Pathological assessment of non-small cell lung cancer resection specimens after neoadjuvant therapy

Abstract

Objective: To pathologically evaluate the surgically resected specimens of three different therapies (neoadjuvant chemotherapy, neoadjuvant targeted therapy and neoadjuvant immunotherapy combined with chemotherapy) for non-small cell lung cancer. Methods: One-hundred and thirteen cases of post neoadjuvant therapy non-small cell lung cancer specimens were collected at Tongji University Affiliated Shanghai Pulmonary Hospital from January 2000 to March 2020. There were ninty patients receiving neoadjuvant chemotherapy (chemotherapy group;26 cases of adenocarcinoma and 64 cases of squamous cell carcinoma), 13 patients receiving neoadjuvant targeted therapy (targeted group;13 cases of adenocarcinoma) and 10 patients receiving neoadjuvant immunotherapy combined with chemotherapy (immune combined chemotherapy group;4 cases of adenocarcinoma and 6 cases of squamous cell carcinoma). They were evaluated for histologic tumor regression responses (necrosis, inflammatory cell infiltration, cholesterol crystal deposition, foam cell infiltration, reactive granuloma and interstitial collagenous formation) and pathological responses [main pathological response (MPR) and complete pathological response (PCR)]. Results: Chemotherapy group, targeted group and immune combined chemotherapy group all showed degenerative changes in residual tumor cells, increased atypia, various degrees of necrosis, foam cell aggregation, cholesterol cleft, inflammatory cell infiltration, and reactive granuloma in the tumor bed. Histologic characteristics of tumor regression reaction were not different between these three groups (P>0.05); the highest percentage of necrosis in the targeted group and immune combined chemotherapy group was only 10% and 20%, respectively, while that in the chemotherapy group was as high as 80%. One case of adenocarcinoma in immune combined chemotherapy group had tumor regression bed. The MPR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 35% (9/26) and 64% (41/64), respectively; the MPR ratio of targeted group was 2/13; the MPR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinoma in immune combined chemotherapy group were 2/4 and 2/6, respectively. The PCR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 11% (3/26) and 3% (2/64), respectively; the PCR ratio of targeted group was 0/13; the PCR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinomain immune combined chemotherapy group were 0/4 and 1/6, respectively. Conclusions: Different neoadjuvant therapy may cause various histopathological changes in non-small cell lung cancer: more necrosis is noted in the chemotherapy group and regression bed frequently appears in the immune combined chemotherapy group. In the immune combined chemotherapy group, there are significant lymphoplasmacytic infiltration and lymphoid follicle formation in the lung parenchyma beside the tumor bed.