Pelvic mass, ascites, hydrothorax: a malignant or benign condition? Meigs syndrome with high levels of CA 125

Prz Menopauzalny. 2021 Jun; 20(2): 103–107.

Published online 2021 May 25. doi: 10.5114/pm.2021.106100

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Introduction

Abdominal-pelvic mass, ascites and pleural effusion are suggestive of malignant metastatic ovarian cancer. This triad is also present in a rare benign condition called Meigs syndrome. Rarely this condition is associated with an increased CA 125 level.

Case report

A 62-year-old woman with a history of abdominal pain underwent an ultrasound (US) examination and a chest X-ray. The imaging revealed the presence of a large pelvic mass and ascites with a monolateral pleural effusion and a high level of the tumor marker CA 125. The patient underwent a total abdominal hysterectomy, salpingoophorectomy, removal of the pelvic mass, pelvic lymphadenectomy and peritoneal biopsies. The histology showed an ovarian fibrothecoma.

Discussion

The US analysis according to international ovarian tumor analysis simple rules revealed “inconclusive results”; the logistic regression model LR2 and Adnex suggested a high risk of malignancy. The presence of ascites and the size of the lesion associated with a high level of CA 125 affected the correct assessment of the risk of malignancy, exposing the patient to overtreatment

Conclusions

Meigs syndrome is characterized by the resolution of symptoms after surgical removal of the pelvic mass. However, it mimics the clinical picture of a malignant metastatic ovarian cancer. Clinicians have to exclude ovarian cancer and recognize the syndrome to reduce inappropriate procedures.

Keywords: Meigs syndrome, CA 125, pelvic mass, ascites, hydrothorax, fibrothecoma, ovarian cancer

Meigs syndrome is a rare gynecological condition characterized by the presence of a benign ovarian solid tumor accompanied by ascites and hydrothorax. Rarely it is associated with high levels of CA 125. Meigs syndrome is more common in postmenopausal women with an average age of about 50 years. Even though it is extremely rare in women aged less than 30 years, some cases have been reported in children aged 4 and 9 years. Surgery is necessary to confirm the diagnosis. Histologically, the majority of cases are represented by fibroma, but thecoma, cystadenoma and granulosa cell tumor are also described. The typical features of the syndrome, ascites and pleural effusion, resolved completely after the surgical removal of the tumor. Although it mimics a malignant condition, Meigs syndrome is a benign disease [1, 2], characterized by a good prognosis.

A Caucasian 62-year-old woman referred to our department due to an abdominal pain since a few days before, associated with nausea and vomiting. She also presented with dysphagia and cachexia. No hirsutism, skin discoloration or other signs of hormonal dysregulation were detected. A history of painless, progressive abdominal distension and increasing weight of more than 15 kg in one year were reported, reaching a body mass index of 30. 5. Her anamnesis was substantially silent and she did not have familiarity for gynecological cancer or pathology. At admission a very distended abdomen was detected upon examination, while massive ascites was observed at the office ultrasound (US) scan. During hospitalization the patient complained of progressive dyspnea, especially in supine decubitus.

Investigations

In the suspicion of a malignant ovarian mass, diagnostic investigations were performed. Ovarian markers showed increased levels of CA 125 (1744.3 mUI/ml), with normal levels of carcinoembryonic antigen (4.2 ng/ml), AFP (3.5 ng/ml) and Ca 19.9 (19.2 UI/ml). The office transabdominal (TA) US showed the presence of massive ascites. A second level US (transvaginal and TA) revealed a 20 cm in diameter mobile solid mass with smooth surface with color score 2 and acoustic shadows in the right adnexal region [3]. There was no sign of pelvic structures’ infiltration or abdominal carcinomatosis (). The uterus was within the normal range and a small fibroma was described.

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A – Ultrasound (US) transabdominal image showing the right adnexal mass and acoustic shadows, B – US transvaginal image showing massive ascites in the pouch of Douglas and a normal uterus

Thoracic and abdominal computed tomography (CT) scans were performed for a better assessment. They revealed conspicuous peritoneal effusion and an abdominal mass of about 17 cm of doubtful origin. A non-homogeneous uterine neoformation of about 43 mm was described and interpreted as a fibroleiomyoma. A chest and chest CT scan confirmed a modest level of monolateral left hydrothorax ().

Differential diagnosis

The combination of ascites, pelvic mass and high levels of CA 125 raised suspicion of a potential ovarian malignancy. The differential diagnosis for the presenting signs and symptoms included malignant ovarian tumor, other bowel or lung cancers, nephrotic syndrome, congestive cardiac failure, liver cirrhosis and tuberculosis [4]. This disease represents a diagnostic and therapeutic challenge for the gynecologist.

Treatment

Due to the progressive dyspnea, the patient was submitted urgently to a preliminary laparoscopic exploration at the subsequent laparotomic access (xypho-pubic or navel-pubic laparotomy) and the radical nature of the intervention. During laparoscopy we performed multiple biopsies and the aspiration of 20 liters of ascitic fluid. Laparoscopic exploration showed stomach, liver, peritoneum, bowel and omentum free of disease. In the right iliac fossa a 20 cm capsulated solid polylobate smooth neoformation was found. The patient was then submitted to a laparotomic hysterectomy, bilateral adnexectomy, asportation of the pelvic mass and multiple biopsies. There was no pelvic or aortic lymphadenomegaly. Histological examination diagnosed an ovarian fibrothecoma with large fibrohyaline areas. The cytologic examination of ascites and hydrothorax did not show any cells suggestive of malignancy.

Outcome and follow-up

The postoperative period was characterized by complete resolution of hydrothorax () and ascites with reduced levels of CA 125 (227.1 mUI/ml) at only 10 days after surgery. CA 125 was within the normal range at one month later. The patient underwent gynecological follow-up examination and US at 1 and 6 months after surgery. Both follow-ups were negative. The patient was asymptomatic and in good health.

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A, B – chest X-ray scans in which a left monolateral hydrothorax is noticeable

Meigs syndrome is characterized by the presence of a benign ovarian solid tumor accompanied by ascites and hydrothorax. Rarely this condition could be associated with high CA 125 levels. Although it mimics a malignant condition, Meigs syndrome is a benign disease [1, 2, 5].

The postmenopausal findings of ascites, solid monoor bilateral adnexal mass, pleural effusion and elevated serum CA 125 are highly suggestive for malignant ovarian tumor. In fact, CA 125 is increased in 80% of advanced epithelial ovarian cancers [6, 7]. Nevertheless, it could be raised during menstruation or pregnancy and in some benign conditions such as endometriosis, peritonitis or cirrhosis, particularly with ascites. Probably in this case its elevation is due to inflammation and secretion from mesothelium cells, and it also happens in pseudo-Meigs syndrome [8, 9].

This disease is usually characterized by the presence of an ovarian fibroma or a fibrothecoma, which is rarely associated with increased levels of tumor markers [10]. Ovarian fibroma is a benign tumor, which accounts for approximately 3% of all ovarian tumors and may be pure and non-secreting. Meigs syndrome occurs in 1–10% of cases associated with this tumor. Ovarian fibroma is the most frequently observed in this syndrome, at the rate of 80–85% [10]. Sometimes thecoma elements (fibrothecomas) are present and responsible for estrogen secretion [11]. Thecomas and fibrothecomas represent 10% of tumors associated with Meigs syndrome. Fibrothecoma is a benign ovarian stromal tumor, usually seen as a unilateral lesion [10]. In contrast, pseudo-Meigs syndrome is characterized by ascites and pleural fluid secondary to other pelvic or abdominal tumors. This condition was further subclassified into 2 categories: benign pseudo-Meigs syndrome and malignant pseudo-Meigs syndrome. The first term was used for patients with symptoms related to any benign pelvic or abdominal tumors located outside the ovaries, fallopian tubes, and broad ligaments, whereas the second refers to patients with malignant pelvic or abdominal tumors (primary or metastatic) [12]. In Meigs syndrome, by definition, peritoneal or pleural spread of the tumor must be excluded (negative pleural and peritoneal fluid cytology and/or no malignant involvement in biopsy samples) and both ascites and hydrothorax should resolve after tumor removal [13].

The pathogenesis of the disease is unknown. The production of ascitic fluid in Meigs syndrome could be due to an imbalance between vascular supply and lymphatic drainage. An alternative hypothesis is the inflammatory origin of the process, with elevation of several inflammatory molecules including cytokines, vascular endothelial growth factor, fibroblast growth factor, interleukin (IL)-1b, IL-6, and IL-8. The detailed underlying mechanism is still unclear. Furthermore, the etiology of pleural effusion is uncertain. It is probably due to the passage of ascitic fluid into the pleural space through the diaphragm or diaphragmatic lymphatic vessels, which are more common on the right side [13, 14]. Indeed, in Meigs syndrome the hydrothorax is mainly unilateral and occurs most often on the right side (75%), rarely on the left side, and sometimes it is bilateral. The size of the pleural effusion is largely independent of the amount of ascites [14].

The general condition of the patient can be of variable severity. The classical triad (ascites, abdominal mass, and hydrothorax) may be a chance discovery during a routine gynecological examination or become symptomatic, causing abdominal tension with bloating and weight gain, respiratory distress associated with cough or abdominal pain secondary to adnexal torsion. In the literature, most patients present with an ovarian asymptomatic large, solid, unilateral mass, mostly left-sided.

Meigs syndrome always requires surgical treatment. A prompt differential diagnosis between benignity and malignancy has to be made in order to choose the appropriate management.

Ovarian tumors are common in women of all ages. It has been estimated that in the female population, the lifetime risk of undergoing surgery for a suspected ovarian neoplasm is 5–10% [15]. However, the incidence of ovarian cancer is low, even though it represents the most lethal gynecological malignancy [15]. In order to ensure that ovarian cancer patients access appropriate treatment to improve the outcome of this disease, accurate characterization before any surgery on ovarian pathology is essential. For this reason, the work of the International Ovarian Tumor Analysis (IOTA) collaboration in standardizing terminology, definitions and characteristics that must be described in adnexal pathology is critical [3]. Being based on diagnostic algorithms, the group developed and validated risk prediction models (simple rules, LR1, LR2, Adnex) on a large sample of patients; these are highly diagnostic and therefore superseded previous algorithms. Even if the assessment according to IOTA rules by an experienced examiner is subjective, it is still widely considered as the most accurate method for classification of preoperative adnexal masses. IOTA risk prediction models showed a high predictive value compared to other, non-IOTA algorithms [16]. The “simple rules” have been shown to apply to over 75% of masses and have been successfully externally validated and implemented in a national protocol [17, 18]. Nevertheless, in our case, the analysis according to IOTA simple rules revealed “inconclusive results”; the logistic regression model LR2 and Adnex [17] suggested a high risk of malignancy. In fact, the presence of ascites and the size of the lesion affected the correct assessment of the risk of malignancy because these are usually characteristics of malignant ovarian cancer. It is also reasonable and evidence-based to believe that the lesion size affects diagnostic performance of IOTA prediction models in discriminating between malignant and benign ovarian pathology [19].

Moreover, the prevalence of different types of histology affects the performance of subjective assessment in correctly classifying adnexal masses as benign or malignant [20, 21]. In this patient, the “subjective assessment” according to IOTA rules by an expert US examiner [16] was used to understand the nature of the mass. This ovarian mass was very large, solid and accompanied by ascites, but presented acoustic shadowing, a smooth external surface, mobility and a low color score (color score 2 according to IOTA terms) [3]. The mass could seem benign, as it was. Type I ovarian tumors (low-grade serous, low-grade endometrioid, clear cell, and mucinous) are slow growing, reaching a large size while still confined to the ovary, and are thus likely to be detected early by transvaginal US. Unfortunately, these lesions constitute only 25% of ovarian cancers and account for only approximately 10% of ovarian cancer deaths. On the other hand, type II ovarian tumors (high-grade serous and undifferentiated carcinomas and carcinosarcomas) represent 75% of all ovarian carcinomas and are responsible for 90% of ovarian cancer deaths and may originate outside the ovary. These tumors are almost never confined to the ovary at first evaluation, making an early diagnosis still a challenge [16]. Usually, the CT scan does not diagnose with certainty the origin of the masses. A diagnostic laparoscopy is useful in patients with potentially malignant tumors, and the tumor resection can also be performed if there are signs of malignancy [22, 23]. Depending on the patient’s age, a unilateral salpingo-oophorectomy is

commonly performed for the treatment of an ovarian type I tumor. For women who desire

preservation of the ovary, an ovarian cystectomy may be performed with complete excision of the fibromatous tissue [24, 25]. However, the optimal approach for its management has still not been sufficiently investigated [26]. Meigs syndrome is curable by tumor resection and should be differentiated from malignancy. The connection between the pelvic tumor and ascites is confirmed by the rapid resolution of symptoms due to the complete disappearance of ascites and/or the fluid in the pleura following the surgical removal of the tumor with a complete “restitutio ad integrum”. The prognosis of Meigs syndrome is favorable, recurrence of peritoneal and pleural fluid after complete removal of the tumor is unlikely to occur, and life expectancy after surgical removal is the same as in the general population [2]. So, fast surgical management of the patients is mandatory. The main limitation of our management is that our therapeutic approach has been radical despite the presence of the classical triad of symptoms suggestive for Meigs syndrome. Otherwise, the main strength of our management is that all clinical, instrumental and histological findings were essential to formulate the correct diagnosis, ensuring the complete regression of the patient’s symptoms. The major message related to this case report is that abdominal tumor, ascites, pleural effusion and elevated CA 125 – symptoms strongly suggesting disseminated malignancy – do not necessarily mean advanced malignant disease.

Clinicians should consider the uncommon Meigs syndrome in the case of a pelvic mass suggestive for an ovarian fibroma/fibrothecoma at US examination, ascites and hydrothorax, especially in the case of low levels of CA 125. Meigs syndrome is often misdiagnosed as a malignant condition in the presence of high levels of CA 125. Life expectancy and prognosis of Meigs syndrome are favorable with the complete “restitutio ad integrum” after surgical removal of the pelvic mass and the subsequent hydrothorax and ascites resolution.

This work was supported by a grant from the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. Grant number: RC 08/20.

Disclosure

The authors report no conflict of interest.

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Ascites or Fluid in the Abdomen

Approved by the Cancer. Net Editorial Board, 06/2021

Ascites is the buildup of fluid in the abdomen. The peritoneum is a membrane that surrounds the organs inside the abdomen that makes ascitic fluid. This fluid is normal in the body, but cancer can cause the peritoneum to produce too much of this fluid. This is called “malignant ascites” and it is often a sign of advanced cancer.

What causes ascites?

Malignant ascites is caused by cancer that has spread to the lining of the organs inside your abdomen. It can also happen when cancer spreads to the liver. You are more likely to develop ascites if you have one of these cancers:

What are symptoms of ascites?

Ascites often causes a lot of discomfort. People with ascites may have the following symptoms:

• Weight gain

• Shortness of breath

• Abdominal swelling

• Feeling full quickly when eating, which is called early satiety

• Sense of fullness or bloating

• Sense of heaviness

• Constipation

• Indigestion, which is a general term for discomfort in your upper abdomen

• Nausea or vomiting

• Changes to the belly button

• Hemorrhoids, which causes painful swelling near your anus

• Ankle swelling

• Fatigue

• Loss of appetite

Tell your health care team if you experience any of the above symptoms. Relieving side effects is an important part of cancer care and treatment. This type of care is called palliative care or supportive care. It helps someone, with any type or stage of cancer, feel better.

How is ascites diagnosed?

Your doctor may use one or more of the following tests to locate, diagnose, or plan treatment for ascites:

• Physical examination

• X-ray, which is a picture of the inside of the body

• Ultrasound

• Computerized tomography (CT or CAT) scan, which creates a 3-dimensional picture of the inside of the body using x-rays.

• Paracentesis, which is when a needle removes fluid from the abdomen for testing or to relieve symptoms.

How is ascites managed and treated?

The goal of treatment is to provide relief from uncomfortable symptoms. You may not need treatment if your ascites is not causing discomfort. Ascites treatment may have unpleasant side effects. Talk with your doctor about the benefits and risks of each option before deciding on a treatment plan. The treatment options for ascites include:

Changes to how you eat. For mild discomfort, eating less salt and drinking less water or other liquids may help. Salt helps your body hold onto water. Making diet changes can be a challenge for many people. Talk to your health care team about how to make these changes.

Diuretics. A diuretic is any substance that makes you urinate more often. This can help reduce the amount of fluid built up in your abdomen. Diuretics can be prescribed as medication. Most people do not experience side effects when taking a diuretic, but they can cause a loss of sleep, skin problems, fatigue, and low blood pressure.

Paracentesis. Paracentesis is a procedure to remove the fluid in the abdomen. It is used to diagnose the cause of ascites (see above), but it is also used to treat it. A doctor places a needle attached to a tube into the abdomen. The fluid drains through the needle and into the tube. Often, the fluid buildup will come back after a paracentesis procedure. Your health care team may decide to do another paracentesis procedure or they may decide to use a catheter.

Catheter. A catheter can be used to drain fluid. A catheter is a thin tube of plastic inserted into your pleural fluid. At home, you or your family member use the catheter to regularly drain the fluid into a bottle as instructed by your health care team. Occasionally, it may be recommended that a catheter be inserted inside the body to bypass or divert fluid from the abdomen into another part of the body. This is called a shunt or a peritoneovenous shunt.

Treating the cancer. Surgery or chemotherapy used to treat the cancer can sometimes also relieve ascites symptoms. This is because the cancerous cells stop making as much fluid.

Managing discomfort. Sometimes, problems caused by ascites keep coming back, even with treatment. Your health care team can help manage your discomfort by treating problems like swelling in the legs, constipation, nausea, and breathing problems.

Questions to ask the health care team

Consider asking your health care team these questions about ascites:

• Is ascites a common side effect of the type of cancer I have?

• What are the signs and symptoms of ascites that I should watch out for?

• Will I need any tests to diagnose ascites?

• What treatment options are available for the symptoms of ascites that I have? Which treatment do you recommend?

• What is causing the ascites?

• Who should I talk to about any discomfort or other side effects I am experiencing?

• How can I get in touch with them during business hours and after hours?

Related Resources

Fluid Retention or Edema

Fear of Treatment-Related Side Effects

More Information

JAMA Oncology Patient Page: Ascites or Fluid in the Belly

Onco Wiki – Treatment of symptoms of endometrial cancer

Patients with a widespread tumor process sometimes complain of:

• pain in the pelvis or abdomen,
• urinary problems,
• appearance of blood during urination or defecation,
• sharp weakness.

Palliative care should be sought if these symptoms are present. Specialists in this field, along with other doctors, can significantly alleviate the manifestations of the disease. Early initiation of palliative care improves the quality of life and psychological well-being of the patient and her loved ones.

Ascites

Ascites is an accumulation of fluid in the abdominal cavity and small pelvis. In oncological diseases, it occurs due to damage by metastases to the peritoneum, the internal lining that covers the walls of the abdominal cavity and the organs located in it. Malignant cells disrupt lymph flow and impair fluid absorption.

Symptoms of ascites

With a small amount of fluid in the abdominal cavity, the patient does not feel it at all, and ascites becomes an accidental finding during instrumental studies.

With a significant amount of fluid, pains appear, an increase in the abdomen. In the abdominal cavity, 5-10 liters of fluid can accumulate, in severe cases – up to 20 liters. The abdomen can be very large. In the standing position, due to the weight of the liquid, the stomach sinks down, and in the prone position it becomes flattened, as the liquid spreads on the sides. The pressure of the liquid on the organs disrupts the functioning of the intestines, making it difficult to urinate.

Treatment of ascites

Your doctor may prescribe conservative medical therapy – diuretics (diuretics) to increase the removal of fluid from the body. When conservative therapy no longer helps, they resort to surgical treatment.

The procedure is called laparocentesis. A puncture is made in the abdominal wall and fluid is pumped out. After removing some of the ascitic fluid, the catheter may be left for several days for further outflow.

Pain

Pain is the most common complaint in the development of any advanced cancer.

Causes of pain in endometrial cancer:

• metastases and their complications, for example, large metastases in the liver due to stretching of the capsule that covers the organ from the outside;
• germination of the primary tumor in nearby organs – the bladder, rectum, nerves and blood vessels;
• ascites;
• Bone metastases and their complications, eg pathological fractures.

Whom should I contact for treatment?

In case of a pain syndrome, they try to eliminate its cause, and if this is not possible, to relieve the pain. Pain therapy is selected by an algologist, a palliative doctor and an oncologist in charge.

The attending physician can choose the initial treatment and coordinate further steps – refer to narrower specialists. Their help may be required at the initial choice of pain relief and in the event that the selected pain treatment ceases to help.

To reduce bone pain in metastases, the oncologist refers to a radiotherapist for radiation therapy to the affected area.

Blood in the urine or stool

If the tumor has grown into the bladder and intestines, blood may appear in the urine and stool. Such symptoms must be reported to the doctor. If active bleeding develops (that is, blood does not appear as streaks in the feces, but flows freely), resort to surgical treatment.

Metastatic symptoms

Lung metastases cause cough, chest pain and shortness of breath. If such symptoms appear, a computed tomography (CT) scan of the chest organs may be additionally prescribed.

Metastases in the liver are manifested by pain in the right hypochondrium, abnormal blood tests. Abdominal CT can confirm or exclude the presence of metastases.

If symptoms of the spread of the disease appear during treatment, this is a reason for additional research. When confirming the progression of old foci and the appearance of metastases, a change in treatment is likely to be required.

Conclusions

• With the development of endometrial cancer, patients complain of pain in the pelvis or abdomen, problems with urination, severe weakness, blood during urination or defecation.
• It is important not to neglect the help of palliative care professionals.
• Report any new or unusual symptoms to the physician as the disease progresses

What else to read?

• Reminder: pain scale for patients from the Pro Palliative website. Helps to learn to determine the intensity of the pain syndrome.
• Learn more about ascites in cancer and non-cancer patients from the Pro Palliative website.
• Compilation of materials from the Pro Palliative website on the treatment of pain.
• Material from the Johns Hopkins clinic website about ascites (in English).
• Material from the Osmosis website about ascites (in English).

Yulia Tyutrina

Oncologist, chemotherapist, graduate of the Higher School of Oncology

December 7, 2022

Fluid behind the uterus on ultrasound

Sometimes during a pelvic ultrasound, the diagnostician may find fluid in the retrouterine (Douglas) space.

As a rule, in such a situation there is nothing to worry about – a small amount of fluid may indicate successful ovulation, puberty or a recent period. However, sometimes there are cases when such a formation is a sign of a serious illness.

Determining the volume of fluid behind the uterus by ultrasound

It is extremely difficult to determine the exact volume of such a formation using ultrasound, since the fluid spreads between the organs. To clarify the amount of liquid, the length of the vertical level of formation is analyzed. So, today the following criteria for assessing the amount of fluid in the retrouterine space have been developed:

• at a height of up to 10 mm, the formation is insignificant;
• with a height of 10 to 50 mm – moderate;
• with a height of more than 50 mm – significant.

The data obtained must be compared with the patient’s menstrual cycle. Additional tests may be needed if the doctor is concerned about the cause of fluid behind the uterus.

What does fluid behind the uterus mean on ultrasound?

The presence of a small amount of fluid behind the uterus in the middle of the menstrual cycle is considered normal. As a rule, this indicates pregnancy. In addition, small volumes of blood can flow into the retrouterine space during periods of menstruation, which is also absolutely natural.

However, sometimes serious diseases (endometritis, peritonitis, endometriosis, purulent salpingitis, oophoritis, adnexitis and others), ectopic pregnancy, neoplasms on the ovaries, etc. can sometimes be the causes of fluid behind the uterus.

To accurately determine the nature of such liquid formations, additional examinations are carried out: puncture (a sample of the component through laparoscopy), a laboratory blood test, a smear from the vagina.

Inflammatory process

If fluid behind the uterus is found against the background of elevated body temperature and pain in the lower abdomen, then this probably indicates inflammation of one of the organs of the genitourinary system (uterus, ovaries, bladder and fallopian tube). In such cases, depending on the stage of the disease, the doctor prescribes either antibiotics or surgery to remove the pus.

What to do if fluid is detected behind the uterus by ultrasound

Fluid behind the uterus is only a sign that indicates a specific process in the body, therefore, treatment should be aimed at eliminating the cause, not the effect.

Therefore, if an ultrasound has detected fluid, then this symptom alone cannot be used to make a diagnosis, and the doctor prescribes additional examinations and tests.