Polypoid endometriosis with endometrioid intraepithelial neoplasia mimicking malignancy: a rare case of a postmenopausal pelvic mass

Abstract

Polypoid endometriosis is a rare variant characterized by mass-forming endometriosis, often mimicking malignancy. This report describes the case of a postmenopausal woman who presented with an incidental complex adnexal mass and elevated tumor markers. She underwent bilateral salpingo-oophorectomy and mass removal. Frozen section suggested endometriosis with possible serous borderline tumor, prompting staging. Final pathology revealed polypoid endometriosis with areas of endometrioid intraepithelial neoplasia. Polypoid endometriosis may present as a postmenopausal pelvic mass with elevated tumor markers and can contain endometrioid intraepithelial neoplasia.

KEY POINTS

• Polypoid endometriosis is a rare, mass-forming variant that can closely mimic gynecologic malignancy in peri- and postmenopausal patients.

• Definitive diagnosis of polypoid endometriosis requires permanent histopathology.

• Polypoid endometriosis may present with elevated CA-125 and CA 19-9.

• Polypoid endometriosis can harbor endometrioid intraepithelial neoplasia, which carries premalignant implications that influence postoperative estrogen management and surveillance.

CME

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CASE PRESENTATION

A 53-year-old nulligravid woman (body mass index 21.75 kg/m²) was referred for an adnexal mass. Her medical history included endometriosis. She previously underwent a laparoscopic subtotal hysterectomy and appendectomy for endometriosis but retained her ovaries and cervix. She reported no vaginal bleeding; her cervical Pap smears showed normal cytology and were negative for human papillomavirus. She was taking oral estradiol (2 mg) daily for menopausal symptoms.

Initially, she presented to the emergency department with epigastric pain. Laboratory tests and imaging confirmed acute pancreatitis. A computed tomography (CT) scan identified a complex cystic mass in the left adnexa measuring 7.3 × 7.3 × 6.0 cm with irregular mural thickening and enhancement. Tumor markers showed elevated CA 19-9 (145.8 U/mL, reference range: 0.0–37.0 U/mL) and CA 125 (121.2 U/mL, reference range: 0.0–34.9 U/mL).

Two weeks later, she was evaluated in the gynecologic oncology clinic. She reported resolution of abdominal pain and denied new symptoms. Left lower quadrant fullness was noted on bimanual exam, and rectovaginal exam revealed a mass abutting the anterior rectal wall. Repeat tumor markers showed persistently elevated CA 125 at 163.5 U/mL and CA 19-9 at 146.7 U/mL.

The patient underwent a robotic-assisted bilateral salpingo-oophorectomy. She desired retention of her cervix. Intraoperatively, ovaries and fallopian tubes appeared grossly normal. A 9 cm multiloculated mass was identified adherent to the left pelvic sidewall and sigmoid colon, partially retroperitoneal, and receiving blood supply from the left uterine artery. The mass was excised and preliminarily reported on frozen section as an adenofibroma with a focal serous borderline component in a background of endometriosis. Given the borderline tumor, staging was obtained with pelvic lymphadenectomy, peritoneal biopsies, and pelvic washings. Final histopathological testing demonstrated extensive polypoid endometriosis (Figure 1a and b) with areas of endometrioid intraepithelial neoplasia (EIN) (Figure 1c) without evidence of carcinoma.

Figure 1.

(a) Low-power image (1× objective magnification) of a portion of the polypoid mass adherent to the pelvic sidewall, as denoted by the lining of fibrous and adipose tissue on the right side. (b) Low-power image (1× objective magnification) of a portion of the polypoid mass demonstrating an admixture of small and cystically dilated endometrioid glands within a fibrous stroma. (c) Representative image (2 × objective magnification) of an area of increased glandular proliferation and epithelial architectural complexity within the mass. The confluent glandular growth was sufficient in quantity for a diagnosis of endometrioid intraepithelial neoplasia.

At 1-month postoperative follow-up, the patient’s tumor markers had normalized. She will undergo continued surveillance with periodic CA-125, Pap smear and endocervical curettage testing, and pelvic exams. She was tapered off her prior estradiol hormone replacement therapy.

CLINICAL QUESTIONS

1. A postmenopausal woman presents with an adnexal mass on physical examination. Which imaging modality is considered first line for evaluation of adnexal masses in this population?

   1. CT of the abdomen and pelvis

   2. Magnetic resonance imaging (MRI) of the pelvis with contrast

   3. Transvaginal ultrasound

   4. Positron emission tomography–CT

2. A postmenopausal woman is found to have a pelvic mass. Histology shows polypoid endometriosis with EIN. Which histopathologic feature best distinguishes EIN from typical endometriosis?

   1. The presence of hemosiderin-laden macrophages surrounding endometrial glands

   2. Architectural glandular crowding with loss of a normal stroma-to-gland ratio

   3. Simple cystic dilation of endometrial glands in a fibrous stroma

   4. Ciliated epithelial metaplasia within endometrial glands

Answers are provided at the end of the article.

DISCUSSION

Polypoid endometriosis is a rare variant with exaggerated proliferation that frequently affects peri- and postmenopausal women.¹ While the disease is incompletely understood, reports implicate endogenous and exogenous estrogen, including retained ovarian function posthysterectomy, hormone replacement therapy, and tamoxifen use.^1,2 In addition to systemic estrogen in polypoid endometriosis, Syrcle et al showed increased local estrogen production via upregulation of aromatase and 3β-hydroxysteroid dehydrogenase and changed expression estrogen receptors (α/β).³ Reduced expression of stromal CD73—an enzyme in ATP regulation—in polypoid lesions compared to ovarian endometriosis and endometrial polyps has also been reported.⁴ Thus, polypoid endometriosis may arise from systemic estrogen exposure, local hormone production, and/or altered signal transduction.

When polypoid endometriosis is symptomatic, the most common symptoms are abdominal pain and abnormal uterine bleeding.¹ Other symptoms often resemble those of malignancy, particularly with large lesions or those involving adjacent organs. Reports have documented bowel obstruction, hematuria, hydronephrosis, and rectal bleeding, sometimes mimicking other malignancies such as renal cell carcinoma.^1,5–7

The definitive diagnosis of polypoid endometriosis is based on histopathology, but imaging may raise suspicion. Lesions often appear as complex cystic-solid masses with irregular borders.¹ On MRI, they show high T2 signal from dilated glands and high T1 foci from cyclic hemorrhage.⁸

While CA-125 is a well-known marker for epithelial ovarian cancers, it can be elevated in settings such as endometriosis and pelvic inflammatory disease.⁹ Similarly, while CA 19-9 is associated with gastrointestinal malignancies, it can be elevated in benign conditions.¹⁰ Thus, tumor markers raise clinical suspicion for malignancy, but should be interpreted alongside other findings.

This patient underwent a robot-assisted bilateral salpingo-oophorectomy, lymphadenectomy, and peritoneal biopsies. In a 15-case series, nine patients underwent total hysterectomy, including five who also underwent bilateral salpingo-oophorectomy. Other procedures included omentectomy, lymph node dissection, low anterior colon resection, and cystectomy.⁴ In extreme cases, adhesions have required organ resection or total pelvic exenteration.^4,11 Polypoid endometriosis can be recurrent, requiring future procedures.¹¹

Within a 15-case series, lesions ranged from microscopic to 13 cm.⁴ Microscopically, all cases showed secretory or proliferative endometrial glands; one ovarian case had EIN and another showed FIGO grade 1 endometrioid adenocarcinoma. Ciliated metaplasia was the most common glandular change, and stroma was typically fibrotic with thick-walled vessels. Six cases showed infiltration into the colon/pelvic tissues, often misdiagnosed as invasive carcinoma on frozen section.⁴

The risk of malignant transformation of typical endometriosis is low, most commonly resulting in endometrioid and clear cell carcinoma.¹² However, EIN is a premalignant lesion with a high risk of progression if left untreated. Furthermore, polypoid endometriosis lies within the broader category of atypical endometriosis, which includes endometriosis with architectural or cytologic atypia.¹² Emerging studies suggest that architectural atypia—particularly architectural crowding—may be associated with a higher risk of malignancy.¹² In cases with atypical architecture, one important consideration is the distinction between atypical endometriosis with EIN and Müllerian adenosarcoma, as the two can mimic each other but require significantly different management.¹²

Our case adds to the literature by further characterizing the role of serum tumor markers in this disease. Importantly, although tumor marker elevation has been reported in isolated cases of polypoid endometriosis, case series have not detailed longitudinal serial tumor marker behavior.⁴ In our patient, CA-125 and CA 19-9 elevations persisted after resolution of an initial confounder (acute pancreatitis) and normalized 1 month after complete excision, supporting a lesion-associated etiology for the preoperative elevations and providing a rationale for individualized postoperative marker surveillance in this patient. However, the generalizability of this approach remains unknown. Additionally, our case expands the anatomic context in which EIN may be encountered in polypoid endometriosis. In the 15-case series by Altay et al, premalignant/malignant endometrioid-type glandular changes were described within ovarian lesions (including atypical complex hyperplasia and FIGO grade 1 endometrioid adenocarcinoma). In contrast, we identified EIN within a large extraovarian, extrauterine mass, demonstrating the importance of applying EIN diagnostic criteria when evaluating nonovarian polypoid endometriosis lesions.

Although postmenopausal complex pelvic masses should be managed with an oncologic approach until proven otherwise, it is important for gynecologic oncologists and gynecologic pathologists to recognize that benign conditions such as polypoid endometriosis can closely mimic malignancy. Awareness supports preoperative counseling that diagnostic certainty and appropriate postoperative management ultimately depend on permanent histopathology.

ANSWERS TO CLINICAL QUESTIONS

Question 1, c. Transvaginal ultrasound is the first-line modality for adnexal mass evaluation, providing the ability to identify cystic/solid areas, septations, papillary projections, and mural nodules, with vascularity being assessed with Doppler. MRI is reserved for indeterminate lesions, while CT and PET-CT are primarily used for evaluating extrapelvic disease and staging.

Question 2, b. EIN is defined by abnormal glandular proliferation with architectural crowding and a reduced stroma-to-gland ratio. Hemosiderin-laden macrophages are a hallmark of typical endometriosis. Simple cystic gland dilation within fibrous stroma may be seen in polypoid endometriosis but does not indicate atypia. Ciliated epithelial metaplasia is a benign alteration without malignant implications.

Disclosure statement/Funding

The planners and faculty for this activity have no relevant financial relationships to disclose. The authors report no funding. The patient consented to publication of this case report.