C80-36 A Cancer Chameleon: Atypical Presentation of Lung Adenocarcinoma Buried Within Progressive Fibrotic Interstitial Lung Disease

Abstract Introduction Patients with ILD are at increased risk of developing non-small cell lung cancer (NSLC), likely through pro-inflammatory proliferation of epithelial cells with resulting cellular dysplasia. Furthermore, NSLC in these patients develops in peripheral/lower lung zones near or within areas of fibrosis, complicating diagnosis. Case Presentation Patient ID: 75 year-old woman (never-smoker) with gastroesophageal reflux disease (GERD), mycobacterial avium complex (MAC), and interstitial lung disease (ILD) secondary to suspected seronegative amyopathic dermatomyositis, diagnosed with lung adenocarcinoma in the background of progressive ILD. ILD history: Patient was diagnosed with ILD in 2016 with subsequent development of a rash across her chest and lower back, raising suspicion for amyopathic dermatomyositis. Mycophenolate was started, and CT scans showed slow ILD progression between 2020-2025. Lung cancer diagnosis: Patient had bilateral lung nodules since 2016. In 2019, a LLL nodular consolidation/confluent fibrosis was increasingly visible within a zone containing ILD. The area continued to enlarge, and in 2024, a percutaneous core needle biopsy sample showed “pneumocyte reactive atypia.” Follow-up scans re-demonstrated this lesion, which was unchanged after an 8-week prednisone course, prompting robotic-assisted transbronchial cryobiopsy in 1/2025. Pathology noted “atypical glandular proliferation in a background of fibrosis and honeycomb change.” A PET-CT then showed minimal FDG avidity, radiographically suggesting lower likelihood of malignancy. However, given increasing clinical suspicion, the patient was referred to thoracic surgery, and underwent LLL lobectomy in 6/2025; pathology revealed “mixed mucinous and non-mucinous adenocarcinoma,” TNM stage pT3N0 and no actionable genetic variants. Discussion This case represents an atypical presentation of lung adenocarcinoma in a patient with progressive fibrotic ILD which both radiographically and clinically obscured her cancer diagnosis. Serial pathology was initially negative for malignancy; it was only after empiric lobectomy that adenocarcinoma was diagnosed. This case raises important points regarding the histopathologic yield of cancer within ILD. The “pneumonic-type spread” of cancer within existing honeycomb changes leads to a “colonization” of tumor rather than a discrete mass. Such patchy tumor involvement may be grossly unappreciable and easily conflated with reactive atypia from surrounding ILD. Figure A shows a high-powered histopathological view of a patchy (rather than uniform) area demonstrating malignancy in the LLL of our patient. Overall, this case highlights the unique challenge of diagnosing lung cancer in patients with fibrotic ILD - clinically, radiographically, histopathologically, and surgically. This remains an emerging but essential area of multidisciplinary inquiry, impacting morbidity and mortality in an already high-risk patient population. Figure A This abstract is funded by: None