AUTHOR=Zhang Yan , Qin Yaping , Xu Hongen , Yao Qihui , Gao Yalan , Feng Yushu , Ren Jingli 

TITLE=Case Report: A Case Report of a Histological Transformation of ALK-Rearranged Adenocarcinoma With High Expression of PD-L1 to Squamous Cell Carcinoma After Treatment With Alectinib

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 27 - 2021

YEAR=2021

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.637745

DOI=10.3389/pore.2021.637745

ISSN=1532-2807

ABSTRACT=Non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangement is a distinct subtype of lung cancer, and it is highly sensitive to the ALK kinase inhibitors such as crizotinib or alectinib[1, 2]. The ALK fusion mutation is called the “diamond mutation”, and the patient who has a tumor harbouring ALK mutation usually has a more prolonged progression-free survival (PFS). For ALK-positive patients taking crizotinib, the median PFS was 11.8 months[3], and 62% of patients can achieve a 3-year PFS after treatment with alectinib[4]. Drug resistance frequently occurs due to alterations in the oncogene-driven genes and phenotypic transformation[3]. Various resistance mechanisms, similar to other oncogene-driven cancers treated with tyrosine kinase inhibitors (TKIs), may be classified into three different groups: (1) alterations in the oncogene-driven genes (such as ALK L1196M or C1156Y mutations [5]); (2) activation of bypass pathways (for example insulin-like growth factor 1 receptor (IGF-1R)[6], SRC proto-oncogene, non-receptor tyrosine kinase  (SRC)[7] and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK/ERK)[8] activation); (3) phenotypic transformation (to small cell lung cancer)[9]. The histological shift has been reported as a resistance mechanism in 3-14% of the patients treated with epidermal growth factor receptor (EGFR) TKIs[10, 11]. However, phenotypic transformation is rarely reported in ALK-positive patients. Herein, we presented a case of ALK rearrangement-positive adenocarcinoma with high expression of programmed death-ligand 1 (PD-L1) that was transformed into squamous cell carcinoma after administration of alectinib.