Classification Of Idiopathic Interstitial Pneumonias Research Articles

Pleuroparenchymal Fibroelastosis: Case Study

Pleuroparenchymal fibroelastosis is a rare and recently recognized condition, first described by Amitani et al. in the 1990s as fibrosis of the upper lobes and later recognized as a new clinicopathological entity by Frankel. In 2013, idiopathic pleuroparenchymal fibroelastosis was classified as a rare subtype in the international classification of idiopathic interstitial pneumonias. The disease can occur at any age, and the diagnosis issuspected in a patient with dyspnea and radiological presentation, characterized by fibrosis of the upper lobe of the pleural and subpleural pulmonary parenchyma. A definitive diagnosis is histopathological, characterized by dense intra-alveolar fibrosis with elastosis of the alveolar walls and fibrous thickening of the subpleural pleura, predominantly in the upper lobes. The disease progresses, with a poor prognosis, and currently, the only therapeutic option is lung transplantation. We describe a rare case of pleuroparenchymal fibroelastosisdiagnosed radiologically in an 83-year-old man

Cluster analysis-based clinical phenotypes of idiopathic interstitial pneumonias: associations with acute exacerbation and overall survival

BackgroundThe precise classification of idiopathic interstitial pneumonia (IIP) is essential for selecting treatment as well as estimating clinical outcomes; however, this is sometimes difficult in clinical practice. Therefore, cluster analysis was used to identify the clinical phenotypes of IIPs, and its usefulness for predicting clinical outcomes was evaluated.MethodsCluster analysis was performed using clinical features including patients’ demographics; histories; pulmonary function test data; and laboratory, physical and radiological findings.ResultsIn 337 patients with IIPs, four clusters were identified: Cluster I, in which > 80% of the patients had autoimmune features; Cluster II, which had the lowest rate of smoking, the lowest percent predicted forced vital capacity (%FVC) and the lowest body mass index (BMI); Cluster III, which had the highest rate of smoking, the highest rate of dust exposure, the second lowest %FVC and normal BMI; and Cluster IV, which exhibited maintenance of %FVC and normal BMI. Cluster IV had significantly longer overall survival than Clusters II and III. Clusters I and III had significantly longer overall survival than Cluster II. Clusters II and III had a significantly higher cumulative incidence of acute exacerbation than Cluster IV.ConclusionCluster analysis using clinical features identified four clinical phenotypes of IIPs, which may be useful for predicting the risk of acute exacerbation and overall survival.

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.

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. 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. 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). Broad airspace consolidation is a characteristic of previously diagnosed CTD-NSIP excluded from the current classification of IIPs.

Discusión multidisciplinaria para el diagnóstico de la fibrosis pulmonar idiopática

Prior to the publication of the 2002 ATS / ERS classification of idiopathic interstitial pneumonias (IIP), the histopathological evaluation was considered the gold standard for the diagnosis of interstitial lung diseases (ILD). However, several subsequent studies showed that interobserver concordances between expert lung pathologists were surprisingly poor, since histopathological appearances may overlap between different entities. Therefore, a new diagnostic system that serves as a gold standard in patients with ILD became necessary. This is how the concept of multidisciplinary discussion was born, to refer to a meeting that allows the integration of all the clinical, radiological and pathological data available for an individual patient and thus be able to determine a working diagnosis.

Update on Rare Idiopathic Interstitial Pneumonias and Rare Histologic Patterns.

- In 2013, the revised American Thoracic Society and European Respiratory Society classification of idiopathic interstitial pneumonias (IIPs) described 2 rare IIPs and 2 rare histologic patterns. Because of the rarity of the disease, there is limited evidence related to the histology. Because the rare histologic patterns are provisional criteria, no unanimous consensus on histologic diagnostic criteria has yet been reached. - To review the histologic features for rare IIPs and rare histologic patterns, and to provide diagnostic aids and discuss the differential diagnosis. - Published peer-reviewed literature and the authors' personal experience. - Following the publication of the international consensus classification, evidence regarding rare IIPs and rare histologic patterns has accumulated to some extent, although to date the amount remains insufficient and further evidence is required. Because the diagnosis is sometimes challenging, a multidisciplinary approach represents the gold standard in reaching an accurate diagnosis for these rare disorders.

Lung histopathology of non-infectious pulmonary complications after allogeneic haematopoietic stem cell transplantation.

Non-infectious pulmonary complications (NIPCs) occur frequently following allogeneic haematopoietic stem cell transplantation (HSCT). As there is no consensus on the description of the related pulmonary pathological lesions, pathologist reports and clinical conclusions are largely inconsistent in routine practice. The aim of our study was to provide an accurate overview of post-allogeneic HSCT NIPCs from a large number of lung biopsies. We reviewed 61 lung biopsies in patients with an NIPC, including 51 surgical lung biopsies, four post-mortem biopsies and six lung explants. We found both bronchiolar (n = 59) and alveolar/interstitial pathologies (n = 27). We describe two types of bronchiolar lesions: bronchiolectasies (n = 37) and fibrous and cellular lesions with luminal narrowing (n = 43). We found a wide spectrum of airway/interstitial pathologies that were labelled using the terminology of the 2013 American Thoracic Society and European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs), including the following: organising pneumonia (OP, n = 8), non-specific interstitial pneumonia (NSIP, n = 9), diffuse alveolar damage (DAD, n = 6), lymphoid interstitial pneumonia (LIP, n = 1) and pleuroparenchymal fibroelastosis (PPFE, n = 2), as well as one instance of associated PPFE and NSIP. Interstitial pathology was associated with bronchiolar lesions in 41% of the cases reviewed (n = 25). Lung airway and interstitial inflammation was still present in lung explants from patients who underwent lung transplantation for post-allogeneic HSCT end-stage respiratory insufficiency. Herein, we describe a wide spectrum of pathological lung lesions encountered in post-allogeneic HSCT NIPCs.

Pleuroparenchymal Fibroelastosis: A Review of Histopathologic Features and the Relationship Between Histologic Parameters and Survival.

Pleuroparenchymal fibroelastosis (PPFE) is now a defined clinicopathologic entity in the updated 2013 ATS/ERS classification of idiopathic interstitial pneumonias (IIPs), which has led to a significant increase in cases being diagnosed at our institution. We have therefore reviewed 43 PPFE cases (58 biopsies in total) to assess whether any clinical or histopathologic features provide prognostic information. A semiquantatitive grading system was used to assess extent of fibroblastic foci, intra-alveolar fibroelastosis, visceral pleural fibrosis, chronic inflammation in areas of fibrosis, vascular fibrointimal thickening, and presence of granulomas. Other patterns of interstitial lung disease were also noted, if present. All biopsies showed intra-alveolar fibroelastosis, fibroblastic foci at the leading edge of fibrosis and chronic inflammation within areas of fibrosis, 91% showed vascular fibrointimal thickening of vessels, 73% showed pleural fibrosis, and 35% showed granulomas. Ten cases showed a coexistent IIP (5 showed usual interstitial pneumonia, 5 showed features of hypersensitivity pneumonitis). There was no significant correlation with mortality and severity of histologic parameters, other than a significant decrease in mortality in PPFE with coexistent granulomas, after adjusting for age and gender (hazard ratio, 0.27; P=0.049). Male gender was also associated with an increased risk of mortality, after adjusting for age (hazard ratio, 4.8; P=0.045). PPFE is more common than previously thought, not infrequently showing coexistent pathology, specifically usual interstitial pneumonia and granulomatous lung disease, our data suggesting the latter may have prognostic significance.

Histological variability and consequences in chronic bird-related hypersensitivity pneumonitis.

Lobar and temporal histological variability in chronic bird-related hypersensitivity pneumonitis (BRHP) has not been clearly elucidated. This study was designed to evaluate the spatio-temporal histopathological variability in chronic BRHP. Fifty-two patients with chronic BRHP who underwent a surgical lung biopsy (SLB) between 1992 and 2008 were evaluated. The histopathological characteristics of the lung biopsy specimens were classified by the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS) consensus classification of idiopathic interstitial pneumonias (IIPs). Autopsy specimens from seven patients were also evaluated to examine the serial changes from SLB to autopsy. In a study of lobar histological variability based on the findings of SLB, 7 patients were diagnosed with cellular nonspecific interstitial pneumonia (NSIP) pattern, 16 with fibrotic NSIP pattern, 20 with fibrotic NSIP pattern and usual interstitial pneumonia (UIP) (discordant UIP) pattern and 9 with UIP (concordant UIP) pattern. In a study of sequential changes, specimens of SLBs with fibrotic NSIP pattern changed to a bronchiolocentric interstitial pneumonia (BIP) pattern or UIP pattern. Interlobar and intralobar histological variability is present in chronic BRHP. In several patients with chronic BRHP, a fibrotic NSIP pattern may be an early lesion that progresses to a UIP pattern.

Diagnostic clues of organizing pneumonia: a case presentation.

Cryptogenic organizing pneumonia (COP) is currently an established clinicopathologic entity, expression of reparative reactions to acute lung injury and the resulting inflammation within the alveoli and distal bronchioles. COP continues to be included in the classification of IIP (Idiopathic Interstitial Pneumonias) because of its idiopathic nature and to date in the last European Respiratory Society (ERS)/American Thoracic Society (ATS) update statement of IIP and according to acute or subacute presentation, is included in section “acute or subacute IIPs” (1). In 1983 Davison was the first to describe this disease, subsequently Epler called this entity “bronchiolitis obliterans with organizing pneumonia” (BOOP) (2,3). HRCT often demonstrates patchy migratory areas of consolidations predominantly with a subpleural, peribronchial distribution. Sometimes HRCT pattern is characterized by “band-like pattern commonly associated to ground glass opacities (GGO). Perilobular opacities and a typical HRCT sign called reverse halo sign or “atoll sign” may be extremely useful for clinic-radiological diagnosis. Slight pleural effusion is also described in literature in few cases (4). We describe a case of COP presenting as fever, productive cough and dyspnea persisting for 4 months, in which the role of CT-PET has been an element of considerable confounding in the therapeutic management and in which a radiological revaluation of the temporal behavior of the disease has allowed us to correctly achieve the diagnosis of organizing pneumonia (OP).

Idiopathic Lung Diseases Other than Pulmonary Fibrosis

Idiopathic lung diseases are diffuse parenchymal lung diseases that are grouped under the term interstitial lung disease (ILD). The term interstitial (or interstitium) is, however, misleading as the term interstitium refers to the microscopic anatomic space between the basement membranes of the endothelial and epithelial cells. The pathologic processes involved in these diseases, however, are not limited to the interstitium and can affect other elements of the gas exchange units as well as bronchiolar lumen, terminal bronchioles, pulmonary parenchyma, and pleural and vascular spaces. Since there are potentially hundreds of agents and clinical situations that are associated with ILD, a simplified grouping scheme includes seven main entities: ILD associated with (1) occupational and environmental factors (inhalation cause), (2) collagen vascular diseases, (3) granulomatous lung disease of known and unknown causes (eg, hypersensitivity pneumonitis [HP], sarcoidosis), (4) inherited diseases, (5) iatrogenic/drug induced, (6) certain specific entities (eg, pulmonary Langerhans cell histiocytosis [PLCH], lymphangioleimyomatosis, and (7) idiopathic interstitial pneumonia (IIP). As idiopathic pulmonary fibrosis (IPF) is a subgroup of IIP, this review focuses on the clinical features and management of the major IIPs, and IPF is discussed more in the review, “Idiopathic Pulmonary Fibrosis,” found elsewhere in this publication. This review also focuses on HP as it is a key disease in the differential diagnosis of the IIPs. Figures depict chest radiographs, high resolution computed topography (HRCT) scans, and histopathologic features of various ILDs. Tables list the American Thoracic Society (ATS) and the European Respiratory Society (ERS) classification of IIPs, and common antigens associated with HP and their potential sources. This review contains 22 highly rendered figures, 2 tables, and 156 references.

Idiopathic Lung Diseases Other than Pulmonary Fibrosis

Idiopathic lung diseases are diffuse parenchymal lung diseases that are grouped under the term interstitial lung disease (ILD). The term interstitial (or interstitium) is, however, misleading as the term interstitium refers to the microscopic anatomic space between the basement membranes of the endothelial and epithelial cells. The pathologic processes involved in these diseases, however, are not limited to the interstitium and can affect other elements of the gas exchange units as well as bronchiolar lumen, terminal bronchioles, pulmonary parenchyma, and pleural and vascular spaces. Since there are potentially hundreds of agents and clinical situations that are associated with ILD, a simplified grouping scheme includes seven main entities: ILD associated with (1) occupational and environmental factors (inhalation cause), (2) collagen vascular diseases, (3) granulomatous lung disease of known and unknown causes (eg, hypersensitivity pneumonitis [HP], sarcoidosis), (4) inherited diseases, (5) iatrogenic/drug induced, (6) certain specific entities (eg, pulmonary Langerhans cell histiocytosis [PLCH], lymphangioleimyomatosis, and (7) idiopathic interstitial pneumonia (IIP). As idiopathic pulmonary fibrosis (IPF) is a subgroup of IIP, this review focuses on the clinical features and management of the major IIPs, and IPF is discussed more in the review, “Idiopathic Pulmonary Fibrosis,” found elsewhere in this publication. This review also focuses on HP as it is a key disease in the differential diagnosis of the IIPs. Figures depict chest radiographs, high resolution computed topography (HRCT) scans, and histopathologic features of various ILDs. Tables list the American Thoracic Society (ATS) and the European Respiratory Society (ERS) classification of IIPs, and common antigens associated with HP and their potential sources. This review contains 22 highly rendered figures, 2 tables, and 156 references.

Pathology of Idiopathic Interstitial Pneumonias.

The updated classification of idiopathic interstitial pneumonias (IIPs) in 2013 by American Thoracic Society/European Respiratory Society included several important revisions to the categories described in the 2002 classification. In the updated classification, lymphoid interstitial pneumonia (LIP) was moved from major to rare IIPs, pleuroparenchymal fibroelastosis (PPFE) was newly included in the rare IIPs, acute fibrinous and organizing pneumonia (AFOP) and interstitial pneumonias with a bronchiolocentric distribution are recognized as rare histologic patterns, and unclassifiable IIP (UCIP) was classified as an IIP. However, recent reports indicate the areas of concern that may require further evaluation. Here, we describe the histopathologic features of the updated IIPs and their rare histologic patterns and also point out some of the issues to be considered in this context.

Rare idiopathic intestinal pneumonias (IIPs) and histologic patterns in new ATS/ERS multidisciplinary classification of the IIPs

The new American Thoracic Society/European Respiratory Society (ATS/ERS) update to the multidisciplinary classification of idiopathic interstitial pneumonias (IIPs) defines both rare IIPs and rare histologic patterns of IIPs. Although these diseases are rare, each has some distinguishing imaging and pathologic characteristics. Common findings for IIPs in computed tomography (CT) include cysts in lymphoid interstitial pneumonia (LIP), upper lobe subpleural consolidation in pleuropulmonary fibroelastosis (PPFE), symmetrical consolidation in acute fibrinous organizing pneumonia (AFOP), and peribronchovascular consolidation or centrilobular nodules in bronchiolocentric pattern of interstitial pneumonia.

Current classification of interstitial pulmonary diseases

The consensus classification of idiopathic interstitial pneumonia (IIP, also known as pulmonary fibrosis) in 2002 has undergone a significant revision in 2013. What are the key points of the new consensus statement of the American Thoracic Society (ATS)/European Respiratory Society (ERS) from 2013 for the classification of pulmonary fibrosis? Evaluation of the available literature on the subject of pulmonary fibrosis in Pubmed. The interdisciplinary approach (i.e. pulmonology, radiology and pathology) for the diagnosis of lung fibrosis subtypes is highlighted. Nonspecific interstitial pneumonia (NSIP) is now a separate specific form of pulmonary fibrosis. Smoking-associated respiratory bronchiolitis with interstitial lung disease (RB-ILD) is now frequently diagnosed without a lung biopsy on the basis of clinical findings, computed tomography and bronchoalveolar lavage. The heterogeneous course of idiopathic pulmonary fibrosis (IPF) is now recognized. The term "acute exacerbation" will now be used for acute attacks (< 30 days) in patients with chronic lung fibrosis (IPF and NSIP). It has been recognized that it is necessary to provide a clinical classification algorithm for the management of IIP cases. Pleuroparenchymal fibroelastosis (PPFE) is recognized as a rare new entity of pulmonary fibrosis. The rapidly evolving field of molecular markers is promising for improving the diagnostic approach. The 2013 ATS/ERS update is a supplement to the previous classification of lung fibrosis from 2002. It outlines progress in recent years and shows potential areas for future innovations.

Pleuroparenchymal fibroelastosis as a late complication of chemotherapy agents

To the Editor: We identified six patients with clinical, radiographic and physiological features typical of pleuroparenchymal fibroelastosis (PPFE). In the six cases, PPFE may have been causally related to prior alkylating drugs used to treat malignacy, namely cyclophosphamide in five of the cases and carmustine (BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea)) in one. Based on an extensive review of the literature, we suspect that similar cases may have already been reported in the past 4 decades but have not been recognised either as PPFE or as drug-induced in nature. In 2004, Frankel et al. [1] described a then-new clinicopathologic entity, which they termed “idiopathic PPFE”. The authors identified five patients who had a clinical presentation suggestive of chronic interstitial pneumonitis that did not fit any previously established category of idiopathic interstitial pneumonia. The patients were characterised by significant pleural involvement in the form of pleural thickening, which was more marked in both upper regions. In all five patients, surgical biopsy demonstrated prominent visceral pleural fibrosis with subpleural fibroelastosis and an abrupt transition between the fibrotic area and the near-normal adjoining lung. There was sparing of the underlying lung parenchyma at some depth from the pleural surface, and sparse fibroblast foci were present at the edge of the fibrotic area. Since that seminal report, several cases and small series have been reported that have demonstrated a strikingly similar clinical, radiological and pathological presentation, also characterised by difficult-to-treat pneumothoraces in a sizable fraction of affected patients. In the updated American Thoracic Society/European Respiratory Society classification of idiopathic interstitial pneumonias [2], PPFE is included as a separate but well-defined category of rare entities. Little is known about the aetiology of PPFE and …

Interstitial lung disease

Interstitial lung diseases are a group of diffuse parenchymal lung disorders associated with substantial morbidity and mortality. Knowledge achieved in recent years has resulted in the publication of the new classification of idiopathic interstitial pneumonias, according to which there are three groups: major, rare and unclassified. The novelty of the new classification comes from the fact that difficult to classify entities can be treated according to the disease behaviour classification. Idiopathic pulmonary fibrosis is the most lethal amongst the interstitial lung diseases and presents high heterogeneity in clinical behaviour. A number of biomarkers have been proposed in order to predict the course of the disease and group patients with the same characteristics in clinical trials. Early diagnosis and disease stratification is also important in the field of other interstitial lung diseases.

Update on idiopathic interstitial pneumonias

The idiopathic interstitial pneumonias (IIPs) comprise a major portion of diffuse infiltrative (interstitial) lung diseases. The classification of IIPs was initially conceived 4 decades ago and has undergone revisions over the intervening years with the most recent version published in 2013. Current classification distinguishes “major” forms of IIPs(idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, respiratory-bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, cryptogenic organizing pneumonia, and acute interstitial pneumonia) from “rare” forms (idiopathic lymphoid interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis). In addition, the category of “unclassifiable” IIP is introduced in recognition of IIP cases that remain difficult to classify even with the current scheme. This review describes the historical background for IIPs, current perspectives, and summarizes the clinical-pathologic entities included in the current classification scheme.

Reproducibility of the ATS/ERS classification of idiopathic interstitial pneumonias

Histopathological diagnosis of interstitial pneumonia (IP) requires experiences and is often challenging for general surgical pathologists. In its context, accurate recognition of histopathological usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) patterns along with separation of idiopathic IPs from ones associated with hypersensitivity pneumonia and systemic connective tissue disease are the critical points. Several reports had indicated insufficient interobserver agreement of IP diagnosis, and we also have investigated the interobserver agreement of chronic interstitial pneumonia in various conditions showing that reproducibility of pathological judgment of above points was not greatest. To improve the reproducibility of diagnosis, recent publication of IPF guidelines set criteria of pathological UIP. It indeed helps pathologists to evaluate definite UIP pattern and works well for pulmonary pathologists, however, it still have some confusions and difficulties to the general surgical pathologists. In the course, summary of interobserver agreement along with our own data among pulmonary and general pathologists before and after the new guidelines will be shown. I will also share possible causes of confusion with audience and suggest a few tips for the improved histological assessment.

Proposed new classification of idiopathic interstitial pneumonias

This presentation reviews the histopathology of the IIPs since the 2002 ATS/ERS classification of IIPs in the light of the 2013 update. The seven histological patterns proposed in 2002 remain, with diagnostic criteria refined but overall unchanged. A multidisciplinary approach is now established as best practice. NSIP is now recognised as a distinct clinicopathological entity. Respiratory bronchiolitis-interstitial lung disease (RB-ILD) is now commonly diagnosed without the need for surgical biopsy. A diagnostic algorithm has been proposed for the correlation of surgical biopsies with imaging in relation to patients with suspected idiopathic pulmonary fibrosis (IPF). Acute exacerbation of IIPs is now well-defined. Some IIP patients remain hard to classify, often due to overlap of patterns, and a classification based on observed disease behaviour is proposed for such patients. Pleuroparenchymal fibroelastosis is included as a rare but distincty clinincopathological entity. Acute fibrinous organising pneumonia and bronchiolocentric interstitial pneumonia are proposed as histologic patterns that may be of benefit in biopsy classification prior to multidisciplinary review, but are not sufficiently characterized to be recognised as distinct clinical entities.

An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias

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. The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. 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. 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.