Pseudo-Meigs' syndrome in mucinous ovarian carcinoma: A case report.

Grace Pipes: Writing – review & editing, Writing – original draft, Conceptualization. Bahaaeldin Youssef: Writing – review & editing, Writing – original draft. Mariam Torossian: Writing – review & editing, Conceptualization. Kenneth H. Kim: Writing – review & editing. Margaret I. Liang: Writing – review & editing, Writing – original draft, Supervision, Resources, Conceptualization.

A 37-year-old woman with a past medical history significant for previous cystectomy of a benign, right serous ovarian cystadenoma and ulcerative colitis presented with worsening abdominal bloating and new onset shortness of breath. She reported a six-month history of abdominal bloating, which she initially attributed to her ulcerative colitis. In addition, she reported having an upper respiratory infection with lingering dyspnea and a minimally productive cough. Chest x-ray demonstrated a large right-sided pleural effusion ( Fig. 1 ). Three thoracenteses were performed extracting 1.1 to 1.6 L of exudative fluid (pleural fluid/serum LDH 0.83, pleural fluid/serum protein 1.0) each time, ultimately necessitating chest tube placement. Pleural fluid cultures returned negative for infection, and cytology was negative for malignancy from three separate collections. Microscopic evaluation of the pleural fluid revealed many histiocytes and mixed inflammatory cells, including eosinophils. Subsequently, a CT of the chest, abdomen, and pelvis revealed a large, complex, cystic pelvic mass with several solid components highly suspicious for a primary ovarian malignancy as well as small volume ascites and some nodular peritoneal stranding concerning for peritoneal carcinomatosis ( Fig. 1 ). Fig. 1 Imaging. (A) CT scan of the chest, abdomen, and pelvis showing large complex cystic pelvic mass with several solid components. (B) Chest x-ray showing large right pleural effusion with right lower lobe and right middle lobe atelectasis. Imaging. (A) CT scan of the chest, abdomen, and pelvis showing large complex cystic pelvic mass with several solid components. (B) Chest x-ray showing large right pleural effusion with right lower lobe and right middle lobe atelectasis. Tumor markers demonstrated an elevated CA-125 of 129 U/mL (normal < 35 U/mL), an elevated CEA of 20.6 ng/mL (normal < 3 U/mL), and an elevated CA 19–9 of greater than 1000 U/mL (normal < 35 U/mL). A CT-guided omental biopsy was performed demonstrating “fibroadipose and skeletal muscle tissue with small clusters of mesothelial cells and lymphohistiocytic inflammation.” In the time needed for the biopsy to result, the patient was experiencing worsening shortness of breath, and her chest x-ray showed reaccumulation of her large, right-sided pleural effusion. Given the concern for malignancy in the setting of a complex adnexal mass, peritoneal nodules, ascites, and a pleural effusion, the patient was urgently taken to the operating room where she had an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omental biopsy, peritoneal biopsy, and appendectomy. Operative findings included a twenty-centimeter and a five-centimeter pelvic mass, both arising from the right ovary ( Fig. 2 ). There was 100 cc of ascites present. There was inflammatory rind coating the entire pelvic peritoneum, including the small bowel mesentery. Exploration of the abdominal and pelvic cavity was otherwise negative for tumor, including the appendix. Frozen pathology intra-operatively revealed mucinous neoplasm, at least borderline versus possible carcinoma of unclear etiology. Final pathology revealed stage IA mucinous cancer of the ovary ( Fig. 2 ). The peritoneum and peri -appendiceal soft tissue were noted with reactive histiocytic reaction. Cytopathology for the peritoneal ascites revealed atypical cells and favored a reactive process. Fig. 2 Tumor Pathology and Histology. (A) A lobulated mass with a smooth, gelatinous surface. The cut surface revealed cystic spaces filled with mucinous material and firm nodular areas. (B) Low-power magnification demonstrates mucinous carcinoma of gastrointestinal type, arising in contiguity with a mucinous borderline tumor, characterized by papillary projections and epithelial stratification with mild nuclear atypia. (C) High-power magnification reveals the carcinoma’s architectural complexity, marked by pronounced nuclear pleomorphism, hyperchromasia, highlighting the neoplastic progression from borderline to invasive phenotype. Tumor Pathology and Histology. (A) A lobulated mass with a smooth, gelatinous surface. The cut surface revealed cystic spaces filled with mucinous material and firm nodular areas. (B) Low-power magnification demonstrates mucinous carcinoma of gastrointestinal type, arising in contiguity with a mucinous borderline tumor, characterized by papillary projections and epithelial stratification with mild nuclear atypia. (C) High-power magnification reveals the carcinoma’s architectural complexity, marked by pronounced nuclear pleomorphism, hyperchromasia, highlighting the neoplastic progression from borderline to invasive phenotype. She had an unremarkable inpatient postoperative course and was discharged home. She was followed outpatient by the pulmonologist with serial chest x-rays that showed complete resolution of her pleural effusion at four weeks after her surgery and at her five month follow up. No adjuvant chemotherapy was indicated; therefore, she was followed closely to ensure that her tumor markers normalized. Her CA-125 and CA 19–9 decreased significantly to 109 U/mL and 352 U/mL, respectively, at her three week follow up. They had normalized by her ten-week follow up. Given that her pleural effusions resolved after operative management, they were attributed to pseudo-Meigs' syndrome. Surveillance was recommended with tumor markers and pelvic exams. There was no evidence of disease at her 15-month follow up.

Meigs’ syndrome is restricted to benign ovarian tumors, including only fibroma, thecoma, or Brenner tumor, therefore ovarian malignancies are excluded by definition ( Mohammed et al., 2024 ). Pseudo-Meigs’ syndrome encompasses all other ovarian tumors (including both benign and malignant processes) and has been described in the setting of struma ovarii, gastrointestinal and breast malignancies metastasizing to the ovaries, ovarian serous cystadenoma, high-grade serous ovarian carcinoma, leiomyoma, and borderline mucinous ovarian tumor, among others ( Chen et al., 2013 , Pauls et al., 2019 , Horimatsu et al., 2015 , Fujiwara et al., 2018 , Fujii et al., 2006 , Dalal et al., 2020 ). However, when an ovarian tumor initially presents with accompanying pleural effusion and ascites, a patient is assumed to have ovarian cancer until proven otherwise. Ovarian carcinomas have diverse initial presentations making diagnosis, staging, and ultimately choice of initial treatment complex. As approximately 75 % of patients with epithelial ovarian cancer are diagnosed at stages III and IV, pleural effusions and ascites in the setting of a pelvic tumor may indicate advanced disease ( Porcel et al., 2012 ). Stage IV ovarian cancer includes liver parenchymal and extra-abdominal metastases, of which the pleural surface is the most common site ( Porcel et al., 2012 ). A pleural effusion is the presenting indication of all malignancies in 29 % of women, and ovarian cancer is the etiology of malignant pleural effusions in 7–14 % of malignancies with pleural effusions in women ( Porcel et al., 2012 , Sharma and Boster, (FL)2024. ). Furthering the complexity of diagnosis, an initial presentation of a pleural effusion with ascites may be mistaken for a variety of other diseases, including disseminated carcinomatosis from some other primary source, cirrhosis, heart failure, endometriosis, ovarian hyperstimulation syndrome, or other infectious or inflammatory cause. Pleural effusions in ovarian cancer result from a combination of pleural invasion or transdiaphragmatic migration of malignant cells through pleuroperitoneal communications and intrinsic and extrinsic factors which decrease pleural fluid resorption leading to pleural fluid accumulation ( Sharma and Boster, 2024 ). Malignant pleural effusions are largely unilateral, favoring the right side, and are exudative with predominant lymphocytes, although they can be bilateral ( Table 1 ) ( Porcel et al., 2012 ). Table 1 Pleural effusion characteristics. Characteristics Meigs’ and Pseudo-Meigs’ Syndrome Ovarian Carcinoma Laterality More often right sided Unilateral, favors the right-side Light’s Criteria and cytologic features Exudative, no consensus of cytology Exudative, predominantly lymphocytes Pathophysiology Translocation of ascites to the pleural space through diaphragmatic pores. Pleural invasion and/or transdiaphragmatic migration of malignant cells through pleuroperitoneal communications coupled with intrinsic and extrinsic factors decreasing pleural fluid resorption. Diagnostic work-up CT Abdomen & Pelvis Chest x-ray (or CT Chest) Fluid cytology of ascites or pleural effusion Biopsy of non-ovarian disease site, if feasible Initial Treatment Surgical resection Neoadjuvant chemotherapy Pleural effusion characteristics. Similarly, pleural effusions in Meigs’ and pseudo-Meigs’ syndrome are exudative and more often right-sided ( Krenke et al., 2015 ). Because there are limited descriptions of cytologic characteristics, the cytologic features of Meigs’-related pleural fluid are not well defined ( Table 1 ). A case report described the presence of eosinophils in the pleural fluid, which our patient exhibited; however, this has not been consistently reported, and the possible cause of the presence of inflammatory cells are not well studied ( Shimoda et al., 2024 ). The main theory for the mechanism of pleural fluid accumulation is the translocation of ascites to the pleural space through diaphragmatic pores ( Meigs, 1954 , Krenke et al., 2015 ). Peritoneal fluid may be caused by stromal tumor edema transudation due to disproportionate arterial supply to lymphatics, lymphatic obstruction by the pelvic tumor, increased permeability of pelvic lymphatics, and/or hyper-secretion of vascular endometrial growth factor from oviducts ( Krenke et al., 2015 ). Patients who present with signs of advanced ovarian cancer, including stage IVA due to pleural effusions, may even undergo neoadjuvant chemotherapy before surgical debulking. There are case reports of ovarian malignancies that were initially treated with neoadjuvant chemotherapy with worsening pleural effusions and ascites that resolved with resection of pelvic pathology leading to the diagnosis of pseudo-Meigs’ syndrome and ultimately a lower stage of cancer that otherwise would not have required neoadjuvant or adjuvant therapy ( Okazaki et al., 2019 ). Multiple case reports of pseudo-Meigs’ syndrome emphasize the importance of histological or fluid cytological confirmation for staging ovarian cancers to avoid unnecessary neoadjuvant chemotherapy ( Chen et al., 2013 , Buttin et al., 2001 ). Our case adds to this literature. In this case, the patient presented with symptoms concerning for at least stage IVA ovarian carcinoma. However, her pleural fluid cytology and omental biopsy were negative for malignancy. These non-diagnostic findings lead the providers to opt for an exploratory laparotomy for debulking and surgical staging. Her final diagnosis was a stage IA mucinous ovarian carcinoma. Her pleural effusion and ascites resolved without further treatment. This exemplifies the importance of a tissue diagnosis prior to treatment decisions. Although rare, cases of pseudo-Meigs’ syndrome should encourage physicians to maintain a broad differential in patients with a pelvic tumor with pleural effusions and ascites. Informed consent Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Prior to discovery of Meigs’ syndrome, patients who presented with a pleural effusion, ascites, and a pelvic mass were assumed to have a malignancy, until the condition resolved following resection of the mass. While it was described as early as the 19th century, Joe Vincent Meigs described the importance of this constellation in 1937 as a benign fibroma or fibroma-like ovarian tumor accompanied by ascites and a pleural effusion that resolves with removal of the tumor ( Mohammed et al., 2024 ). The tumors described by Meigs’ included fibroma, thecoma, granulosa cell tumor, or Brenner tumor ( Mohammed et al., 2024. , Meigs, 1954 ). Pseudo-Meigs’ syndrome has the same clinical presentation as Meigs’, including pleural effusions, ascites, and a pelvic mass, benign or malignant. The mass, however, is not one of the listed tumors described by Meigs’ ( Mohammed et al., 2024. , Peparini and Chirletti, 2009 , Meigs, 1954 ). As this is a very rare condition, incidence of pseudo-Meigs’ has not been described. Tumors described in case reports include cystadenoma, dysgerminoma, struma ovarii, Krukenburg, and breast or colon cancer metastases to the ovaries ( Chen et al., 2013 ). Mucinous ovarian carcinoma is a rare condition accounting for 3 % of ovarian malignancies ( Babaier and Ghatage, 2020 ). No cases of mucinous ovarian carcinoma presenting with pseudo-Meigs’ have been reported in the literature. The objective of this case report was to describe a case of pseudo-Meigs’, review the literature, and make recommendations for evaluation and management of similar presentations.

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.