Role of CD68 immunohistochemistry in categorizing benign nonmesothelial cell population and refining “atypical” category in serous fluid cytology

Abstract

Background: Body fluids are rich in histiocytes and may mimic atypical epithelial cells morphologically. Histiocytes can pose a significant challenge in serous fluid cytology as they tend to appear atypical due to prolonged accumulation in serous fluids in vivo and processing by liquid-based cytology in vitro. Not many studies have documented the utilization of histiocytic marker such as CD68 in serous fluid cytology, which can subsequently reduce the "atypical" diagnostic category. Methods: One thousand one hundred and twenty-nine cases of serous fluid cytology from 2016 to 2019 were reviewed and reclassified based on proposed classification of the international system for reporting serous fluid cytology. There were 133 cases with atypical diagnoses, out of which 51 cases had cellblocks. An immunohistochemistry (IHC) panel, including two mesothelial markers, two epithelial markers, and one histiocytic marker was applied to the atypical samples. Same IHC panel was utilized to evaluate 15 cases each from negative for malignancy (NFM), suspicious for malignancy (SFM), and malignant (MAL) categories for further comparison. Results: After reevaluation of the cytology material with IHC stains, 924 (82%), 133 (12%), 23 (2%), and 49 (4%) of the cases were reclassified as NFM, atypia of uncertain significance, SFM, and MAL, respectively. Twenty-five out of 51 atypical cases (49%) were downgraded to "benign" after reevaluation with CD68 IHC. Conclusion: Histiocytes can mimic atypical epithelial cells in body fluids. Effective utilization of CD68 IHC will be beneficial in further refining the "atypical" diagnostic category in serous fluid cytology.

A Retrospective Analysis of Serous Effusions Based on the Newly Proposed International System for Reporting Serous Fluid Cytopathology: A Report of 3633 Cases in an Oncological Center

“…Our non-diagnostic rate was 0.5%. This is in line with other reports in literature, which present nondiagnostic rates of 0% to 5.6% in serous effusion [6][7][8][9][10][11][12][13][14][15]. The cases classi ed as ND in this series were all due to scant cellularity or excess degeneration, improper preservation and obscuring blood in the serous effusion specimens.…”

“…The malignancy rate (47.8%) detected in our cohort was higher than that reported in the literature, which ranges between 4% and 22.4%[6-9, 11-13, 15], but was similar to other reports in literature from oncological centers[6, 10,14]. The percentage of our SFM cases was also slightly higher than other reported studies (range: SFM, 1.3%-6.3%) [6][7][8][9][10][11][12][13][14][15] . These results are characteristic of a cancer center, where neoplastic conditions are the main cause of cytological examination of body uids, and if one case is diagnosed as SFM, the clinicians will consider it as positive, taking the history into account, hence, the case is failed to be identi ed malignancy by auxiliary examination.…”

“…Up to now, only a few publications supported the use of a particular terminology for serous effusion cytology [6][7][8][9][10][11][12][13][14][15]. In this study, we retrospectively applied TIS recommendations for reporting the cytological diagnosis of serous effusions.…”

Role of Ancillary Techniques in Reporting Serous Fluid Cytology – “Redefining Categories, Refining Diagnosis”

“…Tumors from the breast, stomach, and kidney have been frequently reported to show histiocytoid morphology. [ 19 ]…”

Review of the impact of the International System for Serous Fluid Cytopathology

“…In total, six studies evaluated the TIS categories either without separating the serous effusions into pleural, peritoneal and pericardial when presenting their data or without making that specific distinction when calculating the ROM (Table 4). 19,22,29,[37][38][39] The number of samples/patients ranged from 137 to 1129. The ROM for each category was estimated by in of them: ND, 10% and 23%; NFM, 4.4% and 25%; AUS, 19% and 56%; SFM, 83.3% and 80.6%; MAL, 100% and 90%, respectively.…”