The Brescia panel and The International System for Reporting Serous Fluid Cytopathology

Abstract

The distinction between mesothelial proliferations and metastatic adenocarcinoma in serous fluids remains a common and vexing issue. Whereas cytomorphology allows the identification of one cell type (mesothelial) over another (epithelial), this may be challenging when the number of lesional cells is small, when cells are associated with bland nuclear morphology accompanied by degenerative changes, or when unusual tumor subtypes present in serous fluids. For confirmation of the diagnosis, immunochemical panels using 2 epithelial immunostains and 2 mesothelial immunostains are common practice, with the choice of markers depending on availability and the experience of their usage in a particular institution. Although the value of BRCA-associated protein 1 (BAP1) and Claudin-4 has been documented by many studies, Bernardi and colleagues were the first to draw attention to these 2 markers through their earlier publications. In this issue of Cancer Cytopathology, they propose the name of Brescia panel for the combination of these 2 markers. 1 The panel presents the opportunity to use only 2 markers, given the high sensitivity and specificity of the panel to differentiate between mesothelioma (BAP1-negative/Claudin-4-negative) from metastatic carcinoma (BAP1-positive/Claudin-4-positive). Bernardi et al demonstrate compelling evidence through their pilot study for the cytopathology community to consider validating this panel. The pattern of staining, nuclear with BAP1 and membranous with Claudin-4, makes these immunostains easier to interpret compared with cytoplasmic staining, which is sometimes not as well localized. The panel has been applied successfully to cell block and biopsy specimens. Incidentally, both markers are recommended by The International System (TIS) for Reporting Serous Fluid Cytopathology. 2 The system mentions Claudin-4 as a promising marker for the confirmation of metastatic carcinoma and for the exclusion of mesothelioma. BAP1 is also recommended as an immunostain of choice for the diagnosis of mesothelioma. In the absence of BAP1 loss, clinical data should be taken into account and the mesothelial proliferation should be reported as either atypia of undetermined significance or suspicious for malignancy in TIS, similar to what is proposed by the authors. The Brescia panel holds much promise and merits further validation studies using only Claudin-4 and BAP1 instead of larger panels. This would allow more residual diagnostic material to be available for ascertaining the primary sites and for performing molecular testing of malignant cells in serous effusions. FUNDING SUPPORT No specific funding was disclosed. CONFLICT OF INTEREST DISCLOSURES The author made no disclosures.

A retrospective analysis of pleural effusion specimens based on the newly proposed International System for Reporting Serous Fluid Cytopathology

“…Serous effusion/fluids from pericardial, peritoneal and pleural cavities constitute a large amount of cytological specimens in every cytology laboratory. Serous fluids can reflect a wide range of pathological conditions, including acute/chronic inflammation, infection, injury and neoplasia 1,2 . Given that serous effusion represents the first clinical manifestation of malignant neoplasms, cytological tests can not only detect the formation of tumor cells but also identify the primary site of tumor origin and assess the stage of a cancer 3,4 .…”

“…Serous fluids can reflect a wide range of pathological conditions, including acute/chronic inflammation, infection, injury and neoplasia. 1,2 Given that serous effusion represents the first clinical manifestation of malignant neoplasms, cytological tests can not only detect the formation of tumor cells but also identify the primary site of tumor origin and assess the stage of a cancer. 3,4 Thus, an accurate cytopathological evaluation of pleural effusion specimens is of great importance for the clinical management of cancer patients.…”

Risk of malignancy assessment of the International System for Reporting Serous Fluid Cytopathology: Experience in a community hospital setting and comparison with other studies

“…4 In 2020, the International System for Reporting Serous Fluid Cytopathology (ISRSFC) was published as the first attempt to suggest a tiered structure to provide standard reporting terminology for serous fluid cytopathology, recommending the scenarios in which these terminologies are used, and proposing some diagnostic criteria and clinical management strategies. [4][5][6][7] Similar to other reporting systems for diagnostic cytology, the ISRSFC consists of five diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). [4][5][6][7] The ISRSFC diagnostic categories can provide useful information for appropriate clinical management and follow-up from the calculated risk of malignancy (ROM).…”

“…[4][5][6][7] Similar to other reporting systems for diagnostic cytology, the ISRSFC consists of five diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). [4][5][6][7] The ISRSFC diagnostic categories can provide useful information for appropriate clinical management and follow-up from the calculated risk of malignancy (ROM). 4,5 However, the ROM can be overestimated if only tissue follow-up information is used to calculate it because serous effusion cytology specimens classified as ND, NFM, and AUS often do not have tissue follow-up.…”

“…6 Clinical follow-up, along with close correlation with radiologic findings and medical history, would enable a reasonable assessment of the presence of serous cavity malignant involvement, providing a relatively accurate ROM for each category for benchmarking and clinical triage. 7 The use of established terminology also can enhance the comparison between different studies due to categorization. In the design of a standardization, it is important to speak the same language across pathologists globally; however, revealing the dissimilarities between centers could help provide more realistic approaches to patient care.…”