A G Nicholson

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

BACKGROUNDnIn 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.nnnPURPOSEnThe objective of this statement is to update the 2002 ATS/ERS classification of IIPs.nnnMETHODSnAn international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011.nnnRESULTSnSubstantial 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.nnnCONCLUSIONSnThis update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.

Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis.

Aims and methods:u2002 Pulmonary parenchymal disease is common in patients with connective tissue disorders (CTDs). However, most reports precede recognition of non‐specific interstitial pneumonia (NSIP). We have therefore reviewed 54 lung biopsies from 37 patients with polymyositis/dermatomyositis (PM/DM) (nu2003=u200313), Sjögrens syndrome (nu2003=u20035), rheumatoid arthritis (nu2003=u200317) and systemic lupus erythematosus (SLE) (nu2003=u20032) to assess the overall and relative frequencies of patterns of interstitial pneumonia and their impact on prognosis.

Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease

BACKGROUND Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare form of interstitial lung disease which may present in similar fashion to other types of chronic interstitial pneumonia. The purpose of this study was to undertake a clinicopathological review of 10 patients with RBILD and to examine the clinical and imaging data related to its histopathological pattern, in particular the relationship of RBILD to smoking. METHODS Thirteen out of 168 retrospectively reviewed patients, from whom biopsy specimens were taken for suspected diffuse lung disease, were identified with a histopathological pattern of RBILD. Three cases were rejected as follow up data were unavailable. The 10 remaining cases constituted the study group and both clinical and imaging data were collected from patients’ notes and referring physicians. RESULTS Histopathologically, four cases of RBILD overlapped with the pattern of desquamative interstitial pneumonitis (DIP) and nine also had microscopic evidence of centrilobular emphysema. Nine patients were smokers, ranging from 3 to 80 pack years. The one non-smoker had an occupational exposure to the fumes of solder flux. The sex distribution was equal with an age range of 32–65 years. Two patients were clubbed. Lung function tests showed both restrictive and obstructive patterns together with severe reductions in carbon monoxide transfer factor in seven patients. Chest radiographs showed reticular or reticulonodular infiltrates in five patients and a ground glass pattern in two. CT scans were consistent with either DIP or RBILD in six of eight patients. Although seven patients remained stable or improved, either with or without treatment, three patients deteriorated. CONCLUSIONS This study adds weight to the hypothesis that smoking can cause clinically significant interstitial lung disease, with deterioration in pulmonary function despite treatment. Given the overlapping histopathological patterns of RBILD and DIP and their strong association with smoking, the term “smoking related interstitial lung disease” is suggested for those patients who are smokers.

Reactive pulmonary lymphoid disorders

The two main reactive pulmonary lymphoid disorders are lymphoid interstitial pneumonia and follicular bronchitis/bronchiolitis, both pathological entities with a variety of aetiologies. We reviewed the morphological and immunohistochemical features of 26 cases with one or other of these two diagnoses, to explore the possibility that they represented overlapping patterns of hyperpiasia of the bronchopulmonary immune system. The polymerase chain reaction was used to determine the clonality of the infiltrates. Histologically, there was a spectrum of changes with two main components. An interstitial infiltrate of mainly T lymphocytes, plasma cells and histiocytes predominated in lymphoid interstitial pneumonia, whilst lymphoid follicles predominated around airways in follicular bronchitis/bronchiolitis. Classification of the disorder rested on which component the pathologists believed to be dominant. In two cases, histology and immunohistochemistry suggested lymphoma, and in one of these cases this diagnosis was confirmed by the polymerase chain reaction. One case of lymphoid interstitial pneumonia produced three bands. The remainder produced polyclonal patterns when samples were adequate. Clinically, there was no clear difference between patients with the two disorders, or patients with pathological features of both.

Desquamative interstitial pneumonia, respiratory bronchiolitis and their relationship to smoking

Aims :u2002Respiratory bronchiolitis (RB) and desquamative interstitial pneumonia (DIP) are closely associated histological patterns of interstitial pneumonia, although there are no studies on the extent of individual histological parameters. Furthermore, the term smoking related‐interstitial lung disease (SR‐ILD) has been proposed as a term to encompass patients with both these histological patterns who give a history of smoking, though it is not well defined how this term relates to historical cases of DIP. The aim of this study was to compare histological parameters in cases of DIP and RB and then to review in detail clinical, imaging and histological data for DIP in relation to a history of smoking.

BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1u2005yr, even after adjustment for disease severity, smoking andtreatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.

The value of classifying interstitial pneumonitis in childhood according to defined histological patterns

Aims: Interstitial pneumonitis in children is very rare and most cases have been classified according to their counterparts in adults, although the term ‘chronic pneumonitis of infancy’ has recently been proposed for a particular pattern of interstitial lung disease in infants. We reviewed our paediatric cases of interstitial pneumonitis, first, to look at the spectrum of histological patterns found in this age group and, second, to determine whether the classification of such cases in childhood is both appropriate and worthwhile.

Primary epithelioid angiosarcoma of the lung presenting as pulmonary hemorrhage

Pulmonary angiosarcomas are usually secondary tumors, and only a few primary cases have been described. We report a unique case of epithelioid angiosarcoma arising in the lungs as a bilateral multinodular infiltrate and presenting as pulmonary hemorrhage. Because of its epithelioid histology, this tumor may resemble a carcinoma, also staining positively for keratin markers. Therefore, unless the diagnosis of epithelioid angiosarcoma is considered and endothelial markers used, the diagnosis of epithelioid angiosarcoma may be overlooked at this site.

What is this thing called CFA

The term “cryptogenic fibrosing alveolitis”should now be used as strictly synonymous with “idiopathic pulmonary fibrosis”nnArcane diagnostic labels bother clinicians. The diffuse lung disease lexicon is a notorious example. For decades, “diffuse lung disease speak” consisted of an unholy mix of histopathological and clinical terms, varying between countries, within countries and even between medical teams in the same hospital. Radical change was required and proposals were advanced in a joint American Thoracic Society and European Respiratory Society (ATS/ERS) initiative. Terminology for idiopathic interstitial pneumonia was distilled by a core group of clinicians, radiologists and pathologists, and this was then circulated to a larger group of international reviewers and published in 2002.1 The final consensus classification was not, at first sight, straightforward to apply. Indeed, the amorphous entity of “non-specific interstitial pneumonia” (NSIP) continues to vex clinicians and requires further subclassification. However, teething problems aside, the ATS/ERS initiative has been an outstanding success. Clinicians and researchers worldwide now understand each other better than before. The recent move towards large multicentre treatment studies in idiopathic pulmonary fibrosis (IPF), itself a revolution in slow motion, was made possible, in no small part, by this standardisation of terminology and disease definitions.nnAs the terminology has changed, the article by Rudd et al 2 in the current issue of Thorax (see p 67) is likely to pose difficulties for some non-UK readers. The authors have studied “cryptogenic fibrosing alveolitis” (CFA) as a clinical presentation, as used historically in the UK. The diagnostic criteria, consisting of compatible radiographic, pulmonary function and clinical findings, in the absence of an overt environmental or autoimmune cause, are highly non-specific: compatible, also, with idiopathic interstitial pneumonias other than IPF and a subgroup of patients with hypersensitivity pneumonitis. By contrast, in the ATS/ERS classification,1,3 CFA is explicitly …

Lesson of the month

A 73-year-old woman presented with anaemia, lethargy, weight loss and the passage of altered blood per rectum. Barium enema showed a neoplasm in the caecum and a right hemicolectomy was performed. On opening the intestine a 40 · 30 mm polypoid tumour with an ulcerated surface was present in the caecum. The rest of the colonic mucosa was unremarkable except for the presence of two small polyps. Histology showed a cellular tumour with an ulcerated surface involving the full thickness of the wall of the caecum and extending into the surrounding adipose tissue. There was no evidence of glandular differentiation or any other specific pattern; tumour cells were arranged diffusely (Figure 1). Tumour cells were mainly mononuclear but occasional multinucleate forms were present. Tumour cells had hyperchromatic nuclei with coarse clumped chromatin reminiscent of the clock-face chromatin pattern characteristic of plasma cells (Figure 2) and there was a high mitotic rate with numerous atypical mitotic figures. There was no evidence of nodal involvement by tumour, and examination of the rest of the specimen showed two small tubulovillous adenomas within the appendix and the ascending colon. A wide range of immunohistochemical studies was performed. Tumour cells were negative with the cytokeratin epithelial markers AE1 ⁄ AE3 and CAM 5.2 and with monoclonal CEA. There was no staining with CD45 (LCA), CD20, CD79A, CD3 and CD5. Other immunohistochemical markers which were negative included S100 protein, HMB45, chromogranin A, Tdt and cyclin D1. There was diffuse cytoplasmic positivity with VS38 (Figure 3a) and CD56 (Figure 3b) and focal staining with CD10. Given the morphology of