Masson Bodies Research Articles

Application of Innovative 3D Pathological Tactic for Diagnosis of Organizing Pneumonia.

The pathological diagnosis of organizing pneumonia (OP) relies on conventional traditional histopathological analysis, which involves examining stained thin slices of tissue. However, this method often results in suboptimal diagnostic objectivity due to low tissue sampling rates. This study aimed to assess the efficacy of tissue-clearing and infiltration-enhanced 3D spatial imaging techniques for elucidating the tissue architecture of OP. H&E staining, 3D imaging technology, and AI-assisted analysis were employed to facilitate the construction of a multidimensional tissue architecture using six OP patient specimens procured from Taichung Veterans General Hospital, enabling a comprehensive morphological assessment. Specimens underwent H&E staining and exhibited Masson bodies and varying degrees of interstitial fibrosis. Furthermore, we conducted a comprehensive study of 3D images of the pulmonary histology reconstructed through an in-depth pathology analysis, and uncovered heterogenous distributions of fibrosis and Masson bodies across different depths of the OP specimens. Integrating 3D imaging for OP with AI-assisted analysis permits a substantially enhanced visualization and delineation of complex histological pulmonary disorders such as OP. The synergistic application of conventional histopathology with novel 3D imaging elucidated the sophisticated spatial configuration of OP, revealing the presence of Masson bodies and interstitial fibrosis. This methodology transcends conventional pathology constraints and paves the way for advanced algorithmic approaches to enhance precision in the detection, classification, and clinical management of lung pathologies.

Enhancing Organizing Pneumonia Diagnosis: A Novel Super-token Transformer Approach for Masson Body Segmentation.

In this study, we introduce an innovative deep-learning model architecture aimed at enhancing the accuracy of detecting and classifying organizing pneumonia (OP), a condition characterized by the presence of Masson bodies within the alveolar spaces due to lung injury. The variable morphology of Masson bodies and their resemblance to adjacent pulmonary structures pose significant diagnostic challenges, necessitating a model capable of discerning subtle textural and structural differences. Our model incorporates a novel architecture that integrates advancements in three key areas: Semantic segmentation, texture analysis, and structural feature recognition. We employed a dataset of whole slide imaging from 20 patients, totaling 100 slides of OP, segmented into training, validation, and testing sets to reflect real-world application scenarios. Our approach utilizes a modified multi-head self-attention mechanism combined with ResUNet for semantic segmentation, enhanced by superpixel concepts. This method facilitates the generation of representative token features through iterative super-token blocks, creating high-resolution token maps that leverage local and high-level feature information for improved accuracy. Benefiting from token features and distribution for enhanced texture alignment with fewer false-positives, the super-token transformer (STT) model achieved a mean intersection over union (mIOU) of 72.42%, with a sensitivity of 47.81%, specificity of 99.83%, positive predictive value of 64.03%, and negative predictive value of 99.94%, highlighting superior efficacy in Masson body segmentation in complex cross-tissue analyses. Our team developed an iterative learning model based on the STT approach, emphasizing token features of super token, including texture and distribution, that enable enhanced alignment with the unique textures of Masson bodies to improve sensitivity and mIOU, The development of this STT model presents a significant advancement in the field of medical image analysis for OP that offers a promising avenue for improving diagnostic precision and patient outcomes in pulmonary pathology.

DYSPNEA UNVEILED BY HANDS: A CHALLENGING CASE OF RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Antisynthetase syndrome (ASS) is a rare autoimmune condition characterized by antibodies directed against amino-acyl-tRNA synthetase along with clinical features of myositis, arthritis, Raynaud’s phenomenon and interstitial lung disease (ILD). We present a case of rapidly progressive ASS associated ILD. CASE PRESENTATION: A 40-year-old African American woman with past medical history of smoking and prior hospitalization for presumed pneumonia presented to the emergency department with complaints of ongoing but worsening cough and dyspnea for more than four months. She was hypoxic and lung examination revealed bilateral fine crackles. Chest imaging revealed patchy mixed consolidation and ground-glass opacities at the lung bases (figure 1). Her course worsened needing mechanical ventilation. Given the clinical picture and imaging findings raising concerns for ILD, she underwent VATS/lung biopsy, which revealed pinkish fibrous plugs: Masson bodies, concerning for organizing pneumonia (figure 2). Autoimmune work including ANA and rheumatoid factor was negative. She continued to decline despite broad-spectrum antibiotics and high dose steroids and had to be placed on VV-ECMO for severe ARDS. Hyperkeratosis and hyperpigmentation of her hands were later noted, raising concerns for an autoimmune process. A myositis panel was done, which revealed positive Anti-PL12 antibodies. Lung function recovery was sub-optimal despite ECMO support for 85 days, IVIG, plasma exchange and cyclophosphamide therapy. She had to undergo single left lung transplantation. She eventually was discharged home on immunosuppressants after five months of hospitalization. Her explanted lung showed features of non-specific interstitial pneumonia. She has done well for more than 2 years post-transplant with amelioration in the imaging findings of her native right lung and with no signs of graft rejection. The final diagnosis was rapidly progressive ASS associated ILD with progression to ARDS requiring single lung transplantation. DISCUSSION: ASS is a rare group of idiopathic inflammatory myopathies, characterized by the presence of seven different myositis-specific antisynthetase antibodies with Anti-Jo1 being the most common one. Anti-PL12 antibody type is associated with a severe form of ILD. ANA antibodies are typically negative and hence a high index of suspicion for ASS is warranted. Literature about the management of ASS-ILD is sparse but anecdotal experience favors steroids as first-choice agents and other immunosuppressive agents, plasma exchange therapy, and even lung transplantation in severe and refractory cases. CONCLUSIONS: Our case of ASS-ILD with anti-PL12 antibodies shows the rapid progression of the ILD despite aggressive immunosuppressive therapy and highlights the importance of identification, aggressive therapy and the role of VV-ECMO with lung transplantation as an option for refractory cases. Reference #1: Connors GR, Christopher-Stine L, Oddis CV, et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010;138:1464–1474. Reference #2: Esposito AC, Gige TC, Miot HA. Syndrome in question: antisynthetase syndrome (anti-PL-7). An Bras Dermatol. 2016;91(5):683-685. DOI:10.1590/abd1806-4841.20164449 Reference #3: Witt LJ, Curran JJ, Strek ME. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016;23(5):218-226. DOI:10.1097/CPM.0000000000000171 DISCLOSURES: No relevant relationships by Anas Alameh, source=Web Response No relevant relationships by Ansaam Daoud, source=Web Response No relevant relationships by Sujith Modugula, source=Web Response No relevant relationships by Lokesh Venkateshaiah, source=Web Response No relevant relationships by Elizabeth Verghese, source=Web Response

Cicatricial organizing pneumonia: a clinicopathologic and radiologic study on a cohort diagnosed by surgical lung biopsy at a single institution

Cicatricial organizing pneumonia (CiOP) refers to intraluminal collagen deposition in a background of otherwise classic appearing organizing pneumonia (OP), sometimes with formation of peculiar fibrous nodules or densely fibrotic linear bands. Dendriform ossification has been also described in CiOP cases. This study is to evaluate the clinicopathologic and radiologic characteristics of CiOP identified in a cohort of OP cases diagnosed by surgical lung biopsy at a single institution. Electronic search was performed to find surgical lung biopsy cases with OP as the main histopathologic diagnosis during a 9-year period (2005-2013). The presence of mature collagen deposition in intraluminal plugs of OP (Masson bodies), linear fibrous bands, and ossification in association with OP was evaluated. Pertinent clinical information was obtained from medical records, and available chest computed tomography (CT) scans were reviewed by a chest radiologist. A total of 56 cases met the study criteria. Thirty-two of 56 cases (57.1%) showed at least 10% of cicatricial element within Masson bodies, 9 of which revealed cicatricial elements comprising 50% or higher proportion of OP. All 9 cases with CiOP as the major component (≥50%) revealed some areas of linear fibrous bands. Five of these 9 cases had intraluminal ossification, with features suggestive of dendriform ossification. Twenty of 32 cases with the cicatricial component had postoperative follow-up CT scans ranging from 0.4 to 171 months (median = 44) after the biopsy; 18 of these 20 cases showed stable finding or resolution of radiologic densities. Six of 9 patients with CiOP with major cicatricial change (≥50%) were alive and well at the time of clinical follow-up (median = 47 months; range = 12-125). In summary, minor cicatricial changes involving Masson bodies were seen in more than half of our OP cases, and patients with CiOP seem to follow an indolent and favorable course on radiologic and clinical follow-up, even in those with major cicatricial changes (≥50%) that were often accompanied by linear fibrous bands and/or intraluminal ossification.

Changes in the pattern of fibrosis in the rat lung with repetitive orotracheal instillations of gastric contents: evidence of persistent collagen accumulation.

Recurrent aspiration of gastric contents has been associated with several interstitial lung diseases. Despite this association, the pathogenic role of aspiration in these diseases has been poorly studied and little is known about extracellular matrix (ECM) changes in animal models of repetitive events of aspiration. Our aim was to study the repair phase of lung injury induced by each of several instillations of gastric fluid in Sprague-Dawley rats to evaluate changes in ECM and their reversibility. Anesthetized animals received weekly orotracheal instillations of gastric fluid for 1, 2, 3, and 4 wk and were euthanized at day 7 after last instillation. For reversibility studies, another group received 7 weekly instillations and was euthanized at day 7 or 60 after last instillation. Biochemical and histological measurements were used to evaluate ECM changes. Lung hydroxyproline content increased progressively and hematoxylin and eosin, Masson's trichrome, and alpha-SMA stains showed that after a single instillation, intra-alveolar fibrosis predominated, whereas with repetitive instillations this fibrosis pattern became less prominent and interstitial fibrosis progressively became evident. Both type I and III collagen increased in intra-alveolar and interstitial fibrosis. Imbalance between matrix metalloproteinase-2 (MMP-2) activity and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression was observed, favoring either collagen degradation or accumulation depending on the number of instillations. Caspase-3 activation was also dose dependent. ECM changes were partially reversible at long-term evaluation, since Masson bodies, granulomas, and foreign body giant cells disappeared, whereas interstitial collagen accumulated. In conclusion, repetitive lung instillations of gastric fluid induce progressive fibrotic changes in rat lung ECM that persist at long-term evaluation.

Acute lung injury by gastric fluid instillation: activation of myofibroblast apoptosis during injury resolution

BackgroundGastric contents aspiration in humans has variable consequences depending on the volume of aspirate, ranging from subclinical pneumonitis to respiratory failure with up to 70% mortality. Several experimental approaches have been used to study this condition. In a model of single orotracheal instillation of gastric fluid we have shown that severe acute lung injury evolves from a pattern of diffuse alveolar damage to one of organizing pneumonia (OP), that later resolves leaving normal lung architecture. Little is known about mechanisms of injury resolution after a single aspiration that could be dysregulated with repetitive aspirations. We hypothesized that, in a similar way to cutaneous wound healing, apoptosis may participate in lung injury resolution by reducing the number of myofibroblasts and by affecting the balance between proteases and antiproteases. Our aim was to study activation of apoptosis as well as MMP-2/TIMP-2 balance in the sub-acute phase (4–14 days) of gastric fluid-induced lung injury.MethodsAnesthesized Sprague-Dawley rats received a single orotracheal instillation of gastric fluid and were euthanized 4, 7 and 14 days later (n = 6/group). In lung tissue we studied caspase-3 activation and its location by double immunofluorescence for cleaved caspase-3 or TUNEL and alpha-SMA. MMP-2/TIMP-2 balance was studied by zymography and Western blot. BALF levels of TGF-β1 were measured by ELISA.ResultsAn OP pattern with Masson bodies and granulomas was seen at days 4 and 7 that was no longer present at day 14. Cleaved caspase-3 increased at day 7 and was detected by immunofluorescence in Masson body-alpha-SMA-positive and –negative cells. TUNEL-positive cells at days 4 and 7 were located mainly in Masson bodies. Distribution of cleaved caspase-3 and TUNEL-positive cells at day 14 was similar to that in controls. At the peak of apoptosis (day 7), an imbalance between MMP-2 activity and TIMP-2 expression was produced by reduction in TIMP-2 expression.ConclusionsApoptosis is activated in Masson body-alpha-SMA–positive and –negative cells during the sub-acute phase of gastric fluid-induced lung injury. This mechanism likely contributes to OP resolution, by reducing myofibroblast number and new collagen production. In addition, pre-formed collagen degradation is favored by an associated MMP-2/TIMP-2 imbalance.

Amiodarone-Other Pulmonary Manifestations

Abstract Introduction. Cryptogenic organizing pneumonia (COP), first described in 1985 as BOOP bronchiolitis obliterans organizing pneumonia, is an acute inflammatory disease characterized histopathologically by intracellular granulomas formed by connective tissue and miofibroblasts (Masson bodies). Case presentation. 62-year-old female patient, known with type 2 DZ, ICC, CIND (paroxysmal FiA) and HTAE, under treatment with Amiodarone, is hospitalized with acute respiratory symptomatology. Laboratory tests show bilateral basaltic crepitation risers, biological inflammatory syndrome, and radiologically multiple opacities with ½ inferior condensation appearance for which empiric antibiotic treatment was initiated. Evolution of the patient was unfavourable, despite antibiotic treatment. Therefore, it is decided to do a fibrobronchoscopic examination (bronchial aspiration for cytology and BK), thoracic CT followed by thoracoscopy and pulmonary biopsy. The diagnosis of COP was based on the typical radiological appearance of bronchopneumonia but that is not responding to antibiotic treatment. The bronchoalveolar lavage revealed nonspecific inflammatory infiltration with lymphocytes and polymorphonuclear cells, the histopathological examination revealed the presence of Masson bodies, alveolar fibroblast polyps and bronchiolar polyps. As amiodarone is known to have pulmonary adverse effects, among which COP was very rarely quoted, treatment with amiodarone was discontinued and cortisone treatment with prednisone 70 mg/day was initiated, with rapid progressive improvement of symptomatology and slow improvement of imaging. In treatment month 3, after the decrease in prednisone to 30 mg/day, the general condition of the patient worsens in parallel with the biological and imaging parameters secondary to the reintroduction of the amiodarone treatment, an event treated as a recurrence of drug-induced obliterans pneumonia. The evolution of the patient was favourable, with the remission of clinical symptoms and radiological appearance, in the absence of relapses one and a half years after the end of the treatment. Conclusions. This paper presents a complete case of cryptogenic organizing pneumonia in a patient undergoing amiodarone treatment, which has a complete response to cortisone treatment only after the trigger factor has been removed.

Rattus model utilizing selective pulmonary ischemia induces bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ∼2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP.

S114 Lymphatic vessel distribution in fibrotic lung diseases

Relatively little is known on lymphatic vessel remodelling in lung fibrosis, and whether differences in lymphatic distribution underlie the worse survival seen in idiopathic pulmonary fibrosis, compared to the other...

Acute fibrinous and organising pneumonia: a case report and review of the literature

IntroductionOrganising pneumonia is a distinct histopathological entity characterized by intra-alveolar buds of granulation tissue, called Masson bodies, which mainly comprise of activated fibroblasts and loose connective tissue. This histopathologic pattern has been described in idiopathic cases, characterizing cryptogenic organising pneumonia as well as in the context of pulmonary infection, drug-induced pneumonitis and following lung transplantation. Although distinct as a clinical and pathological entity, community organising pneumonia may present with atypical clinical and pathological features, such as intra-alveolar fillings of fibrin balls and organising tissue that resembles acute respiratory distress syndrome or diffuse alveolar damage. The latter characteristics constitute a recently described anatomoclinical entity called acute fibrinous and organising pneumonia.Case presentationHere, we describe a rare case of acute fibrinous and organising pneumonia, in an otherwise healthy 65-year-old Greek woman who complained of dry cough, fever, weight loss and progressive dyspnoea. She had never been a smoker. Her clinical symptoms showed a rapid deterioration in the two weeks before admission, despite a course of oral antibiotics. After excluding infection and malignancy with routine laboratory tests and flexible bronchoscopy, high resolution computed tomography and video assisted thoracoscopic lung biopsy were performed. Diagnosis was based on radiological features typical of community organising pneumonia coupled with pathologic features characteristic of acute fibrinous and organising pneumonia. The patient was treated with corticosteroids and showed excellent clinical and radiological response three months after treatment initiation.ConclusionAcute fibrinous and organising pneumonia is an extremely rare pathologic entity, often misdiagnosed as typical community organising pneumonia. To our knowledge, this is the seventh case of acute fibrinous and organising pneumonia in the literature, with no identifiable cause or association in a female patient, with no underlying lung disease or known exposures and with an unremarkable previous medical history. We highlight the need for careful review of lung biopsies from patients with clinical and radiologic characteristics typical of community organising pneumonia. Although it remains uncertain whether fibrin alters the favourable prognosis and treatment response of community organising pneumonia, it becomes obvious that a thorough pathologic review, apart from establishing the diagnosis of acute fibrinous and organising pneumonia, may predict a more unfavorable outcome therefore alerting the clinician to administer more aggressive and prolonged therapeutic regimens.

Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis

BackgroundRecent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4) has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM)-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP).MethodsExperimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6- to 8-wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects.ResultsA gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients.ConclusionOur data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease.

Evaluation of Fractional Analysis of Bronchoalveolar Lavage Combined with Cellular Morphological Features

The value of bronchoalveolar lavage (BAL) still remains controversial, prompting a need for further improvement. The purpose of this study was to develop and evaluate a sequential analysis of cell content in fractional BAL (FBAL) from the airways and alveolar sacs with incorporation of the cellular morphologic features. Initially, 30 ml saline was infused into a subsegmental lobe of the lung and the recovered fluid was assigned as FBAL-I being mainly originated from whole airways. The second and third lavages (FBAL-II and FBAL-III) each were performed using 50 ml saline being from more distal portions of airways and alveolar sacs respectively in the same lobe. Total cell number/ml and percentages of macrophages, lymphocytes, neutrophils, and eosinophils in each fraction together with their morphological alterations and mast cells, basophils and Masson bodies were assessed. In the 12 controls, percentage of neutrophils was high and lymphocytes and macrophages were low in FBAL-I while in FBAL-III, neutrophils decreased to nearly nil and lymphocytes and macrophages were increased. Analysis of FBAL from 76 patients with sarcoidosis and 14 with hypersensitivity pneumonitis (HP) revealed that a predominance of small, round and well-differentiated lymphocytes with relative absence of neutrophils, basophils and Masson bodies correlated best with sarcoidosis. In contrast, neutrophil predominance and presence of lymphocytes having deep nuclear indentations and abundant cytoplasm with a process resembling a "hand-mirror" correlated well with HP. Evaluation of FBAL together with cellular morphological features especially characteristics of lymphocytes provides valuable information for establishing the diagnosis in interstitial lung diseases.

Pneumonia em organização criptogénica - caso clínico

Cryptogenic organizing pneumonia (COP) is one of the new recognized histological patterns of idiopathic interstitial pneumonias, in witch no cause or association is identified. Idiopathic bronchiolitis obliterans-organizing pneumonia (BOOP) is a synonymous. This rare entity is characterized by involvement of alveoli and bronchioles, which are filled by intraluminal polyps of fibroblastic tissue (Masson bodies). The clinical presentation often mimics that of community-acquired pneumonia. Persistent non-productive cough, dyspnoea with exertion and weight loss are common features, and in one-half of the cases the onset is heralded by a flu-like syndrome. Definitive diagnosis depends on histological data, and video-assisted thoracoscopic (VAT) has become the established technique. Spontaneous recovery is rare; corticosteroid therapy provides cure in two thirds of cases. The authors present a case of a patient whose lung biopsy by VAT confirmed the diagnosis. She was treated with corticoids without recurrence in a two year follow-up.

Pneumoconiosis in Rush Mat Workers Exposed to Clay Dye “Sendo” Dust: Clinical, Radiologic, and Histopathologic Features in Seven Patients

The purpose of this study was to describe the clinical, chest radiographic, high-resolution CT, and histopathologic features of clay dye "sendo" dust pneumoconiosis in seven rush mat ("tatami") workers. Seven patients with a history of occupational exposure to sendo dust and radiographic changes suggestive of pneumoconiosis were retrospectively reviewed. The duration of exposure ranged from 15 to 45 years (median, 30 years). Three patients had cough, and four patients had abnormal pulmonary function test results. Chest radiographs showed nodular opacities < 3 mm in diameter (types p and q) in all patients. The standard International Labor Office profusion score ranged from 0/1 to 1/1 (median, 1/0). High-resolution CT demonstrated small nodular opacities (types p and q) in all seven patients. In four patients, high-resolution CT demonstrated branching centrilobular structures, airway ectasia, airway wall thickening, and emphysematous changes. None of the patients had conglomerate nodules, large opacities, honeycombing, pleural effusion, or lymphadenopathy. Microscopic examination of the specimens obtained by open lung biopsy or transbronchial lung biopsy revealed nodular fibrosis with accumulation of dust-laden macrophages, but no silicotic nodules. Needle-like particles of 1 to 20 microm in length were evident among the dust deposits, and birefringent crystals were identified under polarizing microscopy. Four of seven patients showed intra-alveolar fibroblastic foci similar to Masson bodies, accompanied by dust deposition. Rush mat workers' sendo dust pneumoconiosis is caused by dust containing free silica. The radiographic and high-resolution CT findings consist of small nodular opacities < 3 mm in diameter and bronchial and bronchiolar abnormalities.

Chronic hypersensitivity pneumonitis in Japan: A nationwide epidemiologic survey

Background: Pulmonary fibrosis inevitably develops in patients with chronic hypersensitivity pneumonitis (HP). Objective: We conducted a nationwide epidemiologic study in Japan to evaluate the frequency and clinical characteristics of chronic HP. Methods: This report is on 36 cases of chronic HP, including 10 patients with summer-type HP, 5 patients with home-related HP, 7 patients with bird fancier’s lung, 5 patients with isocyanate-induced HP, 4 patients with farmer’s lung, and 5 patients with other types of chronic HP. Chronic HP was further subgrouped into 2 types: one type of patients were first seen with chronic disease (9 patients), and the other type became chronic with fibrosis after repeated acute episodes (27 patients). Results: The upper lung field was frequently involved in chronic HP (17%). Ground-glass opacities were observed in 57% and air space consolidation in 30% of the patients. Honeycombing was apparent in 37%. Twenty-six of 28 patients had antibodies to the presumptive antigens. Five of 8 patients with chronic HP were positive for antigen-induced lymphocyte proliferation. In 2 cases patients did not have detectable antibodies to causative antigens, although antigen-induced lymphocyte proliferation was detectable. The ratio of CD4 to CD8 in BAL lymphocytes was lowest in isocyanate-induced HP (mean 0.22) and tended to be high in farmer’s lung and bird fancier’s lung. Granulomas were observed in 39% and Masson bodies in 42% of specimens on histologic examination. Administration of prednisolone was effective in 58% of patients. Conclusions: The insidious form of chronic HP has probably been misdiagnosed as idiopathic pulmonary fibrosis when a good history was not taken and immunologic (especially antigen-induced lymphocyte proliferation) and BAL testing were not counted. (J Allergy Clin Immunol 1999;103:315-20.)

Bronchiolitis obliterans organizing pneumonia-like reactions: A nonspecific response or an atypical form of rejection or infection in lung allograft recipients?

Bronchiolitis obliterans organizing pneumonia (BOOP) is a ubiquitous entity, known to occur either idiopathically or in association with various pulmonary disorders. Histologically, it is characterized by myxomatous connective tissue plugs present in the lumen of bronchioles with extension into the alveoli. Its significance in lung allograft recipients is not well documented. The authors reviewed all post—lung transplant biopsies (565 transbronchial; 19 open), explanted lungs for retransplantation (six), and autopsies (38) from 115 patients. A total of 32 patients (18 females and 14 males) showed histological evidence of BOOP-like reactions (ie, Masson bodies in 44 transbronchial and seven open lung biopsies). The mean age was 47 years (range = 14 to 69 years). Sixteen patients were recipients of single lungs, 14 received bilateral single lungs, and two had heart and double-lung transplants. BOOP-like reactions (BOOP-LRs) occurred as early as day 5 and as late as day 1,208 (40 months) posttransplantation. Twenty patients had one biopsy showing BOOP-LR, of which three patients had resolving mild acute rejection, four had ongoing minimal acute rejection, seven had ongoing mild acute rejection, one each had ongoing moderate and bronchiolar rejection, and four showed associated cytomegalovirus (CMV) pneumonitis. Seven patients had two biopsies each of BOOP-LR, of which six were associated with ongoing minimal or mild acute rejection, and one had resolving mild acute rejection. Three patients had three biopsies each of BOOP-LR, all associated with ongoing minimal or mild acute rejection. Two patients had four biopsies each, showing BOOP-LR, with ongoing mild or moderate acute rejection or CMV pneumonitis. Forty of the total 115 lung transplant patients (34.8%) have developed bronchiolitis obliterans syndrome (BOS) or chronic airway rejection. Twelve of these patients are from the study group, of which five have a biopsy proven histological diagnosis of obliterative bronchiolitis (OB), and the remaining seven patients have been diagnosed clinically by deteriorating lung function tests. The authors conclude that BOOP-LR in the lung transplant setting result from acute epithelial injury secondary to either allograft rejection or an ongoing infection and are not a component of, nor do they necessarily predispose to, chronic rejection.

Clinicopathological study on two types of cryptogenic organizing pneumonitis

Clinical and pathological studies on cryptogenic organizing pneumonitis (COP) were performed in 19 cases diagnosed with transbronchial lung biopsy (TBLB). All patients suffered from fever and several respiratory symptoms. Laboratory data showed increases in erythrocyte sedimentation rate, positivity for C-reactive protein, negative tuberculin reactions and increases in complement level. Pathological findings demonstrated that there were two kinds of organizing processes. Fourteen of the 19 cases were treated with prednisolone, and two cases were observed without administration. The remaining three cases could not be followed up after therapy. In 11 of the 16 cases, abnormal shadows in chest X-ray disappeared, but remained present in five cases. As for the relationship between pathological findings and shadows in chest X-ray, Masson bodies without fibrin were observed in the 11 cases which were without shadows on X-ray, but Masson bodies containing or related to fibrin were observed in the five cases in which abnormal shadows remained. These results suggest that there are two types of organizing process in COP. Type I is an unexplained organizing process in which fibrin is not present or involved. It responds well to steroids and the prognosis is favourable. Type II is an organizing process which involves fibrin, and the character of the fibroblast-like cells is very similar to that of myofibroblasts. Type II organizing process responds poorly to steroids. Both processes can be notified relatively easily, even by TBLB tissues.

The histological diagnosis of clinically documented cases of cryptogenic organizing pneumonia: diagnostic features in transbronchial biopsies.

Eleven cases of clinically diagnosed cryptogenic organizing pneumonia were examined in order to establish the histological features found at transbronchial biopsy and to correlate this with open lung biopsy which followed in six cases. The essential pathological feature was the presence of buds of granulation tissue (Masson bodies) indicating organization of a persistent exudate by fibroblasts and capillaries within alveoli, with preservation of the alveolar architecture. In addition, both acute and chronic inflammatory cells were present in the interstitium. These features, combined with the clinical history, were sufficient for a diagnosis in seven of the 11 cases on transbronchial biopsies. Four biopsies lacked these features. Patients proceeded to open lung biopsy in addition to the two with histological features of cryptogenic organizing pneumonia on transbronchial biopsy, but where the clinician wanted to eliminate other pathology because of rapid clinical deterioration. Five of the six cases coming to open lung biopsy confirmed cryptogenic organizing pneumonia with Masson bodies within alveoli, but changes were focal in three with very few Masson bodies in one. One case which had the features on transbronchial biopsy lacked them in the open lung biopsy. Transbronchial biopsy, therefore, can yield diagnostic material in the majority of patients with cryptogenic organizing pneumonia while open lung biopsy, which is considered the gold standard for interstitial lung disease, may yield negative results because of sampling error and the rapid evolution and changing pattern of the disease.

急性間質性肺炎の1剖検例

An autopsy case of a 77-year-old male with acute interstitial pneumonia (AIP) is reported. The patient died of respiratory failure in the extremely rapid course of 8 days. The histogenesis of the thickening of the alveolar wall and the intraluminal lesions were noticed. Incorporation of the hyaline membrane as well as the intraseptal edema and septal cell proliferation played an important role in the fibrous thickening of the alveolar wall. The intraluminal granulation tissue was observed in the alveolar space and the alveolar duct, often extending into the respiratory bronchioles. Intraluminal granulation tissues in the alveoli frequently had the appearance of intraluminal buds of mesenchymal cells, so-called Masson's bodies, and there was little remodeling of pulmonary structures in this case. These findings suggest an acute, diffuse and severe damage of the peripheral respiratory tract and are consistent with bronchiolitis obliterans with classical interstitial pneumonia (BIP) by Liebow and AIP by Katzenstein. This patient had suffered from suspected "Bronchiolitis obliterans organizing pneumonia" (BOOP) one and half years ago. The relationship between AIP, BIP and BOOP is discussed.

全身性エリテマトーデスの病理学

Histological and histochemcal studies of systemic lupus erythematosus (SLE) were performed on 31 autopsy cases. Results obtained and brief comments on them were as follows. Hematoxylin bodies (HX bodies) and fibrinoid necrosis of the vascular system were the main pathologic condions in SLE. HX bodies were found in 16 cases, with regularity in areas of fibrinoid necrosis. They were considered to represent the in vivo counterpart of the in vitro LE phenomenon, even though some tinctorial characteristics were different. HX bodies were PAS positive, not metachromatic, and might show reduced Feulgen reaction. When some of HX bodies were ingested by polymorphonuclear luekocytes, LE cells could be detected in the tissue. Fibrinoid necrosis had occasionally been described in other conditions and considered not pathognomonic of SLE. However, in SLE vascular lesions were widespread, and so often took the form of fibrinoid necrosis. Not only Libman-Sacks endocarditis but also glomerular lesions called “wire loop” lesion and “hyaline thrombi” could be regarded as variants of fibrinoid necrosis. In this meaning, fibrinoid necrosis could be regarded as almost pathognomonic of SLE. Fibrinoid necrosis of small vessels was frequent and encountered in 16 cases. Severe necrotizing angiitis as seen in periarteritis nodosa was noted in 6 cases. Endocarditis occurred in 10 cases and fully developed lesions conforming to the description of Libman and Sacks were present in 5 cases. Fibrinoid necrosis of the cardiovascular system was a common site of HX bodies, and not infrequently had a diffuse hematoxyphilic tincture suggesting the deposition of the nuclear substance. Lupus nephritis characterized by pleomorphic and irregular glomerular damage was noted in 25 cases. The most distinctive features included necrosis (often fibrinoid necrosis), karyorrhexis, hyaline thrombi, wire loop lesion and HX bodies. The frequency of the latter three findings was 48%, 61% and 39%, respctively. Thickening of the basement membrane refered to as wire loop lesion was brightly eosinophilic and a hard refractile appearance. Hyaline thrombi were eosinophilic globules filling the lumen of capillaries and closely resembled wire loop lesions. Both lesions had similar staining properties as noted in the vascular fibrinoid and were frequent sites of HX bodies. They showed not rarely a rather diffuse hematoxyphilic tincture, where Feulgen reaction was weakly positive. Another important and the most frequent change in SLE was the concentric lamination of dense collagen fibers arround the central arterioles of the spleen. This change called onion skin lesion was noted in 29 cases. The most remarkable pulmonary change in SLE was a variety of the interstitial pneumonia. This lesion occurred in 11 cases and the most distinctive features included were alveolar exsudate containing fibrin, hyaline membrane, HX bodies, formation of Masson bodies, and fibrosis of alveolar septa. The majority of lesions in SLE might be induced by the immune complexes deposited in the affected vessels. The lesion is histologically characterized by changes in the vessel wall leading to fibrinoid necrosis and the basement membrane thickening, in which deposition of immunoglobulin, complement and fibrinogen are detected. The presence of hematoxyphilic substance with positive Feulgen reaction suggests the deposition of the nuclear substance. Actually DNA antigen has been demonstrated in the glomeruli and the acid eluate from affected glomeruli is said to be rich in antinuclear antibodies. When regard to the pathogeneis of SLE, simultaneous presence of DNA and anti-DNA antibodies in the lesion should raise attention to the role of immune complexes on the vascular system including renal glomeruli.