Robot-assisted laparoscopic hysterectomy for endometrial cancer in a patient with Herlyn-Werner-Wunderlich syndrome

Abstract

Herlyn-Werner-Wunderlich syndrome, a rare Mullerian duct anomaly, includes a triad of uterine didelphys, obstructed haemivagina and ipsilateral renal agenesis. A 58-year-old woman with Herlyn-Werner-Wunderlich syndrome, reported of recurrent genital bleeding for 9 years, was finally diagnosed with endometrial cancer. She had a history of vaginal septum resection and nephrectomy of atrophic right kidney. MRI demonstrated uterine didelphys, a tumour filling the left uterus and a cyst on the right lateral side of the uterus. Robot-assisted hysterectomy, including bilateral salpingo-oophorectomy and pelvic lymphadenectomy, was performed. As the cyst communicated with the right cervix, but not with the urinary tract, a Gartner duct cyst was diagnosed. Uncertain diagnosis and delay of treatment in endometrial cancer may occur in patients with Herlyn-Werner-Wunderlich syndrome. We should preoperatively fully evaluate the anatomy of the uterus and surrounding tissues and plan surgical procedures, especially in patients with urogenital malformations.

Background

The incidence of Mullerian duct anomalies is approximately 4–7％ among all women.¹ Herlyn-Werner-Wunderlich syndrome is a rare Mullerian duct anomaly with a triad that includes uterine didelphys, obstructed haemivagina and ipsilateral renal agenesis. Although severe cases of endometrial cancer with Herlyn-Werner-Wunderlich syndrome have been reported,² no reports on the surgical strategy were found. Herein, we describe the use of robot-assisted hysterectomy for endometrial cancer in a patient with Herlyn-Werner-Wunderlich syndrome and discuss surgical procedures.

Case presentation

A 58-year-old woman (gravida 2, para 1） reported recurrent genital bleeding for the last 9 years. The time of menopause was unknown. She had visited a primary care clinic multiple times and endometrial biospy has been performed several times. However, she was diagnosed with endometrial cancer for the first time. Her body mass index is 24.8 and standard body shape. She had no medical histories (hypertension, diabetes, obesity, etc), which were associated risk factors for developing endometrial hyperplasia and cancer. She had a history of vaginal septum resection and nephrectomy of an atrophic right kidney at the age of 22. Her grandparents had a history of colorectal cancer and her father had prostate cancer.

Investigations

On examination, the vaginal wall was irregular following surgery and only one uterine ostium was confirmed. Endometrial biopsy showed atypical endometrial hyperplasia. Pelvic MRI demonstrated uterine didelphys with multiple myomas and a tumour filling the left uterus without myometrium or cervical invasion. It had a high signal intensity on T2-weighted images, high signal intensity on diffusion-weighted imaging and showed poor enhancement. In addition, a tubular structure was noted on the right lateral side of the uterus (figure 1). Chest, abdominal and pelvic CT demonstrated no evidence of metastasis. CA19–9 level was slightly elevated (64.9 U/mL). No other tumour marker level was elevated (CA-125 12.5 U/mL; carcinoembryonic antigen 0.9 U/mL). Endometrial curettage was performed sufficiently under intravenous anaesthesia, and a grade 2 endometrioid carcinoma was detected.

Figure 1.

Pelvic MRI (A) axial T2-weighted imaging. Uterine didelphys with multiple myoma and tumour filling the left uterus (asterisk). cyst (arrow) on the right lateral side of the uterus. (B) Sagittal T2-weighted imaging. Cyst (arrow) showing a tubular structure.

Differential diagnosis

We diagnosed grade 2 endometrioid carcinoma and cT1aN0M0 (FIGO2008) by MRI and CT imaging. Because the tubular structure was close to the cervix and vagina, it could be a residual ureter rather than a fallopian tube. We thought that the cyst and bladder might be connected.

Treatment

Robot-assisted hysterectomy including bilateral salpingo-oophorectomy and pelvic lymphadenectomy was performed (figure 2). We closed the uterine ostium by suturing and coagulated the fallopian tubes bilaterally to prevent tumour scattering at the beginning of surgery. We did not use a uterine manipulator. We found an irregular cyst in the retroperitoneal cavity on the right side of the uterus, which was easily detached from the surrounding tissue. Considering the possibility that the cyst and bladder are connected, we detached the cyst from the uterus and tried to leave the cyst. However, the cyst containing serous fluid was ruptured. The resected uterus was didelphic, and we found tumours on the fundus and lower body of the left uterus and a hole from the right cervix to the cyst (figure 3). Since tumour cells may remain in the cyst, we performed a cystectomy. The cyst and bladder were not connected. There was no peritoneal dissemination or enlarged lymph nodes.

Figure 2.

Surgical findings. (A) Uterine didelphys with multiple myoma. (B) Cyst (asterisk) on the right lateral side of the uterus (triangle). (C) Cystectomy after hysterectomy. Cyst (asterisk), vagina (square).

Figure 3.

Surgical specimen. (A) Tumours (arrow) on the fundus and lower body of the left uterus. (B) A hole (arrow) from the right cervix to the cyst.

Outcome and follow-up

Histopathological examination revealed a grade 1 endometrioid carcinoma arising from the fundus and lower body of the left uterus invading the myometrium slightly but not the cervix. There were no lymphovascular invasion or lymph node metastasis. However, there were micrometastases on the surface of the left ovary, and peritoneal fluid cytology was positive. The cyst wall was lined by columnar, nonciliated, nonmucinous cells, consistent with a diagnosis of Gartner duct cyst (figure 4). The patient was diagnosed with endometrial cancer, pT3aN0M0 (8th UICC), stageⅢA (FIGO2008) and Herlyn-Werner-Wunderlich syndrome. This tumour showed low microsatellite instability. She underwent six cycles of chemotherapy with paclitaxel and carboplatin every 3 weeks and presented no evidence of disease for 6 months after chemotherapy.

Figure 4.

Pathological findings. (A) Lower body of the left uterus (H&E,30×). G1 endometrioid carcinoma invading the myometrium slightly. (B) Left ovary (H&E,15×). Metastasis on the surface. (C) Gartner duct cyst (H&E,75×). The cyst wall is lined by columnar cells.

Discussion

Endometrial cancer associated with uterine anomalies is extremely rare, with only around 30 cases reported in the past 25 years.^{2 3} About 90% of them were endometrioid carcinoma. In the reviews by Gao et al, uterine didelphy was the most common anomaly (52%) and endometrioid cancer involving only one horn of uterus was more common than in both horns (77％).² The diagnosis rate of endometrial biopsy in endometrial cancer was as high as 81.7％ when an adequate specimen was obtained.⁴ A majority of endometrial cancers are diagnosed early (80% in stage Ⅰ).⁵ However, the preoperative pathological diagnosis rate in endometrial cancer with uterine anomalies was only 68％. They speculated that biopsy failure and sampling of the negative cavity resulted in false-negative diagnosis. Only 64％ had stage Ⅰ cancer.² Uterine anomalies delay the diagnosis and treatment of endometrial cancer. In our case, the patient had genital bleeding for 9 years and visited the other clinic several times; however, she was only diagnosed with endometrial cancer in stage ⅢA at her visit to us. Endometrial cancer on the closed side of a didelphic uterus is particularly difficult to detect, however, she had endometrial cancer on the open side. An MRI examination should have been performed earlier to evaluate the morphology and tumour of the uterus.

Herlyn-Werner-Wunderlich syndrome is a rare Mullerian duct anomaly with a triad that includes uterine didelphys, obstructed haemivagina and ipsilateral renal agenesis. It is classified as U3 in the ESHRE/ESGE classification of female genital anomalies¹ and as Class Ⅲ or Ⅳ in the AFS/ASRM classification of Mullerian anomalies.⁶ However, female genital malformation is complicated and the appropriate categorisation is controversial. The anomalies most frequently diagnosed incorrectly are the distal Wolffian anomalies.⁷ Mullerian (paramesonephric) ducts give rise to the fallopian tubes and uterus, and the Wolffian (mesonephric) ducts are typically absorbed. When the Wolffian duct persists as vestigial remnants in the anterolateral vaginal wall, it is called a Gartner duct cyst, which may coexist with ureteric ectopia inserting into an area other than the superolateral portion of the trigone. This is caused by failure of separation of the ureteric bud from the Wolffian duct. When a Gartner duct cyst with ureteric ectopia communicates with the urinary tract, surgical excision can result in an iatrogenic urinary fistula.⁸ In this case, we thought that the cyst and bladder might be connected and were worried about bladder damage after surgical excision. However, the cyst was communicating with the right cervix, and not with the urinary tract. Voiding cystourethrogram and cystourethroscopy are reported to be important in establishing continuity of the Gartner duct cyst and urinary tract.⁸ If these examinations had been performed in this case, the surgical strategy would have changed. Specifically, we would have performed hysterectomy along with the cyst rather than attempting to detach the cyst from the uterus. We should fully evaluate the anatomy of the uterus and surrounding tissues, and develop a surgical strategy.

Minimally invasive surgery is the standard approach in women with endometrial cancer. The proportion of endometrial cancer cases that underwent minimally invasive surgery at NCCN centres was 86.5%, of which 72.5% were robot-assisted hysterectomy.⁹ Robot-assisted surgery is also useful for urogenital malformations. The robotic approach allows good visualisation, intraoperative collaboration between multiple specialties in patients with complex anatomy and easy dissection in a narrow pelvis.¹⁰ In the present case, robot-assisted surgery helped to confirm the anatomy closely and release the appropriate layers.

Patient’s perspective.

I was anxious because I had genital bleeding for 9 years. I wonder why the cause could not be identified immediately and when the endometrioid cancer had developed. I am satisfied that the cause is clear and the tumour has been completely removed.

Learning points.

• Endometrial cancer in a patient Herlyn-Werner-Wunderlich syndrome is very rare. One should be aware of uncertain diagnosis and delayed treatment.

• We should preoperatively fully evaluate the anatomy of the uterus and surrounding tissues and plan surgical procedures.

• Endometrial cancer in a patient Herlyn-Werner-Wunderlich syndrome is very rare. One should be aware of uncertain diagnosis and delayed treatment.