Clinicopathological findings of focal organizing pneumonia: a retrospective study of 37 cases

Background and objective: Focal organizing pneumonia (FOP) is an uncommon disease. The etiology, and in particular the disease’s relationship with infection and the incidence of idiopathic FOP, is relatively unknown. The aim of this study is to review clinical, radiological and pathological features of patients with organizing pneumonia (OP) presenting solitary lesions and to analyze possible causes. Methods: We retrospectively reviewed 37 surgical lung biopsy or resection cases of pathologically confirmed FOP over a period of 10 years. Results: Microscopically, 17 cases showed OP with neutrophilic infiltration or abscess, 11 with epithelioid cell granulomas or scattered multinucleated giant cells, 2 with greater eosinophilic infiltration, and the remaining 7 cases met the diagnostic criteria for pathological cryptogenic OP (COP). The 37 cases of FOP included 22 men and 15 women, aged 29-76 years, and 17 cases had a history of smoking. Cough, fever, sputum, chest or back pain and hemoptysis were the main symptoms. Seven cases were asymptomatic. The diameters of the lesions ranged from 0.2-6.0 cm (median, 3.0 cm). Fever (9/30), high-sensitivity C-reactive protein elevation (9/17) and abnormalities in pulmonary function test (8/24) existed in focal secondary OP (FSOP) patients, but these symptoms were rarely observed in focal COP (FCOP) (0/7, 1/7 and 0/7 cases, respectively). However, no statistically significant differences were found between the FSOP and FCOP. Conclusions: Histologically, secondary factors exist in the majority of FOP cases. Idiopathic FOP is found in a minority. With respect to secondary FOP, acute infection and granulomatous inflammation are the main causes. Surgical resection alone appears sufficient for the management of FOP.     

隐原性机化性肺炎的临床病理学观察

目的探讨隐原性机化性肺炎（COP）的临床病理学特点及其鉴别诊断。方法对11例经电视胸腔镜或小切口开胸肺活检诊断为COP的病例进行临床、影像和病理学比较分析,治疗后随访。结果COP主要发生于40岁以上的女性,临床主要表现为咳嗽和咳痰、活动后气促。高分辨CT表现为两肺散在斑点、斑片和条索状阴影,无蜂窝肺。COP的主要病理变化是呼吸性细支气管及以下的小气道和肺泡腔内有息肉状的肉芽组织增生,病变时相一致,呈斑片状和支气管周围分布。对糖皮质激素的反应率为81．8％（P〈0．01）。随访6～134个月不等,除1例病情呈进行性加重外,其余病例病情稳定。结论COP对糖皮质激素有较好的反应和预后,临床和影像学不典型时进行外科肺活检病理组织学检查是非常必要的,肺活检应多点取材以免误诊。     

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.     

Chronic exposure to particles caused bronchioloalveolar carcinoma in a patient with cryptogenic organizing pneumonia evaluated by elemental analysis

An 81-year-old Japanese man had organizing pneumonia (OP), and he had worked as a painter and had a history of exposure of various paints over 20 years. The major features on computed tomography (CT) in patients were cryptogenic organizing pneumonia (COP) showing airspace consolidation, and air bronchograms were consistent finding in consolidation in right lung of S¹⁰. Such parenchymal abnormalities were clinically and pathologically diagnosed COP and the lesion was improved by corticosteroid therapy. About 1.5 years later, similar shadows emerged in new locations of right S⁴ and left S⁸, and these were bronchioloalveolar carcinoma (BAC) classified as adenocarcinoma. BAC causes similar X-ray changes to COP and inflammation accompanying BAC can also respond to corticosteroids, which may lead to delay in the diagnosis of BAC associated with COP. These radiological features lead to difficulty in making a diagnosis of new parenchymal diseases. The present patient had been painter, and metals of carcinogens were proven in both tissue of COP and BAC. Here, we reported a painter with COP and new-onset BAC who had been exposed to particles proven by elemental analysis. The combination of COP with BAC is considered uncommon, but the risk of BAC may increase when there is a history of particle inhalation.     

Successful salvage treatment of steroid-refractory bronchiolar COP with low-dose macrolides

Cryptogenic organizing pneumonia (COP) is an idiopathic interstitial pneumonia characterized by fibroblastic tissues that occupy the lumina of alveoli and alveolar ducts or respiratory bronchioles. Although adequate doses and durations of glucocorticoids can improve its condition, COP is sometimes resistant to glucocorticoid therapy and is often lethal.Herein, a very rare case of 'bronchiolar COP' that was confined to the respiratory bronchioles is reported. This case indicates that macrolides may act as anti-inflammatory agents in patients with COP. Timely and precise pathological diagnosis may corroborate clinician diagnoses and eventually improve chances to overcome the disease.     

Pathophysiology of acute fibrinous and organizing pneumonia – Clinical and morphological spectra

Acute Fibrinous and Organizing Pneumonitis (AFOP) is a disease with histopathological pattern characterized by the presence of intra-alveolar fibrin in the form of fibrin “balls” and organizing pneumonia represented by inflammatory myofibroblastic polyps. Symptoms of this rare interstitial pulmonary disease can be either acute or sub-acute and it can rapidly progress to death. Diagnosis should be considered in the Intensive Care Unit (ICU) if patients’ symptomatology and radiology correlates with non-responding or progressive pneumonia and when morphology, on biopsies, encompasses criteria of diffuse alveolar damage (DAD) and organizing pneumonia (OP) balancing in between.Three clinical cases of patients presenting severe lung disease requiring mechanical ventilation and prolonged intensive care fitted on the variable spectra of AFOP histopathology and had poor outcome: a 23 year-old women had AFOP in the context of antiphospholipid syndrome pulmonary compromise; a 35 year-old man developed a letal intensive care pneumonia with AFOP pattern registered in post-mortem biopsy; and a 79 year-old man died 21 days after intensive care unit treatment of a sub-pleural organizing pneumonia with intra-alveolar fibrin, seen in post-mortem biopsy.The predominance of acute fibrin alveolar deposition pattern is helpful in raising AFOP differential diagnosis while organizing pneumonia pattern establishes a wider range of diagnosis that can go till solitary pulmonary nodule, remaining indefinite to suggest diagnosis. The performance time of biopsy in a larger number of clinical cases may be helpful in establishing the evolutionary morphological pattern, taking in mind the poor outcome of the disease, deserving rapid diagnosis to define treatment.     

Coinfection of invasive pulmonary aspergillosis and pneumocystis jiroveci pneumonia in a non-HIV patient

Invasive pulmonary aspergillosis (IPA) and pneumocystis jiroveci pneumonia (PCP) are life-threatening opportunistic infections that occur in immunocompromised hosts. Early diagnosis and treatment of these opportunistic infections is essential to the survival of immunocompromised patients. We report a 60-year-old man undergoing short-term steroid therapy after surgical resection of a brain tumor infected with combined invasive pulmonary aspergillosis and pneumocystis jiroveci pneumonia diagnosed by bronchoscopy with bronchoalveolar lavage. Our case demonstrated that short-term systemic steroid therapy in non-HIV patients with underlying chronic lung conditions and malignancies was a risk factor for IPA and PCP, and for a combination of these infections.     

Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals

Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10 000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.     

Nonspecific interstitial pneumonia overlaps organizing pneumonia in lung-dominant connective tissue disease

Here, we reported two cases of nonspecific interstitial pneumonia overlap organizing pneumonia (NSIP/OP) with lung-dominant connective tissue disease (LD-ILD). The first case is a patient with hands of chapped skin, right-sided pleuritic chest discomfort, weakness, positive ANA and antibodies to Ro/SS-A (+++) and Ro-52 (++). In the second case, there were Reynaud’s disease, and nucleolus-ANA increased (1:800). Chest high resolution CT scan in both cases showed ground-glass opacifications, predominantly in basal and subpleural region and the pathologic manifestation were correlated with NSIP/OP, which were previously discovered in Sjogren syndrome, PM/DM and other rheumatic diseases. The two cases of NSIP/OP with LD-CTD we reported expand disease spectrum of NSIP/OP pathological types in ILD. However, it is necessary to process large-scale studies.     

Invasive pulmonary aspergillosis in an ICU patient with Legionnaires’ disease: A diagnostic challenge

Aspergillus fumigatus can cause a wide range of diseases, from hypersensitivity to invasive infection. Invasive disease usually occurs in severely immunocompromised patients with deep and prolonged neutropenia. It is a less well-recognized complication in critically ill patients without traditional risk factors. We describe a case of early invasive pulmonary aspergillosis (IPA) secondary to Legionella pneumophila serogroup 1 pneumonia in a patient on an intensive care unit (ICU). In addition to commonly accepted risk factors for IPA in ICU patients, we hypothesis that L. pneumophilia pneumonia could enhance this type of infection. We also reviewed all published cases of coinfection with L. pneumophila and A. fumigatus to assess whether Legionnaires’ disease could be a risk factor for IPA.     

Secondary organizing pneumonia after recovery of mild COVID-19 infection

A 36-year-old male with diffuse large B-cell lymphoma on maintenance rituximab therapy presented to the emergency department with high fever and fatigue. A chest X-ray showed a lobar infiltrate, 40 days before admission the patient suffered from a mild coronavirus disease 2019 (COVID-19) infection and fully recovered. PCR nasopharyngeal swab was negative for COVID-19. Comprehensive biochemical, radiological, and pathological evaluation including 18-fluorodeoxyglucose positron emission tomography with computed tomography and transbronchial lung biopsy found no pathogen or lymphoma recurrence. Treatment for pneumonia with antibiotic and antifungal agents was nonbeneficial. A diagnosis of secondary organizing pneumonia (OP) was made after pneumonia migration and a rapid response to corticosteroids. OP secondary to a viral respiratory infection has been well described. Raising awareness for post-COVID-19 OP has therapeutic and prognostic importance because those patients benefit from steroid therapy. We believe the condition described here is underdiagnosed and undertreated by doctors worldwide. Because of the ongoing global pandemic we are now encountering a new kind of patient, patients that have recovered from COVID-19. We hope that this case may contribute to gaining more knowledge about this growing patient population.     

COX-2 is widely expressed in metaplastic epithelium in pulmonary fibrous disorders

Idiopathic usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) and asbestosis represent progressive and often fatal pulmonary fibrous disorders, whereas cryptogenic organizing pneumonia (COP), desquamative interstitial pneumonia (DIP), and respiratory bronchiolitis-interstitial lung disease (RB-ILD) usually are reversible or nonprogressive conditions. Prostaglandin E2 (PGE2) inhibits fibroblast proliferation and myofibroblast transition, its production depending on cyclooxygenase-2 (COX-2). In patients with UIP/IPF, levels of PGE2 and COX-2 are reduced in fibroblasts, and levels of PGE2 in bronchioalveolar lavage fluid may be lowered. We analyzed the immunohistochemical expression of COX-2 in UIP/IPF, asbestosis, COP, DIP, and RB-ILD. Our results show that the metaplastic epithelium in UIP/IPF, asbestosis, and COP is widely COX-2+, whereas COX-2 positivity is scant in DIP and RB-ILD. The mesenchymal cells remained negative. Our results suggest that irrespective of the underlying disease, lung injury that causes extensive fibrosis induces wide expression of COX-2 in the regenerating metaplastic epithelium.     

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.     

Comparison of real-time PCR,conventional PCR,and galactomannan antigen detection by enzyme-linked immunosorbent assay using bronchoalveolar lavage fluid samples from hematology patients for diagnosis of invasive pulmonary aspergillosis

An iCycler iQ real-time PCR assay targeting 18S rRNA Aspergillus-specific sequences was developed for the diagnosis of invasive pulmonary aspergillosis (IPA). Positive findings were obtained for 18 of 20 (90%) bronchoalveolar lavage (BAL) fluid specimens from patients with probable or confirmed IPA and were obtained for none of the 24 BAL samples from patients with no clinical evidence of aspergillosis. These results were concordant with those of a nested PCR assay, which detected 90% of the patients with IPA, while galactomannan ELISA revealed positivity for 100% of these patients, suggesting that combined use of methods might improve the diagnosis of IPA.     

Aspergillus detection in airways of ICU COVID-19 patients: To treat or not to treat?

It is now well known that patients with severe COVID-19 are at risk for developing invasive pulmonary aspergillosis (IPA). Nevertheless, the symptomatology of IPA is often atypical in mechanically ventilated patients and the radiological aspects of SARS CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in respiratory tract samples (detected by culture, galactomannan antigen, or specific PCR) is not yet fully understood. Here we report two cases of intubated and mechanically ventilated ICU patients with SARS-CoV-2 pneumonia, in whom Aspergillus was detected in respiratory samples, who had a favorable outcome in the absence of antifungal treatment. These two cases highlight the difficulty of using the new definitions of COVID-19 associated pulmonary aspergillosis for routine management of patients.     

Chronic exposure to particles caused bronchioloalveolar carcinoma in a patient with cryptogenic organizing pneumonia evaluated by elemental analysis

An 81-year-old Japanese man had organizing pneumonia (OP), and he had worked as a painter and had a history of exposure of various paints over 20 years. The major features on computed tomography (CT) in patients were cryptogenic organizing pneumonia (COP) showing airspace consolidation, and air bronchograms were consistent finding in consolidation in right lung of S1?. Such parenchymal abnormalities were clinically and pathologically diagnosed COP and the lesion was improved by corticosteroid therapy. About 1.5 years later, similar shadows emerged in new locations of right S? and left S?, and these were bronchioloalveolar carcinoma (BAC) classified as adenocarcinoma. BAC causes similar X-ray changes to COP and inflammation accompanying BAC can also respond to corticosteroids, which may lead to delay in the diagnosis of BAC associated with COP. These radiological features lead to difficulty in making a diagnosis of new parenchymal diseases. The present patient had been painter, and metals of carcinogens were proven in both tissue of COP and BAC. Here, we reported a painter with COP and new-onset BAC who had been exposed to particles proven by elemental analysis. The combination of COP with BAC is considered uncommon, but the risk of BAC may increase when there is a history of particle inhalation.     

Invasive pulmonary aspergillosis infection in severely ill COPD patients in pulmonary ward and ICU

PurposeThis study was planned to determine the trends and susceptibility pattern of invasive pulmonary aspergillosis (IPA) in severely ill chronic obstructive pulmonary disease (COPD) patients admitted in pulmonary ward and ICU of our tertiary care centre.MethodsFifty COPD patients suspected of IPA from pulmonary ward and ICU from April 2017 to September 2018 were investigated. Samples were processed by standard methods, culture positive isolates were confirmed by MALDI-TOF MS and antifungal susceptibility testing was performed by microbroth dilution method.ResultsTwenty-two critically ill COPD patients were microbiologically positive for IA infection, of which 13 were classified as putative invasive aspergillosis. The most common comorbid illness associated was diabetes. A. flavus and A. fumigatus were the commonest species isolated. The minimum inhibitory concentration of the antifungals was low. Morbidity due to IPA in COPD patients was very high.ConclusionsPrevalence of IPA in the pulmonary ward and ICU was found to be 9.6%. MALDI-TOF seems to be a promising tool for aiding rapid identification especially for slow growing and non-sporulating fungi. Heightened awareness and suspicion for pulmonary mould infections along with early diagnosis can substantially alter the patient prognosis.     

Successful treatment of Bronchiolitis obliterans with organizing pneumonia in dialysis patient

A 42-year-old end stage renal disease (ESRD) patient was admitted with fever, anorexia, malaise, non-productive cough, and dyspnea, of one-week duration. Multiple cultures of the blood, sputum, and urine were negative for microorganisms. The possibility of bronchiolitis obliterans with organizing pneumonia (BOOP) was considered when patient with pulmonary infiltrate did not respond to conventional antibiotic therapy and frequent hemodyalisis. High-resolution computed tomography of the chest revealed patchy air-space consolidation, ground-glass opacities, and small nodular opacities, predominantly located at the peripheral part of the lungs. Cultures and stains of bronchoalveolar lavage (BAL) specimen and bronchoscopic biopsy of lung tissue were negative for organisms [bacteria, mycobacterium tuberculosis, PCP, fungus, and atypical organism] and showed evidence of BOOP. Patient recovered completely with early diagnosis and treatment with steroids and underwent successful renal transplantation with wife as donor without postoperative complication and relapse.     

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation

ObjectivesTo assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT).MethodsWe performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy.ResultsWe identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07–179.46; p 0.009) was identified as an independent risk factor for late IPA.ConclusionMore than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.     

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.