Pathology of Sarcoidosis

Pathologists are frequently involved in the diagnosis of sarcoidosis on conventional biopsies or examining bronchoalveolar lavage fluid and assisting bronchoscopists when performing bronchial or transbronchial biopsies or transbronchial needle aspiration (TBNA)/endobronchial ultrasound (EBUS)-guided biopsies of enlarged lymph nodes. Histology generally does not pose difficult tasks in the correct clinical and imaging scenario, but atypical forms of sarcoidosis exist, and in these cases, the diagnosis may become difficult. When faced with granulomas in the lung, the evaluation of their qualitative features, anatomic distribution, and accompanying findings usually allows the pathologist to narrow considerably the differential diagnosis. The final diagnosis always requires the careful integration of the histology with the clinical, laboratory, and radiologic findings. How robust is the histologic component of the diagnosis varies from case to case, and the pathologist should always clearly discuss this point with the clinician; in general, the weaker the histology is, the stronger should be the clinical-radiologic findings, and vice versa. The differential diagnosis of sarcoidosis includes granulomatous infections, hypersensitivity pneumonitis, pneumoconiosis, autoimmune diseases (e.g., inflammatory bowel disease, primary biliary cirrhosis, several collagen vascular diseases (particularly Sjögren), drug reactions, chronic aspiration, and even diffuse fibrosing diseases. In this review, conventional and unusual histologic findings of pulmonary sarcoidosis are presented, highlighting the role of the pathologist and discussing the main differential diagnoses.