The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique

Abstract

Background: Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN). Methods:We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case. Results:In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases, > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case. Conclusions:Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.

Program death ligand‐1 immunocytochemistry in lung cancer cytological samples: A systematic review

“…Studies analyzing PD‐L1 testing on lung carcinoma cytology specimens originated mostly from the USA, followed by publications arising from Italy, Canada, United Kingdom, China, Germany, Japan, India, Turkey and other countries. The Dako clone 22C3 was the most common clone analyzed on cytology specimens, followed by the Ventana SP263 clone 17–67 . The data collected included the clone type used in each study.…”

PD‐L1 immunohistochemical testing: A review with reference to cytology specimens

“…These studies have been associated with kappas ranging from 0.31, 34 0.38, 35 and 0.39 36 consistent with fair agreement to 0.68, 37 0.91, 38 0.82, 39 and 0.73 40 associated with substantial agreement. Many studies have not published formal kappa statistics for agreement but have published percentage agreements varying from 74.1% to 97.3% 13,18–20,24,41–56 . The concordance rates appear to be impacted by precise specimen type and antibody clone used.…”

“…Overall, cytologic specimens appear to be acceptable specimens for PD‐L1 analysis especially when formalin fixed paraffin embedded cell block specimens are evaluated using the TPS for evaluation 9–13,20,22,24,34–70 …”

“…A large number of studies have investigated PD‐L1 expression in various cytologic preparations. Comparisons have been made among cytology specimens, small biopsy cores and surgical resection specimens 10,12,13,17–52 . Most studies have shown good correlation of PD‐L1 assays performed on cell block specimens with those performed on small biopsies and resection specimens.…”

Pragmatic Expectancy on Microbiota and Non-Small Cell Lung Cancer: A Narrative Review

“…Overall, in the clinical context, together with the fact that, in most cases, NSCLC is diagnosed in advanced disease stage [86], the tumor samples obtained by bioptic procedures are extremely limited. In this perspective, the development of the cell block technique, which consists of processing small tissue fragments derived by fine-needle aspiration to obtain paraffin block, has significantly improved diagnostic accuracy when, as in the case of lung masses, more invasive bioptic approaches cannot be performed [87][88][89][90]. Working on small samples, such as those represented by the cell block technology, has two main implications: (i) the possibility of missing tumor histological and molecular heterogeneity is overcome by performing multiple aspirates in the mass to sample different malignant subclones; (ii) the low number of total cells sampled is highly enriched in tumor cells.…”