cytologic findings return to normal.
The diagnosis of an acute rejection crisis can be made on
the basis of the presence of increased numbers of renal tubu-
lar cells that occur singly or in clusters. Two types of cells are
present. These are normal tubular cells that are round or oval
and have eccentric nuclei and tubular cells with nuclear altera-
tions including prominent nucleoli, degenerative changes, and
pyknosis. Casts are increased in number, and the background is
dirty. Erythrocytes are often present. Lymphocytes may be seen
but in some series are reported in only one-fourth of the cases.67
The presence of epithelial fragments has been emphasized as
an important criterion.68 On occasion, the exfoliation site of
the fragments cannot be determined by the cytologic presenta-
tion, but recognition of morphologic features of renal epithelial
fragments does permit a diagnosis of ischemic necrosis. Such
fragments and pathologic casts are a characteristic background.
In the clinical setting of renal transplantation, their presence is
diagnostic of an acute allograft rejection.
Key features of renal allograft rejection
• Increased number renal tubular cells, single or clusters;
• Nuclear changes as degeneration, pyknosis, prominent
• Casts, WBCs, RBCs; and
• Dirty background.
Severe tubular injury, renal infarction, and papillary necro-
sis may also cause exfoliation of fragments including cells from
collecting ducts. These and the tissue fragments exfoliating after
instrumentation, in lithiasis, or in cases of papillary carcinoma
should be recognized on both clinical grounds and their cyto-
Long-term administration of immunosuppressive medica-
tion may be followed by transient episodes of urothelial cell aty-
pia. Cases of urothelial cancer have been reported after systemic
cyclophosphamide therapy, usually after years of treatment. Rare
cases of transitional cell carcinoma have also been reported in
renal transplant recipients after immunosuppression.
Specific infections occur in allograft recipients, and fungi
may be seen in their urine. CMV infection is particularly com-
mon. The cytologic findings are as described previously. They
are characterized by the presence of epithelial cells with large
eosinophilic nuclear inclusions or cells with dense inclusions
surrounded by a halo and a thickened nuclear membrane, so-
called owl's-eye cells.67
Flow cytometry (FC) measures the content of DNA in a large
number of cells. Peripheral lymphocytes from the same patient
serve as control. The presence of an aneuploid population or a
population with high S-phase fraction is considered a marker
of malignancy. The technique is more complex and costly
than urine cytology and requires bladder washings rather than
voided urine. In combination with cytology, however, it does
enhance the sensitivity of the postoperative follow-up exami-
nations after treatment of bladder cancer for possible recur-
rence and provides important prognostic information.40 Flow