From the time of Yousem et al.’s initial series in the 1980s, it was apparent that follicular bronchiolitis, as seen on lung biopsies, formed three clinicopathologic entities.² The largest group was that associated with autoimmune collagen vascular disease, especially rheumatoid arthritis and Sjögren syndrome. A second important group comprised patients with inherited immunodeficiency syndromes. The third group is heterogeneous and includes hypersensitivity and infectious conditions causing reactive lymphoid hyperplasia in the small airways.² In the largest recent series of biopsy-documented follicular bronchiolitis, 2 of 12 patients had connective tissue disorders (Sjögren syndrome and undifferentiated connective-tissue disease (CTD), respectively), two had common variable immunodeficiency (CVID) syndrome, and the remaining two-thirds had no apparent underlying condition.³ The latter finding highlights the nonspecificity of reactive follicles surrounding airways in biopsies of patients with clinically heterogeneous processes. Follicular bronchiolitis has also been described in patients with HIV,⁷ although the interstitial inflammatory component is typically emphasized in association with HIV (LIP).

Clinically, patients typically have frequent pulmonary infections. Most patients have some degree of dyspnea and cough, and abnormal chest radiographs are common. Bronchoscopic findings are usually nondiagnostic. Respiratory function tests show variable results, but a restrictive pattern may be present. By CT scan, nodular or micronodular lung densities with prominent, thickened distal airways, often with areas of ground-glass opacities or consolidation, are present.³

Follicular bronchiolitis is largely a descriptive diagnosis. By definition, only distal cartilaginous bronchi and bronchioles are involved; reactive hyperplasia around more proximal bronchiectatic airways or follicular lymphoid hyperplasia in the context of prominent acute or necrotizing inflammation is not considered follicular bronchiolitis.

Histologically, follicular bronchiolitis is characterized by lymphoid follicular hyperplasia of small airways, often with reactive germinal centers that may coalesce (Figs. 36.1, 36.2, 36.3).² Other findings and diagnoses may be present, depending on the clinical setting, including emphysema, respiratory bronchiolitis, carcinoid tumors, and granulomas.³ In general, acute inflammation is minimal, unless there is superimposed infection.