Novel Pattern of Nuclear Staining With ROS1 Immunohistochemistry: A Case Report

ROS1 rearrangements are driver events in a subset of nonsmall cell lung carcinomas and may qualify patients for ROS1 ‐directed treatment. ROS1 immunohistochemistry (IHC) is often used for screening of lung carcinomas for ROS1 gene rearrangement and has a cytoplasmic and/or membranous staining pattern. Here, we report an unusual case of a lung adenocarcinoma displaying a strong nuclear staining pattern on ROS1 IHC. ROS1 fluorescence in situ hybridization (FISH) reflex testing was ordered. ROS1 FISH testing showed an isolated 3 ′ signal pattern, indicating a potential rearrangement or deletion in the ROS1 gene. Next‐generation sequencing (NGS) analysis revealed a NMP1::ROS1 rearrangement. The tumor was from a 74‐year‐old male with a previous history of lung squamous cell carcinoma. This new occurrence was determined to be a lung adenocarcinoma and displayed papillary features, whereas concurrent lymphadenopathy was also present. Immunostaining for ALK was negative, and there was no expression of PD‐L1 22C3 IHC. This case report highlights an unexpected ROS1 IHC staining associated with a rare ROS1 gene rearrangement.