Autoantibody positivity and false-negative cytology can mask invasive mucinous adenocarcinoma in patients with IPAFLung cancer can mimic autoimmune lung disease in some patients

BackgroundInterstitial pneumonia with autoimmune features (IPAF) is an exclusionary diagnosis that requires the exclusion of alternative etiologies, including malignancy. Invasive mucinous adenocarcinoma (IMA) of the lung can radiologically and clinically mimic interstitial lung disease (ILD), and some lung cancer patients may present with non-specific autoantibody positivity, creating a diagnostic trap that may lead to misdiagnosis as IPAF.MethodsWe retrospectively analyzed the clinical data, serology, imaging, bronchoalveolar lavage fluid (BALF) cytology, and pathology of a 78-year-old female patient, combined with a literature review.ResultsThe patient presented with cough and sputum production lasting two months. Chest CT showed diffuse bilateral high-density opacities with septal thickening. Pulmonary function tests revealed moderate diffusion impairment, and Velcro crackles were present on auscultation. Autoantibodies were positive for ANA (1:100, cytoplasmic granular pattern), AMA-M2 (161.75 U/mL), RF (78.2 IU/mL), and anti-CCP antibody (300 U/mL). Notably, all systemic inflammatory markers (ESR, CRP, and six cytokines) were normal. BALF and liquid-based cytology revealed no malignant cells. Rheumatology consultation favored a diagnosis of IPAF, and empirical methylprednisolone 40 mg/d was initiated. After one week, chest CT showed no resolution; mycophenolate mofetil and nintedanib were added. Despite standard anti-infective and immunosuppressive therapy, imaging remained unchanged and tumor markers remained persistently elevated. CT-guided percutaneous lung biopsy was performed, and histopathological examination confirmed invasive mucinous adenocarcinoma (CK7+, focal CK20+, TTF-1−, Napsin A−).ConclusionIn patients with suspected IPAF, the combination of normal inflammatory markers with other atypical features should prompt re-evaluation of the autoimmune etiology. The lepidic growth pattern of IMA can lead to false-negative BALF cytology; a negative result does not exclude malignancy. As an exclusionary diagnosis, IPAF must be established only after thorough exclusion of infection, malignancy, and other causes. Immunosuppressive therapy should not be initiated based solely on autoantibody positivity and ILD imaging.