Rare MYH9-ROS1 Fusion Gene-Positive Lung Adenocarcinoma Showing Response to Entrectinib Treatment: A Case Study

Abstract

The c-ros oncogene 1 (ROS1) fusion gene is a rare genomic alteration detected in nearly 1-2% of lung adenocarcinomas. The major partner genes of ROS1 include CD74, SDC4, and EZR. Here, we report a case of MYH9-ROS1 fusion gene-positive lung adenocarcinoma, a rare ROS1 fusion gene. The patient was a woman in her 40s who was diagnosed with advanced primary lung adenocarcinoma after a thorough examination. Initial genetic testing conducted using mediastinal lymph node biopsy specimens collected by endobronchial ultrasound-guided transbronchial needle aspiration revealed no driver gene mutations, including the ROS1 fusion gene. The patient was treated with four courses of immunochemotherapy. As the disease worsened, another genetic test was conducted using FoundationOne^® CDx, and the MYH9-ROS1 fusion gene was detected. Multiple lung metastases disappeared after the administration of entrectinib; the response persisted up to a year. Adverse events of rash, dysgeusia, and peripheral edema were observed, and the patient required temporary drug interruption; however, we were able to continue entrectinib following a short-term drug interruption. This is the first report on the effectiveness of entrectinib against lung adenocarcinoma with the rare MYH9-ROS1 fusion gene.

Keywords: Entrectinib; Erythema; Lung adenocarcinoma; MYH9-ROS1 fusion gene.

Fig. 1

Histopathological images of biopsy samples from the patient. a Mediastinal lymph node specimen showing large, polygonal, atypical cells proliferating in sheets. The atypical cells showed TTF-1 positivity upon immunohistochemical staining. b Bladder tumor biopsy specimen showing enriched atypical cells and cord-like proliferation. The atypical cells showed TTF-1 positivity upon immunohistochemical staining.

Fig. 2

Computed tomography images through the course of treatment. a At first visit. b At the end of immunochemotherapy (before starting entrectinib). Pleural effusion decreased, but multiple lung metastases worsened and the appearance of a bladder tumor was observed. A ureteral stent was inserted. c One week after starting entrectinib. The previously observed multiple lung metastases and bladder tumor largely disappeared. d One year later. Response to entrectinib was sustained.

Fig. 3

Progress of the patient during the course of the treatment. Tumor markers decreased markedly after starting entrectinib (600 mg/day). After 2 weeks of entrectinib treatment, the patient developed generalized erythema and entrectinib was withdrawn for 1 week, following which erythema improved and entrectinib was resumed (at 600 mg/day) without relapse. After this, the patient showed acute cellulitis and edema; however, entrectinib treatment was continued without any major adverse events. CEA, carcinoembryonic antigen; TUR-Bt, transurethral resection of bladder tumor.