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

<i>ROS1</i> rearrangements are driver events in a subset of nonsmall cell lung carcinomas and may qualify patients for <i>ROS1</i>-directed treatment. ROS1 immunohistochemistry (IHC) is often used for screening of lung carcinomas for <i>ROS1</i> 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. <i>ROS1</i> 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 <i>NMP1::ROS1</i> 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 <i>ROS1</i> gene rearrangement.