Malignant serous effusion in the pleura, peritoneum and (less frequently) pericardium is a frequent complication of primary adenocarcinomas, particularly in female patients with breast or ovarian cancer, and in both sexes with lung carcinoma. In female patients, about 2/3 of ovarian carcinoma cases have intraperitoneal free cancer cells (IFCCs) in the peritoneum at the stage of diagnosis. Patients may develop malignant effusions years or, particularly in breast cancer cases, tens of years after the initial diagnosis.
Frequency of primary tumour sites in case of metastatic effusion:
PLEURAL EFFUSIONS
About 50% of carcinomatous effusions are metastatic adenocarcinomas, followed by pulmonary large cell carcinomas and lymphomas/leukemias (about 15% each)
Male patients: lung (50%), lymphoma/leukemia (21%), gastrointestinal tract (7%), genitourinary tract (6%) and malignant melanoma (1.5%)
Female patients: breast (38%), genital tract (ovary: 20%), lung (15%), lymphoma/leukemia (8%) and gastrointestinal tract (4%)
PERITONEAL EFFUSIONS
Malignant ascitis accounts for about 10% of all ascites and occurs as complication of a variety of primary cancers, particularly from the breast, bronchus, ovary, stomach, pancreas and colon sites. Up to 20% of patients with malignant ascitis have primary tumours of unknown origin at time of the diagnosis.
Male patients: colon, rectum, stomach, pancreas
Female patients: ovary (30-54%), endometrium, uterine cervix, pancreas, stomach, uterus + extra-abdominal sites (breast, lung, lymphomas)
Pathophysiology of malignant ascitis is incompletely understood. Accumulation of fluid may result from obstruction of lymphatic vessels by tumour cells. Many patients with malignant ascites having exsudates with high protein content, alteration of vascular permeability has also been implicated. As a consequence of obstructed lymphatics the circulating bloodvolume is reduced and this activates the renin-angiotensin-aldosterone system, leading to sodium retention. Reduced sodium intake together with diuretics is therefore used to treat malignant ascites, although there is no consensus on effectiveness. In contrast to the treatment of underlying cancer, there is no accepted evidence-based guideline for the management of malignant ascites.
PERICARDIAL EFFUSIONS
Primary malignancy of the pericardium is rare, whereas secondary involvement is more common. About 40% of patients with malignancy and pericardial disease have benign alteration of the pericardium. Restrictive pericardial disease with effusion is most commonly associated with radiation therapy (radiation pericarditis), whereas idiopathic pericarditis is usually associated with chest pain, dyspnea, and fever.
Male patients: lung, lymphoma/leukemia, melanoma
Female patients: breast, lung, lymphoma/leukemia, melanoma
Malignant mesothelioma (MM) which also affects the serous cavities as primary malignancy often present as recurrent unilateral haemorragic effusion, with rapid clinical evolution.
Considering the prognostic implications the presence of malignant cells have in effusions, accurate morphological diagnosis is of paramount importance. Therefore, recognition of malignancy needs that reproducible morphological criteria are known and widely diffused. Reactive mesothelial cells may mimic malignant cells, particularly after radio- or chemotherapy, and malignant cells may be as regular as the more benign-appearing cells. In the peritoneum, caution is advised to avoid misinterpretation of endometriosis or endosalpingiosis with adenocarcinoma (Lin, 2009). Malignant cells may be rare and surrounded by many inflammatory and reactive cells, thus rendering their detection harmful.
For both reasons, sensitivity of cytology for the detection of malignant cells varies between 40% and 80%. Such values not only depend on the manner the fluid has been collected, fixed and transported, but also on the quality of preparatory methods. Standardization of concentration and staining procedures has been achieved in most laboratories with cytocentrifugation, liquid-based procedures and staining automatons. The use of cell blocks also has gained wide acceptance, thus allowing immunochemical techniques to be applied more confidently. But even experienced cytopathologists are not always capable to distinguish between reactive, degenerative and malignant cells, particularly in suboptimal conditions.
Panels of immunochemical markers are now used in most cases, and not only in the more difficult ones. For years, authors have attempted to define the best combination of antibodies for diagnostic purpose, particularly for the differentiation between MM and metastatic adenocarcinoma. Advances in immunochemical methods and in molecular biology now allow to study diagnostic, therapeutic and prognostic issues in malignant effusions.
References
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