Histological transformation is an important mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer. Compared with small cell transformation, acquired squamous transformation is uncommon and remains less well characterized. We report a 52-year-old woman who underwent thoracoscopic left upper lobectomy and wedge resection of the left lower lobe for lung adenocarcinoma in April 2021. Molecular testing identified an EGFR exon 19 deletion and a TP53 c.713G>T (p.C238F) mutation. She received osimertinib, and the interval from treatment initiation to the first clinically and radiologically suspected disease progression was approximately 39 months. After this clinically suspected progression, pemetrexed plus cisplatin achieved a partial response. In August 2025, an enlarged left supraclavicular lymph node was detected, and re-biopsy confirmed squamous cell carcinoma. Systemic evaluation did not reveal evidence of a second primary malignancy. Molecular testing of the squamous lesion identified the same EGFR exon 19 deletion and TP53 mutation as those in the primary lung adenocarcinoma, providing molecular evidence consistent with a shared tumor origin and favoring acquired squamous histological transformation over a second primary squamous cell carcinoma. The patient subsequently received carboplatin, nanoparticle albumin-bound paclitaxel, and tislelizumab, achieving a radiologic partial response followed by stable disease during maintenance tislelizumab. This case highlights acquired squamous histological transformation as a rare resistance pattern after long-term osimertinib treatment. Re-biopsy and molecular comparison are important for distinguishing histological transformation from a second primary tumor. The observed response to platinum-taxane chemotherapy combined with tislelizumab should be interpreted cautiously because the relative contributions of chemotherapy and immunotherapy cannot be determined from a single case.

Airway chondronecrosis is a rare but serious manifestation of late radiation-induced toxicity. We report the case of a 67-year-old woman with epidermal growth factor receptor mutation-positive lung adenocarcinoma who developed bronchial chondronecrosis 8 years after proton-beam therapy (PBT) to the right upper lobe nodule. For 2 years, she was treated for cough-variant asthma owing to a persistent cough. Chest computed tomography (CT) showed only a subtle irregularity of the right main bronchial wall. Bronchoscopy revealed yellow necrotic deposits in the right main bronchi. Although a conventional forceps biopsy was nondiagnostic, transbronchial lung cryobiopsy (TBLC) obtained cartilage specimens, confirming bronchial chondronecrosis without malignancy. Hyperbaric oxygen therapy (HBOT) (90 sessions in total) led to symptomatic and bronchoscopic improvement. This case highlights that very-late-onset airway chondronecrosis following PBT must be considered, even with minimal CT findings. TBLC is a valuable tool for diagnosing submucosal lesions and HBOT appears to be an effective therapy.

Daptomycin is an effective antibiotic for resistant gram-positive infections, including MRSA and VRE, but can rarely cause daptomycin-induced eosinophilic pneumonia (DIEP). We present a 73-year-old woman treated for prosthetic joint infection who developed acute hypoxemic respiratory failure and peripheral eosinophilia after 21 days of daptomycin therapy. Chest imaging showed bilateral upper lobe consolidations. Symptoms resolved rapidly after stopping daptomycin, without corticosteroid use. This case highlights the need for early recognition of DIEP in patients presenting with new respiratory symptoms and eosinophilia during daptomycin therapy, enabling timely discontinuation and reducing potential morbidity.

Myoepitheliomas of the respiratory organs are extremely rare. We report a case of endobronchial myoepithelioma in a 43-year-old woman presenting to hospital with a cough. Chest computed tomography (CT) showed consolidation in the lingular segment of her left upper lobe. She was initially diagnosed as having pneumonia and treated with antibiotics, but her symptoms persisted. We then performed diagnostic bronchoscopy and observed a smooth, elevated lesion obstructing the lingular bronchus. Positron emission tomography/CT revealed a nodule in the lingular bronchus of the left upper lobe with fluorodeoxyglucose (FDG) uptake, while the consolidation had disappeared. Left upper lobectomy was performed, and on the basis of the pathological findings including immunostaining, she was finally diagnosed as having myoepithelioma. There has been no recurrence during an 18-month follow-up. Although myoepithelioma is a rare disease, it should be considered in the differential diagnosis of nodules with FDG uptake.

Osimertinib is recommended not only for advanced EGFR-mutated non-small cell lung cancer (NSCLC) but also as adjuvant therapy after complete resection, leading to increasing opportunities for its clinical use. However, interstitial lung disease (ILD) is a serious adverse event, and its incidence and severity have been reported to be higher in Japanese patients. We report a fatal case of osimertinib-related ILD that developed during adjuvant therapy in a patient undergoing maintenance hemodialysis after left pneumonectomy. A 71-year-old man was found to have a left upper lobe mass on chest computed tomography (CT) performed at the initiation of maintenance hemodialysis for nephrosclerosis. Transbronchial biopsy was nondiagnostic; however, lung cancer was strongly suspected clinically, and video-assisted thoracoscopic left pneumonectomy with mediastinal lymph node dissection was performed. Pathological examination revealed lung adenocarcinoma harboring an EGFR exon 19 deletion, pT2aN2bM0 (stage IIIB). Adjuvant osimertinib (80 mg/day) was initiated. Exertional dyspnea developed 37 days after treatment initiation, and chest CT on day 40 revealed peripheral ground-glass opacities in the remaining right lung. Osimertinib was discontinued, and empirical antibiotic therapy was initiated because both osimertinib-related ILD and infection were considered in the differential diagnosis. Shortly after admission, the patient developed rapidly progressive respiratory failure. Although steroid pulse therapy led to temporary improvement, the respiratory status deteriorated again, and the patient died on day 57 after osimertinib initiation despite an additional course of steroid pulse therapy. This case highlights that osimertinib-related ILD can become fatal not only in advanced or recurrent disease but also during curative-intent adjuvant therapy. Careful monitoring and prompt evaluation and intervention are particularly important in patients with poor respiratory reserve.

A 68-year-old man presented to our thoracic surgery department for evaluation of a left upper-lobe pulmonary nodule detected on chest CT scan. The oncologic history extended over 7 years. In December 2014, the patient was diagnosed with colorectal adenocarcinoma (ileocecal junction) by colonoscopy, and he underwent a laparoscopic right hemicolectomy and lymph node dissection. Postoperative pathological examination revealed a grade II-III adenocarcinoma of the ileocecal region (ulcerative type), infiltrating into the muscularis. Surgical margins were free of tumor. No metastasis was identified in the examined lymph nodes, including paracolic (19), paracolic (7), intermediate mesenteric (23), and central vascular (2) lymph nodes, corresponding to a pathologic stage of pT2N0M0. The patient recovered well and was placed on regular follow-up.

Pulmonary tuberculosis (TB) remains a major global health concern and may present with radiographic and laboratory findings that complicate timely diagnosis. Interferon-gamma release assays (IGRAs), including QuantiFERON-TB Gold, are blood tests that measure T-cell immune sensitization to Mycobacterium tuberculosis antigens; they do not distinguish latent infection from active disease and cannot exclude active TB. We report a 23-year-old immunocompetent Venezuelan-born man who presented with fever, night sweats, productive cough, and intermittent hemoptysis after approximately seven months of respiratory symptoms. Chest imaging demonstrated multilobar cavitary disease involving both upper lobes and the left lower lobe. Despite a negative QuantiFERON-TB Gold result, two sputum acid-fast bacilli smears were positive, M. tuberculosis nucleic acid amplification testing was positive, and mycobacterial culture confirmed the M. tuberculosis complex. The patient was placed in airborne isolation and treated with rifampin, isoniazid, pyrazinamide, and ethambutol. Public health authorities coordinated directly observed therapy, contact investigation, and outpatient sputum monitoring. This case demonstrates that a negative IGRA cannot rule out active pulmonary TB and that atypical multilobar cavitation should not lower clinical suspicion when epidemiologic, clinical, and microbiologic findings support the diagnosis.

Combined lung carcinomas containing both non-small cell and high-grade neuroendocrine components are rare and diagnostically challenging due to intratumoral heterogeneity. We report a 61-year-old never-smoking woman with pleuritic chest discomfort and chronic cough. Computed tomography (CT) and positron emission tomography (PET)/CT demonstrated a left upper-lobe pulmonary nodule with intensely FDG-avid hilar and mediastinal lymphadenopathy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of FDG-avid lymph nodes was nondiagnostic. Given persistent clinical and radiologic concern for malignancy, the patient underwent video-assisted thoracoscopic surgery (VATS) for definitive diagnosis. Pathology revealed a rare triple-component malignancy composed of adenocarcinoma, large-cell neuroendocrine carcinoma, and small-cell lung carcinoma, with metastatic neuroendocrine carcinoma involving mediastinal lymph nodes and pleura, consistent with stage IVA disease. The patient was subsequently treated with platinum-etoposide-based systemic therapy, with immunotherapy planned as part of her treatment course. This case highlights that nondiagnostic minimally invasive sampling does not exclude malignancy and underscores the importance of radiologic-pathologic concordance, awareness of sampling limitations, and timely escalation to additional tissue acquisition, including surgical biopsy when appropriate.

Pneumoconiosis complicated with pulmonary tuberculosis is characterized by high prevalence and disability rates, as well as difficulty in early diagnosis, constituting a serious public health problem. The Chinese Society of Tuberculosis (Chinese Medical Association) and the Society of Labor Hygiene and Occupational Diseases (Chinese Preventive Medicine Association) organized multidisciplinary experts in respiratory diseases, occupational diseases, tuberculosis and other related fields to formulate the Chinese expert consensus on the diagnosis and treatment of pneumoconiosis complicated with tuberculosis. This consensus aims to enhance professional practitioners' understanding of the disease, improve the capacity for early clinical diagnosis, and further advance the prevention and treatment of pneumoconiosis complicated with pulmonary tuberculosis in China. It summarizes 12 key clinical issues and proposes 13 targeted recommendations to address difficulties and misconceptions in clinical practice. This consensus was registered on the International Practice Guidelines Registry Platform (PREPARE-2024CN271). It aims to enhance the standardized diagnosis and treatment of pneumoconiosis complicated by pulmonary tuberculosis, improve patient outcomes, and provide practical guidance for the prevention and control of occupational and infectious diseases in China. The main recommendations are as follows.Recommendation 1: Clinicians and pathologists are advised to pay attention to the mixed pathological features of pneumoconiosis complicated with pulmonary tuberculosis. For patients with pneumoconiosis presenting atypical imaging manifestations or poor response to conventional treatment, pathological specimens should be actively obtained to confirm the diagnosis. Combined use of acid-fast staining, Mycobacterium tuberculosis culture or molecular pathological detection is recommended to increase the detection rate (2C).Recommendation 2: When performing chest CT examinations and dynamic follow-up for pneumoconiosis patients, clinicians and radiologists should focus on multifocal and polymorphic lesions, as well as short-term imaging changes suggestive of active tuberculosis (2C).Recommendation 3: For patients with suspected pulmonary tuberculosis complicated with pneumoconiosis: (1) Be aware that sputum bacteriological tests may yield false-negative results due to dust interference. Repeated sampling or combined detection methods are recommended, including bacteriological and molecular tests on bronchoalveolar lavage fluid (BALF) obtained via bronchoscopy. Results of immunological assays such as the interferon-γ release assay (IGRA) and tuberculin skin test (TST)shall also be combined for comprehensive judgment. (2) In cases with atypical imaging findings and clinical symptoms, bronchoscopy-guided pathological sampling (e.g., EBUS-GS [endobronchial ultrasound with guide sheath], ENB [electromagnetic navigation bronchoscopy]) is prioritized. When microbiological evidence is insufficient, percutaneous lung biopsy or pleural biopsy (for patients with pleural effusion) is suggested to clarify the diagnosis (2B).Recommendation 4: The diagnosis of pneumoconiosis complicated with pulmonary tuberculosis shall follow the integrated diagnostic principle. Provided that patients meet the national diagnostic criteria for pneumoconiosis and pulmonary tuberculosis respectively, a comprehensive assessment shall be conducted combining occupational exposure history, dynamic imaging changes and laboratory results. Patients shall be stratified for managementaccording to the activity of tuberculosis (2C).Recommendation 5: For differential diagnosis between pneumoconiosis complicated with pulmonary tuberculosis and non-tuberculous mycobacterial (NTM) lung disease: (1) NTM lung disease commonly involves the apical and anterior segments of the upper lobes, the right middle lobe and the lingular segment of the left upper lobe. Typical imaging manifestations include a combination of centrilobular nodules and bronchiectasis. (2) Multiple thin-walled cavities are frequently seen in silicosis complicated with NTM lung disease. (3) Pathologically, NTM lesions are dominated by epithelioid granulomas with inconspicuous caseous necrosis. (4) Definitive diagnosis relies on mycobacterial culture and species identification, complying with combined clinical, imaging and microbiological criteria (2C).Recommendation 6: For patients with pneumoconiosis complicated with pulmonary tuberculosis who present progressively enlarged cavities or newly developed cavities accompanied by aggravated symptoms after anti-tuberculosis treatment, radiologists shall evaluate imaging signs of pulmonary aspergillosis, such as the early halo sign and the late air crescent sign within cavities (2C).Recommendation 7: For patients with suspected pneumoconiosis complicated with pulmonary aspergillosis: (1) Bronchoscopy is performed to collect BALF or tissue specimens for fungal culture and pathological examination (gold standard). (2) Conduct BALF galactomannan (GM) test, metagenomic next-generation sequencing (mNGS) or other DNA detection assays. (3) Detect serum specific antibodies against Aspergillus fumigatus (e.g., IgE-m3, IgM) (1A).Recommendation 8: For patients with pneumoconiosis complicated with drug-susceptible pulmonary tuberculosis: (1) Adopt the standard first-line four-drug anti-tuberculosis regimen. (2) Ensure a sufficient treatment course (generally ≥6-8 months). (3) Extend the treatment course to≥9-12 months for patients with severe lesions or concomitant tracheal, pleural or extrapulmonary tuberculosis, so as to improve clinical outcomes and reduce recurrence (2A).Recommendation 9: For patients receiving concurrent treatment for pneumoconiosis (including tetrandrine, nintedanib, pirfenidone, glucocorticoids, bronchodilators, etc.) and rifampicin-containing anti-tuberculosis regimens: (1) Be aware that rifampicin, a potent hepatic enzyme inducer, may accelerate the metabolism of concomitant drugs such as glucocorticoids and nintedanib and reduce their efficacy. (2) Adjust the dose of affected drugs accordingly when rifampicin is initiated or discontinued (1B).Recommendation 10: Extracorporeal membrane oxygenation (ECMO) may be used as a bridge to lung transplantation only for end-stage pneumoconiosis patients complicated with pulmonary tuberculosis awaiting transplantation (2D).Recommendation 11: For end-stage patients with pneumoconiosis complicated with pulmonary tuberculosis who have received adequate and standard anti-tuberculosis therapy, the feasibility of lung transplantation shall be evaluated. Pre-transplant precautions: (1) Ensure complete control of active tuberculosis. (2) Optimize the anti-tuberculosis regimen (e.g., replace rifampicin with rifabutin) to maintain the effective concentration of immunosuppressants (2D).Recommendation 12: For patients with severe, end-stage pneumoconiosis complicated with pulmonary tuberculosis who no longer benefit from active treatment, palliative care and hospice care shall be initiated. Clinicians and medical teams shall communicate fully with patients and their families about the condition, prognosis, treatment options and medical burden. The core goals are to relieve symptoms, alleviate suffering and improve quality of life (2D).Recommendation 13: For patients with pneumoconiosis complicated with tuberculosis who meet the indications for surgical or interventional therapy, a multidisciplinary team shall conduct joint decision-making and implement treatment in a timely manner after full assessment of pulmonary function, nutritional status and surgical risks. Surgical treatment is mainly indicated for patients with drug-resistant tuberculosis with localized lesions, persistent cavitary lesions with ongoing mycobacterial excretion, destroyed lung, massive hemoptysis unresponsive to medical treatment, tuberculous empyema and other critical conditions. Interventional therapy can be applied for emergency treatment of massive hemoptysis, as well as palliative treatment for pulmonary artery stenosis secondary to tuberculosis or pneumoconiosis (2C).

Ankylosing spondylitis (AS) is a chronic inflammatory disorder of the axial skeleton, occasionally complicated by uncommon but increasingly recognized pulmonary involvement such as interstitial lung disease (ILD). We report a 35-year-old woman with a year-long history of inflammatory back pain and peripheral arthritis who fulfilled clinical and radiologic criteria for AS. Despite partial response to cDMARDs, she developed a productive cough. High-resolution CT revealed right upper-lobe ground-glass opacities consistent with early cellular ILD, supported by spirometry showing a moderate restrictive defect and negative autoimmune serology excluding overlapping connective tissue diseases. Conservative pulmonary monitoring and escalation to secukinumab resulted in marked improvement in both musculoskeletal and respiratory symptoms. This case highlights clinically under-recognized pulmonary involvement in AS, including early inflammatory (cellular) ILD, emphasizing diagnostic challenges and the importance of timely imaging and multidisciplinary management.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with frequent extra-articular manifestations, of which pulmonary involvement is the most common and clinically significant. Combined pulmonary fibrosis and emphysema (CPFE) is a distinct clinic-radiological syndrome characterized by the coexistence of upper-lobe emphysema and lower-lobe fibrosis and is increasingly recognized in patients with connective tissue diseases, including RA. We describe the case of a 50-year-old nonsmoking woman who presented with a 3-year history of progressive exertional dyspnea and chronic dry cough, preceding the onset of inflammatory polyarthritis by nearly 2 years. She later developed symmetrical involvement of small and large joints with prolonged morning stiffness, along with constitutional symptoms including low-grade fever and weight loss. Physical examination revealed grade IV digital clubbing and bibasilar inspiratory crackles. Laboratory evaluation showed elevated inflammatory markers with negative rheumatoid factor and anticyclic citrullinated peptide antibodies, consistent with seronegative RA. High-resolution computed tomography of the thorax showed upper lobe emphysema and lower lobe honeycombing, confirming the diagnosis of CPFE. Pulmonary function testing showed relatively preserved airflow with mildly reduced diffusion capacity, along with severe exercise-induced desaturation. Echocardiography revealed mild pulmonary hypertension. This case highlights an uncommon presentation of rheumatoid arthritis-associated combined pulmonary fibrosis and emphysema (RA-CPFE), where pulmonary manifestations preceded articular disease, emphasizing the need for a high index of suspicion. Early recognition through high-resolution computed tomography (HRCT) and comprehensive pulmonary evaluation is crucial, as RA-CPFE is associated with significant morbidity, pulmonary hypertension, and poor prognosis. Multidisciplinary management incorporating immunosuppressive therapy, consideration of antifibrotics in progressive disease, and supportive care remains essential. Further studies are required to better define optimal treatment strategies and prognostic markers in RA-CPFE.