Endometrial cancer of both uterine horns in a premenopausal patient with uterine didelphys: Surgical approach and considerations for adjuvant treatment

Highlights

• •Concomitant diagnosis of endometrial cancer (EC) and uterine didelphys is rare.
• •Robotic surgery can safely be performed in patients with EC uterine didelphys.
• •A multidisciplinary team is required to approach treatment and cancer surveillance in those with Mullerian anomalies.

1. Introduction

Mullerian duct anomalies are rare developmental malformations of the female reproductive tract that arise from abnormal fusion or incomplete formation of the paramesonephric ducts. The incidence of these anomalies is likely underestimated, but reported to be between 4–7 % (Grimbizis et al., 2013). Uterine didelphys is a form of Mullerian anomaly defined as the presence of two uterine horns, two cervical canals, and often two vaginal cavities separated by a longitudinal septum (Grimbizis et al., 2013). While endometrial cancer (EC) is one of the most common gynecologic malignancies, there are very few published cases of EC in patients with uterine didelphys (Gao et al., 2017, Bairaktaris et al., 2023). Notably, the occurrence of EC in both uterine horns is exceptionally rare (Chen et al., 2022, Fanfani et al., 2006). We discuss a case of a premenopausal female with uterine didelphys and EC of both uterine horns. To our knowledge, this is the youngest patient to have concomitant uterine didelphys and EC, and her care involved a unique multidisciplinary team approach between reproductive endocrinology, gynecologic oncology, and radiation oncology specialists.

2. Case description

This is a 27-year-old gravida 0 female who initially presented to an outside community emergency department (ED) with heavy vaginal bleeding and associated syncope. Her past medical history was significant for class III obesity with a body mass index (BMI) of 45 kg/m². She had regular periods with occasional intermenstrual bleeding and mild dysmenorrhea relieved with over-the-counter medications. She had never been sexually active, used tampons, or had a pelvic exam. A transabdominal ultrasound in the ED showed a 6.9 × 5.5 cm non-vascular mass in the lower uterine segment with questionable hydrocolpos. She was discharged home from the ED with a 10-day course of medroxyprogesterone 10 mg, which improved her bleeding profile.

Additional workup in the outpatient setting was notable for a pelvic MRI which showed 2 distinct endometrial canals, 2 separate cervices, and 2 vaginal canals. This favored a diagnosis of uterine didelphys. Obstructing hematocolpos of the right cervical canal and upper vagina with right hematometra was noted with secondary mass effect on the left endometrial canal (Fig. 1). A pelvic exam was recommended at multiple clinic visits, however the patient declined. She was then referred to our institution’s reproductive endocrinology and infertility (REI) clinic for likely Mullerian anomaly, favoring uterine didelphys.

Fig. 1.

Pelvic MRI showing 2 distinct endometrial cavities with greater distension of the left endometrial canal compared to right endometrial canal.

At the initial REI consult visit, a single digit pelvic exam was performed noting a small introitus, intact hymen, and vagina deviated to the right with notable bulge on the right aspect of the vagina. A bedside ultrasound showed uterine didelphys with a normal right uterine horn and clot in the right lower uterine segment. A left hematometra with effaced cervix and hematocolpos was also visualized. Review of prior CT imaging showed normal kidneys, which ruled out Obstructed Hemivagina with Ipsilateral Renal Agenesis (OHVIRA) syndrome. This is a rare congenital Mullerian duct anomaly with uterine didelphys, unilateral obstructed hemivagina, and ipsilateral renal agenesis. Given uterine didelphys with obstructed left hemivagina, the patient was scheduled for hysteroscopic resection of vaginal septum.

Two weeks later, she was admitted to her local hospital with pain, worsening hematocolpos on ultrasound and heavy vaginal bleeding. Transabdominal ultrasound showed a right uterine horn measuring 16.2 × 6.5 × 9.1 cm with an endometrial echo complex of 15 mm and the left uterine horn measuring 16.2 × 4.8 × 9.1 cm with endometrial echo complex of 13 mm. She subsequently underwent a dilation and curettage (D&C). Final pathology from the D&C showed a grade 1–2 endometrial adenocarcinoma in both uterine horns and she was referred to a gynecologic oncologist. The initial planned surgery of hysteroscopic vaginal septum resection with REI was subsequently cancelled given this new diagnosis.

At the time of her gynecologic oncology consult, she was counseled on fertility sparing management options for endometrial cancer given her young age. The patient expressed that she desired definitive management of her cancer and did not desire future pregnancies. Through shared decision making, she was scheduled for a hysterectomy with ovarian preservation. Risks and benefits of ovarian preservation were discussed in detail with the patient and her family. Due to her premenopausal status with multiple years until likely onset of menopause, as well as increased risk for cardiovascular comorbidities given her BMI, ovarian preservation was planned. The patient was counseled on the long-term health benefits of continued endogenous estrogen exposure, as well as oncologic safety of ovarian conservation with her low grade endometrial cancer (Wright et al., 2016, Matsuo et al., 2016).

For surgical management, she underwent a robotic total laparoscopic hysterectomy with mini laparotomy for intact specimen removal. A V-Care uterine manipulator was used. During the surgery, sentinel lymph node mapping was attempted, however due to patient’s poor tolerance of steep Trendelenburg positioning and suboptimal visualization of the retroperitoneum, decision was made to forgo lymph node dissection. Colpotomy was made anteriorly but was difficult to follow circumferentially due to uterine didelphys and the patient’s body habitus. A Pfannenstiel incision was made to complete posterior colpotomy and the specimen was removed without complication. Bilateral fallopian tubes were not removed due to patient’s poor tolerance of surgical positioning and limited visualization. She was subsequently discharged home on postoperative day 2. Final pathology showed FIGO stage II, grade 1 endometrioid carcinoma, with 46 % myometrial invasion, intact expression of mismatch repair proteins, and negative lymphovascular invasion of the bilateral uterine horns (Fig. 2,Fig. 3).

Fig. 2.

Gross image of the uterus bisected anterior (left) and posterior (right). The uterus contains dual cervical canals, separated by a thin septum. A 2.3 × 1.2 cm tan, soft lesion is at the anterior right cervical canal, extending to the right lateral wall and midline septum. The left cervical canal is lined by a tan-white ragged mucosa displaying the normal herringbone pattern. The right endometrial cavity is lined by diffuse red-brown excrescences lining the anterior and posterior walls. The left endometrial cavity is lined by tan-white endometrium, with a 3.5 × 2.5 × 1.3 cm exophytic lesion located at the left endometrial dome. This lesion extends to the anterior, posterior and lateral walls, and protrudes into the lower uterine segment.

Fig. 3.

Endometrial endometrioid carcinoma, FIGO grade 1 in the bilateral uterine lower segments of the case with uterine didelphys. Neoplastic cells forming crowed glands were present in the right lower uterine segment (A, right horn, H&E 200×). The neoplastic cells were enlarged with vesicular chromatin, prominent nucleoli and variation of size (B, right horn, H&E 400×). Several areas showed smaller irregular glands infiltrating into myometrium with desmoplastic reaction (C, right horn, H&E 200×). Endometrial endometrioid adenocarcinoma with similar architectural and cytologic atypia were present in the left lower uterine segment (D, left horn, H&E 200×).

Postoperatively, the patient was referred to radiation oncology for discussion of adjuvant treatment options given her FIGO stage II disease. During her consultation, options for whole pelvic radiation, vaginal cuff brachytherapy (VBT), and combination treatment with whole pelvic radiation and VBT were reviewed. Chemotherapy was also briefly discussed in lieu of pelvic radiation, as a method to decrease distant and pelvic recurrences, but not necessarily vaginal cuff recurrences. The patient was counseled that VBT would be a good option for local vaginal control, but would not provide decreased risk of pelvic recurrence compared to whole pelvic radiation. She was further counseled that whole pelvic radiation would increase side effects and would not provide as good of local vaginal cuff control as VBT. The patient was aware that with VBT alone, she would have an increased risk of both regional and distant disease compared to receiving whole pelvic radiation. After discussion of risks and benefits of all options, the patient and her family expressed significant concerns over toxicity with pelvic radiation that would potentially limit pelvic exams in future surveillance visits. Therefore, treatment planning for VBT was initiated.

During initial placement of the brachytherapy device, the vagina was examined and noted to have a right greater than left vaginal cavity. A 2.5 cm cylinder was placed in the right vagina and 2.0 cm cylinder in the left vagina. During CT and MRI for brachytherapy treatment planning, it was noted that the patient still had a portion of her right and left cervix that remained in situ. This tissue extended beyond the vaginal apex and was not able to be safely covered with the planned radiation dose. After multidisciplinary discussion, it was determined that the margin status of her initial resection was unclear, and decision was made to proceed with trachelectomy to ensure no residual disease, as well as vaginal septum resection to allow for surveillance exams. The patient underwent a vaginal septum resection, robotic assisted trachelectomy and cystoscopy and was discharged home on post operative day 1. Final pathology showed no residual disease. After further discussion with the Radiation Oncology team and shared decision making with the patient and her family, the patient elected to forgo radiation unless her cancer were to recur, given her age, desire to avoid toxicity of radiation treatments, and complete resection of cervical tissue with trachelectomy. To date, the patient has had 9 months of surveillance visits without recurrence of disease.

3. Discussion

EC in patients with uterine anomalies is very rare, with only 32 cases reported in the literature to date (Bairaktaris et al., 2023). To our knowledge, the case presented represents the youngest patient with uterine didelphys and EC. Additionally this is only the fourth case report of EC occurring in both uterine horns (Bairaktaris et al., 2023, Chen et al., 2022, Bhalla et al., 2005). In this patient, the diagnosis of uterine didelphys was made prior to her endometrial carcinoma diagnosis, and she had not undergone endometrial sampling prior to scheduling of hysteroscopic vaginal septum resection. Although she had class III obesity, a significant risk factor for EC development, prior ultrasounds demonstrated normal endometrial echo complexes for a premenopausal woman, in addition to overall regular menses. Only about two weeks after her initial REI consult did she present to the ED with heavy vaginal bleeding that required a sharp D&C of both uterine cavities. This eventually revealed grade 1–2 endometrial adenocarcinoma of both uteri. While most endometrial cancers are diagnosed at an early stage due to abnormal uterine bleeding or postmenopausal bleeding, the diagnosis rate via endometrial biopsy of EC in patients with uterine anomalies is only 68 % (Kobayashi et al., 2021). This may likely be secondary to sampling of the negative uterine cavity, resulting in a false negative diagnosis. It is significant that the patient presented here had thorough endometrial sampling via D&C of both uterine cavities, which was facilitated by an already established diagnosis of uterine didelphys.

Surgical planning for EC patients with uterine anomalies is challenging due to uterine size and potentially suboptimal uterine manipulator placement with two cervices and two vaginal canals. Chen et al describe using a uterine manipulator to elevate one side of the uterus toward the opposite side to expose the ipsilateral para-uterine field (Chen et al., 2022). While minimally invasive surgery via laparoscopy is the standard of care for early-stage EC, only three cases of robotic and laparoscopic surgeries have been reported in patients with uterine didelphys and EC (Chen et al., 2022, Kobayashi et al., 2021, Vanichtantikul et al., 2020). These cases performed surgical staging with a complete pelvic lymphadenectomy, without sentinel lymph node mapping. While our patient did require a mini laparotomy via Pfannenstiel incision for specimen removal and to complete the posterior colpotomy, the majority of the hysterectomy was successfully performed robotically. Due to her BMI and inability to tolerate steep Trendelenburg, the decision was made to forgo lymph node sampling after indocyanine green injection. The only case report of sentinel lymph node mapping in a patient with EC and uterine didelphys was performed via exploratory laparotomy (Sassine et al., 2021).

It is important to note that the presence of residual cervical tissue that was noted after the patient’s hysterectomy was most likely due to her poor tolerance of Trendelenberg throughout the surgery. With her large body habitus, the patient had repeated episodes of decreasing oxygen saturation while in Trendelenberg, which severely limited optimal visualization of the cervical tissue, despite use of a uterine manipulator. This necessitated expeditious completion of the surgery.

Adjuvant VBT for EC patients with uterine didelphys requires a closely tailored fit of the brachytherapy device with the vaginal mucosa. Due to separate vaginal canals, often separated by a septum, the standard cylinder is not typically suitable. While vaginal septum resection was not able to be performed at time of hysterectomy for this patient given her poor tolerance of Trendelenberg, we would recommend this for future cases. Morris et al describe a “moulage” technique in which a constructed vaginal mold is used to ensure a precise fit of the brachytherapy cylinder in the vaginal vault (Morris et al., 2012). In our patient, two different size cylinders were placed in each vaginal canal, however due to the residual cervical tissue that was identified on imaging during radiation planning, VBT was not performed and a trachelectomy with vaginal septum resection was subsequently carried out. As there was no residual cervical disease from the second surgery, decision was made to forgo VBT given patient’s young age and desire to reserve adjuvant radiation treatment as an option should recurrence occur. This demonstrates the importance and challenges with full specimen resection in patients with uterine anomalies as well as the complexity of the decision-making process that goes into administration of VBT and adjuvant therapy in young patients with EC.

4. Conclusion

In summary, we report a case of EC in both uterine horns of a premenopausal woman with uterine didelphys. This case is unique in that robotic surgery was used for both the hysterectomy and trachelectomy, compared to other similar cases in the literature that performed an open surgical approach. To date, this is the youngest patient reported with EC and uterine didelphys. The challenges of adjuvant treatment planning involving VBT in this patient illustrate the considerations that must be taken in young women. While Mullerian anomalies are rare, the care of this small subset of patients with uterine malignancies requires a multidisciplinary approach, often incorporating subspecialists in REI, gynecologic oncology, and radiation oncology.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

CRediT authorship contribution statement

Meyha Swaroop: Writing – review & editing, Writing – original draft, Conceptualization. Anna Nevels: Writing – review & editing, Visualization, Resources. Meg Hubregsen: Writing – review & editing, Writing – original draft, Resources. Janelle Darby: Writing – review & editing, Supervision, Project administration.