Malignant transformation of endometriosis within the urinary bladder

Abstract

Although endometriosis of the pelvic organs is common, endometriosis of the urinary bladder is extremely rare. Malignant transformation of atypical endometriotic foci is an uncommon but well-documented sequela, occurring in approximately 1% of cases. This article reports the fourth case in the English literature of clear cell carcinoma arising from foci of endometriosis within the posterior bladder wall.

Endometriosis, the presence of endometrial tissue outside of the uterus, is usually found in the ovary; the most common extraovarian site is the rectovaginal septum (1). The urinary bladder is involved in <1% of extragonadal endometriosis. Sampson documented the association of endometriosis with malignant tumors in 1925 and outlined three criteria for the diagnosis of malignant transformation: 1) the coexistence of carcinoma and endometriosis at the same site, 2) histological similarities between the carcinoma and endometriosis, and 3) exclusion of a malignant tumor elsewhere (2). In 1953, Scott established the additional requirement of a continuum between benign and malignant epithelium (3). These criteria have been challenging to capture within the same histologic section, but were successfully met in this case.

Seven cases of malignant transformation of endometriosis of the urinary bladder have been published: three involved endometrioid adenocarcinoma, one involved endometrial stromal sarcoma, and three involved clear cell carcinoma (1, 2, 4–7). Here we report the fourth case of clear cell transformation of vesical endometriosis found within the English literature.

CASE REPORT

A 54-year-old Caucasian woman presented with gross hematuria and a recent history of irregular menses. She was otherwise well and not on hormone replacement therapy. On endovaginal sonogram, a large hypervascular mass arising from the posterior wall of the urinary bladder was noted (Figure 1). This finding suggested a mucosal malignancy such as a transitional cell carcinoma. Also found was a 6.1 cm cyst of the right adnexa that was thought to be functional.

Figure 1.

Transverse view through the bladder on an endovaginal sonogram with color Doppler analysis reveals hypervascular flow within the mass (arrow).

A delayed-contrast enhanced computed tomography (CT) examination demonstrated a mass within the bladder lumen extending from the posterior bladder wall and into the bladder lumen (Figure 2). There was associated focal wall thickening along the posterior bladder wall surface abutting the anterior surface of the lower uterus/cervix region. A clear fat plane was not visible, and tumor invasion into the adjacent uterus was suggested. The wall thickening along the bladder wall likely represented the endometriotic foci.

Figure 2.

View through the bladder on a delayed postcontrast CT. (a) Axial view reveals an intraluminal mass in the bladder arising from the posterior wall of the bladder. (b) Sagittal view reveals an intraluminal mass arising from the posterior bladder wall with focal bladder wall thickening (short arrow). An incidental cystic lesion in the right ovary was felt to represent a follicular cyst (long arrow).

A transurethral resection of the bladder tumor was performed. The histology of the resection showed clear cell carcinoma involving the bladder wall, bladder mucosa, and submucosa with adjacent extensive endometriosis. The carcinoma was CK7 positive, CK20 negative, WT1 negative, P63 negative, and PAX8 positive, indicating probable Mullerian origin, with a metastasis from a primary clear cell carcinoma of the lower uterine tract unable to be ruled out.

The patient was taken back to the operating room for a total abdominal hysterectomy with bilateral salpingo-oophorectomy, cystectomy, lymph node dissection, and anterior vaginal wall resection. Residual clear cell carcinoma was identified histologically in association with endometriosis that involved the posterior bladder wall into the outer half of the muscularis propria (Figure 3). The tumor had a papillary, glandular, and cystic architecture with individual tumor cells having eosinophilic or clear cytoplasm with prominent hobnailing. The sections with tumor showed a continuum between benign endometriotic foci and malignant epithelium (Figure 4). Atypical epithelium within endometriotic foci was identified adjacent to the tumor and in other areas. These findings supported the idea that the clear cell carcinoma originated from malignant transformation of preexisting endometriosis within the bladder wall.

Figure 3.

(a) Clear cell carcinoma (short arrow) arising within a foci of endometriosis (long arrow) within the bladder wall. Hematoxylin and eosin, ×100. (b) High-power view of clear cell carcinoma. Hematoxylin and eosin, ×200.

Figure 4.

Continuum between benign endometrium and clear cell carcinoma in the bladder wall. Hematoxylin and eosin, ×100.

DISCUSSION

Endometriotic foci can involve the genitourinary tract in up to 20% of cases. The urinary bladder is the most common genitourinary site. Endometriosis predominantly occurs on the serosal surface of the dome of the bladder. These foci can progressively invade through the inner layers of the bladder wall and can present as an intramural mass. This can be indistinguishable from a primary bladder neoplasm on imaging studies (8, 9).

Imaging features of malignant transformation of endometriosis are not well defined in the literature. On ultrasound, the absence of low-level echoes and the presence of nodularity are suggestive of malignancy. Mural nodules within an endometrioma that demonstrate postcontrast enhancement on magnetic resonance (MR) imaging are highly suggestive of malignant transformation. Dynamic subtraction MR imaging is useful in detecting small mural nodular enhancement in a background of intrinsic T1 hyperintensity (a normal feature of an endometrioma). Enlargement of an endometrioma with loss of T2 “shading” (a relatively normal feature of an endometrioma) is also suggestive of malignant transformation (9–13).

The pathophysiology that leads to malignant transformation of endometriotic foci is not well understood. Endometriosis is generally considered to be a result of implantation or metaplasia, but is not considered neoplastic (14). Two plausible hypotheses have been proposed to explain the relationship between endometriosis and intraperitoneal cancer: 1) genetic defects allowing endometriotic implants to thrive and malignantly transform, and 2) defects in immune function allowing endometriosis to grow, leaving the patient more susceptible to subsequent malignant transformation (15).

It is known that extragonadal endometriosis occurs significantly less often than endometriosis of the ovary. More than 200 published cases of vesical endometriosis have been described, making the urinary bladder the most common urinary tract site of involvement. Vesical involvement includes superficial or deep tissue layers and adjacent perivesical soft tissue (14). Most vesical endometriosis occurs in the reproductive age group, but anecdotal cases have been described in postmenopausal women on hormone replacement therapy and rarely in men receiving estrogen therapy for prostate cancer.

The mean age of patients with ovarian clear cell carcinoma is 57 years old. Approximately one third of ovarian clear cell carcinomas can be associated with endometriosis (16). This raises the question of whether endometriosis should be considered a premalignant condition. Studies have shown that carcinomas associated with endometriosis are usually a lower stage, are in a younger population, and have a better prognosis than similar tumors unrelated to endometriosis. Clear cell carcinoma is the most common tumor complicating ovarian endometriosis, and endometrioid adenocarcinoma is the second most common (14). Approximately 90% of cases of extraovarian endometriosis lead to endometrioid adenocarcinomas, with only a few reported examples of clear cell carcinomas (14).

In making a diagnosis of malignant transformation of an endometriotic foci, it is imperative to establish the criteria described earlier. The continuum between benign and malignant epithelium within the lesion needs to be established, as outlined by Scott. Endometriosis must be distinguished from urachal glandular remnants and primary vesical adenocarcinoma (3). CD10 is positive in endometrial stromal cells and can be used as a helpful marker in suspected extraovarian endometriotic sites (1). Vesical mullerianosis encompasses three lesions: endometriosis, endocervicosis, and endosalpingiosis. Malignant transformation of endocervicosis or endosalpingiosis is considerably less common and must be distinguished from malignant transformation of endometriosis. Attention to architectural and cytologic features is key to making the correct diagnosis (1, 17).

Acknowledgments

Thanks to Richard Meyer, MD, for the initial histopathologic workup and diagnosis and to Carol Adair, MD, for subsequent diagnosis and staging of the patient.