Breaking Symmetry: Unilateral Sarcoidosis Presenting as a Diagnostic Challenge

Sarcoidosis is a multisystem granulomatous disorder that classically involves the lungs and intrathoracic lymph nodes in a bilateral distribution. Unilateral disease is rare and may closely mimic malignancy, leading to diagnostic uncertainty. We report the case of a 71-year-old man with a history of coronary artery disease, prior tuberculosis exposure, and a 20-pack-year smoking history, who was found to have pleural-based, calcified pulmonary nodules on screening computed tomography (CT) scan. Initial positron emission tomography (PET) imaging demonstrated no avidity; however, follow-up revealed interval growth and new fluorodeoxyglucose (FDG) uptake, prompting CT-guided biopsy. Histopathology showed chronic inflammation with multinucleated giant cell reaction and focal calcification, consistent with sarcoidosis and without evidence of malignancy. The patient later developed cough and wheezing, with symptoms and imaging findings improving on corticosteroid therapy. This case highlights the diagnostic challenges of unilateral sarcoidosis, the limitations of PET in differentiating granulomatous inflammation from malignancy, and the value of surveillance with targeted biopsy. Learning points Unilateral sarcoidosis can mimic malignancy. Even in the absence of bilateral lymphadenopathy, sarcoidosis should remain in the differential for unilateral, positron emission tomography (PET) fluorodeoxyglucose (FDG)-avid pulmonary nodules to avoid unnecessary surgical interventions. Calcified pleural-based nodules represent an uncommon sarcoid phenotype. The presence of coarse calcification does not exclude active disease, and interval progression with evolving FDG avidity highlights the need for longitudinal imaging surveillance. Targeted biopsy and measured therapy are key . In atypical presentations without accessible lymphadenopathy or extrapulmonary disease, percutaneous parenchymal biopsy is essential for diagnosis. Steroid therapy can be highly effective, and a surveillance-first approach can spare patients from invasive procedures.