PMC9035909_01
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.
cro-0015-0376-g01.jpg
PMC9035909_01_cro-0015-0376-g01.jpg
F1
The patient was then started on immunochemotherapy with carboplatin, paclitaxel, bevacizumab, and atezolizumab. The disease progressed to a stable disease at the end of two courses but exhibited worsened multiple lung metastases and a bladder tumor at the end of four courses. We performed a transurethral resection of the bladder tumor and histologically diagnosed it as bladder metastasis of the lung adenocarcinoma (shown in Fig. 1). The tumor specimen was tested using FoundationOne  CDx (Foundation Medicine, Cambridge, MA, USA) and was found to be positive for the MYH9-ROS1 fusion gene.
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.
cro-0015-0376-g02.jpg
PMC9035909_01_cro-0015-0376-g02.jpg
F2
The cancerous lesions throughout the body disappeared after restarting entrectinib, resulting in a complete response; this effect was sustained for a year (shown in Fig. 2).
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 After 2 weeks of entrectinib treatment, the patient developed generalized erythema and entrectinib was withdrawn for 1 week, following which erythema improved and entrectinib was resumed (at 600 mg/day) without relapse.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.
cro-0015-0376-g03.jpg
PMC9035909_01_cro-0015-0376-g03.jpg
F3
The entire course of this patient is shown in Figure 3.