Distinguishing between life-threatening infection and malignancy in immunocompromised patients remains a major clinical challenge. Individuals with systemic lupus erythematosus (SLE) are at heightened risk for both invasive pulmonary aspergillosis (IPA) and lung cancer, and their coexistence can create a profound diagnostic dilemma. We report the case of a 66-year-old man with a history of SLE and prior IPA who presented with fever, headache, and progressive cognitive decline. Imaging revealed a cavitary lung lesion and multiple brain nodules, initially suggestive of intracranial IPA dissemination. Despite aggressive antifungal therapy, his condition rapidly worsened. A subsequent 18 F-FDG PET-CT scan demonstrated intense hypermetabolism in the lung, brain, and multiple skeletal sites, shifting the diagnostic consideration toward metastatic malignancy. Lung biopsy ultimately confirmed poorly differentiated pulmonary squamous cell carcinoma (cT4N3M1c, Stage IV) with brain and bone metastases. This case highlights the diagnostic delays that can arise from anchoring bias toward prior infection and underscores the importance of recognizing “red flags” such as treatment failure, incorporating PET-CT to reassess disease biology, and relying on histopathological confirmation to overcome cognitive biases and diagnostic inertia in complex immunocompromised patients.
Yu et al. (2026) studied this question.