Diffusely distributed centrilobular micronodules and branching opacities as the main chest computed tomography manifestations in a patient with humidifier lung.

We report a 60-year-old man with humidifier lung showing diffusely distributed centrilobular micronodules and branching opacities on chest computed tomography (CT). Fever and dyspnea occurred 2 months after using an ultrasonic humidifier. KL-6 and SP-D were within normal ranges. Bronchoalveolar lavage showed elevated lymphocytes (53 %) and histological findings of transbronchial lung biopsy demonstrated organizing pneumonia. His condition improved after cessation of the humidifier. A provocation test exhibited a positive response to the humidifier. Humidifier lung should be considered as a differential diagnosis in patients with these CT findings. Detailed clinical, pathological and microbiological examinations are needed to exclude other diseases.

Ocrelizumab-induced organizing pneumonia in multiple sclerosis: case report and literature review.

Patients with relapsing-remitting multiple sclerosis should be offered disease-modifying therapies as part of their management. Recommended options include integrin antagonist therapy including natalizumab as well as anti-CD20 monoclonal antibodies like, ocrelizumab, rituximab, ofatumumab, and ublituximab. These therapies reduce relapse rates and slow brain lesion accumulation. Disease-modifying therapies selection may depend on patient preferences, potential fetal harm, and specific drug risks, requiring continuous monitoring via tracking clinical relapses and new MRI brain lesions. Natalizumab carries a risk of progressive multifocal leukoencephalopathy, particularly in anti-JCV antibody-positive patients, necessitating regular monitoring. Ocrelizumab, rituximab, and ublituximab are associated with an increased risk of infections (especially respiratory and skin infections), infusion reactions, and hypogammaglobulinemia. Ocrelizumab additionally poses a heightened risk of immune-mediated colitis and breast cancer, and it is contraindicated for patients with active hepatitis B due to the risk of viral reactivation. Ublituximab has been noted to be linked to potential fetal harm. We report the case of a 42-year-old male with relapsing-remitting multiple sclerosis on ocrelizumab who developed persistent fever and shortness of breath, two weeks after his last ocrelizumab dose. Despite antibiotic treatment for suspected pneumonia, his symptoms persisted. A chest CT scan revealed multifocal ground-glass opacities suggestive of organizing pneumonia, likely secondary to ocrelizumab. The patient's condition improved with high-dose corticosteroids, underscoring the importance of vigilance for extremely rare ocrelizumab-associated pulmonary side effects and the need for prompt, appropriate intervention.

A Diagnostic Dilemma: A Case of Complicated Pneumonia With Pyelonephritis and Subclinical Myocarditis.

A 41-year-old woman presented with a 3.5-month history of fever, weakness, productive cough, and burning micturition along with generalized weakness and significant weight loss. Chest X-ray revealed bilateral infiltrates and bilateral pleural effusion, and the workup suggested community-acquired pneumonia (CAP). However, the course was complicated by persistent fevers, elevated inflammatory markers, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and pelvic fluid collection. Extensive investigations, including bronchoscopy and lung biopsy, failed to identify a specific pathogen. Pulmonary vasculitis and lymphoma were ruled out. Antibiotic and corticosteroid therapy resulted in clinical improvement. While the cause remains unknown, brucellosis and aspergillosis were considered but ruled out with advanced testing. The underlying etiology remains elusive, highlighting the diagnostic challenges in CAP with atypical presentations.

Organizing Pneumonia With Diffuse Alveolar Hemorrhage Induced by the Kampo Medicine Choreito.

Kampo medicine, a traditional Japanese herbal medicine, is covered by the Japanese National Health Insurance and prescribed for various purposes. While relatively safe with few adverse effects, it may potentially cause severe adverse effects, such as lung injury. Herein, we describe the case of a 61-year-old Japanese woman with choreito-induced lung injury that manifested as organizing pneumonia (OP) with diffuse alveolar hemorrhage (DAH). She was referred to our department due to multiple abnormal opacities detected on annual chest radiography. Chest computed tomography (CT) revealed multiple nodules in bilateral lungs. Bloody bronchoalveolar lavage fluid was obtained from the left lingular lobe, appearing nearly normal, while a transbronchial lung biopsy from a subpleural nodule in the left lower lobe was pathologically consistent with OP. The drug lymphocyte stimulation test result was positive for choreito, which the patient had regularly consumed for 6 - 7 months to treat hematuria. Consequently, a diagnosis of choreito-induced OP and DAH was made. Owing to the discontinuation of choreito alone and without the introduction of systemic steroid therapy, the multiple nodules shrank and eventually disappeared on follow-up chest CT. Regardless of the type of crude drug used in Kampo medicine, clinicians must always be careful for potential lung injury, which may present as OP with DAH.

Rapidly Progressing Secondary Organizing Pneumonia Due to Underlying Immunosuppression With Rituximab in SARS-CoV-2 Patients.

Secondary organizing pneumonia (SOP) as a sequela to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually has a prolonged benign course with a good response to corticosteroids. We present a case series of three patients who developed rapid progression to organizing pneumonia, after initial presentation with SARS-CoV-2. Imaging revealed rapid interval progression of bilateral subpleural ground glass opacities, and lung biopsy showed dense fibroblastic plugs within the alveoli. Two patients were steroid-responsive, and one patient succumbed to his illness despite maximal therapy. We postulate that B-cell depletion and immunosuppression may cause rapid progression to SOP, as all three patients were immunosuppressed and on chronic rituximab therapy.

Cryptogenic organizing pneumonia: clinical outcomes of 60 consecutive cases.

Background: Cryptogenic organizing pneumonia (COP) improves rapidly following corticosteroid treatment; however, relapse is common. Therefore, this retrospective observational study aimed to clarify the clinical outcomes of COP and identify the predictive factors for relapse. Methods: The laboratory findings, pulmonary function test results, computed tomography (CT) findings, and clinical outcomes of 60 consecutive COP patients treated at our institution between 2007 and 2013 were retrospectively reviewed. The clinical characteristics of COP patients who did and did not show improvement were compared to identify the predictive factors for relapse in patients showing improvement. Results: Forty-one patients showed improvement without relapsing (Group 1), whereas thirteen relapsed after showing improvement (Group 2). Six patients did not show any improvement (Group 3). The serum Krebs von den Lungen-6 (KL-6) levels in Group 3 were greater than those in Groups 1 and 2 (P=0.004). The incidence of traction bronchiectasis and reticular opacities in Group 3 was higher than that in Groups 1 and 2 (P=0.048 and P=0.006, respectively). The cut-off levels of C-reactive protein (CRP), blood neutrophil fraction (%neutrophils) and lymphocyte fraction (%lymphocytes) for predicting relapse were 6.84 mg/dL, 68.7% and 14.1% in Groups 1 and 2, respectively. The log-rank test revealed that high serum CRP levels (P<0.001), high %neutrophils (P=0.003) and low %lymphocytes (P=0.006) showed significant correlations with a shorter time to the first relapse episode. Conclusions: Chest CT findings depicting pulmonary fibrosis and high serum KL-6 levels were correlated with the non-improvement of COP. Blood test results indicating inflammatory reactions were correlated with relapse in patients with COP showing improvement.

Imaging of Pulmonary Manifestations of Connective Tissue Disease.

The majority of connective tissue diseases (CTDs) are multisystem disorders that are often heterogeneous in their presentation and do not have a single laboratory, histologic, or radiologic feature that is defined as the gold standard to support a specific diagnosis. Given this challenging situation, the diagnosis of CTD is a process that requires the synthesis of multidisciplinary data which may include patient clinical symptoms, serologic evaluation, laboratory testing, and imaging. Pulmonary manifestations of connective tissue disease include interstitial lung disease as well as multicompartmental manifestations. These CT imaging patterns and features of specific diseases will be discussed in this article.

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

BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Presenting clinical and imaging features of patients with clinically amyopathic interstitial lung disease associated with myositis-specific autoantibodies.

Background: Lung involvement in the context of idiopathic inflammatory myopathies has significant impact on outcome; early and accurate diagnosis is important but can be difficult to achieve. In particular, patients without clinically evident muscle involvement pose a significant diagnostic challenge. Methods: A computer-assisted search was conducted to identify patients with amyopathic interstitial lung disease associated with the presence of myositis-specific autoantibodies. Medical records and chest imaging studies were reviewed to identify clinical and radiologic features at presentation. Results: Of the 35 patients with amyopathic interstitial lung disease associated with myositis-specific autoantibodies, the median age was 65 years (range 43-78) and 20 were women (57%). Of the patients, 34% had previously visited the rheumatology department. Presenting symptoms consisted of dyspnea (94%), cough (43%), and arthritis (23%). Raynaud phenomenon, "mechanic hands," Gottron papules, and inspiratory crackles were present in 23, 31, 9, and 74% of patients, respectively. After a detailed history, none of the patients reported muscle weakness, while four (11%) exhibited increased CK levels; of these four, two had a concomitant increase in aldolase levels. Median FVC was 79% predicted (range: 49-135) and median DLco was 50% predicted (range: 17-103). HRCT pattern was suggestive of an alternative to UIP pattern in 31/33 (94%) patients; the most common imaging patterns were NSIP (49%) and NSIP/OP (39%). Conclusion: In patients with NSIP and NSIP/OP pattern, the presence of amyopathic interstitial lung disease associated with myositis-specific autoantibodies should be considered even in the absence of clinical evident myositis.

The degree of HLA matching determines the incidence of cytokine release syndrome and associated nonrelapse mortality in matched related and unrelated allogeneic stem cell transplantation with post-transplant cyclophosphamide.

Cytokine release syndrome (CRS) occurs frequently after haplo-identical allogeneic stem cell transplantation (alloSCT) with post-transplant cyclophosphamide (PTCy), increasing nonrelapse mortality (NRM) and decreasing survival. Data on CRS in HLA-matched alloSCT are limited and effects of specific HLA-mismatches on CRS development unknown. We hypothesized that in HLA-matched alloSCT increasing degrees of HLA-mismatching influence CRS incidence, NRM and survival. Retrospective analysis of 126 HLA-matched PTCy-alloSCT patients showed that higher degrees of HLA-mismatching significantly increased CRS incidence (26%, 75% and 90% CRS with 12/12, 10/10 and 9/10 matched donors, respectively). Maximum temperature during CRS increased with higher HLA-mismatch. Specific associations between HLA-mismatches and CRS could be determined. Grade 2 CRS and CRS-induced grade 3 fever were associated with significantly increased NRM (p < 0.001 and p = 0.003, respectively) and inferior survival (p < 0.001 and p = 0.005, respectively). NRM was mainly caused by disease conditions that may be considered CRS-induced inflammatory responses (encephalopathy, cryptogenic organizing pneumonia and multi-organ failure).

Imaging of the Spectrum of Acute Lung Injury.

Organizing pneumonia, acute fibrinous and organizing pneumonia, and diffuse alveolar damage, represent multi-compartment patterns of lung injury. The initial region of injury in all remains the same and is centered on the fused basement membrane (BM) between the capillary endothelium and type I pneumocyte. Injury leads to cellular death, BM denudation, increased cellular permeability, and BM structural damage, which leads to exudation, organization, and attempts at repair. When acute lung injury does lead to fibrosis, in some instances it can lead to histologic and/or radiologic usual interstitial pneumonia or nonspecific interstital pneumonia patterns suggesting that lung injury is the primary mechanism for the development of fibrosis.

TOM5 regulates the mitochondrial membrane potential of alveolar epithelial cells in organizing pneumonia.

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.

Concentrically expanded reversed halo sign caused by nivolumab-related pneumonia.

Among immune-related adverse events, pneumonitis is relatively uncommon, and nivolumab-related pneumonitis may present with a reversed halo sign.

Idiopathic dendriform pulmonary ossification as the phenotype of interstitial lung abnormalities: CT-pathologic correlation and prevalence.

BACKGROUND AND PURPOSE: Idiopathic dendriform pulmonary ossification (DPO) is mostly asymptomatic, and detected incidentally in lung CT. There have been no reports on the precise CT-pathologic correlation and the prevalence of idiopathic DPO. This study aimed to clarify the histological background and prevalence of idiopathic DPO. MATERIALS AND METHODS: Sixteen patients with histologically confirmed idiopathic DPO (12 men and 4 women; mean age, 38.8 years; range 22-56 years) were identified in a nationwide epidemiological survey. Local HRCT findings of pre-biopsy examinations, such as branching, round, linear structures with or without high attenuation were compared side by side with histological findings. The attenuation of branching, round, and linear structures was classified into three-point levels on bone window images (width, 2500 HU; level, 500 HU). Furthermore, we collected continuous pulmonary CT images of 8111 cases for checking up metastasis from extrathoracic malignancy at a single institution, and evaluated the prevalence of interstitial lung abnormalities (ILAs) and DPO. RESULTS: In all 16 cases, branching (n = 15, 93%), round (n = 5, 31%), or linear (n = 5, 31%) structures were identified, histologically corresponding to dendriform ossification and cicatricial organizing pneumonia (OP)/fibrosis. Histologically, ossification was confirmed in all the 16 patients. However, in two cases, a highly attenuated structure could not be detected on the pre-biopsy CT of the same area. Regarding the prevalence of idiopathic DPO, 283 (3.5%) of 8111 patients had ILAs, of which a total of 26 (0.3% of all cases, 9.2% of ILAs cases) had DPO. CONCLUSION: Idiopathic DPO showed linear or branching structures with or without high attenuation on CT, corresponded to ossification, cicatricial OP/fibrosis. DPO was seen in 9.2% of ILAs cases. Idiopathic DPO is one of pathologic phenotypes of ILAs.

Brentuximab-induced pneumonitis and organizing pneumonia: a case report with literiture review.

Introduction and importance: Brentuximab vedotin (BV) is an anti-CD30 antibody approved for various cancers, including refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL) among others. In general, BV has been found to be well-tolerated, with the most frequently reported side effects being peripheral neuropathy and neutropenia. BV-induced pneumonitis is extremely rare. To the best of our knowledge, this is the sixth reported instance of BV-induced lung toxicity. Case presentation: This case presents a female patient in her forties diagnosed with cutaneous T-cell lymphoma undergoing BV treatment. She developed acute hypoxic respiratory failure, ultimately, underwent a diagnostic evaluation including a computed tomography (CT) scan, which showed bilateral airspace consolidations and ground-glass opacities, suggestive of organizing pneumonia and diffuse alveolar damage. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy ruled out infection, and pulmonary lymphoma and confirmed the diagnosis of BV-induced pneumonitis. The patient had significant clinical improvement after stopping the offending agent, and starting steroids, with optimal clinical recovery at 8 weeks follow-up. Clinical discussion: Drug-related pneumonitis poses a significant concern in the management of cancer patients. Numerous chemotherapeutic agents, such as bleomycin, cyclophosphamide, methotrexate, thalidomide, and others, have been associated with pulmonary-related toxicities. These adverse effects primarily stem from direct toxicity or immunosuppression-related infections. Less commonly, immune-mediated injury may occur. Conclusion: Physicians must have a high index of suspicion for BV-induced pneumonitis, hence, early recognition with subsequent holding of the causative agent, initiation of immunosuppression with steroids, and occasionally steroid-sparing medications, prevent an otherwise fatal outcome.

Multidisciplinary Approach to the Diagnosis of Idiopathic Interstitial Pneumonias: Focus on the Pathologist's Key Role.

Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.

COVID-19-Associated Cognitive Biases on Pneumonia Differential Diagnosis.

The coronavirus disease 2019 (COVID-19) pandemic favors cognitive biases such as anchoring and availability biases. The first refers to overvaluing some of the initial information and establishing a diagnosis too early, with resistance to future adjustments. The latter happens when diagnoses more frequently considered are regarded as more common in reality. This case, in which the correct diagnosis was delayed due to these biases, highlights the need to remain aware of them as a means toward timely diagnosis and therapeutic success of pneumonia cases. An 84-year-old woman presented with a mild non-productive cough for two months and fever. She had a history of breast carcinoma treated with radiotherapy in the previous year. Computerized tomography (CT) showed extensive bilateral consolidation foci with ground-glass-opacification areas and bilateral pleural effusion, CO-RADS 3. COVID-19 with bacterial superinfection was suspected and levofloxacin was initiated. Nasopharyngeal swab polymerase chain reaction (PCR) was carried out three times, always negative for SARS-CoV-2. As the patient remained with fever and cough, the antibiotic was escalated to piperacillin/tazobactam and then to meropenem/vancomycin. She underwent bronchofibroscopy and alveolar lavage, with negative SARS-CoV-2 PCR. The re-evaluation CT scan maintained bilateral consolidations, with an aerial bronchogram. The biopsy of pulmonary consolidation allowed the diagnosis of radiation-induced organizing pneumonia. Prednisolone was initiated and achieved clinical remission and radiological improvement. This case highlights the need to remain aware of cognitive biases both when COVID-19 is suspected or ruled out and to consider other diagnoses when there is a lack of therapeutic response.

A challenging case of drug-related acute fibrinous and organizing pneumonia: A rare case report.

A 65-year-old man presented with intermittent fever and progressive shortness of breath. He responded poorly to antibiotics and corticosteroids (methylprednisolone 40 mg/d). Chest computed tomography scans showed diffuse consolidations and ground glass density patchy opacities in both lungs and these lesions progressed rapidly. The diagnosis of acute fibrinous and organizing pneumonia (AFOP) was confirmed through transbronchial cryobiopsy. This patient had prostate cancer with bone metastasis for 4 months and took the anti-prostate cancer medications including apalutamide and leuprorelin acetate. Considering his medication history, the patient was diagnosed with AFOP induced by anti-prostate cancer medications through panel discussion of multidisciplinary teams. Intravenous methylprednisolone of 500 mg/day was administered for 3 days and then slowly tapered. The patient's shortness of breath gradually subsided. In addition, the lesions in the lungs improved significantly on follow up imaging. AFOP induced by anti-prostate cancer medications is rare. To our knowledge, this is the first reported case and high-dose glucocorticoid treatment may be required in some of these cases.