Nonspecific interstitial pneumonia (NSIP) is defined as a chronic idiopathic interstitial pneumonia that is temporally “uniform” (the process is of the “same age” or same duration throughout the biopsy). Biopsies of several specific entities can also show features that meet the criteria for NSIP, as discussed further later. NSIP occurs most often in middle-aged adults and usually presents as shortness of breath. Histologically, NSIP is divided into cellular and fibrotic forms. Most cases of NSIP show cellular interstitial infiltrates composed of lymphocytes and plasma cells arranged in a homogeneous “linear” pattern in which the lung architecture is preserved (cellular type of NSIP). Less often, cases show predominantly interstitial fibrosis arranged in a homogenous “linear” pattern in which the lung architecture is largely preserved (fibrotic type of NSIP). Some cases may show varying amounts of both cellular interstitial infiltrates and interstitial fibrosis. In contrast to usual interstitial pneumonia (usual interstitial pneumonia [UIP]; see Chapter 92), NSIP has minimal or absent honeycombing. NSIP lacks the fibroblast foci that represents the temporal heterogeneity of UIP. In contrast to UIP, cellular NSIP has a good response to steroids and a good prognosis. Fibrotic NSIP may respond to steroids, although generally fibrotic NSIP has a much worse prognosis than cellular NSIP, and therefore is more similar to UIP in prognosis and response to steroids.

NSIP is a common histologic pattern in collagen vascular diseases involving the lung (see Chapters 86 and 113). Some cases of NSIP are hypersensitivity pneumonitis (extrinsic allergic alveolitis; see Chapter 82). In particular, some biopsies of hypersensitivity pneumonitis have temporally homogeneous interstitial lymphoplasmacytic infiltrates consistent with NSIP but lack the poorly formed granulomas characteristic of hypersensitivity pneumonitis. Areas with histopathologic features of NSIP may sometimes be present in cases of UIP and may be the only areas sampled on a biopsy. Other types of interstitial fibrosis or inflammation that may have an NSIP-like pattern include drug reactions and organized diffuse alveolar damage (see Chapter 87) or acute interstitial pneumonia (see Chapter 91).