MEIGS Syndrome

Meigs syndrome is defined as the triad of benign ovarian tumor with ascites andpleural effusion that resolves after resection of the tumor. The ovarian tumor in Meigs syndrome is a fibroma. In 1934, Salmon described the association of pleural effusion with benign pelvic tumors. In 1937, Meigs and Cass described 7 cases of ovarian fibromas associated with ascites and pleural effusion. [1] In 1954, Meigs proposed limiting true Meigs syndrome to benign and solid ovarian tumors accompanied by ascites and pleural effusion, with the condition that removal of the tumor cures the patient without recurrence. Histologically, the benign ovarian tumor may be a fibroma, thecoma, cystadenoma, or granulosa cell tumor. Pseudo-Meigs syndrome consists of pleural effusion (an example of which can be seen in the image below), ascites, and benign tumors of the ovary other than fibromas. These benign tumors include those of the fallopian tube or uterus and mature teratomas, struma ovarii, and ovarian leiomyomas.[2] This terminology sometimes also includes ovarian or metastatic gastrointestinal malignancies.

Chest radiograph showing left-sided pleural effusion.

Atypical Meigs characterized by a benign pelvic mass with right-sided pleural effusion but without ascites has been reported at least twice. As in Meigs syndrome, pleural effusion resolves after removal of the pelvic mass. Pseudo-pseudo Meigs syndrome includes patients with systemic lupus erythematosus and enlarged ovaries.

Pathophysiology
Etiology of ascitic fluid
The pathophysiology of ascites in Meigs syndrome is speculative. Meigs suggested that irritation of the peritoneal surfaces by a hard, solid ovarian tumor could stimulate the production of peritoneal fluid. Samanth and Black studied ovarian tumors accompanied by ascites and found that only tumors larger than 10 cm in diameter with a myxoid component to the stroma are associated with ascites.[4] These authors believe that their observations favor secretion of fluid from the tumor as the source of the ascites. Other proposed mechanisms are direct pressure on surrounding lymphatics or vessels, hormonal stimulation, and tumor torsion. Development of ascites may be due to release of mediators (eg, activated complements, histamines, fibrin degradation products) from the tumor, leading to increased capillary permeability.

Origin of pleural effusion

The etiology of pleural effusion is unclear. Efskind and Terada et al theorize that ascitic fluid is transferred via transdiaphragmatic lymphatic channels. The size of the pleural effusion is largely independent of the amount of ascites.

Efskind's study: Efskind injected ink into the lower abdomen of a woman with Meigs syndrome and found that the ink particles accumulated in the lymphatics of the pleural surface within half an hour. Blockage of these lymphatics prevented accumulation of pleural fluid and caused an increase in ascitic fluid. Terada and colleagues' study: In 1992, Terada and colleagues injected labeled albumin into the peritoneum and found that the maximum concentration was detected in the right pleura within 3 hours.

Nature of the ascitic and pleural fluid

Ascitic fluid and pleural fluid in Meigs syndrome can be either transudative or exudative. Meigs performed electrophoresis on several cases and determined that pleural and ascitic fluids were similar in nature. Tumor size, rather than the specific histologic type, is thought to be the important factor in the formation of ascites and accompanying pleural effusion.

Epidemiology
Frequency
United States Ovarian tumors are more prevalent in upper socioeconomic groups. Ovarian fibroma is found in 2-5% of surgically removed ovarian tumors, and Meigs syndrome is observed in about 1%. Ascites is present in 10-15% of those with ovarian fibroma and hydrothorax in 1%, especially with larger lesions. International Prevalence is unknown.

Mortality/Morbidity
Although Meigs syndrome mimics a malignant condition, it is a benign disease and has a very good prognosis if properly managed. Life expectancy after surgical removal of the tumor mirrors that of the general population.

Age
The incidence of ovarian tumor begins to increase in the third decade and increases progressively to peak in the seventh decade. Meigs syndrome in prepubertal girls with benign teratomas and cystadenomas has been reported.

Patients with Meigs syndrome may have a family history of ovarian cancer. The chief complaints are vague and generally manifest over time.

Fatigue Shortness of breath Increased abdominal girth Weight loss Nonproductive cough Bloating Amenorrhea for premenopausal women Menstrual irregularity

Physical
Positive signs include the following:

Vital signs

Tachypnea Tachycardia

Lungs
Dullness to percussion Decreased tactile fremitus Decreased vocal resonance Decreased breath sounds are noted, suggesting pleural effusion. Pleural effusion is mostly observed on the right side, but it can also be left sided.

Abdomen
Examination may reveal a small or large pelvic mass, or no mass may be felt. Ascites is present, with shifting dullness and/or fluid thrill.

Pelvis
Examination reveals a pelvic mass.

Causes
When an ovarian mass is associated with Meigs syndrome and an elevated CA-125 serum level, a malignant process may be suspected. A negative cytologic examination result of ascitic effusion, the absence of peritoneal implantation, and benign histology should limit surgical procedures. This decision should be made by an experienced gynecologic surgeon or a gynecologic oncologist.

Case reports exist of pseudo-Meigs syndrome associated with malignantstruma ovarii and elevated CA-125 levels.[5, 6] The choice of not performing adjuvant therapy is feasible after optimal surgery and adequate staging procedure given to the usually clinical benign course and the low incidence of metastases in malignant struma ovarii. Careful patient counseling is required. Struma ovarii is a rare cause of ascites, hydrothorax, elevated CA-125 levels, and hyperthyroidism.[6] This rare condition should be considered in the differential diagnosis in patients with ascites and pleural effusions but with negative cytologic test results. The combination of ascites, pleural effusion, CA-125 level elevation, and no tumor in a patient with systemic lupus erythematosus is either a Tjalma syndrome or due to the migrated Filshie clips a pseudo-Meigs syndrome

Differential Diagnoses

Ascites Cirrhosis Colon Cancer, Adenocarcinoma Hypoalbuminemia Lung Cancer, Non-Small Cell Lung Cancer, Oat Cell (Small Cell) Malignant Effusion Milroy Disease Nephrotic Syndrome Ovarian Cancer Pleural Effusion Tuberculosis Proceed to Workup

Laboratory Studies

Lab studies for patients with Meigs syndrome include the following:

CBC count
This study provides information about hemoglobin, hematocrit, and platelet levels. A low hemoglobin count requires further workup, including reticulocyte count, total iron-binding capacity, and iron and ferritin levels. Anemia in patients with Meigs syndrome is most likely due to iron deficiency. Anemia can be corrected emergently by blood transfusion in patients undergoing surgery for Meigs syndrome. Anemia can be treated with iron supplementation postoperatively.

Basic metabolic profile

Studies of sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, and glucose levels are included. These electrolytes are checked before the patient undergoes surgery. If necessary, corrections of these electrolytes are made.

Prothrombin time
Prothrombin time is checked before surgery. If elevated, it is a marker of coagulopathy. Elevated prothrombin time is corrected before surgery, either by administering vitamin K to the patient or by transfusing fresh frozen plasma.

Serum cancer antigen 125 test

Other than serum electrolytes and CBC count, the study of interest is the serum cancer antigen 125 (CA-125) test. Tumor marker serum levels of CA-125 can be elevated in Meigs syndrome, but the degree of elevation does not correlate with malignancy. In fact, a normal CA-125 level does not exclude the possibility of malignancy.[8] The CA-125 level is not used as a screening test. The highest reported level of CA-125 after laparotomy is 1808 U/mL. This would be a false-positive result. Physiologic sources of CA-125 are fetal coelomic epithelium and its derivatives, including the following:

Mllerian epithelium Pleura Pericardium Peritoneum Pathologic conditions related to an elevated CA-125 level include the following: Pelvic inflammatory disease (PID) Peritoneal damage or regeneration (eg, abdominal surgery) Ovarian malignancy Endometriosis In 1992, Lin et al conducted a study to determine whether the ovarian fibroma was the source of serum CA-125 elevation. Using an immunohistochemical technique specific for the tumor marker, they localized CA-125 expression in the omentum and peritoneal surfaces rather than in the fibroma.[9]

Laboratory Studies
Lab studies for patients with Meigs syndrome include the following:

CBC count
This study provides information about hemoglobin, hematocrit, and platelet levels. A low hemoglobin count requires further workup, including reticulocyte count, total iron-binding capacity, and iron and ferritin levels. Anemia in patients with Meigs syndrome is most likely due to iron deficiency. Anemia can be corrected emergently by blood transfusion in patients undergoing surgery for Meigs syndrome. Anemia can be treated with iron supplementation postoperatively.

Basic metabolic profile

Studies of sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, and glucose levels are included. These electrolytes are checked before the patient undergoes surgery. If necessary, corrections of these electrolytes are made.

Prothrombin time
Prothrombin time is checked before surgery. If elevated, it is a marker of coagulopathy. Elevated prothrombin time is corrected before surgery, either by administering vitamin K to the patient or by transfusing fresh frozen plasma.

Serum cancer antigen 125 test

Other than serum electrolytes and CBC count, the study of interest is the serum cancer antigen 125 (CA-125) test. Tumor marker serum levels of CA-125 can be elevated in Meigs syndrome, but the degree of elevation does not correlate with malignancy. In fact, a normal CA-125 level does not exclude the possibility of malignancy.[8] The CA-125 level is not used as a screening test. The highest reported level of CA-125 after laparotomy is 1808 U/mL. This would be a false-positive result. Physiologic sources of CA-125 are fetal coelomic epithelium and its derivatives, including the following:

Mllerian epithelium Pleura Pericardium Peritoneum Pathologic conditions related to an elevated CA-125 level include the following:

Pelvic inflammatory disease (PID) Peritoneal damage or regeneration (eg, abdominal surgery) Ovarian malignancy Endometriosis In 1992, Lin et al conducted a study to determine whether the ovarian fibroma was the source of serum CA-125 elevation. Using an immunohistochemical technique specific for the tumor marker, they localized CA-125 expression in the omentum and peritoneal surfaces rather than in the fibroma.[9]

Other Tests

Papanicolaou test findings are normal.

Procedures
Paracentesis: Ascitic fluid is mostly transudative. Findings are negative for malignant cells but can be positive for reactive mesothelial cells. Thoracentesis: Pleural fluid is usually transudative. Findings can be exudative and negative for malignant cells.

Procedures
Paracentesis: Ascitic fluid is mostly transudative. Findings are negative for malignant cells but can be positive for reactive mesothelial cells. Thoracentesis: Pleural fluid is usually transudative. Findings can be exudative and negative for malignant cells.

Surgical Care
Exploratory laparotomy with surgical staging is the treatment of choice. Perform a frozen section of the ovarian mass during exploratory laparotomy. If the frozen section is consistent with benign tumor, conservative surgery (salpingo-oophorectomy or oophorectomy) is appropriate. Findings of lymph node biopsies and omentum and pelvic washings are negative for malignancy if these procedures are performed during surgery. In women of reproductive age, perform unilateral salpingo-oophorectomy. In postmenopausal women, options include bilateral salpingo-oophorectomy with total hysterectomy and unilateral or occasionally bilateral salpingo-oophorectomy. In prepubertal girls, options include wedge resection of ovary and unilateral salpingo-oophorectomy. The cure rate after either type of surgery is high and recurrence is rare.

Consultations
Consult with a gynecologic surgeon for surgical management of the patient.

Prognosis
Life expectancy of patients with Meigs syndrome mirrors that of the general population after surgery.

Meigs' Syndrome
The three cardinal features of Meigs' syndrome are:

A benign ovarian tumour Ascites and pleural effusion If the tumour is resected, the fluid resolves

The ovarian tumour is usually a fibroma but may be a thecoma, cystadenoma, or granulosa cell tumour. When the histology is other than fibroma, it is sometimes referred to as pseudo-Meigs' syndrome.

On this page
Pathogenesis Epidemiology

Presentation Differential diagnosis Investigations Associated diseases Management Prognosis History References

Pathogenesis
There appears to be an inflammatory reaction that causes the peritoneal and pleural fluid but the underlying aetiology is unclear.[1] Even the source of the fluid is unclear.

A study of ovarian tumours with ascites found that only those larger than 10 cm in diameter with a myxoid component to the stroma were associated with ascites. These authors suggested that this favours secretion of fluid from the tumour rather than the peritoneum or pleura.[2]

The tumour marker CA-125 is often elevated but usually less so than in malignancy. CA-125 expression is localised on the peritoneum rather than the ovary.[3]

Epidemiology
Meigs' syndrome accounts for about 1% of ovarian tumours. It is very uncommon before 40 years of age and becomes more frequent as the years progress but there are some reports of it arising from teratomas or cystadenomas in pre-pubertal girls.

Presentation
Most features are related to ascites and pleural effusion but before the menopause there may be menstrual symptoms too.

Fatigue Dyspnoea (initially on exertion) Swollen abdomen with associated weight gain Non-productive cough Amenorrhoea or irregular menstruation Reduction in lung capacity may produce tachypnoea and tachycardia Examination of the chest will reveal dullness to percussion over the effusion. There will be decreased breath sounds and decreased tactile vocal fremitus. The effusion tends to be right-sided but can be bilateral. There appears to be no adequate explanation for this unilaterality. A large right-sided effusion will displace the mediastinum to the left with deviation of the trachea to the left and displacement of the apex beat. Abdominal examination may reveal a tumour arising from the pelvis but this may be obscured by ascites. The features of ascites include a fullness of the flanks and shifting dullness. Pelvic examination may reveal an ovarian mass.

Examination

Differential diagnosis
The main differential diagnosis is with a malignant ovarian tumour: They are much more common than Meigs' syndrome and tend to produce profuse ascites with a high protein content. Pleural effusion is less common unless due to pulmonary metastases. Other considerations include:

Other cancers including colon and lung[4] Tuberculosis Nephrotic syndrome Congestive heart failure

Cirrhosis

Investigations
Check urine for protein. Routine blood tests would include FBC, U & E, LFTs, including plasma proteins. CA-125 is a tumour marker that tends to be mildly elevated in Meigs' syndrome and markedly elevated in ovarian malignancy. This is not reliable and cases are described with very high CA-125 and normal levels.[5] It can also be normal in ovarian malignancy. CXR (AP and lateral) will show the degree of pulmonary effusion. Abdominal ultrasound will demonstrate the ascites and should outline the ovarian tumour too. For ovarian tumours, MRI is the first line after CT but CT is rarely used. Paracentesis and aspiration of pleural fluid serves two purposes. It helps to relieve symptoms and fluid should be sent for cytology. This is very important in distinguishing malignant ascites from Meigs' syndrome. The fluid tends to have the features of a transudate although sometimes it does appear to be an exudate. In ovarian carcinoma the protein content is usually high. Pleural and ascitic fluid should also be examined for protein, glucose, amylase, cell count, organisms and AAFB if indicated. If congestive heart failure is suspected, ECG will be required. Echocardiogram is indicated only if the ECG is abnormal.

Associated diseases

Pseudo-Meigs' syndrome is characterised by pleural effusion, ascites, and benign ovarian tumours (other than fibromas).[6] The tumours may include those of the fallopian tube, uterus, mature teratomas, struma ovarii and ovarian leiomyomas. Ovarian or metastatic gastrointestinal malignancies are sometimes included within this terminology. Atypical Meigs' syndrome consists of a benign pelvic mass with a right-sided pleural effusion, but no ascites is present. This is rare. The pleural effusion resolves after resection of the tumour. Pseudo-pseudo Meigs' syndrome may occur in patients with systemic lupus erythematosusand enlarged ovaries.

Management
The essential management is surgical removal of the tumour but before operation, aspiration of pleural effusion and ascites should be performed to improve pulmonary function.[6]

The operation includes full laparotomy to exclude other causes of malignancy including bowel. In women of reproductive age a unilateral salpingo-oophorectomy is usually performed. In girls who are before the menarche, wedge resection may be preferred if feasible. After the menopause an operation of total abdominal hysterectomy with bilateral salpingo-oophorectomy is usual.

Prognosis
Within weeks to months of operation the ascites and pleural effusion resolve and the CA-125 returns to normal. Postoperative resolution of the fluid is part of the definition of the disease. As it is a benign tumour the prognosis is excellent. If there is functioning ovarian tissue, fertility should be preserved.

History

In 1934 Salmon described the association of pleural effusion with benign pelvic tumours. In 1936 Meigs and Cass described 7 cases of ovarian fibromas associated with ascites and pleural effusion. [7][8] In 1954 Meigs proposed limiting the diagnosis of Meigs' syndrome to benign and solid ovarian tumours with ascites and pleural effusion, and the condition that removal of the tumour cures the patient without recurrence.

Joe Vincent Meigs was an American Obstetrician and Gynaecologist who was born in 1892 and died in 1963.