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Progressive Dry Cough in a Patient With ROS1-Rearranged Lung Adenocarcinoma Undergoing Crizotinib Therapy

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 69-year-old man with a smoking history and complaints of back pain and cough for 2 weeks was found to have a right lung mass on chest radiography results. A chest computed tomography (CT) scan showed a right upper lobe lung mass with multiple lymphadenopathies (N3), and bone scan and brain magnetic resonance imaging results showed multiple metastatic foci. A biopsy was performed, and the pathologic report showed a poorly differentiated lung adenocarcinoma with ROS1 rearrangement identified by immunohistochemical staining (clone: D4D6; H-score: 280) and further confirmative fluorescence in situ hybridization. The patient received ceritinib, 450 mg/day, and his tumor and brain and bone metastatic lesions subsequently decreased in size. The ceritinib was then shifted to crizotinib, 500 mg/day, when the reimbursement of crizotinib as a first-line therapy was approved by Taiwan's National Health Insurance system.

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D. Perform a CT-guided biopsy for histological confirmation of recurrence or identification of other benign disease, such as granulomatous inflammation

The pathological findings of the patient’s CT-guided biopsy were compatible with inflammation or SLR. The main feature of this patient was the mild presenting symptom but with the rapid development of consolidated lung with interstitial pneumonia on his CT scan. The diagnosis of bacterial pneumonia was rejected because the patient had a dry cough only, and findings of bronchial washings were negative. Disease recurrence was considered, but the decreasing carcinoembryonic antigen levels seemed inconsistent. Although a similar CT finding can be found in tyrosine kinase inhibitor (TKI)–induced interstitial lung disease (ILD), the mild symptom was incompatible with this diagnosis. There was no direct evidence to support the change of treatment to chemotherapy or steroids. With this in mind, clinicians must consider rebiopsy, and the diagnosis of the SLR was compatible with clinical symptoms and CT findings.

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Article Information

Corresponding Author: Chien-Chung Lin, MD, PhD, National Cheng Kung University Hospital, 138 Sheng Li Rd, Tainan 704, Taiwan (joshcclin@gmail.com).

Published Online: October 1, 2020. doi:10.1001/jamaoncol.2020.2809

Conflict of Interest Disclosures: The authors acknowledge the financial support of the Center of Applied Nanomedicine, National Cheng Kung University, from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project of the Ministry of Education in Taiwan, as well as grant MOST108-2314-B-006 -092 -MY2 from the Ministry of Science and Technology, Taiwan.

Additional Contributions: We thank the patient for granting permission to publish this information.

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