Histopathologic Variability in Usual and Nonspecific Interstitial Pneumonias

Abstract

Findings of surgical lung biopsy (SLB) are important in categorizing patients with idiopathic interstitial pneumonia (IIP). We investigated whether histologic variability would be evident in SLB specimens from multiple lobes in patients with IIP. SLBs from 168 patients, 109 of whom had multiple lobes biopsied, were reviewed by three pathologists. A diagnosis was assigned to each lobe. A different diagnosis was found between lobes in 26% of the patients. Patients with usual interstitial pneumonia (UIP) in all lobes were categorized as concordant for UIP (n = 51) and those with UIP in at least one lobe were categorized as discordant for UIP (n = 28). Patients with nonspecific interstitial pneumonia (NSIP) in all lobes were categorized as having fibrotic (n = 25) or cellular NSIP (n = 5). No consistent distribution of lobar histology was noted. Patients concordant for UIP were older (63 +/- 9 [mean +/- SD] yr; p < 0.05 as compared with all other groups) than those discordant for UIP (57 +/- 12 yr) or with fibrotic NSIP (56 +/- 11 yr) or cellular NSIP (50 +/- 9 yr). Semiquantitative high-resolution computed tomography demonstrated a varied profusion of fibrosis (p < 0.05 for all group comparisons), with more fibrosis in concordant UIP (2.13 +/- 0.62) than in discordant UIP (1.42 +/- 0.73), fibrotic NSIP (0.83 +/- 0.58), or cellular NSIP (0.44 +/- 0.42). Survival was better for patients with NSIP than for those in both UIP groups (p < 0.001), although survival in the two UIP groups was comparable (p = 0.16). Lobar histologic variability is frequent in patients with IIP, patients with a histologic pattern of UIP in any lobe should be classified as having UIP.

Gene Expression Profiling of Familial and Sporadic Interstitial Pneumonia

“…This speculation is supported by independent observations. First, it is well known that a substantial number of patients have histologic evidence of both UIP and NSIP in the same lung (6). Moreover, we have found that a substantial portion of the families with familial IIP had several radiographic or histologic patterns of IIP (most often including UIP and NSIP), suggesting that the different histologic types of IIP may be related etiologically and even pathogenically (7).…”

“…Although these diseases are thought to be clinically distinct (5), the transcriptional features of the different types of IIP have received little attention. In fact, two publications (6,7) indicate that these distinct clinical-pathologic processes (UIP and NSIP) appear to be related etiologically and pathogenically.…”

Matrix Metalloproteinase 3 Is a Mediator of Pulmonary Fibrosis

“…1 Histologically, IPF is characterized by dispersed myofibroblast proliferation and deposition of collagen and other extracellular matrix proteins within alveolar walls resulting in diminished lung compliance and ultimately leading to respiratory failure and death. 2 Despite advances in the understanding of the basic molecular pathways that drive this uncontrolled fibrotic process, no effective therapy is currently available.…”

Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis

“…However, this does not exclude a role for inflammation in an earlier stage of the disease. An interesting paper in this context is the study by Flaherty et al [26], in which the co-existence of UIP and non-specific interstitial pneumonia (NSIP) has been described in a considerable amount of patients who had multiple lung biopsies, demonstrating the presence of chronic inflammation and fibrosis next to each other. This pleads for a hypothesis in which UIP and NSIP are two different entities in one continuum.…”