Selpercatinib is the first targeted therapy for rearranged during transfection (RET) fusion-positive unresectable non-small-cell lung cancer (NSCLC). The main adverse effects of selpercatinib include hypertension, liver dysfunction, diarrhea, and QT prolongation on electrocardiograms. However, instances of drug-induced interstitial lung disease (DI-ILD) are infrequently reported. We describe the first case of a patient with RET fusion-positive NSCLC treated with selpercatinib who developed DI-ILD, confirmed pathologically. The patient, a 72-year-old woman, initiated selpercatinib treatment following the postoperative recurrence of lung adenocarcinoma. After 15 months of treatment, computed tomography scans revealed multiple infiltrates and ground-glass opacities in both lungs. A thoracoscopic lung biopsy identified organizing pneumonia, attributed to DI-ILD caused by selpercatinib. Although she was asymptomatic, the patient\'s selpercatinib treatment was discontinued, leading to a gradual improvement in the lung infiltrates. Despite the lack of detailed reports, DI-ILD with selpercatinib represents a potentially serious adverse event and should be approached with caution.

BACKGROUND: Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis.
METHODS: Comprehensive multi-omics profiling approaches, including single-cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages.
RESULTS: The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis.
CONCLUSIONS: CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti-ferroptosis and anti-fibrosis effect of CD36 mediated, at least in part, by ceramides.
CONCLUSIONS: Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.

Pneumocystis jirovecii pneumonia (PCP) typically presents as a predominant ground-glass opacity (GGO) in the upper lobes. We report a case of a patient with PCP that mimicked organizing pneumonia or nonspecific interstitial pneumonia, showing peripheral predominant consolidation with traction bronchiectasis and peribronchovascular thickening in the lower lobes on high-resolution computed tomography (HRCT). Pneumocystis jirovecii was detected in bronchoalveolar lavage (BAL), and no other pathogens were isolated. After confirmation of a high plasma human immunodeficiency virus (HIV)-RNA titer and a low CD4+ cell count, the patient was diagnosed with PCP associated with HIV infection. The peripheral predominant consolidation was successfully resolved after treatment with trimethoprim-sulfamethoxazole. To the best of our knowledge, no previous case of PCP presenting with peripheral predominant consolidation, traction bronchiectasis, or peribronchovascular thickening has been reported. Physicians should consider PCP as a differential diagnosis even in cases suspected as organizing pneumonia or nonspecific interstitial pneumonia on HRCT.

Respiratory syncytial virus (RSV) usually causes acute respiratory tract infection in infants. In recent years, it has gradually become an important pathogen of lower respiratory tract infection in elderly people with an underlying disease. However, at present, the treatment of severe RSV pneumonia in adults is unclear, and organizing pneumonia (OP) after severe RSV infection has rarely been reported. We reported a 76-year-old man with multiple chronic heart and lung diseases who presented with fever, cough and progressive dyspnea. Finally, severe RSV pneumonia was diagnosed after his nasopharyngeal swabs and bronchoalveolar lavage metagenomic next-generation sequencing tests were positive for RSV. After combined treatment with oral ribavirin, intravenous immunoglobulin and corticosteroids, the patient\'s condition largely resolved, and he was discharged. However, when the corticosteroids were gradually tapered, the disease relapsed twice, and the patient experienced fever and aggravated dyspnea. Despite the lack of pathological evidence, we highly suspected organizing pneumonia secondary to severe RSV pneumonia based on the typical imaging manifestations and the clinical characteristics of a good response to corticosteroids. Finally, this patient was successfully treated with a course of corticosteroids and followed up for 14 months in total.

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.

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.

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.

OBJECTIVE: 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.
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.
CONCLUSIONS: 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.

BACKGROUND: Reactivation of cytomegalovirus is more common in lymphoma patients undergoing hematopoietic stem cell transplantation, but reactivation of cytomegalovirus due to chemotherapy for lymphoma has rarely been reported. We report a case of a lymphoma patient with secondary pulmonary fungal infection and cytomegalovirus infection after chemotherapy, which ultimately led to organizing pneumonia.
METHODS: Percutaneous lung biopsy, Next Generation Sequencing (NGS).
RESULTS: NGS examination suggestive of cytomegalovirus infection, percutaneous lung biopsy suggests the presence of organizing pneumonia. The patient was discharged after a combination of antifungal and antiviral treatment with posaconazole, ganciclovir, and anti-inflammatory treatment with methylprednisolone.
CONCLUSIONS: In patients with lymphoma, one should be alert for fungal and viral infections of the lungs when lung related clinical manifestations occur. Patients with persistent unrelieved symptoms after treatment should undergo lung biopsy or bronchoscopy to obtain pathologic tissue for definitive diagnosis.

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.