EZR-ROS1-rearranged lung adenocarcinoma presenting as diffuse cystic lung disease mimicking lymphangioleiomyomatosis: a case report

Background: Diffuse cystic lung disease (DCLD) in women of reproductive age is often attributed to lymphangioleiomyomatosis (LAM), but malignancy should be considered when atypical features are present.

Case Description: We report the case of a 27-year-old never-smoking woman initially diagnosed with LAM based on high-resolution computed tomography (HRCT) findings, who was subsequently found to have metastatic lung adenocarcinoma on supraclavicular lymph node biopsy. Her first HRCT showed diffuse thin-walled lung cysts, and in 6 months, the second HRCT showed diffuse cysts (2–14 mm) with heterogeneous cyst-wall thickness plus a left upper-lobe patchy opacity, as well as beaded pleural-based fissural nodules in the right lung. Meanwhile, her serum carcinoembryonic antigen (CEA) was 21.96 ng/mL and the supraclavicular node biopsy confirmed metastatic lung adenocarcinoma (cT4N3M1a, stage IVA). DNA-based next-generation sequencing (NGS) identified an EZR-ROS1 rearrangement. After 8 months of crizotinib therapy, she achieved a partial response (PR) with CEA normalization. As of 77 months after treatment initiation, the patient maintains a PR without progression or documented acquired resistance.

Conclusions: In a LAM-like cystic background, the presence of superimposed focal opacities or nodules, fissural beading, and heterogeneous cyst-wall thickness should prompt an expedited malignancy work-up rather than an HRCT-only diagnosis, as this case demonstrates that systematic evaluation of atypical features in presumed LAM can identify treatable oncogene-driven malignancies amenable to highly effective targeted therapy.