EZR-ROS1-rearranged lung adenocarcinoma presenting as diffuse cystic lung disease mimicking lymphangioleiomyomatosis:...

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.

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.

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.