The pleural, peritoneal, and pericardial serous cavities, usually referred to as body cavities, are lined by a single layer of mesothelial cells and, in the healthy person, contain very little fluid. Serous effusions occur when fluid, either as a transudate or exudate, accumulates in the cavities. Transudates have a low protein content and specific gravity and are mostly caused by cirrhosis or congestive cardiac failure. Exudates, in contrast, have a high protein content and specific gravity. They have a broader etiology and include inflammatory, neoplastic, connective tissue, and iatrogenic disorders. Serous effusions can occur at any age and may be the initial presentation of the disorder or a later manifestation. Most serous cavity-fluid specimens are effusions, but some are obtained by using a saline wash to exfoliate cells from the mesothelium.
Cytologic examination of the cellular features of fluids is a valuable adjunct to patient diagnosis and the staging and management of tumors, in particular, gynecologic tumors.1 The German-language literature contains the earliest references to the cytology of malignant cells in fluid specimens. Lücke and Klebs2 in 1867 may have been the first to make reference to their appearance in an ascitic fluid, but Quincke3 in 1882 is credited with the first detailed description of ovarian and pulmonary malignancies in fluid samples. Almost a hundred years later, Keettel and Elkins4 from Iowa conceived the idea of washing the peritoneal cavity with normal saline to examine the spread of ovarian cancer and in 1956 published their results.
Today, body-cavity fluid cytology is a routine diagnostic tool. Preparation of the specimen has evolved from unstained wet smears to protocols that generally include centrifugation and the generation of stained smears and a cell block.5 The smears may be alcohol-fixed direct smears, cytospins, or a liquid-based preparation, and they are usually stained with the Papanicolaou method. The cell block is processed as a tissue specimen and usually stained with hematoxylin and eosin. The fluid is also suitable for ancillary testing using histochemistry, immunohistochemistry, electron microscopy, flow cytometry, and molecular techniques.1 The cell block is the optimal specimen for immunohistochemical testing.6
The 6 cases presented in this issue taken separately represent common diagnostic problems in effusion cytology and illustrate the importance of ancillary testing, as well as clinicopathologic correlation. Taken as a whole, they represent a comprehensive review of effusion cytology.
Drs. Bhatti and Tabbara begin our issue with a case presentation of malignant mesothelioma and address one of the fundamental diagnostic problems in effusion cytology: the differentiation of reactive mesothelial effusions, mesothelioma, and metastatic disease. They present a comprehensive discussion of the cytomorphologic features and histochemical and immunohistochemical stains that aid in the diagnosis.
The identification of metastatic disease in a body-cavity fluid may be the first indication of an underlying malignancy. Drs. Filie and Jones extend discussions from the first case to present the workup of malignant effusion from an unknown primary site. Although clinical statistics suggest a differential diagnosis based on gender and location of the malignancy (pleural, pericardial, or pelvic cavity), immunohistochemistry still represents the best ancillary testing available to confirm a primary site.
Lymphocytic effusions are fairly common, although their etiologies may range the gamut from reactive and infectious to lymphomas. Primary effusion lymphomas (PEL) are rare and typically associated with HIV infections. Dr. Caraway presents a case of PEL and focuses on its distinctive immunophenotypic and molecular features. The differential diagnosis of lymphomatous effusions rounds out her discussion.
Dr. Boerner uses a straightforward case as a platform for an extensive discussion of mimicry in effusions. He addresses 2 major areas of concern: false negatives, in which malignancies may resemble mesothelial cells or may blend into the background and be overlooked; and false positives, in which mesothelial cells may resemble adenocarcinoma or the “benign interlopers,” cells that are occasionally seen in effusions that cause overreaction.
Dr. Jain discusses the role of pelvic washings in the clinical management of gynecologic tumors. Normal peritoneal cytology, as well as endosalpingiosis, is reviewed and compared with the cytomorphology of the various gynecologic tumors that may spread to the peritoneal surface. The utility of immunohistochemical staining is also reviewed.
The role of molecular techniques in cytopathology is increasing and evolving almost exponentially. In our last case presentation, Dr. Demetrick explores the role of forensic DNA identification as a method for troubleshooting rare cases where concerns of contamination or misidentification may have profound clinical consequences. Molecular diagnostic techniques are highly sensitive and specific and are often readily adaptable to cytologic specimens. Their efficacy is proven and their once-exorbitant costs are becoming cost-effective.
We sincerely thank the contributors for their valuable and insightful contributions. We hope that this series of cases has provided not only a comprehensive review of effusion cytology but has also addressed many of the issues, challenges, and difficulties we all encounter in our own practice.
1. Davidson B. Malignant effusions: from diagnosis to biology. Diagn Cytopathol
2. Lücke KE, Klebs E. Beitrag zur ovariotomie und zur kenntniss der abdominalgeschwülste. Arch Path Anat
3. Quincke H. Über diegeformten bestandtheile von transsudaten. Deutsches Arch Klin Med
4. Keettel WC, Elkins HB. Experience with radioactive colloidal gold in the treatment of ovarian carcinoma. Am J Obstet Gynecol
5. Filie AC, Copel C, Wilder AM, et al. Individual specimen triage of effusion samples: an improvement in the standard of practice, or a waste of resources? Diagn Cytopathol
6. Fetsch PA, Abati A. Immunocytochemistry in effusion cytology: a contemporary review. Cancer Cytopathol