Meigs SyndromeINTRODUCTION

Background: Meigs syndrome is defined as the triad of benign ovarian tumor with ascites and pleural 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 1936, Meigs and Cass described 7 cases of ovarian fibromas associated with ascites and pleural effusion. 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 might be a fibroma, thecoma, cystadenoma, or granulosa cell tumor.

Pseudo-Meigs syndrome consists of pleural effusion, ascites, and benign tumors of the ovary other than fibromas. These benign tumors include mature teratomas, struma-ovarii, leiomyoma of ovary, and benign tumors of the fallopian tube or uterus.

Atypical Meigs: Two case reports have been made of atypical Meigs characterized by a benign pelvic mass with right-sided pleural effusion but without ascites. As in Meigs syndrome, pleural effusion resolves after removal of pelvic mass.

　

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 myxoid component to the stroma are associated with ascites. These authors believe that their observations favored 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 theorize that ascitic fluid is transferred via transdiaphragmatic lymphatic channels. The size of the pleural effusion is largely independent of the amount of ascites.

Study by Efskind: Efskind injected ink into the lower abdomen of a woman with Meigs syndrome and found that, within half an hour, the ink particles had accumulated in the lymphatics of the pleural surface. Blockage of these lymphatics prevented accumulation of pleural fluid and caused an increase in ascitic fluid.

Study by Terada: In 1992, Terada et al injected labeled albumin into the peritoneum and found that within 3 hours the maximum concentration was detected in the right pleura.

Nature of the ascitic and pleural fluid: Ascitic fluid and pleural fluid in Meigs syndrome can be either transudate or exudate. 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.

　

Frequency: 　

In the US: 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% of them.

Internationally: Prevalence is unknown.

Mortality/Morbidity: Meigs syndrome, being a benign condition, has a very good prognosis if properly managed, though it mimics a malignant condition. Life expectancy after surgical removal of the tumor is the same as in the general population.

Age: Incidence of ovarian tumor begins to increase in the third decade and increases progressively to peak in the seventh decade. Case reports have been made of Meigs syndrome in prepubertal girls with benign teratomas and cystadenomas.

CLINICAL

History: Patients may have a family history of ovarian cancer. The chief complaints are vague and generally present over a period of 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

o Tachypnea

o Tachycardia

Lungs

o Dullness to percussion

o Decreased tactile and vocal fremitus

o Decreased breath sounds are noted, suggesting pleural effusion. Pleural effusion is seen mostly on the right side but can also be left-sided.

Abdomen

o Examination can be positive for a pelvic mass, small or large, or no mass may be felt.

o Ascites will be present, with shifting dullness and/or fluid thrill.

Pelvis: Examination reveals a pelvic mass.

DIFFERENTIALS

Cirrhosis   Colon Cancer, Adenocarcinoma   Hypoalbuminemia   Lung Cancer, Non-Small Cell   Lung Cancer, Oat Cell (Small Cell)   Nephrotic Syndrome   Ovarian Cancer   Pleural Effusion   Tuberculosis

Other Problems to be Considered:

Congestive heart failure

WORKUP

Lab Studies: 　

Complete blood count: This provides information about levels of hemoglobin, hematocrit and platelets. A low hemoglobin count requires further workup, including reticulocyte count, total iron-binding capacity, and iron and ferritin levels. If anemia is present in patients with Meigs syndrome it is most likely due to iron deficiency. Anemia can be corrected emergently by blood transfusion in those 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. Corrections of these electrolytes are made, if necessary.

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 giving vitamin K to the patient or by transfusing fresh frozen plasma.

Other than serum electrolytes and complete blood count, the lab test of interest is serum CA 125. Tumor marker serum CA 125 can be elevated in Meigs syndrome, but the degree of elevation does not

correlate with malignancy. CA 125 level is not used as a screening test. (The highest reported level of CA 125 after laparotomy was 336 U/mL).

o Physiologic sources of CA 125 are fetal coelomic epithelium and its derivatives, including the following:

o Mulerian epitheliumo Pleurao Pericardiumo Peritoneum

Pathologic conditions related to elevated CA 125o Pelvic inflammatory disease (PID)o Peritoneal damage or regeneration, eg, abdominal surgeryo Ovarian malignancy

In 1992, Jeffery and Lin carried out a study to determine whether the ovarian fibroma was the source of serum CA 125 elevation. They localized CA 125 expression in the omentum and peritoneal surfaces, rather than fibroma, using immunohistochemical technique specific for the tumor marker.

Imaging Studies: 　

Chest radiography confirms pleural effusion.

Abdominal and pelvic ultrasound confirms the ovarian mass and ascites.

CT scan of the abdomen and pelvis

o CT scan confirms ascites and ovarian, uterine, fallopian tube, or broad ligament mass.

o No signs of distant metastasis are seen.

Procedures: 　

Paracentesis: Ascitic fluid mostly is transudative. Fluid is negative for malignant cells but can be positive for reactive mesothelial cells.

Thoracentesis: Pleural fluid usually is transudative. It can be exudative and negative for malignant cells.

Papanicolaou smear: Smear is normal.

Histologic Findings: Ovarian tumors are divided into the following histologic subgroups, and Meigs syndrome can be seen with any of the benign tumors.

Coelomic epithelial tumors: These tumors, which originate from the coelomic epithelium, constitute 80%-85% of all ovarian tumors.

o Serous cystadenoma and mucinous cystadenoma (15-20% are malignant)

o Endometrioid type and clear cell (95-98% are malignant)o Brenner tumor (2% are malignant).

Germ cell tumors: These tumors originate from the germ cell and constitute 10-15% of all ovarian tumors. All are malignant except mature teratoma and gonadoblastoma, which are always benign.

o Mature teratomao Immature teratomao Dysgerminomao Gonadoblastomao Endodermal sinuso Embryonal carcinomao Nongestational choriocarcinoma

Gonadal-stromal cell tumor: These constitute 3-5% of all tumors.

o Granulosa cello Fibroma (<5% malignant)o Thecoma (<5% malignant)o Sertoli-Leydig cell (<5% malignant)o Lipid cell type (30% malignant)o Gynandroblastoma (100% malignant)

TREATMENT

Medical Care:

Provide symptomatic relief of ascites and pleural effusion by means of therapeutic paracentesis and thoracentesis.

Surgical Care:

Exploratory laparotomy with surgical staging is the treatment of choice.

Perform biopsy of the ovarian mass during exploratory laparotomy. Biopsy findings are consistent with benign tumor. Lymph node biopsies and omentum and pelvic washings if done during surgery are negative for malignancy.

In women of reproductive age, perform unilateral salpingo-oophorectomy.

In postmenopausal women, options include bilateral salpingo-oophorectomy with total hysterectomy and unilateral salpingo-oophorectomy.

In prepubertal girls, options include wedge resection of ovary and unilateral salpingo-oophorectomy.

Consultations: Gynecologic-surgical consult for surgical management of the case

Activity: Activity as tolerated

FOLLOW-UP

Further Inpatient Care:

Postsurgical management

Further Outpatient Care: 　

As described by Meigs, ascites and pleural effusion dramatically resolve within a few weeks to months after removal of the pelvic mass without any recurrence.

The serum CA 125 level also returns to normal levels after surgery.

Prognosis: 　

Life expectancy of patients with Meigs syndrome is the same as in the general population after surgery.

MISCELLANEOUS

Medical/Legal Pitfalls: 　

This benign condition can be confused with malignant disease because of the presence of ascites and pleural effusion with pelvic mass.

An elevated serum CA 125 does not always indicate malignancy.

BIBLIOGRAPHY

Aoshima M, Tanaka H, Takahashi M, et al: Meigs' syndrome due to Brenner tumor mimicking lupus peritonitis in a patient with systemic lupus erythematosus. Am J Gastroenterol 1995 Apr; 90(4): 657-8[Medline].

Carson SA, Mazur MT: Atypical endometrioid cystadenofibroma with Meigs' syndrome: ultrastructure and S-phase fraction. Cancer 1982 Feb 1; 49(3): 472-9[Medline].

Dunn JS Jr, Anderson CD, Method MW: Hydropic degenerating leiomyoma presenting as pseudo-Meigs syndrome with elevated CA 125. Obstet Gynecol 1998 Oct; 92(4 Pt 2): 648-9[Medline].

Jones OW, Surwit EA: Meigs syndrome and elevated CA 125. Obstet Gynecol 1989 Mar; 73(3 Pt 2): 520-1[Medline].

Lacson AG, Alrabeeah A, Gillis DA, et al: Secondary massive ovarian edema with Meig's syndrome. Am J Clin Pathol 1989 May; 91(5): 597-603[Medline].

Lin JY, Angel C, Sickel JZ: Meigs syndrome with elevated serum CA 125. Obstet Gynecol 1992 Sep; 80(3 Pt 2): 563-6[Medline].

Meigs JV, Cass JW: Fibroma of the ovary with ascites and hydrothorax: with a report of seven cases. Am J Obstet Gynecol 1937; 33: 249-267.

Samanth KK, Black WC: Benign ovarian stromal tumors associated with free peritoneal fluid. Am J Obstet Gynecol 1970 Jun 15; 107(4): 538-45[Medline].