Bladder Endometriosis with Mucinous Metaplasia
Washington University in Saint Louis
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Bladder Endometriosis with Mucinous Metaplasia
Endometriosis of the bladder
Bladder endometriosis was first reported in 1921 . Since then more than 300 cases have been
reported in the literature . In women with endometriosis, bladder involvement is seen in
approximately 1-2% cases 
and bladder is the only site of involvement in 12% cases . Patients are
usually in their reproductive age but some patients are postmenopausal who received estrogen treatment.
Some patients have a history of prior pelvic or abdominal surgery. The symptoms of the bladder
endometriosis are variable, depending on the location and size of the lesion, and the phase of menstrual
cycle. Small lesions may be asymptomatic. Symptomatic bladder endometriosis is almost always related to
mural involvement. Endometriosis involving the detrusor muscle is symptomatic in 75% of the cases,
almost always in a cyclic manner, being more intense during the premenstrual period . The most
frequent presenting symptoms in bladder endometriosis include urinary urgency, frequency, suprapubic
pain, nocturia, hematuria, urge incontinence, and dyspareunia .
Although bladder endometriosis is a female disease, it is also very rarely seen in men who have
received estrogen treatment for prostate carcinoma
Low power view shows variable-sized glands infiltrating within the muscularis propria of the bladder.
At high power view of figure 1, one gland in the center is lined by mucinous epithelium.
Other small glands in figure 1 are tubular in shape and are lined by cuboidal to columnar nonmucinous cells. Although some nuclei have prominent nucleoli, no cytologic atypia is seen. Some glands also show nuclear stratification.
Low power view of several glands within the muscularis propria in a different fragment: small tubular glands and two cystically dilated ones.
The two cystically dilated glands in figure 4 are lined by one single layer of cuboidal cells with mucinous cytoplasm and bland nuclei. The tubular glands are lined by nonmucinous columnar cells (with some cautery effect).
Another fragment contains multiple tubular glands and few cystically dilated glands that are infiltrating the muscularis propria of the bladder.
Medium power view of the glands and their surrounding stroma of figure 6.
Some glands in figures 6 contain subnuclear cytoplasmic vacuoles. The lining cells are stratified cuboidal to columnar cells. The surrounding stroma consists of spindled to epithelioid cells. There is some collagen within the stroma.
The glands and their surrounding stromal cells seen in figures 6-8 are diffusely and strongly positive for estrogen receptor (ER). The smooth muscle cells of the muscularis propria of the bladder (left and right upper corners) are negative for ER.
The glands and their surrounding stromal cells seen in figures 6-8 are diffusely and strongly positive for progesterone receptor (PR). The smooth muscle cells of the muscularis propria of the bladder (left and right upper corners) are negative for PR.
The stroma cells surrounding the glands seen in figures 6-8 are diffusely positive for CD10. The smooth muscle cells of the muscularis propria of the bladder (left and right upper corners) are negative for CD10.
Pathologic and Immunohistochemical Features
The typical locations of bladder endometriosis are the posterior wall, dome, trigone, and base
Grossly the lesion is usually a solitary mass that thickens the bladder wall and sometimes projects into
the lumen. The average diameter of the lesion is about 3-4 cm in most series
the lesion typically involves the muscularis propria. Involvement of lamina propria is seen in more than
half of the cases and rarely it involves the bladder mucosa. The lesion usually contains both
glands and stroma but sometimes the endometrial glands are atrophic and cystically dilated and devoid of
associated stroma, posing diagnostic challenge. Sometimes there are abundant pseudoxanthomatous
histiocytes in the stroma. Stromal elastosis can be occasionally seen around the glands. There is often
fibrosis and proliferation of smooth muscle around the endometriosis.
In ovary, epithelial metaplasia in endometriosis is a common finding. The most common types of
metaplasia are ciliated cells and eosinophilic type (44%, respectively), followed by hobnail (13%) and
mucinous metaplasia (4%) . However, mucinous metaplasia in bladder endometriosis was only very
rarely observed .
Immunohistochemically the glandular and stroma cells in endometriosis are positive for ER and PR. The
endometrial stroma cells are also positive for CD10.
Treatment and Prognosis
Treatment of bladder endometriosis depends on several factors including patient age, desire to
fertility, disease extent, severity of lower urinary symptoms, presence of other pelvic disease, and the
degree of menstrual dysfunction . For disease involving the muscularis propria, medical therapy
is usually suboptimal and palliative only because the disease often recurs when therapy is discontinued
Transurethral resection rarely suffices as a definitive treatment . Partial cystectomy with
complete excision of all endometriosis is the treatment of choice for bladder endometriosis and gives the
Although endometriosis involving the bladder is a benign process in the vast majority of cases, rarely
it may undergo malignant transformation. Theoretically any malignancy arising in the eutopic endometrium
can arise from bladder endometriosis. Up to date, only 10 cases of primary malignancies
arising in bladder endometriosis have been reported in the English literature including 6 cases of clear
2 cases of endometrioid adenocarcinoma
and 2 cases of adenosarcoma
One case of endometrial stromal sarcoma arising in bladder endometriosis was also reported in Japan
Although diagnosis of bladder endometriosis is usually straightforward if one pays attention to the
morphologic features of glands and stroma, other glandular lesions of the bladder should be considered in
the differential diagnosis:
(1) Endocervicosis: Bladder endocervicosis usually occurs in women of reproductive
age. It typically presents as a mass in the posterior wall or dome of the bladder
Histologically the endocervical type glands infiltrated the deep muscularis propria. Some cases also had
extravasated mucin in the stroma secondary to glandular rupture. Foci of endometriosis were also present
in some cases
(2) Mullerianosis: Drs. Young and Clement first described 3 cases of bladder
mullerianosis in 1996 . All 3 cases formed a mass up to 4 cm in the posterior wall. The
predominant component in each case was endosalpingiosis (tubal type epithelium). All 3 cases also had
foci of endocervicosis and 2 of them had additional foci of endometriosis. They coined a succinct term
"mullerianosis" to describe lesions containing admixtures of at least 2 of the 3 different types of
mullerian epithelium (endometrial, endocervical, tubal) of any site. Some may consider the mucinous
glands in the current case as endocervical glands and thus render a diagnosis of mullerianosis. This
probably has more academic rather than practical significance. However, the mucinous glands in the
current case are surrounded by endometrial type stroma, in my opinion, and therefore more consistent with
mucinous metaplasia than endocervicosis.
(3) Cystic cystitis and cystitis glandularis: Cystitis cystica and cystitis glandularis
do not involve the muscularis propria  though rarely florid cystitis glandularis with intestinal
metaplasia and mucin extrasavation may focally involve the superficial muscularis propria . In
addition, cystitis cystica and cystitis glandularis do not have the endometrial type stroma as seen in
(4) Nephrogenic adenoma: Nephrogenic adenoma can demonstrate prominent infiltration
among the muscle bundles of the lamina propria . However, bladder nephrogenic adenoma almost always
does not involve the deep muscularis propria though one may see rare cases of nephrogenic adenoma
involving the superficial aspect of the muscularis propria . Typically it contains tubules and
cystic glands with inflammatory cells in the stroma though cystically dilated tubules may be predominant
in some cases . The lining cells do not have mucinous cytoplasm. Nuclear atypia is typically
absent with absent or rare mitotic figure. Presence of a prominent hyaline base membrane around tubules
in some cases is also a characteristic feature in nephrogenic adenoma but not in endometriosis.
(5) Urachal remnants: Urachal remnant is often an incidental finding and usually
consists of a single canal-like gland lined by urothelium. One third of them may also contain mucinous
epithelium . The surrounding stroma is fibromuscular in contrast to the endometrial type stroma in
endometriosis. In addition, urachal remnants are localized in the apex and anterior aspect of the
bladder dome. However, rarely urachal remnants and endometriosis may coexist in the same specimen
or even merge with each other .
(6) Primary bladder adenocarcinomas: They include urachal and non-urachal origins.
Histologically sometimes it is difficult to distinguish them. Diagnosis of urachal adenocarcinoma
requires specific clinicopathologic criteria. Urachal adenocarcinomas usually involve the dome or apex
of the bladder . Both urachal and non-urachal bladder adenocarcinomas are subdivided into mucinous,
enteric, not otherwise specified, signet ring cells, and mixed subtypes. In addition, non-urachal
adenocarcinomas also include clear cell carcinoma. Bladder adenocarcinoma should be easily distinguished
from endometriosis (with or without mucinous metaplasia) by their cytologic features and lack of
endometrial type stroma. Rarely primary bladder non-urachal adenocarcinomas may be deceptively bland
, but they typically demonstrate more cytologic atypia than endometriosis and do not have the
endometrial type stroma.
(7) Secondary adenocarcinomas of the bladder: These include metastatic adenocarcinomas
to the bladder and those secondarily involving the bladder from adjacent organs such as intestines,
uterus, cervix, and vagina. The distinction from endometriosis is usually easily made based on
clinical history, imaging data, cytologic features, and lack of endometrial stroma.
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