Immunohistochemical detection of cytotoxic lymphocytes in malignant serous effusions

Abstract

The use of ancillary techniques to aid in the diagnosis of metastatic carcinoma in serous effusions has been the subject of numerous studies. In this article, we study 35 cases of malignant effusions (metastatic adenocarcinoma) and 20 benign effusions using a panel of immunohistochemical markers to determine whether changes in the subpopulations of accompanying lymphoid cells can be detected with this technique and whether such changes are associated with the presence of malignancy. We noted a significant increase in cytotoxic lymphocytes, defined as the percentage of all lymphoid cells staining with an antibody to TIA‐1 (an antigen localized to the cytotoxic granule membranes of cytotoxic T cells and natural killer cells) in malignant compared with benign effusions (23% vs. 12%; P < 0.05). In addition, nearly all cases in which cytotoxic lymphocytes composed >20% of the lymphoid cell population contained metastatic tumor. Thus, immunohistochemical staining for TIA‐1 can reliably detect cytotoxic lymphocytes in cell blocks of serous effusions; in addition, a relative increase in their number is associated with the presence of malignancy. Diagn. Cytopathol. 1999;21:18–21. © 1999 Wiley‐Liss, Inc.

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“…In theory, detecting a high percentage of NK cells in MPE could help establish their tumoral nature. Despite some authors having observed a higher NK cell percentage in MPE, [5][6][7] others have reported a lower percentage, [8] and some groups, including our own, have not even found any differences [9]. It would appear that published data may indicate that determining only total NK cells is not sufficient to distinguish MPE from BPE.…”

“…In theory, the presence of a high percentage of NK cells in pleural fluid could help establish its neoplastic nature. However, total NK (CD3-CD56+) quantification in pleural effusions has provided contradictory results in former studies [5][6][7][8][9].…”

Flow cytometric quantitation of natural killer cells and T lymphocytes expressing T‐cell receptors alpha/beta and gamma/delta is not helpful in distinguishing benign from malignant body cavity effusions

“…The study by Sikora (6) used only CD56, not CD16/CD56 coexpression, as a marker for NK cells. The IHC study by Yu et al (4) reported an increased percentage of NK cells in malignant effusions based on increased numbers of cells staining positive for TIA‐1, a marker now known to stain also NK‐like T cells. Finally, the reporting of data in several studies raises questions about the results.…”

“…In numerous reports, the degree of tumor infiltration by NK cells correlates directly with prognosis (1, 2). Comparison of percentage of NK cells in malignant versus benign cavity effusions has yielded conflicting results, with some studies showing a significant increase (3–5), others a significant decrease (6), and still others showing no difference (7, 8). One frequently quoted 1996 study from the Houston Veterans Affairs (VA) Hospital reported a highly statistically significant ( P < 0.00001) association between a high percentage of NK cells and metastatic malignancy in pleural and peritoneal effusions and asserted that (flow cytometric) measurement of NK cells in effusions was “a new, sensitive means of detecting carcinoma” (3).…”