Radiologic-Pathologic Correlation
Usual interstitial pneumonia end-stage features from explants with radiologic and pathological correlations

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Abstract

Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia, with typical high-resolution computed tomography (HRCT) features and histologic pattern of usual interstitial pneumonia (UIP); its main differential diagnosis is fibrotic nonspecific interstitial pneumonia (F-NSIP). Usual interstitial pneumonia was mainly described from lung biopsies, and little is known on explants. Twenty-two UIP/IPF explants were analyzed histologically and compared with previous open lung biopsies (OLBs; n = 11) and HRCT (n = 19), when available. Temporospatial heterogeneity and subpleural and paraseptal fibrosis were similarly found in UIP/IPF explants and OLB (91%-95%). Fibroblastic foci were found in 82% of OLBs and 100% of explants, with a higher mean score in explants (P = .023). Honeycombing was present in 64% of OLBs and 95% of explants, with a higher mean score in explants (P = .005). Almost 60% of UIP/IPF explants showed NSIP areas and 41% peribronchiolar fibrosis; inflammation, bronchiolar metaplasia, and vascular changes were more frequent in UIP/IPF explants; and Desquamative Interstitial Pneumonia (DIP)-like areas were not common (18%-27%). Numerous large airspace enlargements with fibrosis were frequent in UIP/IPF explants (59%). On HRCT, honeycombing was observed in 95% of the cases and ground-glass opacities in 53%, correlating with NSIP areas or acute exacerbation at histology. Six patients had combined IPF and emphysema. Lesions were more severe in UIP/IPF explants, reflecting the worsening of the disease. Usual interstitial pneumonia/IPF explants more frequently presented with confounding lesions such as NSIP areas, peribronchiolar fibrosis, and airspace enlargements with fibrosis sometimes associated with emphysema.

Introduction

Idiopathic pulmonary fibrosis (IPF) is the most frequent and the most severe idiopathic interstitial pneumonia. It is a chronic and progressive fibrotic disease limited to the lung, which predominates in males and smokers. Idiopathic pulmonary fibrosis is a clinicopathologic entity with a dismal prognosis and no response to anti-inflammatory therapy. According to the 2011 ATS/ERS/JRS/ALAT guidelines, the diagnosis of IPF is based on high-resolution computed tomography (HRCT) findings, including reticulations and honeycombing predominating in subpleural regions, with or without traction bronchiectases, a histologic pattern of usual interstitial pneumonia (UIP), and the exclusion of known causes of interstitial pneumonias, especially environmental exposure, medication, or systemic disease [1]. The histologic pattern of UIP is defined by dense fibrosis responsible for architectural distortion, subpleural and paraseptal honeycombing, patchy involvement of the lung with areas of normal lung, fibroblastic foci, and none of the following criteria, that is, hyaline membranes, organizing pneumonia (except in the setting of an acute exacerbation [AE] of the disease), marked inflammation, predominant airways changes, and other features suggesting an alternative diagnosis. However, because of interobserver discrepancies between pathologists reported in several studies and the possibility of sampling issues, histopathology is no longer the criterion standard for the diagnosis of IPF [2], [3], [4], [5], [6]. Pathologists are asked to describe the pattern of interstitial lung disease rather than to make definite diagnosis, patterns being further discussed along with clinicoradiologic findings and included in a final consensus diagnosis [1].

The main clinical and histologic differential diagnosis of UIP/IPF is represented by nonspecific interstitial pneumonia (NSIP) [7], which is associated with a better prognosis and response to corticosteroids [8], [9]. In contrast to UIP, the NSIP pattern is characterized histologically by uniform distribution of interstitial inflammation and fibrosis lacking the patchwork involvement of UIP. However, the NSIP fibrotic pattern may be difficult to distinguish from the UIP pattern.

As most histologic criteria for interstitial lung diseases have been described from open lung biopsies (OLBs), the present study was conducted to describe the end-stage histologic features of UIP on explants, to compare them with previous OLB when available, and to make a correlation between radiology, OLB, and explants.

Section snippets

Materials and methods

Twenty-two patients transplanted for pulmonary fibrosis were identified from the University Hospital of Grenoble files between 1991 and 2009 and from the University Hospital Lyon-Est files between 2000 and 2009.

Lung explants' specimens were available for analysis in all cases. In addition, OLBs performed prior to the lung transplantation were available for review in 11 cases (50%). All biopsies and explants were retrospectively analyzed by 4 pathologists (M.R., S.L., F.T., L.C.) blinded to the

Clinical data

Fourteen patients (64%) were smokers, and 20 were men and 2 were women; the mean age at the time of lung transplantation was 55 years. One patient had been formerly treated for tuberculosis, and for 3 patients, lung cancer (1 squamous cell carcinoma and 2 adenocarcinomas) was incidentally found on explants (Table 2).

The mean data of pulmonary function before transplantation were as follows: forced vital capacity 43.1% ± 12.0% of predicted; forced expiratory volume in 1 second, 44.9% ± 12.2%

Discussion

ATS/ERS/JRS/ALAT have recently published guidelines for the diagnosis and treatment of IPF [1], acknowledging the determinant role of CT scan for the diagnosis of IPF; OLBs are now only performed in a minority of the cases, around 30% [11], [12], mainly because surgical lung biopsies are potentially responsible for complications [13], [14], [15]. Because only 16% of IPF patients benefit from lung transplantation [11], clinical and radiologic features as well as OLB are rarely compared with

References (31)

  • A.G. Nicholson et al.

    Inter-observer variation between pathologists in diffuse parenchymal lung disease

    Thorax

    (2004)
  • M. Thomeer et al.

    Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis

    Eur Respir J

    (2008)
  • A.L. Katzenstein et al.

    Nonspecific interstitial pneumonia and the other idiopathic interstitial pneumonias: classification and diagnostic criteria

    Am J Surg Pathol

    (2000)
  • V. Cottin et al.

    Nonspecific interstitial pneumonia. Individualization of a clinicopathologic entity in a series of 12 patients

    Am J Respir Crit Care Med

    (1998)
  • R. du Bois et al.

    Challenges in pulmonary fibrosis × 5: the NSIP/UIP debate

    Thorax

    (2007)
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    Conflicts of interest and source of funding: the authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this study.

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