PD‐L1 and beyond: Immuno‐oncology in cytopathology

Abstract

Over the past decade, immunotherapy has emerged as one of the most promising cancer treatments. Several monoclonal antibodies targeting the programmed death 1 (PD‐1)/ programmed death ligand‐1 (PD‐L1) pathway have been integrated into standard‐of‐care treatments for a wide range of cancer types. Although all the available PD‐L1 immunohistochemistry (IHC) assays have been developed on formalin‐fixed histological specimens, a growing body of research has recently suggested the feasibility of PD‐L1 testing on cytological samples. Although promising results have been reported, several important issues still need to be addressed. Among these are pre‐analytical issues, cyto‐hystological correlation, and inter‐observer agreement. This review will briefly summarise the knowledge gaps and future directions of cytopathology in the immuno‐oncology scenario.

Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer

“…A significant part of NSCLC is diagnosed on cytological specimens [13][14][15]. The suitability of cytology for PD-L1 testing has been discussed [16][17][18], and the lack of comprehensive data and validation has prevented wide acceptance. PD-L1 expression in paired histological and cytological materials from NSCLC patients has been compared in several studies [19,20].…”

“…Both methodological and biological aspects should be taken into account when comparing histology and cytology. The choice of PD-L1 assay, platform, and cut-off for a positive staining may have an impact on PD-L1 results regardless of specimen type, while fixation and preparation, specimen cell content, sampling site, heterogeneous expression, and interobserver agreement may be different for histological and cytological specimens [16][17][18]. Additionally, there is a mixture of both histological (biopsies, resections, and tissue microarrays) and cytological specimens (fine-needle aspirations, bronchoalveolar lavage [BAL], bronchial brush [BB], and pleural effusions [PE], etc.…”

Diagnostische und prädiktive Marker in der Harntraktzytologie

“…2 ). Die immunzytochemische Untersuchung der PD-L1-Expression zur Selektion von Patienten für eine Behandlung mit Immuncheckpoint-Inhibitoren (ICI) ist an Papanicolaou-gefärbten zytologischen Präparaten oder Zellblockpräparaten grundsätzlich möglich [ 17 ]. Allerdings können an zytologischen Präparaten nur Tumorzellen gewertet werden, sodass nur eine Bestimmung des PD-L1-Tumor-Proportion-Score (TPS) möglich ist.…”

Tissue Microarray from Cell Block Material (cbTMA)—An Additional Shot for Cytology in the Predictive Pathology Era: The PD-L1 Experience

“…As immunotherapy has emerged as one of the most promising cancer treatments, the process of technical and clinical validation of predictive biomarkers for immune-checkpoint inhibitors on cytological specimens is plainly foreseeable [7][8][9][10][11][12]. Not surprisingly, the last couple of years have witnessed a plethora of studies evaluating the feasibility of assessing PD-L1 expression on cytological samples, particularly in terms of adequacy rate, level of PD-L1 expression, and clinical outcomes [8,9,13,14].…”

“…As immunotherapy has emerged as one of the most promising cancer treatments, the process of technical and clinical validation of predictive biomarkers for immune-checkpoint inhibitors on cytological specimens is plainly foreseeable [7][8][9][10][11][12]. Not surprisingly, the last couple of years have witnessed a plethora of studies evaluating the feasibility of assessing PD-L1 expression on cytological samples, particularly in terms of adequacy rate, level of PD-L1 expression, and clinical outcomes [8,9,13,14]. Building on such compelling research and going beyond PD-L1, our research team and others have also very recently demonstrated the technical feasibility of assessing tumor mutational burden (TMB) and mismatch repair deficiency (dMMR) by immunohistochemistry (IHC) testing [11][12][13][14] on cytology material processed as cell blocks (CBs), as evidenced by a high concordance rate between cytological and surgical specimens [8,9].…”