Clear-cell borderline tumor with pseudo-Meigs’ syndrome: a case report and review of the literature

Introduction

Ovarian borderline tumors were initially introduced as semi-malignant ovarian tumors with histologies between benign and frankly malignant (1). Various other names have since emerged over the years as our ability to characterize these masses have evolved (2,3). In 2020, the World Health Organization officially established the title of “borderline tumor” as the accepted term (4).

It is estimated ovarian borderline tumors account for up to 20% of all primary ovarian neoplasms (5). Roughly one-third of cases occurring in women under forty years of age and most are serous or mucinous histology. Rarer subtypes including endometrioid and Brenner tumors also are occasionally encountered (6,7). Whereas, clear-cell borderline tumors (CCBTs) are estimated to comprise less than 1% of all ovarian borderline tumors, and occur most commonly in post-menopausal patients with a median age between 59 and 67 years (8).

Patients with ovarian borderline tumors can be asymptomatic, with masses being incidentally found on physical exam during routine health maintenance checks or during imaging ordered for other indications (9,10). This likely is due to borderline tumors not typically exhibiting traits that would otherwise result in ascites, pleural effusions, bowel obstruction, or venous thrombotic events, in contrast to ovarian cancers (11). We present a case of a 68-year-old woman who was admitted with ascites, pleural effusion, and a large abdominal pelvic mass, found to be a CCBT on histopathologic evaluation. We present this article in accordance with the CARE and Narrative Review reporting checklists (available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-16/rc).

Case presentation

A 68-year-old G2P2002 patient presented to the Emergency Department following evaluation at her primary care physician’s office for several months of progressively increasing abdominal swelling, difficulty breathing, and productive cough without hemoptysis. She also complained of a hard lump in her abdomen and significant back pain with performing routine tasks. She denied nausea, vomiting, chest pain, changes in appetite, or unintended weight loss. Her past medical history was notable for well-controlled hypertension, and she otherwise did not possess notable surgical, family, or social history. An abdominal ultrasound completed earlier by her primary care physician noted ascites and possible pneumonia.

Her vitals were stable and afebrile, with an oxygen saturation within normal limits on room air. She had decreased breath sounds on her right side and a protuberant abdomen, which contained a firm 25-cm mass with irregular contours that was noted to be mobile and separate from the uterus on pelvic exam. Her white blood cell and red blood cell counts, liver enzymes, creatinine, and electrolytes were all within normal limits. Troponin, B-type natriuretic peptide, D-dimer, and plasma procalcitonin levels were all negative.

A chest computed tomography (CT) scan was negative for pulmonary embolism but revealed a large right-sided pleural effusion with left mediastinal shift and ascites. The abdomen-pelvis CT scan revealed a large, solid, multi-lobulated 26 cm mass arising from the left ovary and a large amount of ascites (Figure 1). CA-125 was 645 U/mL and carcinoembryonic antigen (CEA) was 1.6 U/mL. Gynecologic Oncology was consulted at this time.

Figure 1 Coronal (A) and sagittal (B) views of pelvic mass (arrowheads) arising from the left adnexa, with significant ascites (asterisks) and pleural effusion (arrows) appreciated.

Following evaluation by our Gynecologic Oncology service, she underwent thoracentesis and paracentesis which provided her symptomatic relief, and fluid cytology from these procedures was negative for malignancy. Subsequent chest X-ray revealed improvement in mediastinal position. An echocardiogram demonstrated normal ejection fraction and cardiac function with minimal pericardial effusion. She was counseled about her findings appearing consistent with a Meigs’ syndrome-like picture which generally entailed a favorable prognosis following surgical removal of the mass though cancer could not be ruled out. She was also counseled that without surgical removal of the mass, she likely would experience recurrence of her pleural effusion and ascites. She was cleared for outpatient follow-up with Gynecologic Oncology, where she subsequently consented to proceeding with surgery to remove the mass.

She presented to the Emergency Department again one week prior to her scheduled surgery due to findings of large right pleural effusion noted again on chest X-ray performed during her preoperative risk-stratification evaluation. She reported experiencing progressively increasing shortness of breath again but otherwise was asymptomatic. Her vital signs again remained stable and afebrile, with an oxygen saturation within normal limits on room air. She had decreased breath sounds on her right side again and her abdomen was similarly distended. Her blood counts and metabolic panel labs were stable, and swabs for novel coronavirus 2019, influenza A and B, and respiratory syncytial virus were negative. She was admitted for monitoring and Gynecologic Oncology was again consulted. She underwent repeat thoracentesis and paracentesis the next day which again provided her symptomatic relief, and a post-procedure chest X-ray completed the following day noted minimal pleural effusion. She felt well-enough for discharge in anticipation of her upcoming scheduled surgery.

She felt overall well on the day of surgery aside from continued discomfort from her abdominal mass, and she denied recurrence of respiratory symptoms. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, omental biopsy, and pelvic washings. Intra-operatively, a large solitary solid mass resembling a fibroma on inspection was appreciated and there was no gross evidence of metastatic disease. At the completion of surgery, there was no residual disease present.

Her postoperative course was uncomplicated, and her preoperative symptoms had completely resolved. She was discharged home on postoperative day three. She was doing well at her post-operative follow-up appointment and denied recurrence of any previous symptoms.

Pathology

Gross exam of the left ovary revealed a large 26 cm × 22 cm × 15 cm solid mass with whorled cut surfaces and no cysts or necrosis, resembling a fibroma. On microscopy, the histologic sections demonstrated fibromatous stroma with embedded variably-crowded and -sized glands. These glands were lined by flat to cuboidal cells with occasional hobnail features. The cells contained clear to eosinophilic cytoplasm and displayed a spectrum of no atypia to low-grade atypia (Figure 2). No severe cytologic atypia was appreciated and mitotic activity was low. In addition, no secondary architecture, such as papillary or cribriform patterns, was identified. No immunostains were performed. The combination of the adenofibromatous features with variable glandular crowding and nuclear atypia best classified this neoplasm as a clear-cell borderline tumor.

Figure 2 Focally crowded glands viewed at 100× magnification (A) lined by cuboidal cells with low grade atypia viewed at 40× magnification (B) embedded in fibromatous stroma. Both slides were stained using hematoxylin and eosin.

The left fallopian tube, uterus, cervix, right fallopian tube and ovary, omental biopsy and pelvic washings were negative for neoplasm, resulting in a pathologic stage of pT1aNX.

Her case was discussed at our institution’s Multi-Disciplinary Gynecologic Oncology Tumor Board and she was recommended to proceed with close outpatient observation.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Informed consent was obtained from the patient to share this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Our patient’s clinical picture of a large ovarian mass, ascites, and pleural effusions initially aroused suspicion for a Meigs’ syndrome picture. This was further substantiated when our patient’s symptoms abated in the immediate post-operative period. However, upon reviewing her surgical pathology which resulted as being a CCBT rather than a fibroma, it became apparent she did not meet the traditional criteria for Meigs’ syndrome (12,13). This resulted in her diagnosis being re-classified as pseudo-Meigs’ syndrome (14-16). We believe this is the first case report to describe a CCBT presenting with pseudo-Meigs’ syndrome.

Pseudo-Meigs’ syndrome is described in patients with symptoms of ascites and pleural effusions generally associated with ovarian tumors other than fibromas (14,17). These tumors include but are not limited to benign pathology such as teratomas, struma ovarii, and cystadenomas (14,18). Involvement of extra-ovarian sources such as leiomyomas have also been implicated (19,20). Malignancies have been implicated as well with development of pseudo-Meigs’ syndrome (16,21-25). Unfortunately, healthcare teams are handicapped by the paucity of high-level evidence available to counsel patients about pseudo-Meigs’ syndrome, particularly in the setting of a concomitant CCBT.

Given the rarity of CCBTs, clinical care recommendations up to this point have largely been guided by case reports. There were an estimated 30 case reports in English on CCBTs in 2014 and this increased to 81 in 2021 (10,26,27). The pathophysiology driving pseudo-Meigs’ syndrome remains poorly understood and, similar to patients with symptoms of Meigs’ syndrome, patients with symptoms of pseudo-Meigs’ syndrome should be managed expeditiously to mitigate potential morbidity and mortality (25,28). This entails initial assessments of patient hemodynamic and blood chemistry statuses and judicious employment of thoracenteses and paracenteses for symptomatic treatment as was done in our patient for acute management of dyspnea and abdominal distension and discomfort. Once stabilized, patients can then be counseled about and optimized for curative treatment involving surgical removal of the identified masses. While peritoneal staging should be considered during these surgeries, lymph node sampling is generally deemed unnecessary in the absence of compelling findings such as enlarged pelvic or para-aortic lymph nodes (10,29-31). Borderline ovarian tumors such as CCBT also typically occur unilaterally although bilateral disease is also possible (30,32). A majority of cases were classified as International Federation of Gynecology and Obstetrics (FIGO) stage 1 disease, and prognoses typically are considered to be positive with a low long-term risk of recurrence (10,33).

The origins of CCBTs and their natural course remain unclear, and debate continues about whether CCBT instead of endometriosis is the primary predecessor of clear-cell carcinoma (29,34-36). As a result, differentials including fibromas, adenofibroma, and Brenner tumors must be entertained. In our patient’s case, the non-clear-cell entities closest to the described overall morphology include (I) endometrioid adenofibroma, which would demonstrate columnar-type endometrioid epithelium with or without metaplastic changes including ciliated, mucinous and/or squamous metaplasia, which was not appreciated; (II) fibroma with minor sex-cord elements, which would exhibit clusters of sex-cord element cells or Sertoli tubules rather than the epithelial glands visualized in this case; and (III) Brenner tumor, which possesses nests of transitional-type epithelium in a fibromatous background which were not identified here. Amongst the clear-cell entities, the process of distinguishing a CCBT from a clear-cell adenofibroma or a clear-cell carcinoma with a prominent fibromatous component is likely to be more challenging. The former presents with widely-spaced glands without cytologic atypia whereas the latter typically is associated with a combination of architectural patterns, including solid, tubulocystic, and papillary patterns lined by flat to cuboidal epithelial cells with conspicuous cytologic atypia. Performing immunostains would not assist in the distinction among the entities within the clear cell spectrum. Thus, the presence of variably crowded glands lined by flat to cuboidal cells with subtle cytologic atypia and low mitotic activity in a fibromatous background ultimately guided classification of our patient’s pathology toward CCBT.

Unfortunately, there remains insufficient longitudinal data specific to CCBT on patient outcomes and follow-up to quantify a more specific level of risk and generate resultant recommendations. Reported patient follow-up periods after index surgery have varied significantly (10,37,38). A study from the Netherlands in particular found patient survival rates did not plateau even after fifteen years following index surgeries (39). This heightens suspicions for potential late recurrences and progression to invasive disease (29,40). As a result, the significance of thoroughly counseling patients about the role of routine follow-up and engaging in shared decision-making as part of ongoing surveillance cannot be overstated.

Conclusions

In conclusion, CCBT can be associated with development of pseudo-Meigs’ syndrome, which can be resolved with complete excision. Patients generally can be closely monitored post-operatively and do not require further therapy.

Acknowledgments

We wish to express our gratitude to our patient for her permission to share her story.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE and Narrative Review reporting checklists. Available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-16/rc

Peer Review File: Available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-16/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-16/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Informed consent was obtained from the patient to share this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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