Ovarian Low-Grade Mucinous Tumor Combined with Pseudo-Meigs’ Syndrome: Report of Two Cases and Literature Review

Introduction

In 1937, Meigs reported seven cases of ovarian fibromas complicated by pleural effusion and ascites, in which the pleural effusion and ascites rapidly disappeared after tumor resection. Later, in 1954, Meigs reviewed 84 cases and formally proposed the definition of Meigs syndrome; the primary tumor was ovarian fibroma, theca cell tumor, granulosa cell tumor, or brenner tumor, accompanied by pleural effusion and ascites; after tumor resection, the pleural effusion and ascites disappeared and did not recur.^1,2 The clinical picture of PMS is similar; however, the types of primary tumors differ, including other primary benign and malignant ovarian tumors, metastatic tumors, and uterine myoma, etc.³ During the initial clinical evaluation, particularly when both imaging findings and serum tumor markers (such as elevated CA-125 and CA19-9) raise suspicion of malignancy, PMS can be readily misdiagnosed as advanced ovarian cancer, which significantly complicates the differential diagnosis. However, the two conditions differ fundamentally in treatment strategy and prognosis. In patients with PMS, associated symptoms typically resolve rapidly following tumor resection, and most patients are cured through surgery alone. In contrast, advanced ovarian cancer is associated with a poor prognosis, and the standard clinical approach often involves neoadjuvant chemotherapy followed by reevaluation of surgical eligibility—a strategy that may exert a significant physical and psychological toll on patients. Therefore, establishing an accurate diagnosis prior to treatment is of critical importance.

Mucinous ovarian tumors account for 10%–15% of ovarian tumors and are classified as benign, borderline, or malignant. Borderline mucinous tumors account for 16%–17% of mucinous tumors.⁴ Primary mucinous carcinoma of the ovary is even rarer, representing only 3%–4% of malignant ovarian tumors.⁵ Furthermore, reports of primary mucinous carcinoma or borderline mucinous tumors of the ovary that cause PMS are extremely rare. This article reviews the existing literature and offers guidance on the assessment and management of ovarian mucinous tumors presenting with clinical features of PMS.

Case Presentation

Case One

A 39-year-old unmarried female patient with no history of sexual activity presented with abdominal distension that gradually worsened over two months and was accompanied by dull pain in the lower abdomen. In the past week, she had developed chest tightness, was unable to lie flat or walk quickly, and experienced unformed stools and frequent urination. Based on these symptoms and pelvic ultrasound findings, the outpatient doctors considered the pelvic mass to be a malignant adnexal tumor with distant metastasis (pleural effusion). The patient was admitted to the Gynecology Department for further treatment. No family history of malignant tumors. No history of surgery. No medical history of heart failure, breast cancer or chronic kidney disease. Physical examination revealed a poor general condition, heart rate of 110 beats/min, respiratory rate of 20 breaths/min, and distended abdomen. Digital rectal examination revealed an empty recto-uterine pouch.

The serum tumor markers: CA125 203.00 U/mL (0.00–47.00 U/mL), CA19-9 > 1000.00 U/mL (0.00–30.00 U/mL), CEA 594.00 ng/mL (0.00–5.00 ng/mL), HE4 156.0 pmol/L (15.0–60.50 pmol/L), SCC 2.10 ng/mL (0.00–1.90 ng/mL). Pelvic ultrasonography (US): A mass with mixed echogenicity was observed at the upper pole of the uterus, just above the pubic symphysis, measuring approximately 24×15 × 22 cm. Anechoic areas consistent with fluid collection were observed in the pelvic and abdominal cavities. The depth of the pelvic fluid collection measured 5.46 cm, the fluid in the left iliac fossa measured approximately 6.49 cm in depth, and the collection above the bladder measured 10.6 cm. Contrast-enhanced computed tomography (CT) revealed a large mass in the abdominal and pelvic cavities, measuring approximately 21.6×16.2 × 22.8 cm (Figure 1A). Multiple sheet-like, mixed-density areas, and septations were visible within the mass. The solid components showed CT attenuation values ranging from 53 to 65 Hounsfield Units (HU) on unenhanced images, with mild enhancement of both the solid components and septations observed on contrast-enhanced scans, where the CT values increased to approximately 58–78 HU. Areas of fat density were also observed in the masses. Adjacent structures were compressed and displaced. In addition, thickening of the peritoneum and omentum was observed, which demonstrated enhancement on contrast-enhanced imaging. No abnormalities were detected during gastrointestinal endoscopy.

Figure 1 (A) Contrast-enhanced abdominal CT: a large amount of fluid around the liver (bold arrow), spleen, and pelvic cavity (bold arrow); the pelvic tumor (bold arrow) shows uneven enhancement, measuring approximately 21.6×16.2 × 22.8 cm, within the mass, multiple sheet-like mixed-density areas and septations were visible. (B) Lung CT: Bilateral pleural effusion, significant on the right side (bold arrows indicate right and left pleural effusion).

Chest CT revealed a large amount of fluid in the right thoracic cavity, with reduced expansion of the right lung. The mediastinum shifted to the left. Fluid was also present in the left thoracic cavity with reduced expansion of the left lung. Thoracic US: An anechoic area was visible in the right thoracic cavity, measuring approximately 11.96 cm in the maximum anteroposterior diameter in sitting position. An anechoic area was also visible in the left thoracic cavity, measuring approximately 3.82 cm in the maximum anteroposterior diameter (Figure 1B).

Considering the patient’s medical history and imaging results, the pelvic mass was likely of ovarian origin with a high likelihood of malignancy. To confirm the diagnosis, an ultrasound-guided omental puncture biopsy was performed after admission. Pathological examination revealed atypical cells, and tumor lesions could not be excluded. Due to the large amount of pleural effusion, a right-sided chest tube was inserted after admission, intermittently draining 2880 mL of pale-yellow pleural fluid over several days. Cytological examination of pleural fluid revealed mesothelial cells and lymphocytes. After the lung function improved, a comprehensive assessment suggested that cytoreductive surgery was feasible and satisfactory. Accordingly, an exploratory laparotomy was performed under general anesthesia. During surgery, the uterine body measured 5×6 × 6 cm, with a smooth surface and good mobility. The right ovary contained a solid tumor, approximately 30 cm in diameter, with a smooth surface and an intact capsule. The left ovary was normal in size and appearance, and both fallopian tubes appeared normal. No abnormalities were observed in the recto-uterine pouch or bladder folds of the peritoneum. Although thin membranous adhesions were observed in the small intestine, the omentum, colon, and cecum exhibited no abnormalities. The parietal peritoneum of the abdominal wall was congested and edematous, whereas the retroperitoneum appeared normal. No abnormalities were observed in the diaphragm, liver, gallbladder, spleen or kidneys. No enlarged lymph nodes were palpated in the pelvis or abdomen. Approximately 1500 mL of lightly blood-tinged ascitic fluid was observed. Inspection of the right ovarian tumor revealed a smooth outer wall with a mixed cystic-solid interior and multiple cystic compartments containing white-to-yellow mucinous material. The solid component was slightly friable, and several samples of this friable solid part were submitted for frozen section examination, which indicated mucinous cystadenoma with focal borderline changes. The patient was unmarried and nulliparous. The family requested fertility preservation. The final surgical procedure included right adnexectomy, omentectomy, appendectomy, and multiple peritoneal biopsies. Surgical evaluation indicated a complete resection with clear margins. Postoperative pathological diagnosis revealed that the right adnexa was a mucinous cystadenoma with focal borderline changes (Figure 2A and B). No metastatic foci were found in the omentum, appendix, intestinal adhesion band, right paracolic peritoneum, or the right pelvic peritoneum. Cytological examination of ascitic fluid revealed the presence of mesothelial and inflammatory cells.

Figure 2 (A) Microscopic examination reveals abundant extracellular mucin and a multicystic architecture, with cystic spaces lined by a single layer or focally stratified mucinous columnar epithelium embedded in a cellular stroma (HE ×40). (B) Microscopic evaluation of a focal area reveals borderline changes, characterized by epithelial hyperplasia with stratification and mild to moderate cytologic atypia, in the absence of stromal invasion (HE ×200).

On postoperative day 9, serum tumor markers were reviewed: CA125:44.80 U/mL; CA19-9:8.82 U/mL; CEA:1.55 ng/mL; HE4:67.4 pmol/L. The patient showed a good postoperative recovery and was discharged without complications. The discharge diagnosis was borderline ovarian mucinous cystadenoma (stage IA). Three months after surgery, follow-up imaging showed resolution of the pleural effusion. Currently, the patient is in good general condition and is undergoing follow-up care.

Case Two

The patient was a 34-year-old female (G2P1) at 20 months postpartum. She visited a local hospital with chest tightness accompanied by dyspnea for 1 week. CT of the lung showed a large pleural effusion in the right thoracic cavity and poor expansion of the right lung. To relieve the symptoms, right thoracic puncture drainage was performed, and pleural effusion was drained intermittently, with a total of 1900 mL of light-yellow pleural fluid drained over 3 days. Abdominal CT revealed a mass in the pelvic and abdominal cavities, suggesting a tumor originating from the right adnexal region. She had a family history of hepatic carcinoma (grandfather). The patient had undergone benign ovarian cystectomy (approximately 12 cm) via laparotomy 5 years previously, and appendectomy more than 10 years ago. On admission, examination revealed a pulse rate of 110 beats/min and a respiration rate of 18 breaths/min. Gynecological examination: A hard, fixed, and tender mass, approximately 20 cm in diameter, was palpated behind the uterus.

Serum tumor markers: CA125: 594.00 U/mL, CA19-9: 18.7 U/mL, CEA: 2.08 ng/mL, HE4: 66.9 pmol/L, SCC: 0.70 ng/mL. Pleural fluid cytology revealed mesothelial and inflammatory cells. Pelvic US: An irregular, cystic mass with predominantly mixed echogenicity was seen above the posterior uterus, measuring approximately 19.4×8.67 x 13.2 cm. An anechoic area was seen in the right iliac fossa, with a depth of approximately 4.72 cm. Abdominal contrast-enhanced CT: A huge irregular cystic-solid mass extending from the lower abdomen into the pelvic cavity was observed, compressing adjacent organs and measuring approximately 16.7×13.3 x 16.7 cm. The solid component showed significant enhancement on contrast-enhanced scanning, with septations visible inside. The mass was closely related to the right adnexa and surrounded branches of the uterine artery with thickened and tortuous vessels. A small fluid-dense shadow was observed in the pelvic cavity (Figure 3A).

Figure 3 (A) Contrast-enhanced abdominal CT: a small amount of fluid around the liver (bold arrow) and pelvic cavity (bold arrow); the pelvic tumor (bold arrow) shows uneven enhancement, measuring approximately 16.7×13.3 x 16.7 cm. The solid component showed significant enhancement on contrast-enhanced scanning, with septations visible inside. (B) Lung CT: Bilateral pleural effusion, significant on the right side (bold arrows indicate right and left pleural effusion).

Chest CT revealed a large right pleural effusion, with signs suggestive of prior drainage, poor expansion of the right lung, and a small pleural effusion on the left side (Figure 3B).

Considering the patient’s medical history and imaging results, the pelvic mass was likely of ovarian origin with a high likelihood of malignancy. To improve lung function, 3800 mL of light-yellow pleural effusion was drained preoperatively. Subsequently, exploratory laparotomy was performed under general anesthesia. During the operation, the omentum was found to be edematous and adhered to the surface of the pelvic mass and the intestines. Some adhesions were dissected sharply. No lesions were observed on the surfaces of the omentum, liver, stomach, intestines, or colon. The uterine body measured 6 cm and was slightly enlarged, with a uniform texture. The left ovary appeared normal and adhered to the posterior leaf of the broad ligament, and no significant abnormalities were observed in the left fallopian tube, which had partial adhesion to the surrounding tissues. The right ovary had a solid mass approximately 15 cm in size, adhered to the posterior leaf of the broad ligament and the surface of the rectum, with adhesion and capsular rupture. An infected mass was observed with pus attached to the surface of the rectum and the posterior leaf of the broad ligament. There was 100 mL of free serous fluid in the abdominal cavity, and no enlargement of the abdominal or pelvic lymph nodes was observed. The right ovarian mass was a solid cystic mass containing mucus, with dense cystic areas locally; the tissue was tough and not brittle. Intraoperative frozen pathology revealed that the right ovarian mass was a mucinous tumor consistent with a borderline mucinous adenoma. The patient’s family requested fertility preservation. Accordingly, the final procedures were right adnexectomy and omentectomy. Postoperative pathological diagnosis: Right ovary: borderline mucinous tumor with localized carcinoma in situ and microinvasive carcinoma (Figure 4A and B), no neurovascular invasion observed, and no metastatic foci in the right fallopian tube and omentum. Immunohistochemical results: CK7 (+); P53 (approximately 60% strong+); PR (-); CK20 (-); CDX2 (+); ER (-); Claudin18.2 (approximately 90% 2+); Ki-67 (approximately 80%+); P16 (-); PAX8 (-); WT1 (-); SATB2 (focal positivity); PMS2 (+); MLH1 (+); MSH6 (+); MSH2 (+); CEA (partial+).

Figure 4 (A) The tissue displays a multicystic pattern, with cyst walls lined by mucinous columnar epithelium showing varying degrees of stratification and forming villous or delicate filiform papillary projections. Most epithelial areas exhibit mild to moderate dysplasia, while a small focus shows moderate to severe dysplasia confined to the epithelium (HE ×40). (B) A microscopic focus demonstrates confluent glands forming a cribriform pattern, with moderate nuclear atypia and identifiable mitotic figures, consistent with stromal invasive growth measuring less than 5 mm in greatest dimension (HE ×400).

The postoperative recovery was good. The final diagnosis was a stage IIB ovarian mucinous cystadenocarcinoma (microinvasive carcinoma; T2bN0M0). The patient was transferred to the medical oncology department for postoperative chemotherapy. One month after the operation, the serum tumor marker levels returned to normal and the pleural effusion completely resolved, as confirmed by imaging. The patient is currently in good general condition and under follow-up.

Discussion

As previously noted, primary mucinous carcinoma or borderline mucinous tumors of the ovary that present with pseudo-Meigs syndrome are extremely rare. In 2025, Pipes et al reported a case of stage IA ovarian mucinous carcinoma presenting with PMS. Prior to this, no such cases had been documented.⁶ Chen et al reported a case of a borderline mucinous ovarian tumor associated with PMS as early as 2013; no similar cases have been reported since then.⁷ Based on the two cases reported in this study, ovarian low-grade malignant mucinous tumors associated with PMS should be considered in the differential diagnosis of advanced ovarian cancer. Table 1, summarizes 55 reported cases of PMS associated with primary ovarian tumors, excluding other reproductive tumors such as uterine myoma and ovarian metastatic tumors. These include 32 cases of ovarian germ cell tumors (16 cases of struma ovarii, 29.1%; 6 cases of benign teratoma, 10.9%; 4 cases of yolk sac tumor, 7.3%; 2 cases of dysgerminoma, 3.6%; 1 case of mixed germ cell tumor, 1.8%); 1 case of ovarian sex cord-stromal tumor (1 case of malignant granulosa cell tumor, 1.8%); 18 cases of ovarian epithelial tumors (8 cases of serous tumor, 14.5%; 4 cases of mucinous tumor, 7.3%; 4 cases of endometrioid tumor, 7.3%; 1 case of clear cell carcinoma, 1.8%); 4 cases of mesenchymal tumors (1 case of sarcoma, 1.8%; 3 cases of hemangioma, 5.5%); and 1 case of combined tumor (sex cord-stromal tumor + epithelial tumor, 1.8%). The chief complaints include “dyspnea or shortness of breath” (34/55), “abdominal distension” (18/55), “abdominal pain” (7/55), and “abdominal bulge or abdominopelvic mass” (5/55). Most of the patients had significantly elevated serum CA125 levels (38/55). The mechanism underlying elevated CA-125 levels in PMS remains unclear, although it has been reported to result from inflammation of the pleural and peritoneal surfaces stimulated by free fluid.⁸ Some patients also exhibited elevated serum CA199 level (7/55), particularly in mucinous carcinomas and borderline mucinous tumors. The pleural effusion was mostly located in the right thoracic cavity, or more significantly in the right thoracic cavity (34/55, 61.8%), with lymphocytes as the main component. In most cases, pleural effusion and ascites significantly decreased or resolved within 2 months after primary tumor resection (42/55, 76.4%). Interestingly, the analysis showed that ovarian germ cell tumors were more commonly associated with large-volume ascites (≥3000 mL) (14/26, 53.8%), followed by ovarian epithelial tumors (6/15, 40.0%).

Table 1 Clinical Features of Primary Ovarian Tumor with PMS

Therefore, the presence of an ovarian mass accompanied by pleural effusion and ascites, along with negative cytology for tumor cells and elevated serum CA125, should first be considered in Meigs’ syndrome or ovarian germ cell tumors with PMS. If other serum tumor markers are elevated, such as serum CA19-9, a diagnosis of a mucinous tumor should be considered, as observed in this case.

In this report, the pathological diagnosis of the first case was mucinous cystadenoma, with focal borderline changes. In the second case, the diagnosis was a borderline mucinous tumor exhibiting areas of intraepithelial carcinoma and microinvasion, without evidence of neural or vascular invasion. In 2022, Karen et al conducted a detailed analysis of other subtypes of borderline mucinous tumors, including intraepithelial carcinoma, microinvasion, and microinvasive carcinoma.⁶² When the epithelium exhibited severe nuclear atypia without infiltration, it was diagnosed as an intraepithelial carcinoma. When considering a diagnosis of intraepithelial carcinoma, extensive tissue sampling or additional histological sections should be performed to exclude invasion. In cases of diffuse severe cytological atypia, a diagnosis of mucinous carcinoma, whether primary or metastatic, should be considered. Microinvasion can be focal or multifocal and may include single cells or small nests of cells, sometimes characterized by abundant eosinophilic granules in the cytoplasm exhibiting mild to moderate atypia. In contrast, microinvasive carcinomas exhibit marked nuclear atypia in the invasive component and are typically composed of irregular infiltrating glands, nests, cords, or single cells, accompanied by a desmoplastic stromal reaction. Therefore, Karen et al suggested coding microinvasion as “mucinous borderline tumor” and coding “microinvasive carcinoma” as mucinous carcinoma.⁶² Therefore, in the second case, we ultimately diagnosed ovarian mucinous cystadenocarcinoma stage IIB (microinvasive carcinoma, T2bN0M0) and administered postoperative adjuvant intravenous chemotherapy. Given the rarity of mucinous microinvasive carcinoma, there is no established consensus regarding its biological behavior or optimal follow-up strategy.⁶³ We recommend that this patient undergo long-term follow-up in accordance with the surveillance strategy for ovarian mucinous invasive carcinoma.

Mucinous ovarian tumors are typically unilateral and large multicystic, with an average size of 20 cm for borderline tumors and 16 cm for malignant tumors.⁶⁴ In this report, both patients had tumors with diameters exceeding 20 cm that presented as multicystic lesions. Similarly, previous cases of borderline or malignant mucinous tumors had diameters of > 20 cm. Generally, mucinous tumors cause no significant symptoms and are often discovered during the examination of pelvic masses or abdominal distention. However, patients with PMS mostly present with dyspnea or shortness of breath. Both patients sought further medical attention because of progressively worsening dyspnea. Both patients had significantly elevated serum tumor markers (CA125, CA19-9, etc)., which led to the preoperative suspicion of advanced malignant tumors of ovarian origin. CA19-9 is frequently elevated in ovarian mucinous tumors, especially in mucinous carcinomas, whereas it is typically not significantly increased in serous ovarian cancers.⁶⁵ In the first case, because of a significant elevation in CA19-9 levels, mucinous carcinoma could not be excluded preoperatively; therefore, gastrointestinal endoscopy was performed to rule out metastatic mucinous tumors. Both cases were consistent with those of previous reports, with pleural and abdominal effusions resolving within a short postoperative period. However, the causes of ascites and hydrothorax remain unclear to date.⁶⁶ Pleural effusion may occur due to the excessive migration of ascitic fluid into the pleural cavity through specific lymphatic channels in the diaphragm.⁶⁷ The fact that most pleural effusions are almost entirely on the right side, even when pelvic masses are located on the left side or bilaterally, supports this theory. Nonetheless, in a small number of cases, large pleural effusions do not accompany significant ascites, and large volumes of serous ascites do not necessarily accompany pleural effusions, as listed in the table Subsequent studies have proposed various possible mechanisms, including peritoneal irritation, tumor inflammatory cytokines (such as IL-6), and the release of vascular endothelial growth factor, which lead to increased vascular permeability of the chest and peritoneum. Other proposed mechanisms include tumor compression, which causes lymphatic and venous obstruction and hypoproteinemia.^68,69 However, these mechanisms do not explain the predominance of right-sided pleural effusions.

Conclusion

Overall, the two cases reported in this article exhibited symptoms similar to those of advanced ovarian cancer (stage IV). However, cytological examination of the pleural fluid and histopathological diagnosis of the omental tissue biopsy were negative. These nondiagnostic findings prompted the surgeon to perform a comprehensive staging surgery. This highlights the importance of cytological and histopathological diagnosis before making treatment decisions. Patients with suspected advanced ovarian cancer, unsuitable for primary surgery, and significant hydrothorax should receive neoadjuvant chemotherapy prior to cytoreductive surgery. Despite the low incidence of PMS, histological or cytological confirmation of malignancy must be performed before administering neoadjuvant chemotherapy to avoid unnecessary treatment. To minimize patient discomfort, reduce hospitalization costs, and shorten hospital stay, image-guided needle biopsy is preferred over surgical exploration.

In conclusion, although PMS associated with ovarian mucinous tumors is relatively rare, it should be considered in the differential diagnosis when patients present with pelvic neoplasms accompanied by pleural effusion and ascites, particularly in the presence of elevated serum CA19-9 levels and corresponding imaging findings.