Fig. 15.11 Birefringent uric acid crystals in urine (Papanicolaou x MP).
Key features of normal voided urine
• Urothelial cells single, loosely cohesive clusters;
• Variably sized cells;
• Opaque, granular or vacuolated cytoplasm;
• Squamous cells;
• Metaplastic cells;
• WBCs, RBCs; and
• Other (spermatozoa,
The most important step to eliminate degenerative changes is
immediate fixation of the collected urine with an equal amount
of 50% alcohol. If this prompt fixation is then followed by well-
controlled cytopreparation, with smears or filtration or cyto-
centrifugation-based preparations degenerative changes do not
interfere with interpretation. Reactive changes may be difficult
to differentiate from neoplastic ones, as described later, but the
most significant problem in interpretation is the distinction of
the large superficial cells from tumor cells. The morphology of
these cells must be known. Their prominence in ureteral cath-
eterization specimens is particularly striking. This misinterpreta-
tion may lead to nephrectomies of non-neoplastic kidneys.
Patency of the urachus at the vesicle end of the structure may
lead to a urachal diverticulum or to the presence of remnants
of columnar epithelium in this area. This may be a source of
exfoliated columnar cells in the urine, and adenocarcinomas are
known to develop from this tissue. Exstrophic bladders may also
be lined by columnar epithelium that may become the site of
adenocarcinomas. Cytology does not have a role in the evalua-
tion of this abnormality.
Endometriosis is the growth of endometrial glands accompanied
by endometrial stroma in abnormal locations. It commonly
involves the ovaries and pelvic peritoneum and less commonly
the colon, appendix, vagina, and umbilicus. Although even less
common than at those sites, endometriosis of the urinary tract
Fig. 15.12 Lubricant in catheterized urine (Papanicolaou x MP).
has been reported, and the bladder is the most common site of
involvement.18 The condition usually occurs in women of child-
bearing age. The symptoms include hematuria, which may be
cyclic, dysuria, and suprapubic pain. If the surface epithelium is
involved and the urothelium is penetrated, endometrial stromal
and glandular cells may be shed into the urine. The cytologic
presentation of these endometrial cells in urine is very similar
to that seen in vaginal smears. The presence of small cells with
a high nucleocytoplasmic ratio in a urinary specimen raises the
possibility of poorly differentiated urothelial carcinoma or lym-
phoma, but the marked uniformity of the cells and their occur-
rence in exodus-type clusters should suggest the possibility of
endometriosis of the bladder.
Diverticulosis of the Urinary Bladder
Diverticula of the urinary bladder may be congenital, but they
often develop because of partial urinary obstruction in the blad-
der neck region, most commonly caused by nodular hyperpla-
sia of the prostate. The ostium into the bladder is usually large
but may be narrow or pinpoint in size. The bladder mucosa is
often chronically inflamed, and in many cases, the urothelium
is replaced by metaplastic squamous epithelium. The mere pres-
ence of squamous cells in urine obviously does not permit a
diagnosis of diverticulum, but if this finding can be combined
with the clinical information, it may suggest such a diagnosis.
Evidence of hyperkeratosis and of squamous dysplasia must be
reported because squamous as well as transitional cell carcino-
mas may develop in diverticula.
Nonspecific and Bacterial inflammation
Inflammation of the lower urinary tract is commonly caused
by bacteria, usually as a complication of an obstructive process
such as prostatic hyperplasia or carcinoma, strictures, or calculi.
Positive urine cultures most frequently contain
(32%), streptococcus group D (10%),
organisms. Tuberculosis of the bladder is usually associated
with and secondary to tuberculosis of the kidneys.
Regardless of the etiology, cystitis is cytologically charac-
terized by the presence of polymorphonuclear leukocytes,