Cavitating lung lesions are a common radiological finding with a broad differential diagnosis, including infectious, malignant and inflammatory causes. Management of infective lesion is often challenging, particularly when disease progresses despite appropriate medical therapy. We report a case of progressive, unilobar cavitating lung disease in a 59-year-old man related to Aspergillus colonization and Streptococcus constellatus infection, despite prolonged optimal antibacterial and antifungal treatment. Initial bronchoscopic investigations identified Aspergillus hyphae, but repeated conventional microbiological sampling failed to detect the underlying bacterial pathogen. Serial imaging demonstrated persistent progressive cavitation coalescing into large fluid-filled abscess confined to upper lobe, prompting surgical intervention. The bacterial pathogen was only identified after lobectomy, with cultures confirming S. constellatus. This case highlights the limitations of standard diagnostic techniques, the importance of recognising failure of medical therapy and the role of timely thoracic surgical resection in achieving definitive source control in anatomically localised infective cavitating lung disease.

While adeno-associated virus (AAV) vectors have demonstrated efficacy in multiple organ systems, gene delivery to the lung remains an unmet therapeutic target. To treat a monogenic lung disease like surfactant protein B deficiency, a gene delivery system must overcome pulmonary barriers and be validated in models that closely resemble the human respiratory tract. Here, we optimized the endotracheal delivery of AAV6.2FF, an engineered capsid with enhanced pulmonary tropism, in neonatal piglets with lung features comparable to those of human newborns. We optimized delivery parameters that improved pulmonary distribution and applied them to administer AAV6.2FF expressing secreted alkaline phosphatase (SEAP) at two different doses: 5 × 1012 vg/kg and 1.73 × 1013 vg/kg to assess transgene expression, biodistribution, and the safety and tolerability of this AAV platform. Transgene expression was dose-dependent, with the higher dose producing more robust and widespread SEAP expression across the cranial, middle, accessory, and upper caudal lobe regions. Both doses were well tolerated, with low anti-AAV6.2FF IgG titers and no hematology and biochemistry markers showing trends indicative of systemic toxicity. This study establishes the neonatal pig as a clinically relevant model for optimizing lung-directed AAV dosing and delivery, while also highlighting the need for further optimization to maximize this platform's therapeutic potential.

Stereotactic body radiotherapy (SBRT) is an established non-invasive treatment for early-stage non-small cell lung cancer (NSCLC) in patients who are medically inoperable or who decline surgery. However, delivering SBRT to tumors within atelectasis presents unique challenges due to anatomical distortion, impaired tumor visualization, and uncertainties in target motion and localization. A 61-year-old woman with severe chronic obstructive pulmonary disease on long-term home oxygen therapy was diagnosed with biopsy-confirmed right upper lobe lung adenocarcinoma located within an area of atelectasis. She was medically inoperable due to critically reduced pulmonary reserve. Staging positron emission tomography-computed tomography (PET-CT) revealed a focal hypermetabolic right upper lobe lesion with no evidence of nodal or distant metastases. The patient received single-fraction SBRT (SF-SBRT) to 34 Gy using a 1 cm isotropic planning target volume margin to account for increased planning and treatment-related uncertainties. Target delineation was guided by PET-CT to distinguish metabolically active tumor from surrounding atelectasis, and image guidance was performed using cone-beam CT matching to surrogate anatomic landmarks due to limited direct tumor visualization. At 6.1 months after SBRT, the patient demonstrated significant metabolic response on PET-CT but developed rapidly progressive brain metastases and died 6.6 months after SBRT. This case demonstrates the feasibility of SF-SBRT for early-stage NSCLC within atelectasis. While short-term metabolic response was achieved, long-term local control remains unclear and further research into the management of lung tumors within atelectasis is warranted.

Pulmonary nodules detected in patients with a history of malignancy are often clinically presumed to represent metastatic disease until proven otherwise. Granular cell tumor (GCT) is an uncommon, usually benign neoplasm of presumed Schwannian origin, which rarely occurs in the lung. Our aim is to emphasize the diagnostic challenges and the crucial role of histopathology in preventing overtreatment in oncology patients. Herein, we report the case of a 56-year-old woman with a previous history of papillary renal cell carcinoma diagnosed one year earlier, staged as pT1, WHO/ISUP grade 2, and treated with partial nephrectomy, with no evidence of residual disease or distant metastases at follow-up. During routine surveillance, she developed a solitary pulmonary nodule. Chest computed tomography (CT) showed a 12 mm solid nodule in the left upper lobe which was then further investigated with a positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose [(18F)-FDG PET/CT, revealing a low glucidic uptake (SUVmax 4 and SUV mean 1.4). Endobronchial ultrasound-guided biopsy was non-diagnostic. Given the patient's oncological history, the solid appearance on CT, and the mild FDG uptake, metastatic disease could not be excluded, and a parenchyma-sparing diagnostic wedge resection was performed. Histology showed a well-circumscribed proliferation of epithelioid cells with abundant granular eosinophilic cytoplasm and bland nuclei. Immunohistochemistry demonstrated diffuse S100 and CD68 positivity, supporting the diagnosis of primary pulmonary granular cell tumor. This case underscores the critical role of histopathological evaluation in the assessment of solitary pulmonary nodules, emphasizing that lesions identified during oncologic surveillance are not invariably indicative of malignancy.

Pleural plaques are the most common manifestation of asbestos-related pleural disease and function primarily as markers of prior exposure rather than as direct causes of clinically significant symptoms, often appearing several decades after initial contact. They are typically asymptomatic and discovered incidentally on imaging studies or at autopsy, and they initially present as small, well-circumscribed lesions along the parietal pleura, most commonly over the rib surfaces while sparing the intercostal spaces. They may progressively enlarge, coalesce, and undergo calcification over time. Although asbestos exposure is the primary etiology, pleural plaques and pleural calcifications may also arise from prior infections such as tuberculosis or empyema, trauma, hemothorax, end-stage renal disease, or chronic inflammatory and autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis, and in some instances they may be idiopathic. Additionally, pleural plaques can be associated with mesothelioma. When extensive, pleural plaques may restrict lung expansion, leading to exertional dyspnea that can progress to dyspnea at rest and, in advanced cases, respiratory insufficiency. During routine cadaveric dissections conducted as part of the preclinical medical curriculum at the Geisinger Commonwealth School of Medicine (GCSOM), Scranton, Pennsylvania, extensive bilateral pleural thickening, predominantly involving the diaphragmatic pleura, was observed in an 89-year-old male cadaver. After the opening of the thoracic cage and removal of the lungs and heart, pleural plaques were identified, examined, and measured. The pleural cavities were relatively free, with minimal adhesions involving the bases of both lungs in the diaphragmatic regions, and any evidence of pleural effusion was likely lost during the dissection process. Small, isolated pleural plaques were also noted along the anterior aspect of the right parietal costal pleura. A small, firm mass was palpated within the anterior border of the right upper lobe. Tissue specimens were obtained from the pleural plaques of the anterior chest wall and diaphragmatic pleura, as well as from the pulmonary mass, for histopathological evaluation. Microscopic examination demonstrated abundant fibrocollagenous thickening of the parietal pleura with adjacent fibro-adipose connective tissue and associated inflammation, without evidence of asbestos fibers. Histological analysis of the pulmonary mass was consistent with acute pneumonia. Pleural plaques are frequently encountered as incidental findings on chest radiographs and computed tomography scans in elderly individuals, particularly those with prior asbestos exposure, yet many such findings remain clinically uninvestigated during life. Establishing an etiology in cadaveric cases poses a significant challenge due to the absence of reliable occupational, environmental, and medical histories. While the histopathologic features observed in this case are consistent with previously published descriptions, the gross anatomical documentation of extensive pleural plaques predominantly confined to the diaphragmatic pleura, including detailed measurements, texture, and imaging, has not been previously reported. Dissemination of these findings aims to enrich anatomical and pathological educational resources, support future research, and deepen the understanding of pleural pathology encountered during cadaveric dissection and medical education.

Mediastinal displacement toward the side of lung volume loss is a well-recognized radiographic feature of atelectasis. Significant mediastinal shift most commonly occurs when larger lung segments, such as the right upper or lower lobes, collapse. Because the right middle lobe (RML) contributes a relatively small proportion of total lung volume, isolated RML collapse typically produces minimal mediastinal deviation. The case in this report is of an 83-year-old woman with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF), who presented with progressive dyspnea and increased oxygen requirements. Chest radiography demonstrated opacification of the right middle lobe with marked rightward displacement of the cardiac silhouette. Computed tomography (CT) of the chest confirmed isolated collapse of the right middle lobe with rightward mediastinal and cardiac displacement, without involvement of the right upper or lower lobes. Bronchoscopy revealed narrowing of the right middle lobe bronchus due to floppy cartilage consistent with bronchomalacia and no evidence of endobronchial mass or malignancy. The patient improved with conservative medical management, including diuresis, bronchodilators, and pulmonary hygiene. This case demonstrates that isolated RML collapse can produce significant mediastinal and cardiac displacement. Clinicians should recognize that even the collapse of relatively small lung segments may generate substantial radiographic shift, particularly in patients with underlying airway structural abnormalities or pulmonary hyperinflation.

BACKGROUND Patients with primary or secondary immunosuppression can be treated with trimethoprim-sulfamethoxazole (TMP-SMX) as long-term prophylaxis to prevent opportunistic infections. Nocardia africana/nova is an aerobic, gram-positive opportunistic organism. This case report describes a patient with systemic lupus erythematosus (SLE) on low-dose TMP-SMX prophylaxis who developed nocardiosis due to N. africana/nova. CASE REPORT A 56-year-old Chinese woman with SLE on long-term low-dose TMP-SMX prophylaxis underwent partial right lung lobectomy in July 2023 after incidental pulmonary lesions were detected. Pathology revealed a cryptococcal granuloma, which was treated with fluconazole. In November 2024, chest computed tomography (CT) showed progressive pulmonary nodules and right upper lobe consolidation despite antibacterial and antifungal therapy, including voriconazole guided by next-generation sequencing. CT-guided lung biopsy confirmed pulmonary nocardiosis caused by N. africana/nova, susceptible in vitro to TMP-SMX. High-dose TMP-SMX plus linezolid led to radiologic improvement, after which TMP-SMX monotherapy was continued. In March 2025, she was readmitted with acute altered mental status, recurrent cavitary pulmonary disease, pleural effusion, and multiple ring-enhancing cerebral abscesses, consistent with disseminated nocardiosis. Further aggressive treatment was declined, and she was discharged for palliative care. CONCLUSIONS Nocardiosis is challenging to diagnose and treat in immunocompromised patients, as breakthrough infections can occur despite in vitro susceptibility, reflecting the roles of host immunity and drug factors. Clinicians should maintain a high index of suspicion for nocardiosis in patients receiving corticosteroids or other immunosuppressive therapies and recognize that in vitro susceptibility does not always predict in vivo therapeutic success. This report highlights that breakthrough nocardia can occur with appropriate low-dose TMP-SMX prophylaxis.

Cutibacterium acnes (formerly Propionibacterium acnes) is a gram-positive, strict anaerobic bacillus that is part of the normal skin and mucosal microbiota. It is recognized as an opportunistic pathogen, mainly involved in implant-associated infections. Pleuropulmonary localizations remain exceptional, and parenchymal involvement is rare, most often in immunocompromised patients or those with severe underlying respiratory diseases. We report the case of a 34-year-old chronic smoker, immunocompetent, who presented with a one-year history of productive cough, progressive dyspnea, hemoptysis, fever, and weight loss. Chest imaging revealed a cavitary consolidation in the right upper lobe associated with mediastinal lymphadenopathy, initially suggestive of pulmonary tuberculosis or lung malignancy. Laboratory findings showed an inflammatory syndrome (white blood cell count 12,000/mm[3]; C-reactive protein 132 mg/L). Repeated microbiological investigations as well as bronchial and CT-guided transthoracic biopsies were negative, showing neither malignancy nor granulomatous inflammation. Due to clinical and radiological worsening, a surgical biopsy via thoracotomy was performed. Bacteriological analysis yielded a positive culture for C. acnes, leading to the diagnosis of lung abscess caused by this organism. The patient received ceftriaxone 2 g/day for six weeks, with favorable clinical, biological, and radiological outcomes, including resolution of hemoptysis, improvement of respiratory symptoms, normalization of inflammatory markers, and significant radiological regression. Pleuropulmonary infections of C. acnes are rare and typically characterized by an insidious clinical presentation related to the organism's slow growth. Diagnosis is challenging because of the risk of sample contamination and the need for prolonged and appropriate anaerobic culture conditions. This case highlights that C. acnes may cause lung abscess even in immunocompetent patients and may mimic more common conditions such as tuberculosis or lung cancer. Early recognition and appropriate antibiotic therapy are essential to ensure favorable outcomes.

BACKGROUND Hepatocellular carcinoma (HCC) most commonly metastasizes to the lungs, but endobronchial metastasis is an exceedingly rare manifestation associated with a poor prognosis. Surgical resection is seldom considered, with only 2 previously reported cases. This case is presented to highlight the diagnostic challenges of endobronchial metastasis and to report the novel use of an anatomic lung-preserving sleeve resection for definitive treatment, an approach not previously described for this condition. CASE REPORT A 62-year-old man with a history of hepatitis B virus infection and prior right hepatectomy for HCC (pT2N0M0, CNLC Ib) presented with a 5-month history of hemoptysis 43 months after the initial liver surgery. Chest computed tomography (CT) and positron emission tomography (PET)-CT identified a right hilar mass. Two preoperative bronchoscopies with immunohistochemical staining (TTF-1, Napsin A, GPC3, Arg-1) were inconclusive, suggesting a poorly differentiated non-small cell carcinoma. Following disease progression on 3 cycles of neoadjuvant chemoimmunotherapy, the patient proceeded to multidisciplinary team-recommended surgery 4 weeks after the final cycle. The patient successfully underwent a uniportal video-assisted thoracoscopic surgery, during which a right upper lobe sleeve resection was performed, accompanied by resection and repair of the superior vena cava wall. Final histopathology confirmed metastatic HCC. The patient's postoperative recovery was uneventful, with complete resolution of symptoms, and no recurrence was observed during the 3-month postoperative follow-up. CONCLUSIONS This case underscores that endobronchial metastasis from HCC can pose a significant diagnostic dilemma, often requiring surgical resection for definitive diagnosis. It demonstrates that sleeve resection is a technically feasible and oncologically sound option for solitary endobronchial metastasis, achieving complete tumor removal while preserving lung function. This approach should be considered in carefully selected patients with controlled primary disease and good status. The decision-making process emphasizes the critical role of a multidisciplinary team in managing complex metastatic HCC.