Active surveillance of an endometriosis-related, hormone-responsive pelvic adenosarcoma during pregnancy: A case report

A 32-year-old G2P0010 presented to our Gynecologic Oncology clinic in September 2023 at 16 weeks of gestation for evaluation of a newly diagnosed extrauterine adenosarcoma. The patient had a history of pelvic pain, intermenstrual bleeding, and rectal and vaginal pain predating pregnancy that had been evaluated at an outside institution. In June 2020 (3 years prior to cancer diagnosis), she underwent excision of a 4.5 x 3.6 x 0.5 cm vaginal mass; pathology was consistent with endometriosis. The mass was not completely resected; thus, an MRI was completed and revealed a residual 4.7 x 3.8 x 3.3 cm irregular and slightly spiculated mass in the pelvic cul-de-sac immediately adjacent to the posterior cervix, lower uterus, superior vagina, and rectum. A CT-guided biopsy confirmed endometriosis. Medical therapy was not initiated due to pregnancy desires. In May 2021, the patient conceived her first pregnancy, which miscarried during the first trimester. She was subsequently started on the gonadotropin-releasing hormone (GnRH) antagonist elagolix for management of endometriosis. In January 2023, repeat MRI showed a dimensionally stable pelvic mass, and the patient discontinued elagolix under the direction of her local physician to attempt conception. MRI in March 2023 redemonstrated a stable 4.0 x 3.3 x 3.2 cm enhancing soft tissue mass in the rectovaginal space with possible cervical and rectal involvement. In August 2023 she presented with a positive pregnancy test and vaginal bleeding; exam was notable for multiple large polyps originating from the posterior vaginal fornix without a morphologically recognizable cervix. Rectovaginal exam revealed a similar polypoid mass located approximately 5 cm from the anal verge, and sigmoidoscopy showed near complete obstruction of the rectum. Biopsy of the vaginal and rectal masses showed mullerian adenosarcoma without poor prognostic factors (lymphovascular invasion, high-grade sarcomatous component, heterologous elements, or sarcomatous overgrowth) ( Fig. 1 ). The sarcoma cells were hormone-receptor positive, low grade, and expressed both ER (70%) and PR (100%). An outside institution recommended pregnancy termination with radical surgical resection of the tumor, however the patient desired to continue the pregnancy and presented to our institution for a second opinion. Fig. 1 Low-grade adenosarcoma (50X magnification) with atypical, mitotically active stroma showing periglandular condensation and benign glands with phyllodes-like architecture. Insert: Associated stroma with decidualization and mitotic activity (400X). Low-grade adenosarcoma (50X magnification) with atypical, mitotically active stroma showing periglandular condensation and benign glands with phyllodes-like architecture. Insert: Associated stroma with decidualization and mitotic activity (400X). Following multidisciplinary tumor board review, two options were proposed: 1) termination of pregnancy to expedite definitive treatment, or 2) continuation of the pregnancy, intestinal diversion, and surveillance with MRI every 4–6 weeks. The patient strongly desired pregnancy continuation and underwent an uncomplicated laparoscopic diverting loop sigmoid colostomy in September 2023. Exam at that time revealed a polypoid vaginal mass extending to the introitus and a large pelvic mass extending to bilateral pelvic sidewalls, invading through the rectovaginal septum, and completely obstructing the rectum. On cystoscopy, the bladder was not involved. Restaging MRI measured the mass at 8 x 11.7 x 11.7 cm ( Fig. 2 ). Over the antepartum interval the mass grew to 11.5 x 9.1 x 14.4 cm in October 2023 then 13.7 x 9.7 x 14.7 cm in December 2023. After discussion with Maternal Fetal Medicine and Neonatology, cesarean delivery was planned at 30 weeks of gestation due to continued tumor growth in the context of the potentially stimulating hormonal milieu of pregnancy. After completion of a course of antenatal corticosteroids, the patient underwent a classical cesarean delivery through a midline vertical incision at 30w3d gestation with delivery of a preterm female infant weighing 1460 g; there was no evidence of peritoneal disease upon exploration. Placental pathology revealed a 248-gram placenta (small for gestational age, <10%) with villous edema but no other pathologic abnormalities. One week postpartum, she began dual antiestrogen therapy with the GnRH agonist leuprolide and the aromatase inhibitor letrozole. At 4 weeks postpartum, MRI showed a 50% decrease in the size of the mass to 5.4 x 6.1 x 7.7 cm ( Fig. 3 ). Imaging 2 months later showed continual decrease in the size of the mass to 3.5 cm in greatest dimension ( Fig. 3 ). The patient underwent definitive surgical management in April 2024 (4 months postpartum), consisting of an exploratory laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial vaginectomy, low anterior resection with end-to-end anastomosis, omental flap, colostomy closure, and temporary diverting loop ileostomy. Pathology demonstrated a 5 mm focus of residual viable low-grade mullerian adenosarcoma in a background of treatment effect and extensive, deeply infiltrative endometriosis. Admixed treated tumor and deeply infiltrative endometriosis spanned from the posterior cervical and vaginal mucosa through the anterior rectal muscularis propria to involve the rectal mucosa, with additional extension into the myometrium of the uterine corpus. Her postoperative course was complicated by midline wound separation and post-coital vaginal cuff separation. Hormonal therapy was not continued post-operatively due to severe arthralgias and weight gain experienced with aromatase inhibition. Fig. 2 Sagittal T2-weighted MRI with vaginal gel performed at 16 weeks gestation demonstrates the gravid uterus (black star) and a large mass arising from the rectum (white arrow) with a “mushroom cap” morphology commonly seen in bowel endometriosis. However, the large size, heterogeneously increased signal and invasion of the lower uterine segment and cervix with polypoid extrusion into the vagina (curved black arrow) are in keeping with biopsy proven malignancy. Fig. 3 (A) Sagittal T1-weighted MRI with fat saturation, intravenous gadolinium and vaginal gel acquired 4 weeks postpartum demonstrates enhancement of the large mass arising from the rectum (white arrow) with persistent invasion of the lower uterine segment and cervix with polypoid extrusion into the vagina (curved black arrow). The mass has regressed in size by 50%. (B) Sagittal T2-weighted MRI with vaginal gel performed at 3 months postpartum, prior to surgery, demonstrates significant post-treatment regression of the large mass arising from the rectum (white arrow) with minimal polypoid extrusion into the vagina (curved black arrow). Sagittal T2-weighted MRI with vaginal gel performed at 16 weeks gestation demonstrates the gravid uterus (black star) and a large mass arising from the rectum (white arrow) with a “mushroom cap” morphology commonly seen in bowel endometriosis. However, the large size, heterogeneously increased signal and invasion of the lower uterine segment and cervix with polypoid extrusion into the vagina (curved black arrow) are in keeping with biopsy proven malignancy. (A) Sagittal T1-weighted MRI with fat saturation, intravenous gadolinium and vaginal gel acquired 4 weeks postpartum demonstrates enhancement of the large mass arising from the rectum (white arrow) with persistent invasion of the lower uterine segment and cervix with polypoid extrusion into the vagina (curved black arrow). The mass has regressed in size by 50%. (B) Sagittal T2-weighted MRI with vaginal gel performed at 3 months postpartum, prior to surgery, demonstrates significant post-treatment regression of the large mass arising from the rectum (white arrow) with minimal polypoid extrusion into the vagina (curved black arrow). Three months after surgical resection of the tumor, she underwent ileostomy closure, exam under anesthesia, vaginal biopsies, and closure of the vaginal cuff; pathology on all biopsies returned benign. Postoperative recovery was complicated by ileus, and on postoperative day four, the patient experienced a small bowel perforation proximal to the anastomotic site that required an exploratory laparotomy with abdominal washout, enterotomy repair, and wound VAC placement. Ten days later, she developed hemorrhagic shock from a spontaneous splenic capsule rupture and underwent repeat exploratory laparotomy, hematoma evacuation, and splenectomy. Subsequent outpatient recovery was notable for symptomatic rectovaginal fistula that healed spontaneously without intervention. Most recent evaluation with imaging in July 2025 (15 months after definitive surgical management and 20 months after delivery) was notable for no evidence of recurrent disease.

Amar Zaidan: Writing – original draft, Project administration, Investigation, Data curation, Conceptualization. Kelly H Bruce: Writing – review & editing, Writing – original draft, Supervision, Investigation, Data curation, Conceptualization. Mark R Hopkins: Writing – review & editing, Visualization, Supervision, Resources. Steven I Robinson: Writing – review & editing, Supervision, Resources, Investigation. Carl H Rose: . Wendaline M VanBuren: Writing – review & editing, Visualization, Supervision, Resources. Carrie L Langstraat: Writing – review & editing, Supervision, Resources, Conceptualization.

This case report details the management of a bulky, endometriosis-related, hormone-receptor-positive, low-grade adenosarcoma during pregnancy and postpartum. The patient presented with an obstructing pelvic mass in the second trimester of pregnancy and underwent bowel diversion followed by surveillance imaging of the mass throughout gestation. She underwent an indicated preterm delivery followed by anti-estrogen therapy and surgical resection inclusive of bilateral oophorectomy and remains without evidence of disease more than one year after definitive management. The risk of malignant transformation of endometriosis is well established. The most common cancers are endometrioid and clear cell carcinomas arising within ovarian endometriomas ( Saavalainen et al., 2018 ). In one epidemiologic study, the risk of ovarian cancer increased by 2.6-fold in the setting of ovarian endometriosis, although the absolute risk was quite small, with approximately 2 excess cases among 1,000 patients over 10 years ( Saavalainen et al., 2018 ). Approximately 25% of endometriosis-associated malignancies are extra-ovarian in origin ( Gadducci and Zannoni, 2020 ); similar to endometriosis-associated ovarian cancers, histology is often endometrioid or clear cell carcinoma, whereas non-epithelial tumors such as extrauterine adenosarcomas are rare ( Gadducci and Zannoni, 2020 ). Our patient developed a low-grade adenosarcoma within a known extra-ovarian focus of endometriosis. Like endometriosis, low-grade adenosarcomas often express estrogen receptors ( Marcus et al., 2018 ), suggesting a role for systemic endocrine therapy. In this case, histology was notable for 70% ER and 30% PR positivity in the absence of aggressive features (e.g., lymphovascular invasion, sarcomatous overgrowth). Prior case reports detail treatment success with hormonal agents including aromatase inhibitors, medroxyprogesterone acetate, and tamoxifen ( Carroll et al., 2014 , Poon and Rome, 2020 ). Our patient received intramuscular leuprolide and oral letrozole for 4 months postpartum, resulting in a 50% reduction in tumor size, thus facilitating surgical resection. Although she stopped hormonal therapy after surgery due to side effects (in the setting of complete gross resection and surgical ovarian suppression), she remains without evidence of disease over one year after surgery. In a prior review of available literature, recurrence of extrauterine/extraovarian adenosarcoma was reported in 18 of 34 (53%) cases over a mean follow-up of 27 months; mean disease-free survival was 11.8 months ( Mandato et al., 2018 ). Nine patients died of disease, none of whom had received previous hormonal therapy ( Mandato et al., 2018 ). Prior endometriosis, absence of sarcomatous overgrowth, and complete surgical resection were positive prognostic factors ( Mandato et al., 2018 ). Our patient had all three of these positive factors. We believe that our case supports the efficacy of anti-estrogen therapy in ER-positive extrauterine adenosarcoma and provides precedent for neoadjuvant hormone therapy to facilitate surgery. Our patient had a known endometriotic mass that was appropriately surveilled with repeat imaging and tissue sampling. The tumor did not grow out of proportion to that expected of endometriosis until pregnancy, when it grew acutely due to an increase in pregnancy-related hormones. Rapid growth of endometriosis mass lesions can occur due to the hormonal state of pregnancy, however a low threshold for biopsy to exclude malignant transformation should be considered. Prior case reports have similarly shown multiple benign biopsies prior to cancer diagnosis, supporting the need for repeat tissue sampling when there is substantial interval growth ( Pontrelli et al., 2016 ). Management of cancer during pregnancy requires careful consideration of maternal and fetal factors and often presents an ethical dilemma. Creation of treatment plans require balance of the ethical principles of autonomy, beneficence, non-maleficence, and justice. Oncologic recommendations should account for type of cancer, tumor biology, tumor stage, and gestational age ( Silverstein et al., 2020 , Amant et al., 2019 ). In cases of cancers diagnosed at an advanced stage or with aggressive tumor biology, pregnancy termination should be offered if the diagnosis is made at an early gestational age ( Silverstein et al., 2020 ). Prior to presentation at our institution, our patient was appropriately offered pregnancy termination at 16 weeks gestation; however, she wished to continue the pregnancy and sought out alternative options. Of note, due to the size and location of this patient’s tumor, termination would have required a hysterotomy. A tumor board discussion at our institution weighed the pertinent disease factors including locally advanced disease but absence of aggressive histological features and felt that the tumor represented a low-grade entity. With consideration of patient autonomy, we offered her close monitoring with intentional delay of definitive treatment. Additional considerations including cytotoxic chemotherapy and proton beam radiation were discussed as possible antepartum temporizing measures. Of note, treatment with standard sarcoma chemotherapy regimens including anthracyclines and/or ifosfamide during pregnancy is rare but has been linked to high rates of fetal demise, especially when administered early in gestation ( Miller et al., 2022 ). Ultimately, these additional measures were not required, and the patient achieved delivery of a viable infant at 30 weeks gestation without medical or surgical oncologic intervention. Safe surveillance of this patient required continual communication between her multidisciplinary team of gynecologic oncologists, maternal fetal medicine specialists, and radiation oncologists. In summary, this case has multiple learning points. First, it supports the role of systemic hormone therapy for hormone-receptor positive extrauterine adenosarcoma, including as a neoadjuvant therapy to facilitate definitive surgical resection. Second, it emphasizes the importance of maintaining an index of suspicion for malignant transformation in patients presenting with presumed endometriosis that does not follow the typical clinical course or demonstrates appreciable interval growth. Finally, it demonstrates the importance of patient-centered care and consideration of the ethical pillars when creating individualized treatment plans. Informed consent We obtained informed consent from the patient to publish her deidentified information. Funding This case report did not require funding. Presentations This case report has not previously been presented.

Mullerian adenosarcomas are rare gynecologic malignancies accounting for 5–7% of all uterine sarcomas ( Nathenson et al., Nov 2016 ). They are biphasic tumors composed of benign epithelial and malignant mesenchymal components. Common clinical presentations include abnormal uterine bleeding, pelvic pain, and pelvic masses ( Clement and Scully, 1990 ). Adenosarcomas are frequently identified at an early stage with a 5-year survival of 60–80% ( Pinto and Howitt, 2016 ). Important prognostic factors include age, myometrial invasion, lymphovascular space invasion, and sarcomatous overgrowth ( Clement and Scully, 1990 , Marcus et al., Mar 2018 , Carroll et al., 2014 ). In low-grade adenosarcoma, the mesenchymal component often expresses estrogen (ER) and progesterone receptors (PR) ( Marcus et al., Mar 2018 , Soslow et al., 2008 ). Adenosarcomas with sarcomatous overgrowth are more aggressive and may not express ER and/or PR ( Marcus et al., 2018 ). Endometriosis may precede the development of extrauterine adenosarcoma ( Liu et al., 2003 , Mandato et al., 2017 ). Complete surgical resection, when feasible, is the mainstay of treatment. In this report, we present the case of a 32-year-old pregnant patient with a history of pelvic endometriosis who was diagnosed with a bulky extrauterine adenosarcoma early in pregnancy and managed with active surveillance until viability. We describe the natural history of this hormone-responsive tumor during pregnancy and outline our peripartum management approach.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.