Müllerianosis of the urinary bladder with unilateral complete renal agenesis: a rare coincidental finding causing delayed presentation

Müllerianosis is a rare benign lesion of the urinary bladder, which is constituted by two or more of the Müllerian-duct-derived tissues. We report a 45-year-old perimenopausal multiparous woman presenting with occasional episodes of dysuria and lower abdominal discomfort of recent duration. Ultrasound examination revealed a well-defined lesion in urinary bladder and the absence of left kidney. Contrast-enhanced CT of the abdomen confirmed the findings. During diagnostic cystoscopy, haemorrhagic polypoidal lesions were noted in the left side of the posterolateral wall and dome of urinary bladder along with the absence of left ureteric orifice. Transurethral resection of the bladder lesions was done and histology examination confirmed the diagnosis of Müllerianosis. She was administered Luteinizing hormone-releasing hormone (LHRH) agonist monthly. At 1 year of follow-up, cystoscopy showed only scar tissue. The case was reported for the rarity of Müllerianosis noted in a patient with unilateral agenesis of kidney, a possible cause of delayed presentation.

pathology, urological surgery, urology, urological cancer

Müllerianosis of the urinary bladder is a rare type of lesion having mixture of two or more tissue components derived from paramesonephric (Müllerian) duct, namely endocervix, endometrium and endosalphinx.1 It often affects the base and dome of the bladder. Even though these lesions are benign, a rare case of malignant transformation has been reported.2 Most of the patients are symptomatic and require intervention. We report a rare case of Müllerianosis of urinary bladder in a patient with unilateral renal agenesis. Case presentation A 45-year-old woman presented with dysuria and lower abdominal discomfort of short duration. She is married and had two normal vaginal deliveries in the past. Her menstrual habits were irregular with oligomenorrhagia. She denied other lower urinary tract symptoms (LUTS) and gross haematuria. Her history was significant for hypertension and was on regular medications. She never had any pelvic surgeries in the past. The gynaecological examination was unremarkable except for hypertrophied cervix with erosion and palpable mass in pelvis. Investigations Her routine blood investigations were of normal values. Urine dipstick examination showed microscopic haematuria. Urine cytology was negative for malignant cells. Transabdominal ultrasound examination showed a polypoidal lesion (figure 1A, B) with increased vascularity in the left side base of the urinary bladder with absent left kidney. Her ovaries and uterus were normal. Contrast-enhanced CT of the abdomen confirmed absent left kidney and compensatory hypertrophy of right kidney with a small angiomyolipoma (figure 1C) and enhancing polypoidal lesion in the left posterolateral wall of the urinary bladder (figure 1D). Uterus was normal. Diagnostic cystoscopy showed 1 cm size polypoidal haemorrhagic lesion in the dome of bladder (figure 2A) and sessile non-papillary growth of 4×4 cm size in the left posterolateral wall of the bladder with surrounding oedema (figure 2B). Left ureteric orifice and left half of trigone was not seen. Treatment She underwent transurethral resection of the bladder tumours (TURBT). Both the lesions in urinary bladder were completely excised. During resection, haemorrhagic exudate was noted from the lesion in the dome of urinary bladder. Deep muscle biopsy was taken from the base of left posterolateral wall lesion. Histopathological section showed hyperplastic urothelium, benign endometrial cuboidal glands with surrounding endometrial stroma deep in the muscularis propria (figure 3A, B) and the presence of benign columnar endocervical glands with the presence of mucin in lamina propria of bladder wall (figure 3C). Immunohistochemistry (IHC) showed cytoplasmic positive staining with CA125 in the endometrial glands (figure 4A), strong nuclear positivity with oestrogen receptor (ER) (figure 4B) and progesterone receptor (PR) (figure 4C) in endometrial and endocervical glands. GATA3 was negative in glands and positive in urothelium (figure 4D). Uroplakin is negative in endocervical glands present in lamina propria (figure 4E). Diagnosis of Müllerianosis was confirmed with the presence of endometrial and endocervial tissues with mucin secretion. Outcome and follow-up In view of benign nature of Müllerianosis occurring in a perimenopausal woman, it was decided to keep her in medical management till menopause. She was started on leuprolide acetate 3.75 mg intramuscular every month till menopause. She had an uneventful recovery. One year after TURBT, she was voiding well. Her renal function was normal. The cystoscopy done during follow-up showed only scars of previous resections. No evidence of mass lesion was seen in the ultrasound imaging. She stopped having menstruation for the last 9 months and hence, the hormonal suppression was stopped.

Müllerianosis of the urinary bladder is a rare lesion, first described by Young and Clement.1 The lesion is the benign ectopic mixture of two or more of the Müllerian duct derivatives, namely, endometrial, endocervical and endosalphinx tissues in lamina and muscularis propria of the urinary bladder. Apart from the urinary bladder, it is also been reported in ureter, inguinal lymph nodes, chest and spinal cord.3 Even though it is a benign lesion, malignant transformation of Müllerianosis to endometroid carcinoma has been reported.2 It differs from endometriosis by the fact that the disease is well within the urinary bladder, whereas endometriosis of the urinary bladder is by contiguous involvement from outside. The pathogenesis of Müllerianosis is unknown; possible theories of occurrence are (1) implantation theory and (2) metaplastic theory.4 The implantation theory propounds that the Müllerian tissue gets implanted in the bladder during pelvic surgery. However, it fails to explain the occurrence of the condition in patients who never had pelvic surgery. The metaplastic theory explains that there are multipotent cells in the urinary bladder that can differentiate to Müllerian tissues like endometrial, endocervical and tubal tissues.4 This theory is popularly accepted and supported by the following facts: (1) the presence of the lesion always in posterior wall of urinary bladder, which is sensitive for female hormones4 and (2) the histological presence of tubular epithelium in continuity with lesions like cystitis glandularis and cystitis cystica, which are positive for ER and PR.5 Other possible theory of Müllerianosis is secondary Müllerian system. During peritoneal development, secondary Müllerian system may retain its multipotency to differentiate to endometrial, endocervical and tubal tissues.3 Storage LUTS, haematuria, pelvic pain and dysuria are often the presenting symptoms. Asymptomatic presentation and upper tract involvement have not been noted in the reported cases of Müllerianosis. In our case, the absence of left renal system delayed the presentation due to lack of obstruction to upper tract. Classically, cystoscopy clinches the diagnosis by noticing a polypoidal mass in the posterior wall or dome of urinary bladder. The appearance of haemorrhagic cysts like chocolate cysts are also noted in Müllerianosis.6 Jiménez-Heffernan et al have demonstrated that urine cytology could be useful in differentiating the lesion from urothelial tumours; however, the results are not consistent and reproducible by many authors. The presence of macrophages and tall mucin-rich cells might point towards Müllerianosis rather than carcinoma which is characterised by dysplastic urothelial cells and signet ring cells.7 8 Histologically, the diagnosis is established by the appearance of gland-type architecture in lamina propria and muscularis propria of the urinary bladder with lining by endometrial, endocervical and fallopian tube epithelium with mucin secretion.1 During IHC, the lining epithelium of these glands are positive for ER and PR indicating hormonal sensitivity. The glandular part can be positive for CA125 marker, as in our case. Transurethral resection of the lesion is the treatment of choice in Müllerianosis. Partial cystectomy is done for more symptomatic larger lesions, often in combination with transurethral resection.9 Concomitant ureteric reimplantation may be necessary in selected cases.10 It is also done in certain cases when concurrent hysterectomy is performed.11 After initial surgery, hormonal suppression is often followed as additional treatment as the Müllerian tissues are hormonal responsive.10 Reducing hormonal responsiveness improves the symptoms secondary to the lesion and reduce the size after 3–6 months of treatment.6 12 Watchful waiting is also given as an option for those who have trivial symptoms.12 Even though the lesion is a benign one, regular follow-up may be required to observe for recurrence which is rare. Association of Müllerian anomalies are often seen in females with unilateral renal agenesis to extent of 30%.13 Müllerian duct anomalies like unilateral ovarian agenesis, unicornuate uterus and absent of ipsilateral horn, tubal agenesis occurs in patients with unilateral renal agenesis.14 However, Coincidental presence of Müllerianosis and unilateral renal agenesis has not been reported so far. It needs to be found whether this finding is a mere coincidental finding or a rare embryological abnormality. Learning points. Müllerianosis is a rare benign bladder lesion in women, which can mimic malignant tumours. Transurethral resection ensures diagnosis and complete resection of the lesion. Partial cystectomy is required in those with larger lesions. Hormonal therapy is useful in regression of Müllerianosis after complete resection. Acknowledgments We acknowledge Mr Balasubramanian Rajendran, MIOT International, for editing and summation of the images. Footnotes Contributors: SR and LM prepared the manuscript, provided patient care and did the literature review. JD and SCN did the evaluation, analysis of the study and corrected the manuscript. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Patient consent for publication: Obtained. Provenance and peer review: Not commissioned; externally peer reviewed.

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