Article Type : Case Report
Authors : Kumar P, Malau-Aduli P, Mathew M, Jayasekara JGGDA and Whitton L
Keywords : Meigs’ syndrome, Pseudo-Meigs’ syndrome, Cytological
Meigs’
syndrome is classically defined as the triad of a benign ovarian fibroma (or
fibroma-like tumour), ascites, and pleural effusion, with complete resolution
of the fluid accumulations following surgical resection of the tumour. Pseudo-Meigs’ syndrome broadens this
presentation to other pelvic or ovarian tumours (benign or malignant) but is
strictly characterised by the absence of malignant cells in the ascitic or
pleural fluid. We report a 79-year-old
woman who presented with progressive abdominal distension and imaging features
suggestive of ovarian malignancy, initially raising suspicion for a Meigs’-like
physiology. However, cytological examination of the ascitic fluid revealed
metastatic adenocarcinoma with immunohistochemical features consistent with
epithelial origin, confirming peritoneal carcinomatosis and malignant ascites.
This finding definitively excluded both Meigs’ and pseudo-Meigs’ syndromes. The
case underscores the indispensable role of ascitic fluid cytology in
differentiating benign transudative processes from true malignant
dissemination, with major implications for accurate staging, therapeutic
planning, and prognosis in suspected gynaecological malignancies.
Ascites in
postmenopausal women with suspected pelvic pathology poses a significant
diagnostic challenge. The differential includes benign entities such as Meigs’
syndrome, inflammatory or infectious peritonitis, and advanced malignancies
with peritoneal spread. Meigs’ syndrome, first systematically described in 1937
by Joe Vincent Meigs and John W. Cass, involves a benign solid ovarian tumour
(most commonly fibroma), ascites, and often right-sided pleural effusion that
resolves after tumour removal. The pathophysiology
is thought to involve transudation of fluid from the tumour surface due to
mechanical irritation, lymphatic obstruction, or cytokine release, without
direct malignant involvement. Pseudo-Meigs’ syndrome extends the triad to other
ovarian or pelvic tumours, including non-fibromatous benign lesions (e.g.,
struma ovarii, mucinous cystadenoma, mature teratoma) or even malignant
neoplasms and metastatic deposits to the ovary, provided the effusions remain
cytologically negative for malignant cells.
In contrast, malignant ascites—typically associated with peritoneal
carcinomatosis—features positive cytology, low serum-ascites albumin gradient
(SAAG), high protein content, and persistent fluid accumulation driven by
increased vascular permeability (mediated by factors such as vascular
endothelial growth factor, VEGF), lymphatic obstruction, and direct tumour
infiltration. Distinguishing these entities is critical: Meigs’ and
pseudo-Meigs’ syndromes are potentially curable with surgery alone, whereas malignant
ascites signals advanced-stage disease (often FIGO stage III or IV ovarian or
primary peritoneal carcinoma) with poorer prognosis and the need for systemic
therapy. Elevated serum CA-125, while sensitive for ovarian/peritoneal
malignancy, lacks specificity and can occur in both benign and malignant
conditions with peritoneal irritation.
This case illustrates how imaging and tumour markers may mimic a
Meigs’-like syndrome, only for cytology to reveal the malignant nature [1-13].
A 79-year-old woman was admitted to hospital with diarrhoea and abdominal discomfort, ultimately diagnosed with Salmonella gastroenteritis. Her medical history included chronic obstructive pulmonary disease (COPD) with recurrent infective exacerbations. During the admission, she developed progressive abdominal distension. Physical examination demonstrated shifting dullness consistent with moderate ascites. There were no stigmata of chronic liver disease, cardiac failure, or peripheral oedema suggestive of hypoalbuminaemia-related fluid overload.
Laboratory Investigations
Serum biochemistry showed hypoalbuminaemia (albumin 28 g/L) with total protein 55 g/L, mild hypokalaemia (potassium 3.3 mmol/L), and low fasting glucose (3.2 mmol/L). Renal function was preserved (creatinine 57 µmol/L, eGFR 85 mL/min). Liver enzymes and coagulation profile were unremarkable. Tumour marker evaluation revealed a markedly elevated CA-125 level of 1876 U/mL (normal <35 U/mL), raising strong suspicion for ovarian or primary peritoneal carcinoma.
Imaging Findings
Contrast-enhanced CT of the abdomen and pelvis demonstrated multiple enhancing peritoneal nodules, nodular infiltration extending to the umbilicus (consistent with a Sister Mary Joseph nodule), and peritoneal disease outlining the pelvis with involvement surrounding the uterus and adnexa. There was small-volume ascites but no discrete visceral mass in the liver, pancreas, adrenals, or kidneys. Additional findings included hepatomegaly, aortoiliac atherosclerosis with mild infrarenal aortic ectasia, and pelvic floor descent with a posterior perineal hernia. CT chest showed no pleural effusion, pulmonary embolism, thoracic lymphadenopathy, or osseous metastases. Background centrilobular nodular opacities and mild emphysematous changes were consistent with her known COPD. A 6 mm subsolid nodule in the right lower lobe was noted for interval surveillance, but there was no evidence of thoracic metastatic disease (Figure 1).
Ascitic Fluid Analysis
Diagnostic paracentesis yielded fluid with albumin 20
g/L. The serum-ascites albumin gradient (SAAG) was calculated as 0.8 g/dL
(serum albumin 28 g/L minus ascitic albumin 20 g/L, converted appropriately). A
low SAAG (<1.1 g/dL) indicated non-portal hypertensive ascites, favouring
peritoneal carcinomatosis, infection, or inflammatory causes over cirrhosis.
Cytopathology
Cytological examination revealed clusters of malignant
epithelial cells exhibiting nuclear atypia, prominent nucleoli, and cytoplasmic
vacuolation consistent with adenocarcinoma. Immunohistochemistry on the cell
block showed positivity for broad-spectrum cytokeratins (AE1/AE3), epithelial
membrane antigen (EMA), BerEP4, and Claudin-4, with negativity for CK5 and
calretinin. These markers confirmed metastatic adenocarcinoma of epithelial
(non-mesothelial) origin and effectively excluded reactive mesothelial proliferation
or malignant mesothelioma.
Diagnosis
The integrated clinical, radiological, biochemical, and cytopathological findings established advanced intra-abdominal malignancy, most consistent with ovarian or primary peritoneal serous carcinoma, manifesting as:
The presence of malignant cells in the ascites definitively excluded Meigs’ and pseudo-Meigs’ syndromes.
Pathophysiology
of Ascites in Ovarian and Peritoneal Malignancy
Malignant ascites in advanced ovarian/peritoneal
carcinoma arises through multiple mechanisms: tumour-induced neovascularisation
and increased permeability via VEGF and other cytokines; lymphatic obstruction
by peritoneal deposits; direct exudation from tumour surfaces; and systemic
effects such as hypoalbuminaemia reducing oncotic pressure. The fluid is
typically exudative with low SAAG, high protein, and often elevated lactate
dehydrogenase. Cytology is positive in a significant proportion of cases, though
sensitivity can vary (approximately 60–90% in ovarian cancer-related ascites).
Meigs’ syndrome
True Meigs’ syndrome requires a benign ovarian fibroma
(or similar solid tumour), ascites, and pleural effusion (classically
right-sided), with resolution after tumour resection and negative
cytology. The exact mechanism remains
unclear but is postulated to involve fluid transudation from the tumour surface
or lymphatic leakage, possibly exacerbated by tumour size or mobility. Elevated
CA-125 can occasionally occur due to peritoneal irritation but does not
indicate malignancy.
Pseudo-Meigs’ syndrome
This term encompasses similar fluid accumulations with
ovarian or pelvic tumours other than fibromas, including malignant lesions,
provided cytology remains negative.
Reported associations include struma ovarii, leiomyomas, teratomas, and
even Krukenberg tumours or other metastases when effusions lack malignant
cells. Resolution after tumour removal remains a key criterion.
Malignant ascites in this case
In the present patient, positive cytology for
metastatic adenocarcinoma, imaging evidence of diffuse peritoneal disease,
Sister Mary Joseph nodule, and markedly elevated CA-125 confirmed true
malignant ascites secondary to peritoneal carcinomatosis. Unlike Meigs’ or
pseudo-Meigs’ syndromes, the fluid accumulation here reflects direct malignant
involvement rather than a reversible paraneoplastic or mechanical phenomenon.
The low SAAG further supported an exudative peritoneal process.
Diagnostic pitfalls and the role of
cytology
This case highlights a common pitfall: ascites with
pelvic masses and elevated CA-125 can mimic Meigs’-like syndromes, potentially
delaying recognition of advanced malignancy. The Sister Mary Joseph nodule—a
metastatic deposit at the umbilicus—is a classic sign of intra-abdominal
adenocarcinoma (particularly ovarian, gastric, or colorectal) and is not
associated with benign Meigs’ or pseudo-Meigs’ syndromes. Ascitic fluid cytology with immunohistochemistry
(e.g., BerEP4 and Claudin-4 positivity for adenocarcinoma; calretinin
negativity excluding mesothelial origin) is pivotal for definitive diagnosis.
Failure to perform or correctly interpret cytology risks misclassification and
inappropriate management. In ambiguous cases, additional markers (e.g., PAX8, WT1
for serous ovarian carcinoma) or biopsy of peritoneal nodules may be required.
Prognostic
and Management Implications
Malignant ascites with peritoneal carcinomatosis
typically indicates stage III/IV disease and portends a poorer prognosis
compared with resectable benign tumours in Meigs’ syndrome. Management involves
systemic chemotherapy (often platinum-based), targeted therapies (e.g., PARP
inhibitors in BRCA-mutated cases), and palliative measures such as repeated
paracentesis or indwelling catheters for symptomatic relief. Surgical debulking
may be considered in select patients with good performance status.
This case demonstrates that while clinical and radiological features may suggest a Meigs’-like syndrome, cytological confirmation of malignant cells is essential to establish the diagnosis of malignant ascites and peritoneal carcinomatosis. Routine performance of diagnostic paracentesis with cytopathology in such presentations prevents diagnostic error and ensures timely oncological intervention.