Pulmonary pathologists were aware of cases of
idiopathic interstitial pneumonia (IIP) that morphologically did not fit Liebow's classification scheme. These cases were labeled as "cellular
interstitial pneumonia" or "chronic
interstitial pneumonia not otherwise specified." The term nonspecific
interstitial pneumonia (NSIP) was first used in relation to a pattern of lung interstitial
inflammation seen in association with human immunodeficiency virus (
HIV) infection. In 1994 NSIP was used to indicate a group of subacute or chronic
interstitial pneumonias characterized morphologically by interstitial
inflammation or
fibrosis or both, with preservation of the lung architecture and the absence of typical findings for any of the other main categories of IIP (mainly
usual interstitial pneumonia, desquamative
interstitial pneumonia, and
bronchiolitis obliterans organizing pneumonia). Although these patients presented with "nonspecific" lung histology (categorized as cellular and fibrotic variants), and with a broad spectrum of associated clinical conditions, such as
connective tissue diseases (
CTDs), environmental exposure, and previous
acute lung injury, they showed some peculiar clinical aspects, including favorable response to
corticosteroid treatment and overall good prognosis.The clinical and radiographic profiles were better defined in the last decade. The NSIP pattern is the histological background of a subacute/chronic
interstitial pneumonitis that may be observed in many conditions, including CTD,
drug-induced
lung disease,
hypersensitivity pneumonitis, slowly healing diffuse alveolar damage (DAD), relapsing
organizing pneumonia, occupational exposure, immunodeficiency (mainly
HIV infection),
graft versus host disease (GVHD), familial
pulmonary fibrosis,
immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlap features with
Rosai-Dorfman disease, multicentric
Castleman disease, and
myelodysplastic syndrome. Rarely, NSIP is the histology recognized in patients with idiopathic
interstitial pneumonitis, in whom efforts to find potential causative exposures are futile. This entity occurs mostly in middle-aged, never-smoker women, with a likely association with an autoimmune background. High-resolution computed tomographic (HRCT) scans typically demonstrate ground-glass attenuation with a bibasilar distribution, or in the fibrotic variant, ground-glass attenuation along with reticular lines and
traction bronchiectasis. The prognosis is good compared with
idiopathic pulmonary fibrosis (IPF), and therapeutic options include mainly
corticosteroids and
immunosuppressive agents. Recently a more precise definition of clinical profiles and radiographic findings of idiopathic NSIP allows consideration of less invasive diagnostic procedures (bronchoalveolar lavage, transbronchial lung biopsy). Better understanding of pathogenetic mechanisms might widen the therapeutic horizon giving a role to new therapeutic options in more severe cases.