Table 2.

Differential diagnoses of pulmonary sarcoidosis, related to site of thoracic involvement.

Site of Thoracic Involvement	Infectious Granulomatous Diseases	Non-Infectious Granulomatous Diseases
Lung parenchyma	Tuberculosis	Hypersensitivity pneumonitis (many causal antigens)
	NTM infections	Chemical induced granulomatosis (e.g., beryllium, aluminum, zirconium, silica, and talc)
	Histoplasmosis (very rare in Europe)	Drug-induced granulomatosis (e.g., TNF-alpha antagonists, immune checkpoint inhibitors, targeted therapies, and interferons)
	Parasitic infections (very rare, e.g., leishmaniosis, paragonimiasis, and schistosomiasis), occurring mainly in endemic countries	Aspiration pneumonia with foreign body granulomatosis
	Viral infections (very rare, e.g., varicella zoster and cytomegalovirus), mainly in immunocompromised patients)	Vasculitis, CTD, and inflammatory disease (e.g., GPA, EGPA, NSG, ILD in Sjogren’s syndrome, and Crohn’s disease)
	Other infections (very rare, e.g., Whipple’s disease, cryptococcosis, coccidioidomycosis, and mucormycosis), mainly in immunocompromised patients	Immune deficiency granulomatosis (e.g., granulomatous-associated CVID and CGD)
		Genetic disorders: Blau syndrome
		Malignancy-associated granulomatosis (e.g., cancer and lymphoma)
		Other proliferative disorders (e.g., LCH, ECD, and lymphomatoid granulomatosis)
Thoracic lymph nodes	Tuberculosis	Sarcoid-like reaction (especially occurring in linkage to malignancies but also in rare occasions of hypersensitivity pneumonitis and CTD such as Sjogren’s syndrome)
	NTM infections	Chemical-induced granulomatosis (e.g., beryllium, aluminum, zirconium, silica, and talc)
	Histoplasmosis (very rare in Europe)	Drug-induced granulomatosis (e.g., TNF-alpha antagonists, immune checkpoint inhibitors, targeted therapies, and interferons)
	Other infections (very rare, e.g., Whipple’s disease and fungal infections)	Immune deficiency granulomatosis (e.g., granulomatous-associated CVID and CGD)
		Malignancy-associated granulomatosis (e.g., cancer and lymphoma)

Definition of abbreviations: CGD, chronic granulomatous disease; CTD, connective tissue disease; CVID, common variable immune deficiency; ECD, Erdheim–Chester disease; EGPA, eosinophilic granulomatosis with polyangiitis; GPA, granulomatosis with polyangiitis; ILD, interstitial lung disease; LCH, Langerhans cell histiocytosis; NSG, necrotizing sarcoid granulomatosis; NTM, nontuberculous mycobacteria; TNF, tumor necrosis factor. The differential diagnosis should be prioritized on the basis of the individual’s clinical history and presentation and can depend on geographic location.