Continuing Education Activity

Meigs syndrome is an uncommon presentation, where a benign ovarian tumor presents along with ascites and pleural effusion. About 1% of ovarian tumors can present as Meigs syndrome. A similar presentation can be seen in many metastatic malignancies. This article will present findings to aid clinicians in the diagnosis and treatment of this syndrome. It will help to differentiate it from malignant ovarian conditions. Some patients have either ascites or pleural effusion with benign ovarian tumors and are classified as atypical/incomplete Meigs syndrome. This activity reviews the role of the interprofessional team in the presentation, evaluation, and treatment/management of Meigs syndrome.

Objectives:

• Identify the etiology of Meigs syndrome.

• Review the evaluation of Meigs syndrome.

• Outline the management options available for Meigs syndrome.

• Explain the importance of coordination and communication by the interprofessional team in evaluating and managing patients with Meigs syndrome.

Introduction

In 1937, Joe Vincent Meigs and John W Cass reported a series of 7 cases of ovarian fibroma associated with ascites and hydrothorax. It was later termed Meigs syndrome by Rhodes and Terrell. Even though the association of benign ovarian tumors and pleural effusion was reported before, it was Meigs and Cass who reported the resolution of ascites and pleural effusion after removing the tumor. Eventually, several authors reported similar cases, and Meigs syndrome became a distinct entity.

Meigs eventually redefined the syndrome in 1954. The following criteria are to be met for the diagnosis of Meigs syndrome – a) Presence of the benign tumor of the ovary – Fibroma, thecoma, granulosa cell tumor or Brenner tumor b) ascites c) pleural effusion, and d) a resolution of ascites and pleural effusion after removal of the tumor. This syndrome is sometimes called Demons-Meigs syndrome after another author who described a similar presentation before Meigs.[1][2][3][4]

Some patients have either ascites or pleural effusion with benign ovarian tumors and are classified as atypical/incomplete Meigs syndrome.

Pericardial effusion is not included in the definition of Meigs syndrome; however, there have been case reports in patients with unexplained persistent pericardial effusion, which resolved after resectioning a benign ovarian tumor.[5]

Etiology

The etiology of Meigs syndrome is unknown.[6]

Epidemiology

[2]Meigs syndrome happens in 1% of all ovarian tumors. It is most commonly associated with ovarian fibroma. Ovarian fibromas are diagnosed in 2 to 5% of excised ovarian tumors.

Although cases have been reported in women before their third decade, Meigs syndrome is extremely rare in women younger than 30 years old. The syndrome is much more common in postmenopausal women, especially those around 50 years, and its peak incidence is in women in their seven-decade.[2][7]

Pathophysiology

The pathophysiology of ascites and pleural effusion in Meigs syndrome is not well established. Meigs theorized that ascites are due to the pressure of the tumor on the abdominal lymphatics, and the ascitic fluid then transudates into the pleural cavity. He demonstrated the presence of India ink particles in the thoracic cavity when injected into the ascitic fluid.

Another theory is fluid enters the peritoneum through the ovarian tumor capsule. The fluid can enter the pleural cavity through diaphragmatic defects or via the lymphatic channels to cause pleural effusion.  

Stromal edema may lead to transudation due to changes in venous and lymphatic drainage. An imbalance between the blood supply to a large tumor and its venous and lymphatic drainage may be responsible for stromal edema and transudation.[2]

The other proposed theories are hormonal stimulation, torsion of the tumor, and vascular endothelial growth factor (VEGF) production by the tumor, increasing capillary permeability. However, these theories are not proven, and there is no consensus on the pathophysiology of Meigs syndrome.[6][7][8][9]

Histopathology

In Meigs syndrome, the benign tumor may be a fibroma, thecoma, cystadenoma, or granulosa cell tumor, histologically. 

History and Physical

A typical presentation is in a post-menopausal woman or, uncommonly, in a younger woman. Ovarian tumors in children and adolescents could be associated with Gorlin syndrome.[10]. Gorlin syndrome is a rare autosomal dominant disease. It is characterized by the development of basal cell carcinomas in children and has been associated with cases of Meigs syndromes.[11]

Symptoms related to ovarian tumors could remain indolent for a long time unless the tumor secretes steroid hormones. Androgen excess may present as virilization, and estrogen excess may present as abnormal uterine bleeding, endometrial neoplasm, and in a child as precocious puberty. Other symptoms related to the tumor are abdominal distension due to a large tumor, uterine prolapse, urinary incontinence, fatigue, weight loss, and pedal edema.

Symptoms related to pleural effusion include dyspnea, dry cough, and pleurisy. The pleural effusions are usually right-sided, even though the left and bilateral effusions are possible. The size of the pleural effusion is independent of the size of the ascites.[12]

Symptoms related to ascites include abdominal distension.

The physical exam may show palpable adnexal masses on abdominal or transvaginal examination, signs of pleural effusion like diminished breath sounds, egophony on pulmonary auscultation, dullness on chest percussion, jugular venous distension, and/or signs of ascites such as distended abdomen with fluid thrill. A thorough lymph node and skin examination should be conducted to look for skin cancers, especially basal cell cancer.[1][6][13][10]

Evaluation

A good history and physical examination are essential first steps in diagnosing Meigs syndrome. Any woman with signs and symptoms of ascites and pleural effusion would warrant evaluation for pelvic masses. Every effort should be made at the evaluation stage to rule out important differential diagnoses, especially carcinomatoses. A definitive diagnosis of Meigs syndrome could only be made after removing the tumor, followed by the resolution of the ascites and pleural effusion. Also essential to diagnosing Meigs syndrome is that histopathology of the ovarian mass has to be a benign tumor.[1][2]

Laboratory studies: Routine blood tests like complete blood count, comprehensive metabolic panel, lipid panel, PT/INR, pro-BNP, and urine analysis will help recognize conditions like anemia, macrocytosis, hypoalbuminemia, proteinuria, liver failure, congestive heart failure.

Even though the elevation of serum CA 125 is suggestive of ovarian cancer, its co-incidence with Meigs syndrome has been described in the literature.[9] The scope of this test in Meigs syndrome is limited. Like many other tumor markers, its real value lies in the surveillance and evaluation response to cancer treatment.[2]  Immunohistochemical studies suggest that serum CA-125 elevation in patients with Meigs syndrome is caused by mesothelial expression of the antigen rather than by fibroma.[14]  CA-125 levels should return to normal after treatment. 

Monitoring serum sex hormones will help evaluate ovarian lesions in patients with virilization or symptoms of estrogen excess.

Imaging: Chest X-ray helps us recognize the pleural effusion and also evaluate for metastases.

CT scan abdomen helps us delineate an alternative etiology for ascites like malignant lesions, metastases, and liver cirrhosis.

Pelvic ultrasound is a key imaging modality to evaluate pelvic organs, especially for smaller lesions.

PET CT Scan time may help delineate malignant tumors if there is strong suspicion.[15] 

Endoscopy: In patients with risk factors for gastrointestinal malignancy, an esophagogastroduodenoscopy and colonoscopy should be considered to rule out esophageal, gastric, and colon cancers.

Fluid Analysis and cytology: Thoracentesis and paracentesis are diagnostic modalities and will provide temporary symptomatic relief for the patients with ongoing investigations.

The pleural fluid analysis includes testing for protein, LDH, cytology, gram stain, and cultures. Even though in most patients with Meigs syndrome, the pleural fluid is an exudate, there have been reports of transudative effusions. Hence, either type of pleural fluid can be seen in these patients.[16] 

Similarly, peritoneal fluid is analyzed for cytology, gram stain, and cultures. Albumin levels might be of value as a SAAG (Serum Ascites Albumin Gradient) > 1.1 g/dL may indicate portal hypertension.

Tuberculosis testing, including TB skin tests, pleural and peritoneal fluid testing for AFB smears and cultures, adenosine deaminase test on pleural fluid, and molecular testing, could be considered on the patients with risk factors based on their symptomatology.

Treatment / Management

Once malignancy and other differential diagnoses are ruled out, the mainstay of treatment in patients with Meigs Syndrome could be placed in two categories.[2][1]

Symptomatic treatment: Patients with large pleural effusions need recurrent thoracentesis to manage dyspnea. Likewise, paracentesis will help them with abdominal discomfort and troubled breathing.

Curative treatment: Abdominal surgery (laparotomy or laparoscopy) with removing the tumor to perform a frozen section is the initial evaluation. If the tumor is benign, especially in young patients who want to preserve their fertility, a unilateral salpingo-oophorectomy is performed. In postmenopausal women, a total abdominal hysterectomy with bilateral salpingo-oophorectomy is performed.

Differential Diagnosis

Meigs syndrome cannot be diagnosed until the patient has surgery. Hence, it is essential that alternative diagnoses are considered and, to an extent, ruled out before contemplating abdominal surgery. The following are the important differential diagnoses.[2][3][4][6][16][17]

• Ovarian carcinoma
• Cirrhosis of liver
• Other cancers - gastrointestinal cancers, lung cancers
• Congestive heart failure
• Nephrotic syndrome
• Tuberculosis
• Pseudo Meigs syndrome: Ascites and pleural effusion in a patient with pelvic or abdominal tumor (other than the benign tumors included in the definition of Meigs syndrome). The tumors in pseudo-Meigs syndrome could be benign or malignant.
• Pseudo-pseudo Meigs syndrome: Also called Tjalma syndrome, is a condition where there is a combination of ascites, pleural effusion, and elevated serum levels of CA 125 in a patient with systemic lupus erythematosus.[18]

Prognosis

Meigs syndrome is a benign condition, and early detection and intervention result in a good prognosis. The pleural effusion and ascites will resolve permanently once the patient’s tumor is resected. The life expectancy postoperatively is equivalent to the general population post-surgery.[6]

Complications

Unrecognized and untreated patients will be subjected to multiple thoracenteses and paracenteses. And this could lead to complications related to these repetitive procedures, including infection, bleeding, dehydration, and hypoalbuminemia.

Patients may develop complications from ovarian tumors, including ongoing cachexia, severe pedal edema, deep venous thrombosis, severe fatigue, uterine prolapse, urinary frequency, and incontinence. In addition, hormone-producing ovarian tumors may cause severe anemia due to abnormal uterine bleeding and, on rare occasions, could cause the development of endometrial cancer.

Deterrence and Patient Education

Patients should be advised that if they develop shortness of breath or a distended abdomen, they should seek medical help for evaluation. Even though Meigs syndrome is a treatable condition, its diagnosis is only made after a systematic assessment of the patient with a good history, physical examination, and appropriate initial laboratory testing and imaging studies. Patients should be counseled about the benign nature of the condition. Timely referral to a subspecialist could eventually cure this condition. It is imperative to note that the differential diagnoses include cancers of various primaries, which, if ignored, could lead to potentially terminally ill conditions.

Enhancing Healthcare Team Outcomes

The clinical presentation of Meigs syndrome could mirror the clinical picture of a malignant ovarian tumor with pleural and abdominal metastases. If the tumor is deemed inoperable without evidence of the malignant nature of the tumor, a potential opportunity for cure could be missed. Hence health care professionals need to keep Meigs syndrome in the differential in any female with ascites and pleural effusion.[7]

The pathophysiology of Meigs syndrome is still not well explained. Further studies on this topic may shed light on obtaining an earlier diagnosis of the condition. [Level 4]

Meigs syndrome requires the diagnostic and therapeutic efforts of an interdisciplinary and interprofessional healthcare team. This includes clinicians (MDs, DOs, NPs, and APs), specialists (who may need to help eliminate other systemic diagnostic possibilities), and nurses, all working in a coordinated fashion and openly sharing information and documenting all observations, interventions, and concerns in the patient's medical record. This approach will ensure that the entire interprofessional team has the same data and can reach out to other members to manage the case. Nurses will help coordinate the various disciplines and assist in patient counseling. This interprofessional approach will derive optimal outcomes for patients with Meigs syndrome. [Level 5]