Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non‑caseating granulomas. Skeletal involvement, present in up to 13% of cases, frequently remains underrecognized due to its asymptomatic course and imaging features that closely mimic metastatic disease, creating significant diagnostic challenges.
Case Presentation: A 63‑year‑old woman presented for neurological evaluation of potential early cognitive decline prompted by family history. Neuroimaging incidentally revealed multiple osteolytic calvarial lesions. Further imaging demonstrated widespread mixed osteolytic and osteoblastic lesions involving the skeleton, bilateral perilymphatic pulmonary nodules, mediastinal and hilar lymphadenopathy, and hepatic lesions. Laboratory investigation showed elevated CA 15‑3 (43.7 kU/l) with normal CEA and CYFRA 21‑1. Whole‑body FDG PET/CT revealed hypermetabolic osteolytic lesions and metabolically active pulmonary infiltrates. An interdisciplinary tumor board considered carcinoma of unknown primary with suspected breast origin; however, breast MRI revealed no suspicious findings. Multiple myeloma was excluded by negative immunofixation electrophoresis. Percutaneous liver biopsy demonstrated non‑caseating granulomas without malignancy, with negative special stains for acid‑fast bacilli and fungi, establishing sarcoidosis as the underlying diagnosis.
Management and Outcome: The patient was initiated on corticosteroids with calcium and vitamin D supplementation. At one‑month follow‑up, symptomatic improvement was noted with normalization of serum ACE levels and decline in CA 15‑3. Pulmonary function remained stable with mild DLCO reduction. The patient was continued on a corticosteroid taper with addition of inhaled corticosteroids for residual bronchial hyperreactivity.
Conclusion: This case emphasizes the critical importance of maintaining broad differential diagnosis in multisystem disease with skeletal involvement. Although metastatic malignancy must be considered, sarcoidosis remains a key diagnostic consideration. Definitive histopathological confirmation is essential for accurate diagnosis and prevention of unnecessary oncologic intervention.
