Non-solid Neoplastic Nodules Are Associated with Low PD L1 Expression

Few data are known on the molecular features characterizing neoplastic lesions presenting as non-solid nodules (NSN), the specific pattern of tumour presentation and growth. We retrospectively reviewed the CT scans of 36 patients who underwent transthoracic CT-guided fine needle aspiration of suspected NS pulmonary lesions from october 2016 to december 2017 who received a final diagnosis of malignancy. Exhaustive clinical and radiological features were available for each case. In all cases the diagnosis of adenocarcinoma (ADC) was reached. EGFR mutations were identified in 2 of the 28 cases (7%) with adequate material (one exon 19 deletion and L858R); no case showed ALK/EML1 or ROS1 translocations. PD-L1 immunostains could be evaluated in 30 cytological 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. Overall PD-L1 immunostains 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