Jonathan Epstein Johns Hopkins University Baltimore, Maryland
A 42 year old man with hematuria was found to have a large mass involving the base of the bladder.
Colonoscopy revealed no GI malignancy.
Areas of the specimen show classic features of extensive colonic metaplasia. The unusual feature in this
case is that areas of colonic metaplasia merge in with identical glands situated in the muscularis propria,
which favors the diagnosis of adenocarcinoma. The total absence of cytologic atypia is not a feature of
Since the patient was
initially diagnosed at an outside hospital as having adenocarcinoma and the findings were unusual, a 2nd TUR
was performed one month later that showed no residual disease. A repeat cystoscopy was done 9 months after
the initial surgery which also showed no clinical evidence of disease.
Discussion and Differential Diagnosis:
Glandular lesions occurring in the bladder and urethra are entirely analogous to glandular lesions seen in
the intestinal tract both in term of types of lesion and their morphology. The full spectrum of lesions may
be seen in the bladder and urethra including: villous adenoma; villous adenoma with in-situ adenocarcinoma;
villous adenoma with infiltrating adenocarcinoma; and in-situ with or without infiltrating adenocarcinoma
without villous adenoma. Villous adenomas and adenocarcinonus in the bladder occur in one of two general
locations. They may arise within the urachus where they are seen at the dome or anterior wall of the
bladder. Typically urachal lesions do not show a significant mucosal component, yet rather arise within the
muscle wall and extend out of the bladder toward the umbilicus. The other situation in which glandular
lesions arise in the bladder is from a process of metaplasia in which they may occur anywhere in the
bladder, typically near the trigone.
For both villous adenoma and adenocarcinoma of the bladder there is a male predominance.
Patients with villous adenoma or adenocarcinoma may present with either non-specific findings or
occasionally present with mucusuria. If the lesion is pure villous adenoma with or without in-situ
adenocarcinoma and the lesion is entirely resected, then the prognosis is excellent. However, if the lesion
has been only sub-totally removed, especially in the setting of coexistent in-situ adenocarcinoma, the
tumors have the potential to progress to infiltrating adenocarcinoma. As infiltrating adenocarcinoma is
frequently present with villous adenoma, it necessitates thorough san1pling of any lesion diagnosed by
biopsy as villous adenoma.
Adenocarcinomas of the bladder account for <2% of malignant bladder tumors. The majority of bladder
adenocarcinomas contain lakes of extracellular mucin. These mucinous pools may be lined by tall colunmar
epithelium with goblet cells and/or contain mucin-positive signet cells. Papillary mucinous fronds are
common. Bladder adenocarcinomas have prominent nuclear atypia, which is often more readily appreciated in
non-mucinous areas. Some poorly differentiated adenocarcinomas of the bladder are primarily composed of
round uniform cells with occasional cytoplasmic vacuoles. This pattern resembles prostate adenocarcinoma,
except that these vacuoles are mucin-positive. The finding of a transitional or squamous component or
extensive cystitis glandularis also favors a bladder primary. Bladder adenocarcinomas, either when the sole
component or admixed with transitional cell elements, in a minority of cases may show cross-reactive
staining with antisera to PSAP. Although most bladder adenocarcinomas with PSA or PSAP positivity are
focally positive as contrasted to the diffuse reactivity in prostate adenocarcinomas, careful consideration
of the light microscopic appearance of the tumor is necessary to distinguish between an adenocarcinoma of
the bladder and prostate.
Prostate ductal adenocarcinomas may resemble bladder adenocarcinomas cytologically and by the presence of a
papillary component. However, ductal adenocarcinomas of the prostate do not contain a lot of extracellular
mucin or prominent goblet cells. Mucinous adenocarcinomas of the prostate that are not ductal typically
reveal cords of epithelium and cribriform glands with bland cytology floating in mucin. The uniform
cytology is typical of prostate cancer and differs from the greater anaplasia seen in bladder
adenocarcinoma. The punched out round lumina seen in the cribriform formations within prostate
adenocarcinomas also help. True signet cell formation mucin production is very rare in prostate cancer and
usually indicates an adenocarcinoma of the bladder.
In-situ adenocarcinoma is a rare lesion that is often associated with invasive transitional cell
carcinoma. In our series, in-situ adenocarcinoma had a high incidence of association with small cell and
micropapillary transitional cell carcinomas. When identified, in-situ adenocarcinoma is at least as
worrisome as CIS and may indicate subsequent development of specific types of prognostically poor invasive
carcinomas. When identified, in-situ adenocarcinoma is at least as worrisome as CIS and may indicate
subsequent development of specific types of prognostically poor invasive carcinomas.
A mimicker of adenocarcinoma of the bladder is endocervicosis. This lesion typically occurs in women in
their 30s and 40s. Symptoms are those of either hematuria or those mimicking urinary tract infection. In
addition to the bladder, this lesion may be seen in the uterine cervix and vagina. The lesion is composed
of benign glands resembling endocervical glands that involve all layers of the bladder and occasionally the
extravesicle tissue. In contrast to adenocarcinoma, there is no atypia, no mitotic figures, and no tissue
reaction. Occasionally, there may be a suggestion of stroma surrounding the glands as seen in
endometriosis. The lesion may grossly mimic cancer presenting as a mass lesion up to 5 cm. with occasional
The other lesion that may mimic adenocarcinoma is nephrogenic metaplasia (nephrogenic adenoma). Nephrogenic
metaplasias usually arise in the setting of prior urothelial injury, such as past surgery (60%), calculi
(14%), or trauma (9%). Eight percent have a history of renal transplantation. Approximately two-thirds of
individuals affected with nephrogenic metaplasias are male, and in one-third the lesion is found when
patients are less than 30 years of age. Nephrogenic metaplasias appear as papillary, polypoid,
hyperplastic, fungating, friable, or velvety lesions. They are located throughout the bladder, though
rarely found on the anterior wall. Eighty per cent are localized to the bladder, with 12% seen in the
urethra and 8% in the ureter. Most nephrogenic metaplasias measure less than 1 cm., although they may
attain dimensions as large as 7 cm. In eighteen percent of cases, multiple lesions are identified.
Nephrogenic metaplasias have a broad histologic spectrum A common pattern consists of tubules lined by low
columnar to cuboidal epithelium. Nuclear atypia is virtually absent with mitoses either absent or rare.
Nuclear atypia, when present, appears degenerative. Nuclei are enlarged and hyperchromatic, yet have a
smudged indistinct chromatin pattern. These atypical nuclei often reside in cells with an endothelial or
hobnail appearance lining vascular-like dilated tubules. Cystic tubules may contain colloid-like
eosinophilic or basophilic secretions. Uncommonly, tubules are lined by either more columnar cells with
pale cytoplasm or signet appearing cells; clear cells are rare and glycogen is usually absent. Nephrogenic
metaplasias may also be papillary, usually lined by low cuboidal cells with scant cytoplasm or on occasion
by oxyphilic cells. In contrast to adenocarcinoma, nephrogenic adenomas lack solid growth patterns, mitotic
activity, prominent cytological atypia, and are not typically large deeply invasive tumors. We have seen
rare cases of nephrogenic adenomas focally involve the superficial aspects of the muscularis propria.
Occasionally, extensive cystitis glandularis is difficult to distinguish from adenocarcinoma of the urinary
bladder, as in the current case. Cystitis glandularis is a lesion of the urinary bladder that is thought to
evolve either from von Brunn's nests in the setting of chronic irritation and infection or in some cases as
a congenital process reflecting partial origin of the bladder from the embryonal cloaca. Two distinct
patterns exist. The typical form is composed of glands lined by cuboidal to columnar epithelium overlying
layers of transitional epithelium The second variant is termed cystitis glandularis, intestinal type, or
colonic metaplasia. Colonic metaplasia is relatively uncommon and is characterized by glands lined with
mucinous columnar epithelium (goblet cells) with basally located nuclei. Both may present clinically as
large, exophytic masses, and histologically, colonic metaplasia may mimic well-differentiated
adenocarcinoma. Although there is overlap between colonic metaplasia and well-differentiated adenocarcinoma
in some of the histological features (dissecting mucin, infiltration of muscularis propria, atypia, and
mitoses), the degree and extent of these findings differ between the two conditions. In contrast to the
extensive mucinous pools seen in some adenocarcinomas, colonic metaplasia has only focal areas of mucin
extravasation. Whereas adenocarcinomas typically show deep muscle invasion, the muscle invasion seen in
colonic metaplasia tends to be more limited, although the case for this slide seminar is unusual in its
extent of muscle invasion. Although rare adenocarcinomas may show bland cytology, most will have areas of
the tumor with overt cytological atypia. The atypia seen in colonic metaplasia is not as severe and by
itself would not be diagnostic of malignancy. Similarly, mitoses, although frequent in adenocarcinoma, are
found only rarely in colonic metaplasia. Other cases of adenocarcinoma that are less differentiated show
signet cells and necrosis, which are not found in colonic metaplasia.
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