Rare idiopathic interstitial pneumonias: LIP and PPFE and rare histologic patterns of interstitial pneumonias: AFOP and BPIP.

In the 2013 reclassification of the idiopathic interstitial pneumonias (IIPs), two rare IIPs (idiopathic lymphoid interstitial pneumonia (LIP), idiopathic pleuroparenchymal fibroelastosis (IPPFE)) and two rare histologic patterns (acute fibrinous and organizing pneumonia (AFOP), bronchiolocentric pattern of interstitial pneumonia (BPIP)) are described. All these entities are rare with small series published to date, mostly containing primary and secondary forms of disease. LIP is histologically characterized by diffuse polyclonal lymphoid cell infiltrate surrounding the airways and expanding the interstitium. Thin-walled cysts and diffuse ground glass are considered the typical radiologic features. The clinical course is highly variable with corticosteroid responsiveness evident in approximately half of cases. IPPFE is defined histologically by coexisting upper lobe pleural and intra-alveolar fibrosis with elastosis. Dense subpleural irregular fibrosis and consolidation are the cardinal radiologic features. A history of recurrent lower respiratory tract infection is frequent. Responses to immunomodulation have not been reported and the rate of progression appears to be highly variable. AFOP is a rare histologic pattern lying within the spectrum of acute/subacute lung injury, characterized by organizing pneumonia and intra-alveolar fibrin deposition without hyaline membranes. BPIP is characterized histologically by fibrosis and/or inflammation confined to the alveolar interstitium around bronchovascular bundles, overlapping with peribronchial metaplasia and fibrosis in some series. Currently, AFOP and BPIP are both best viewed as histological entities rather than true clinical disorders, in the absence of characteristic associated imaging patterns and clinical features.

American Thoracic Society-European Respiratory Society Classification of the Idiopathic Interstitial Pneumonias: Advances in Knowledge since 2002.

In the updated American Thoracic Society-European Respiratory Society classification of the idiopathic interstitial pneumonias (IIPs), the major entities have been preserved and grouped into (a) "chronic fibrosing IIPs" (idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia), (b) "smoking-related IIPs" (respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia), (c) "acute or subacute IIPs" (cryptogenic organizing pneumonia and acute interstitial pneumonia), and (d) "rare IIPs" (lymphoid interstitial pneumonia and idiopathic pleuroparenchymal fibroelastosis). Furthermore, it has been acknowledged that a final diagnosis is not always achievable, and the category "unclassifiable IIP" has been proposed. The diagnostic interpretation of the IIPs is often challenging because other diseases with a known etiology (most notably, connective tissue disease and hypersensitivity pneumonitis) may show similar morphologic patterns. Indeed, more emphasis has been given to the integration of clinical, computed tomographic (CT), and pathologic findings for multidisciplinary diagnosis. Typical CT-based morphologic patterns are associated with the IIPs, and radiologists play an important role in diagnosis and characterization. Optimal CT quality and a systematic approach are both pivotal for evaluation of IIP. Interobserver variation for the various patterns encountered in the IIPs is an issue. It is important for radiologists to understand the longitudinal behavior of IIPs at serial CT examinations, especially for providing a framework for cases that are unclassifiable or in which a histologic diagnosis cannot be obtained.

Changes in the current classification of IIP: A critical review.

Idiopathic interstitial pneumonias (IIP) are a heterogeneous group characterized by unknown aetiology. Establishment of a correct diagnosis of a distinct IIP requires a multidisciplinary approach integrating clinical presentation, physiological data, radiological appearance and histological findings. The 2013 update of the American Thoracic Society/European Respiratory Society classification summarises progress in the field of IIP and outlines potential areas for future research. The main entities defined by the 2002 statement on IIP are preserved, but major IIP are now distinguished from rare IIP and the new category of unclassifiable IIP is introduced. In addition, the existence of idiopathic non-specific interstitial pneumonia as a separate chronic fibrosing IIP and idiopathic pleuroparenchymal fibroelastosis as a specific rare entity are acknowledged. Moreover, the major IIP are categorized according to the features chronic fibrosing, smoking-related and acute/subacute clinical course. Furthermore, a clinical classification of IIP according to disease behaviour with suggestions for treatment goals and monitoring strategies is provided. The goal of this review is to discuss the areas of uncertainty in the updated multidisciplinary classification of IIP and point out potential consequences for clinical management.

An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias.

BACKGROUND: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs. PURPOSE: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. METHODS: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. RESULTS: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. CONCLUSIONS: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.

[Idiopathic interstitial pneumonias]. / Pneumopathies interstitielles diffuses idiopathiques.

Idiopathic interstitial pneumonias represent approximately 30% of all interstitial lung diseases. The new classification of idiopathic interstitial pneumonias published in 2013 distinguishes 6 major entities, including chronic fibrosing forms (idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia), acute/subacute forms (cryptogenic organizing pneumonia and acute interstitial pneumonia) and smoking-related disorders (respiratory bronchiolitis interstitial lung disease and desquamative interstitial pneumonia). Pleuroparenchymal fibroelastosis is individualized as a new rare clinco-pathologic entity. For cases not fitting any specific clinic- pathological category, a pragmatic classification based on disease behavior is proposed.

[Radiological diagnostic approach to idiopathic interstitial pneumonias: findings in high resolution computed tomography]. / Aproximación al diagnóstico radiológico de las neumonías intersticiales idiopáticas. Hallazgos en tomografía computarizada de alta resolución.

A review is presented on the histological and radiological findings in idiopathic interstitial pneumonias, which are included among the diffuse parenchymal lung diseases. Although they may affect other compartments, the lung interstitium is the initial substrate of the parenchymal lesion due to different patterns of inflammation and fibrosis. The current classification, proposed in 2002 as an international multidisciplinary consensus document promoted by the American Thoracic Society and the European Respiratory Society, includes 7 conditions. Based on histological criteria, each histological pattern is associated with an image pattern. They are a group of conditions of unknown origin with common characteristics and differential features that enable them to be individualised as diseases with a different prognosis and treatment. They are rare as idiopathic forms, but share a morphological substrate with other more common diseases of unknown cause, which means they have to be excluded to reach a definitive diagnosis. For this reason it is important that the radiologist is familiar with their characteristic imaging findings.

Computed tomography findings of current nonspecific interstitial pneumonia based on the 2013 updated classification of idiopathic interstitial pneumonias: What is a characteristic of previously diagnosed nonspecific interstitial pneumonia excluded from the updated classification.

PURPOSE: To evaluate computed tomography (CT) findings of nonspecific interstitial pneumonia (NSIP) based on the current classification of idiopathic interstitial pneumonias (IIPs) and elucidate a characteristic of previously diagnosed NSIP excluded from the current classification. MATERIALS AND METHODS: The study included 74 patients with biopsy-proven NSIP (idiopathic NSIP [I-NSIP], 39 patients; NSIP associated with connective tissue disease [CTD-NSIP], 35 patients). Among patients who were compatible with the current classification of IIPs, 29 and 21 were categorized as having current I-NSIP and current CTD-NSIP, respectively. The remaining 24 patients were categorized as having previous I-NSIP or previous CTD-NSIP due to the primary pathologic diagnosis of cellular NSIP or associated findings of acute inflammatory changes. CT findings were evaluated and compared among the four groups. RESULTS: Current I-NSIP was indicated by ground-glass attenuation and reticulation with traction bronchiectasis/bronchiolectasis in predominantly peribronchovascular areas of the lower lung zone. The previous I-NSIP group tended to show broader airspace consolidation than the current I-NSIP group (p = 0.068). The previous CTD-NSIP group showed significantly broader airspace consolidation than the current I-NSIP group (p = 0.035). CONCLUSION: Broad airspace consolidation is a characteristic of previously diagnosed CTD-NSIP excluded from the current classification of IIPs.

Collaborative radiologic and histopathologic assessment of fibrotic lung disease.

The idiopathic interstitial pneumonias (IIPs) are a seemingly disconnected collection of diseases usually associated with the presence of pulmonary fibrosis. Categorization of the IIPs continues to be problematic despite recent attempts to refine the diagnostic criteria and suggests that rather than separate diseases, these pneumonias represent a spectrum of injury and abnormal repair of the alveolar wall. Although the initiating injury or injuries are unknown, the IIPs share a restricted number of final common abnormal pathways that lead to volume loss and lung distortion. The pathways include (a) alveolar collapse, (b) incorporation of fibroblastic material into alveolar walls, and (c) cigarette smoke-related inflammation and fibrosis. A collaborative diagnostic process in which data from radiologic and histologic assessments are combined allows a more reliable identification of the predominant pathways leading to pulmonary fibrosis. This approach has implications for therapy and the future direction of research.

The idiopathic interstitial pneumonias: understanding key radiological features.

Many radiologists find it challenging to distinguish between the different interstitial idiopathic pneumonias (IIPs). The British Thoracic Society guidelines on interstitial lung disease (2008) recommend the formation of multidisciplinary meetings, with diagnoses made by combined radiological, pathological, and clinical findings. This review focuses on understanding typical and atypical radiological features on high-resolution computed tomography between the different IIPs, to help the radiologist determine when a confident diagnosis can be made and how to deal with uncertainty.

[Clinic pathologic analysis and evaluation of fibrosis in 17 cases of idiopathic interstitial pneumonia].

OBJECTIVE: To explore the general principles and the significance of histopathology for idiopathic interstitial pneumonia (IIP) diagnosis; and to investigate the quantitative parameters in evaluation of fibrosis degree of IIP. METHODS: 17 cases of IIP were collected from Peking University 1st Hospital between 2004 and 2009, which had relatively integrated clinical, radiological and pathological materials. Combining clinical and radiological characteristics, histological manifestations and fibrosis degree were analyzed according to American Thoracic Society/European Respiratory Society (ATS/ERS) international consensus classification. Immunohistochemical staining for CD34 and SMA were performed and the correlation between their expressive extent and fibrosis degree were analyzed. RESULTS: 17 cases of IIP were diagnosed by clinical-radiological-pathological comprehensive analysis, which included 9 cases of usual interstitial pneumonia, 5 cases of cryptogenic organizing pneumonia and 3 cases of nonspecific interstitial pneumonia; SMA expression showed positive correlation with degree of fibrosis (r=0.928, P=0.01), and CD34 expression showed negative correlation with degree of fibrosis (r=-0.606, P=0.01). CONCLUSION: Histopathology plays an important role in the diagnosis and classification of IIP. By combining histopathologic pattern, clinical and radiological features, a definite type of IIP can be confirmed. Proper and sufficient biopsy specimens are the premise of right diagnosis.CD34 and SMA immunohistochemical staining can be used in routine practice to evaluate the fibrosis degree of IIP.

[Clinical pathologic classification of idiopathic interstitial pneumonia: review and perspectives]. / Classification anatomo-clinique des pneumopathies interstitielles diffuses idiopathiques: synthèse et perspectives.

The international classification of idiopathic interstitial pneumonia published in 2002 includes seven clinical-pathologic entities distinguished by their clinical features, aspect on high-resolution computed tomography, and histopathologic findings on lung biopsy. These seven entities are idiopathic pulmonary fibrosis (with features typical of interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organising pneumonia, respiratory bronchiolitis with interstitial lung disease, desquamative interstitial pneumonia, lymphocytic interstitial pneumonia, and acute idiopathic interstitial pneumonia (with features of diffuse alveolar damage). This classification provides clearer diagnostic criteria for each entity, has fostered clinical research and therapeutic trials, and forms the basis for international guidelines on patient care. The classification is currently being revised in order to better integrate the recently identified syndrome of combined pulmonary fibrosis and emphysema, acute exacerbations of fibrosis, and new pathophysiologic and genetic findings.

[Histopathological classification of idiopathic interstitial pneumonias]. / Histopatologická klasifikace idiopatických intersticiálních pneumonií.

The classification scheme of interstitial lung diseases has undergone numerous revisions. The criteria for distinguishing seven distinct subtypes of idiopathic interstitial pneumonias are now well defined by consensus in the recently published ATS/ERS classification of these lung diseases. In our present review the histological patterns of the different types are described and the differential diagnosis of idiopathic interstitial pneumonias is discussed. Surgical lung biopsy remains the gold standard for the diagnosis of interstitial pneumonias, and sampling from at least 2 sites is recommended. Video-assisted thoracoscopic surgical biopsy is the preferred method for obtaining lung tissue as this procedure offers a similar yield as an open thoracotomy The most common histological subtype of chronic interstitial lung disease is the usual interstitial pneumonia [UIP] which makes up 47-71% of cases. The key histologic features include patchy subpleural and paraseptal distribution of remodeling lung architecture with dense fibrosis, frequent honeycombing, and large fibroblastic foci. Temporal and spatial heterogeneity are the hallmarks. Nonspecific interstitial pneumonia [NSIP] occurs primarily in middle-aged women who have never smoked, with more than 5-years survival rate in 80% of patients. The major feature of NSIP is a uniform interstitial thickening of alveolar septa by a fibrosing or cellular process. The cardinal histological feature in respiratory bronchiolitis and desquamative pneumonia is an excess of intraalveolar histiocytes. In both patterns, there is variable interstitial fibrosis and chronic inflammation, and a strong association with a history of smoking. Organizing pneumonia (idiopathic bronchiolitis obliterans-organizing pneumonia [BOOP]) is not strictly an interstitial process, because the alveoli and bronchioles are filled by intraluminal polyps of fibroblastic tissue and the expansion of the interstitium is mild. Lymphocytic interstitial pneumonia [LIP] is currently viewed as a pattern of diffuse reactive pulmonary hyperplasia associated in most cases with EB virus, immunosuppression, or a connective tissue disorder. Malignant transformation may rarely occur. A dense mixed interstitial lymphoid infiltrate is a typical histological finding. Diffuse alveolar damage [DAD] from unknown causes is termed acute interstitial pneumonia [AIP], and is synonymous with cases of Hamman-Rich disease. Hyaline membranes in the exsudative phase and marked expansion of the interstitium later are present.

[Idiopathic interstitial pneumonia: classification and diagnostic work-up]. / Les pneumopathies interstitielles diffuses idiopathiques: classification et démarche diagnostique.

Idiopathic interstitial pneumonias represent a group of complex lung diseases among which the most frequent types are idiopathic pulmonary fibrosis (IPF), idiopathic non-specific interstitial pneumonia (idiopathic NSIP), and cryptogenic organizing pneumonia (COP). Clinicians may rely on a precise classification of these diseases from an America-European consensus that has been published in 2002. However it appears that diagnosis should always be confirmed by a multidisciplinary team discussion with experience in the field. There are generally tremendous prognostic and therapeutic implications for the patient.

Pathology of Idiopathic Interstitial Pneumonias.

This review discusses diagnostic pathology in idiopathic interstitial pneumonias (IIPs). Accurate understanding of basic structure of lung lobules is critical because the location of abnormalities inside the lobule is an important effector of pathology diagnosis. Depending on the method of obtaining tissue, recognition of the location may be difficult or impossible. Cryobiopsy is a new technology and its coverage of lung lobules is limited. This article discusses fundamental anatomy and approach to interstitial pneumonia. In addition, most histologic types of IIPs are covered, but the focus is on diagnosis of usual interstitial pneumonia because of its clinical importance.

The significance of multidisciplinary classifications based on transbronchial pathology in possible idiopathic interstitial pneumonias.

Surgical lung biopsy is regarded as the golden standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). Here, we attempted to show the diagnostic accuracy of multidisciplinary classifications based on transbronchial pathology including transbronchial lung cryobiopsy (TBLC) , bronchoalveolar lavage fluid (BALF) and endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA).Patients with suspected interstitial lung diseases admitted from June 1, 2016 to December 31, 2018 were involved. Patients with known causes of interstitial lung diseases and typical idiopathic pulmonary fibrosis diagnosed through clinical, radiological information were excluded. Patients with atypical idiopathic pulmonary fibrosis and possible IIPs accepted transbronchial pathological evaluation. Initial multidisciplinary diagnosis (MDD) classifications were made depending on clinical, radiological and transbronchial pathological information by a multidisciplinary team (MDT). The final MDD classifications were confirmed by subsequent therapeutic effects. All patients were followed up for at least 6 months.A total of 70 patients were finally involved. The samples of lung parenchyma extracted through TBLC were enough for confirmation of pathological diagnoses in 68.6% (48/70) cases. Samples of 6 cases were extracted by EBUS-TBNA. Bacteriological diagnoses were positive in 1 case by BALF. Pathological diagnoses of 77.1% (54/70) cases were achieved through TBLC, EBUS-TBNA and BALF. During the follow up study, the pulmonary lesions of 60% patients were improved, 11.43% were relapsed when glucocorticoid was reduced to small dose or withdrawal, 14.29% were leveled off and 8.57% were progressed. The diagnoses of 4 patients with progressed clinical feature were revised. As a result, 94.3% initial MDD classifications based on transbronchial pathology were consistent with the final MDD, and the difference of diagnostic yield wasn't significant between initial and final MDD (Z = -1.414, P = .157).Classifications of IIPs based on transbronchial pathology were useful and quite agreed with final MDD.

Beyond a consensus classification for idiopathic interstitial pneumonias: progress and controversies.

Histopathological classification schemes provide the underpinnings for separating idiopathic interstitial pneumonias into clinically meaningful groups. An interdisciplinary classification system based on a combination of evidence and expert opinion was published in 2002 and set the stage for controversy in several areas, including not only nomenclature but also the role of surgical lung biopsy and pathologists in diagnosis. We provide a brief overview of the clinical and histological features of the idiopathic interstitial pneumonias, and focus on selected topics of interest that have emerged in recent years.

[Interstitial lung diseases]. / Interstitielle Lungenkrankheiten.

Interstitial lung diseases comprise a heterogeneous group of about 200 entities. In the classification of these diseases, diffuse parenchymal lung diseases with known cause, granulomatous diseases, and other specific interstitial lung diseases are separated from the important group of idiopathic interstitial pneumonias, which are classified according to the 2002 ATS/ERS consensus classification. Concerning the histological pattern, this classification differentiates between "usual interstitial pneumonia" (UIP), "nonspecific interstitial pneumonia" (NSIP), "organising pneumonia" (COP), "diffuse alveolar damage" (DAD), "respiratory bronchiolitis" (RB), "desquamative interstitial pneumonia" (DIP), "lymphocytic interstitial pneumonia" (LIP) and "unclassifiable interstitial pneumonias". A key message of this classification is that the pathologist will give the diagnosis of a histological pattern, whereas the final clinicopathologic diagnosis can be made only by the clinical pulmonologist after careful correlation with the clinical and radiologic features, which is essential in the diagnosis of interstitial lung diseases.