Hypersensitivity pneumonia: role of surgical lung biopsy

Lung biopsy often plays a key role in identifying patients with hypersensitivity pneumonia, especially in the absence of a typical history. A 69-year-old woman with a 2-year history of unexplained dyspnea on exertion underwent surgical lung biopsy for diagnosis of diffuse lung disease thought to represent idiopathic pulmonary fibrosis. Her biopsy showed honeycomb change and fibroblast foci suggestive of usual interstitial pneumonia, but also showed areas of cellular interstitial pneumonia with chronic bronchiolitis and a pattern of granulomatous inflammation typical of hypersensitivity pneumonia. The classic features of hypersensitivity pneumonia in surgical lung biopsy are emphasized, including a bronchiolocentric cellular interstitial pneumonia, chronic bronchiolitis, and poorly formed nonnecrotizing granulomas. As illustrated in our patient, sometimes subtle histologic clues are key in separating hypersensitivity pneumonia from usual interstitial pneumonia and other forms of idiopathic interstitial pneumonia. Making the distinction is important given differences in treatment strategies and natural history.     

Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia

Takemura T, Akashi T, Kamiya H, Ikushima S, Ando T, Oritsu M, Sawahata M & Ogura T
(2012) Histopathology
Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia Aims: To evaluate the histological characteristics differentiating chronic hypersensitivity pneumonitis (chronic HP) with a usual interstitial pneumonia (UIP)‐like pattern from idiopathic pulmonary fibrosis (IPF)/UIP. Methods and results: Surgical lung biopsy specimens from 22 patients with chronic HP diagnosed as having a UIP‐like pattern upon histological examination and 13 patients with IPF/UIP were examined and the incidences of bronchiolitis, perilobular fibrosis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, fibroblastic foci, honeycombing, granulomas, giant cells, lymphocytic alveolitis and lymphoid follicles were compared. Bronchiolitis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, granulomas, giant cells and lymphocytic alveolitis were significantly more frequent among patients with chronic HP than among patients with IPF (all P < 0.01). Conclusions: Centrilobular fibrosis, bridging fibrosis and organizing pneumonia, in addition to bronchiolitis, granulomas and giant cells, are characteristic features of chronic HP with a UIP‐like pattern. These features are therefore important in differentiating chronic HP from IPF/UIP, as management strategies differ for the two disorders.     

Iatrogenic pulmonary lesions

Treatment of patients often includes the administration of medications and sometimes radiation. While the intent is to treat an underlying condition, in some cases, adverse effects occur due to these agents. Most of these adverse effects are mild, however, some can be severe and life-threatening. Furthermore, while these effects are often reversible upon cessation of exposure, especially if the inciting agent is recognized and withdrawn early, others might be permanent or even progressing.Most common histopathologic findings in drug-induced interstitial lung disease include nonspecific interstitial pneumonia (cellular and/or fibrotic), organizing pneumonia with or without bronchiolitis, eosinophilic pneumonia, pulmonary edema, diffuse alveolar damage, hypersensitivity pneumonitis, granulomatous interstitial lung disease, chronic bronchiolitis, and pulmonary hemorrhage. Pulmonary vascular changes or constrictive bronchiolitis can also occur. Drugs that are more commonly associated with lung toxicity include nitrofurantoin, amiodarone, and chemotherapeutic agents such as bleomycin and methotrexate. More recently introduced immune modulating agents including rituximab and immune checkpoint inhibitors such as anti-CTLA4, anti-PD-1 and anti-PD-L1 agents have also been associated with adverse effects in the lung.Radiation therapy to the chest can trigger acute or chronic lung toxicity. While newer radiation techniques are aimed to decrease and minimize side effects other risk factors such as additional chemotherapy, oxygen, and older age may be rising.Foreign substances such as talc, hydrogel, and medical devices such as hydrophilic polymer coated catheter may rarely also lead to pulmonary complications.It is important that clinicians and pathologists are aware of these potential adverse effects of drugs, radiation and medical devices and raise the possibility of drug-induced lung toxicity after exclusion of other differential diagnoses. It is the role of the clinician to provide the pathologist with an appropriate drug history. Early intervention to a drug-induced lung toxicity might prevent progression of side effects and permanent changes.     

Histopathological classification of idiopathic interstitial pneumonias

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.     

慢性过敏性肺炎引起弥漫性肺间质纤维化的病理特征

目的 观察慢性过敏性肺炎的病理形态特征,特别是其引起的肺间质纤维化的特点,并比较其与特发性肺间质纤维化的差异和鉴别.方法 选择2000年10月至2008年1月间lO例慢性过敏性肺炎患者活检组织及临床资料,活检肺组织全部取材,石蜡包埋、HE染色.结果 10例慢性过敏性肺炎患者,男性6例、女性4例,年龄23-59岁,平均47.2岁.主要表现为慢性咳嗽,气短等,病程4个月～6年不等.7例表现为普通性问质性肺炎(UIP)样的纤维化,肺组织内斑片状纤维化,病变沿胸膜下、小叶间隔分布,同时又有细支气管周边病变.7例均有纤维母细胞灶,并可见明显的细支气管周边肺泡上皮的细支气管化生和轻度细支气管炎.3例有轻度蜂窝肺.3例为非特异性间质性肺炎(NSIP)样纤维化,表现为肺泡间隔增宽,间质纤维组织和胶原纤维增生,保留肺泡结构.伴中-重细支气管炎,肺泡间隔可见较多淋巴细胞浸润.未见蜂窝肺结构.1例可见Schaumann小体.慢性过敏性肺炎的UIP样的纤维化与特发性UIP相比,除了间质中有松散的肉芽肿和多核巨细胞以外,表现为:(1)发病年龄较轻;(2)慢性过敏性肺炎CT上病变常同时有中、上肺病变,甚至以中、上肺为主,并可见磨玻璃影和马赛克征;(3)二者病变分布不同,特发性UIP的纤维化主要分布在胸膜下和沿小叶周边分布;而慢性过敏性肺炎的UIP样的纤维化常同时累及胸膜下/小叶周边和细支气管周围(小叶中心);(4)慢性过敏性肺炎的UIP样纤维化蜂窝肺相对较轻;(5)常伴有细支气管上皮化生.慢性过敏性肺炎的NSIP样的肺间质纤维化与特发性NSIP相比,除了间质中有松散的肉芽肿和多核巨细胞以外,二者在病理形态上很难区别.结论 慢性过敏性肺炎可以引起UIP样或NSIP样的间质纤维化.按照目前过敏性肺炎的诊断标准,部分表现为NSIP样的肺间质纤维化的慢性过敏性肺炎患者,有可能被误诊为NSIP,值得注意.     

Acute exacerbations of fibrotic interstitial lung disease

Churg A, Wright J L & Tazelaar H D
(2011) Histopathology  58 , 525–530
Acute exacerbations of fibrotic interstitial lung disease An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre‐existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non‐specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high‐dose steroid therapy.     

Ultrastructural evidence of alveolar epithelial injury in idiopathic bronchiolitis obliterans-organizing pneumonia.

The ultrastructural features of idiopathic bronchiolitis obliterans-organizing pneumonia (BOOP) were studied in 9 patients. As expected, the characteristic air space fibrosis was composed of spindled fibroblasts and myofibroblasts arranged concentrically within an electron-lucent stroma. In 6 patients there was evidence of incorporation of air space fibrosis into the interstitium. A surprising finding in all patients was the presence of extensive epithelial damage involving peribronchiolar alveolar septa. Necrosis and sloughing of alveolar lining cells resulted in denuding of epithelial basal laminae. Complex infoldings and deep invaginations of the denuded basal laminae into alveolar septa were common. These ultrastructural changes involving the interstitium are similar to those occurring in the interstitial pneumonias, and suggest that BOOP also results from acute epithelial injury. The different clinical manifestations and prognosis of these entities may relate to the peribronchiolar localization of the epithelial damage in BOOP compared with more diffuse involvement of distal lung in the interstitial pneumonias.     

Interstitial lung diseases

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.     

Bronchiolitis interstitial pneumonitis: a pathologic study of 31 lung biopsies with features intermediate between bronchiolitis obliterans organizing pneumonia and usual interstitial pneumonitis, with clinical correlation

Bronchiolitis combined with interstitial pneumonitis generally has been equated with bronchiolitis obliterans organizing pneumonia (BOOP). We describe our experience with lung biopsies that had both bronchiolar and interstitial diseases. We studied 31 patients who had respiratory difficulty leading to open lung biopsy, which showed a combination of both prominent bronchiolitis and prominent interstitial pneumonitis. We compared these cases clinically and pathologically with 6 other pulmonary diseases, namely, bronchiolitis obliterans, BOOP, nonspecific interstitial pneumonitis, usual interstitial pneumonitis, airway-centered interstitial fibrosis, and idiopathic bronchiolocentric interstitial pneumonia, and with 10 cases of cystic fibrosis, an unrelated disease with both bronchiolar and interstitial pathology. The commonality of our cases was a combination of bronchiolitis and interstitial inflammation and fibrosis but little or no intra-alveolar organizing pneumonia. Bronchiolitis obliterans with organizing pneumonia involved less area than the interstitial pneumonitis in each case. All 19 patients for whom we had follow-up received corticosteroids for their pulmonary diseases. Seven patients had improvement in symptoms and pulmonary function test results and radiographic findings, 5 patients experienced subjective improvement with unchanged results of pulmonary function tests or chest x-ray, 1 patient's condition was unchanged, 6 patients' disease worsened, and 4 of these 6 died. The natural history of these cases, which we have designated bronchiolitis interstitial pneumonitis, seems more sanguine than usual interstitial pneumonitis and worse than BOOP at least in the short term. On the one hand, response to corticosteroids was not as frequent as generally accepted for BOOP. On the other hand, disease did not progress in most patients on corticosteroids.     

Nonspecific interstitial pneumonia: pathologic features and clinical implications

Nonspecific interstitial pneumonia (NSIP) is a form of chronic interstitial pneumonia that should be separated from the other idiopathic interstitial pneumonias, including most importantly, usual interstitial pneumonia (UIP). Diagnosis is predicated on identification of characteristic findings in a surgical lung biopsy in the appropriate clinical and radiological context. Affected patients may have a variety of underlying or associated conditions, although most have a form of idiopathic lung disease associated with a more favorable prognosis than UIP/idiopathic pulmonary fibrosis (IPF). Keys to distinguishing NSIP from UIP include absence of heterogeneous lung involvement, architectural distortion in the form of fibrotic scarring and/or honeycomb change, and fibroblast foci in NSIP.     

Acute fibrinous and organizing pneumonia in systemic lupus erythematosus: a case report and review of the literature

Pulmonary manifestations of systemic lupus erythematosus (SLE) typically include pleuritis, alveolar hemorrhage, and infectious pneumonia due to immunosuppression with less common entities including bronchiolitis, interstitial pneumonia, and pulmonary fibrosis. More rare manifestations include organizing pneumonia (OP) and diffuse alveolar damage (DAD). A similar but distinct entity of acute fibrinous and organizing pneumonia (AFOP), characterized by intra-alveolar fibrin deposition and associated organizing pneumonia, has been reported in association with connective tissue disorders, but has not been described in association with SLE. Reported herein is a patient with SLE and accompanying antiphospholipid syndrome with recent pulmonary embolism, persistent respiratory symptomology, and persistent radiographic abnormalities who underwent lung biopsy displaying features of AFOP. This case in conjunction with previous literature indicates that AFOP can be a manifestation of connective tissue disease including SLE and may be an underreported variant of medical lung disease due to overlap in histological characteristics with OP and DAD.     

A clinicopathologic study on three cases of constrictive bronchiolitis

We describe the characteristic clinical and pathologic findings of three cases of constrictive bronchiolitis. All three patients were middle-aged women with chronic respiratory illness characterized by chronic cough, dyspnea, mild to severe obstructive pulmonary dysfunction, relatively normal chest radiographs with occasional peribronchial infiltration, and lack of response to bronchodilators or prednisolone. The patients also had medical diseases such as non-Hodgkin's lymphoma and hyperprolactinemia in case 1 and 3, respectively. None of the patients smoked cigarettes and had clinical evidence of recent viral lower respiratory tract infection. Histologic study by open lung biopsy revealed a spectrum of changes ranging from active cellular bronchiolitis to obliterative peribronchiolar fibrosis. The intervening interstitial and alveolar areas showed no remarkable lesion. Immunohistochemically, the bronchiolar or peribronchiolar inflammatory infiltrates mainly comprised of mixed T- and B-lymphocytes. It may be possible that the active form of constrictive bronchiolitis is initiated by attendant lymphocytic inflammation of the airways, which is followed by fibrous obliteration of bronchioles.     

Fibrosis with emphysema

Wright J L, Tazelaar H D & Churg A (2011) Histopathology  58 , 517–524
Fibrosis with emphysema The concept of fibrosis with emphysema is confused by the existence of two very different clinical/pathological scenarios: first, cases in which a diffuse fibrosing interstitial pneumonia, most commonly usual interstitial pneumonia (UIP), occurs in a patient with emphysema. This combination is largely of clinical interest because of its effects on pulmonary function and pulmonary hypertension, but can produce unusual appearances in surgical lung biopsies when the fibrotic areas are wrapped around emphysematous spaces. However, the underlying morphology of emphysema and UIP or other interstitial lung disease remains unchanged. Radiological consultation is often helpful to show that the patient has both lesions; secondly, cases in which there is localized fibrosis that is part of emphysema, or related to respiratory bronchiolitis, or both. These lesions have been called ‘respiratory bronchiolitis’ (RB), ‘respiratory bronchiolitis–interstitial lung disease’ (RB‐ILD), ‘airspace enlargement with fibrosis’, ‘RB‐ILD with fibrosis’ and ‘clinically occult interstitial fibrosis in smokers’, but are probably all the same entity. Such changes are associated only rarely with the physiological or radiological features of an interstitial lung disease. Care should be taken when describing these lesions in biopsies so as not to give the impression that a diffuse interstitial lung disease is present.     

Organic antigen-induced interstitial lung disease: diagnosis and management.

BACKGROUND: Traditionally, chronic idiopathic interstitial pneumonia/fibrosis (IIP/F) had included usual interstitial pneumonia, desquamative interstitial pneumonia, and nonspecific interstitial pneumonia (NSIP). More recent classifications have included bronchiolitis obliterans-organizing pneumonia (BOOP), respiratory bronchiolitis-associated interstitial lung disease, and acute interstitial pneumonia. Some chronic eosinophilic pneumonias (CEP)/pulmonary infiltrate with eosinophilia (PIE) have obvious causes, but many lack an identifiable etiology. We felt that hypersensitivity pneumonitis (HP) was being underdiagnosed and was hidden within this large heterogeneous group of interstitial lung disorders of unrecognized cause. OBJECTIVE: We sought to prove that detailed environmental histories and investigations would reveal causative contaminations in the home or workplace of some patients with idiopathic interstitial lung disease and remediation of the contamination would stabilize the disorder. METHODS: Consecutive cases of IIP/F were investigated. Patients were identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and lung biopsies. They were further evaluated with detailed environmental histories, serologic tests, and investigation into the suspected causative environment. Environmental and specific antigen challenges were done in some cases. Remediation of contaminations or moving into another environment were the methods used as therapy. RESULTS: Eighty-six consecutive patients with IIP/F were evaluated. Twelve patients were subsequently diagnosed with specific causes for interstitial lung disease. Fifty-seven of 74 patients were identified by clinical evaluation and lung biopsy with HP, CEP/PIE, NSIP, BOOP, UIP, and nonclassifiable morphologic patterns. Seventeen patients were not biopsied or had an inadequate transbronchial biopsy but had consistent findings radiographically and clinically of idiopathic interstitial lung disease. Contamination of the home was causative in 69 of 74 and the workplace in 3 of 74 cases. There were 9 positive and 33 negative environmental challenges with 4 positive and 1 negative specific challenges. Fifty of 74 (67%) patients are receiving no treatment and are free of active disease after remediation of the environmental contamination, with a mean survival of 8.2 years. CONCLUSIONS: Our data show that UIP, BOOP, NSIP, CEP/PIE, and nonclassifiable morphologic patterns represent a spectrum of interstitial lung disease that may be caused by inhalation of organic dusts in the home or workplace as described with HP. Remediation of, or moving from the contamination, can lead to arrest of the active inflammatory process and stability of the lung disorder.     

Chronic transmural bronchiolitis: a non-specific lesion of small airways.

AIMS: To investigate nine patients with histological changes at open lung biopsy compatible with so-called "small airways disease"; to define these changes and distinguish them from other types of bronchiolitis; and to correlate them with clinical features, respiratory physiology, and other laboratory investigations. METHODS: The open biopsy sections and the clinical records were reviewed. RESULTS: There was chronic inflammation of the walls of centri-acinar respiratory bronchioles and peribronchiolar alveoli. Peripheral alveoli of affected acini were spared. Although lumens were narrowed and distorted, obstruction by granulation tissue plugs was not a feature. Clinical backgrounds included Hodgkin's disease, yellow nail syndrome, sicca syndrome, asthma and psoriasis. The main presenting symptoms were cough, dyspnoea and wheeze, often associated with basal crackles and basal shadowing. There was no consistent immunological or haematological abnormality. Sputum culture was negative in six patients, and a variety of organisms were cultured from three others. In most cases respiratory function tests revealed an irreversible obstructive defect (combined in some cases with a restrictive defect), gas trapping, and well preserved gas transfer. Lung volumes were normal. Bronchodilators, with steroids and azathioprine in more seriously affected patients, stabilised the disease process. CONCLUSIONS: The histological changes may be distinguished from bronchiolitis obliterans and bronchiolitis obliterans organising pneumonia by the absence of intraluminal granulation tissue plugs, and from the obliterative bronchiolitis of rheumatoid disease and diffuse peribronchiolitis on clinical grounds. Although often striking, this lesion does not represent a clinico-pathological entity, and may occur in the distal lung in association with a number of different diseases. "Small airways disease" is often used by clinicians in a functional context, and may lead to confusion. It is suggested that "chronic transmural bronchiolitis" is a more appropriate term.     

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.     

Diagnosis and classification of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a difficult disease to diagnose. Idiopathic pulmonary fibrosis is a member of a class of diseases known as idiopathic interstitial pneumonias. Other members include nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and lymphocytic interstitial pneumonia. Usual interstitial pneumonia (UIP) is the pathological equivalent of idiopathic pulmonary fibrosis. Prior to 2011, the diagnosis was based on major and minor criteria, but because these criteria were not evidence based, the criteria were modified by consensus from the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. These new criteria now include satisfying three core requirements, including exclusion of other possible cause of interstitial lung disease, specific findings of usual interstitial pneumonia on high resolution computed tomography, and a combination of “possible UIP” findings on high resolution computed tomography and UIP findings on lung biopsy. Idiopathic pulmonary fibrosis is a severe, progressive disease with limited treatment options, and exacerbations are associated with a high degree of morbidity and mortality.     

Interrelationship of chronic eosinophilic pneumonia, bronchiolitis obliterans, and rheumatoid disease: a hypothesis.

Three patients with histologically proven bronchiolitis obliterans are presented, two of whom had rheumatoid disease. All three patients had, in addition, clinical and radiological evidence of chronic eosinophilic pneumonia; open lung biopsy in two showed coexistent features of chronic eosinophilic pneumonia and bronchiolitis obliterans. The association of both rheumatoid disease are chronic eosinophilic pneumonia with bronchiolitis obliterans in these patients may simply be coincidental, but the striking similarities between the cases suggest that a real interrelationship of these disease entities may exist.     

Classification of idiopathic interstitial pneumonias: making sense of the alphabet soup

Since Liebow and Carrington's original classification of idiopathic interstitial pneumonias, there have been controversies over which histological patterns should be included and how they relate to clinicopathological diseases such as cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis (CFA/IPF). Because of these differences and the wealth of overlapping terminology, a consensus classification system has been proposed, devised by a group of clinicians, radiologists and pathologists. Seven histological patterns are recognized: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), diffuse alveolar damage (DAD), organizing pneumonia (OP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis (RB) and lymphocytic interstitial pneumonia (LIP), each with a clinicopathological counterpart, the most well defined being UIP and CFA/IPF. The system is applicable both in terms of the pathologist identifying histological patterns in isolation and in terms of the pathologist's role in contributing to the final clinicopathological diagnosis. It will probably provide greater consistency in diagnosis, early studies suggesting that the system is reproducible, and also identify purer cohorts for studies investigating causation. It also highlights the fact that the 'gold standard for diagnosis' is no longer a surgical lung biopsy in isolation but more the clinicopathological conference, when clinical, imaging and histological data are jointly discussed to produce the final clinicopathological diagnosis.     

Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis

Hypersensitivity pneumonitis is an inflammatory lung disease that develops in response to exposure to antigen. Cases can be stratified by the duration of exposure and speed of symptom progression into acute, subacute, and chronic hypersensitivity pneumonitis. Although the pathologic features of subacute hypersensitivity pneumonitis are well established and those of chronic hypersensitivity pneumonitis have been reported, little is known about the histopathology of acute hypersensitivity pneumonitis. We evaluated the pathologic features of 5 patients with clinically confirmed hypersensitivity pneumonitis and rapid onset of symptoms and 3 patients with subacute or chronic hypersensitivity pneumonitis with symptom exacerbation. Histopathologic features assessed in each case included those characteristic of subacute hypersensitivity pneumonitis (bronchiolocentric chronic inflammation, histiocytic aggregates, and bronchiolitis obliterans), those associated with acute inflammation (fibrin deposition and neutrophilic infiltrate), and fibrosis. The classic features of hypersensitivity pneumonitis were identified in all 8 cases, with 1 also exhibiting fixed fibrosis confirming underlying chronic hypersensitivity pneumonitis. Fibrin deposition was present in 8 (100%) of 8 cases, and its extent was significant (28% surface area fibrin deposition/total disease area on average). Two had intra-alveolar fibrin so marked that it resembled acute fibrinous and organizing pneumonia. In addition, prominent interstitial neutrophilic infiltrate (≥5 cells/high-power field) was seen in all cases. These features have not been reported as characteristics of subacute or chronic hypersensitivity pneumonitis. Increased fibrin deposition and neutrophilic infiltrate may characterize acute hypersensitivity pneumonitis or abrupt exacerbation of hypersensitivity pneumonitis, and these along with characteristic features of subacute hypersensitivity pneumonitis (granulomatous inflammation and bronchiolocentricity) are sufficient to establish a morphologic diagnosis, particularly in conjunction with clinicoradiologic features.