Pulmonary Sarcoidosis: Diagnosis and Differential Diagnosis

Abstract

Sarcoidosis is a multisystem disorder of unknown origin and poorly understood pathogenesis that predominantly affects lungs and intrathoracic lymph nodes and is characterized by the presence of noncaseating granulomatous inflammation in involved organs. The disease is highly heterogeneous and can mimic a plethora of other disorders, making diagnosis a challenge even for experienced physicians. The evolution and severity of sarcoidosis are highly variable: many patients are asymptomatic and their disease course is generally benign with spontaneous resolution. However, up to one-third of patients develop chronic or progressive disease mainly due to pulmonary or cardiovascular complications that require long-term therapy. The diagnosis of sarcoidosis requires histopathological evidence of noncaseating granulomatous inflammation in one or more organs coupled with compatible clinical and radiological features and the exclusion of other causes of granulomatous inflammation; however, in the presence of typical disease manifestations such as Löfgren's syndrome, Heerfordt's syndrome, lupus pernio and asymptomatic bilateral and symmetrical hilar lymphadenopathy, the diagnosis can be established with high level of certainty on clinical grounds alone. This review critically examines the diagnostic approach to sarcoidosis and emphasizes the importance of a careful exclusion of alternative diagnoses.

Keywords: biomarkers; diagnosis; differential diagnosis; histology; imaging; sarcoidosis.

Figure 1

Irregularly marginated nodule surrounded by multiple small nodules (“Galaxy sign”, yellow narrow), this is typical of sarcoidosis (a); ground-glass-like increased attenuation resulting from diffuse micronodules randomly distributed (“Miliary sarcoidosis”) (b); enlarged and partially calcified (yellow narrows) bilateral hilar lymph nodes (c); fibrotic sarcoidosis with cystic changes and traction bronchiectases (yellow narrows) predominantly in the perihilar region and upper lobes. Nodular abnormalities are minimal/absent, but the appearance and the location of the fibrosis are very suggestive of the diagnosis of sarcoidosis (d).

Figure 1

Irregularly marginated nodule surrounded by multiple small nodules (“Galaxy sign”, yellow narrow), this is typical of sarcoidosis (a); ground-glass-like increased attenuation resulting from diffuse micronodules randomly distributed (“Miliary sarcoidosis”) (b); enlarged and partially calcified (yellow narrows) bilateral hilar lymph nodes (c); fibrotic sarcoidosis with cystic changes and traction bronchiectases (yellow narrows) predominantly in the perihilar region and upper lobes. Nodular abnormalities are minimal/absent, but the appearance and the location of the fibrosis are very suggestive of the diagnosis of sarcoidosis (d).

Figure 2

Pulmonary silicosis with predominantly upper lobes fibrosis and traction bronchiectasis (yellow narrow) (a); conglomerate masses and pulmonary micronodules (yellow narrow) in patient with tuberculosis (b); enlarged bilateral hilar lymph nodes (yellow narrow), a sarcoid-like-reaction in patient with mammal carcinoma (c).