Genitourinary Pathology

Bladder Endometriosis with Mucinous Metaplasia

Dengfeng Cao
Washington University in Saint Louis


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Final Diagnosis:
Bladder Endometriosis with Mucinous Metaplasia

Endometriosis of the bladder

Clinical Features
Bladder endometriosis was first reported in 1921 [1]. Since then more than 300 cases have been reported in the literature [2]. In women with endometriosis, bladder involvement is seen in approximately 1-2% cases [3] and bladder is the only site of involvement in 12% cases [4]. 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 [3]. The most frequent presenting symptoms in bladder endometriosis include urinary urgency, frequency, suprapubic pain, nocturia, hematuria, urge incontinence, and dyspareunia [3].

Although bladder endometriosis is a female disease, it is also very rarely seen in men who have received estrogen treatment for prostate carcinoma [5, 6, 7].


Slide 1
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Figure 1
Low power view shows variable-sized glands infiltrating within the muscularis propria of the bladder.
Figure 2
At high power view of figure 1, one gland in the center is lined by mucinous epithelium.
Figure 3
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.

Figure 4
Low power view of several glands within the muscularis propria in a different fragment: small tubular glands and two cystically dilated ones.
Figure 5
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).
Figure 6
Another fragment contains multiple tubular glands and few cystically dilated glands that are infiltrating the muscularis propria of the bladder.

Figure 7
Medium power view of the glands and their surrounding stroma of figure 6.
Figure 8
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.
Figure 9
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.

Figure 10
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.
Figure 11
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 [8, 9, 10, 11]. 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 [8, 9, 10, 11]. Microscopically 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%) [12]. However, mucinous metaplasia in bladder endometriosis was only very rarely observed [13].

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 [3]. For disease involving the muscularis propria, medical therapy is usually suboptimal and palliative only because the disease often recurs when therapy is discontinued [3, 14]. Transurethral resection rarely suffices as a definitive treatment [3]. Partial cystectomy with complete excision of all endometriosis is the treatment of choice for bladder endometriosis and gives the best result [3, 9, 10, 11].

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 cell carcinoma [15, 16, 17], 2 cases of endometrioid adenocarcinoma [18, 19], and 2 cases of adenosarcoma [9, 20]. One case of endometrial stromal sarcoma arising in bladder endometriosis was also reported in Japan [21].

Differential Diagnosis
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 [13, 22]. 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 [13, 22].

(2) Mullerianosis: Drs. Young and Clement first described 3 cases of bladder mullerianosis in 1996 [23]. 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 [23] though rarely florid cystitis glandularis with intestinal metaplasia and mucin extrasavation may focally involve the superficial muscularis propria [24]. In addition, cystitis cystica and cystitis glandularis do not have the endometrial type stroma as seen in endometriosis.

(4) Nephrogenic adenoma: Nephrogenic adenoma can demonstrate prominent infiltration among the muscle bundles of the lamina propria [25]. 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 [24]. Typically it contains tubules and cystic glands with inflammatory cells in the stroma though cystically dilated tubules may be predominant in some cases [25]. 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 [26]. 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 [27].

(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 [28]. 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 [29], 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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