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A radiographic image of the fibrous dysplasia disorder of a 12-year-old boy diagnosed with Hodgkin's disease is presented.

Background and Objectives: Since the launch of ChatGPT in 2023, large language models have attracted substantial interest to be deployed in the health care sector. This study evaluates the performance of ChatGPT-4o as a support tool for decision-making in multidisciplinary sarcoma tumor boards., Methods: We created five sarcoma patient cases mimicking real-world scenarios and prompted ChatGPT-4o to issue tumor board decisions. These recommendations were independently assessed by a multidisciplinary panel, consisting of an orthopedic surgeon, plastic surgeon, radiation oncologist, radiologist, and pathologist. Assessments were graded on a Likert scale from 1 (completely disagree) to 5 (completely agree) across five categories: understanding, therapy/diagnostic recommendation, aftercare recommendation, summarization, and support tool effectiveness., Results: The mean score for ChatGPT-4o performance was 3.76, indicating moderate effectiveness. Surgical specialties received the highest score, with a mean score of 4.48, while diagnostic specialties (radiology/pathology) performed considerably better than the radiation oncology specialty, which performed poorly., Conclusions: This study provides initial insights into the use of prompt-engineered large language models as decision support tools in sarcoma tumor boards. ChatGPT-4o recommendations regarding surgical specialties performed best while ChatGPT-4o struggled to give valuable advice in the other tested specialties. Clinicians should understand both the advantages and limitations of this technology for effective integration into clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2025 Ammo, Guillaume, Hofmann, Ulmer, Buenting, Laenger, Beier and Leypold.)

A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged researchers to extend these studies to ACD and compare the changes of the microvasculature. Lung tissue samples of children with ACD (n = 12), adults with non-specific interstitial pneumonia (n = 12), and controls (n = 20) were studied using transmission electron microscopy, single-gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1, PTK2B, and FN1 and decreased VIT expression, confirmed by immunohistochemistry. In contrast, non-specific interstitial pneumonia samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1 + vessels. This study provides insight into the ultrastructure and pathophysiology of ACD. The lack of normally developed lung capillaries appeared to cause a replacement by COL15A1 + vessels, a mechanism recently described in interstitial lung disease. The VIT loss and FN1 overexpression might contribute to the unique appearance of basement membranes in ACD. Future studies are needed to explore the therapeutic potential of down-regulating the expression of FN1 and balancing VIT deficiency., Competing Interests: Disclosure Statement J.C.S. received fees for lectures from Boehringer Ingelheim and Kinevant, all outside the present study. T.W. declares funding by the German Ministry of Research and Education. M.M.H. received fees for lectures and consultations from Acceleron, Actelion, AOP, Bayer, Janssen, MSD, and Pfizer, all outside the present study. J.F. received personal fees/speaker honoraria from AstraZeneca, outside the submitted work. M.G. received fees for lectures from Boehringer Ingelheim, participates in an adjudication board in a nintedanib clinical trial, and received a research grant from Boehringer Ingelheim. D.D.J. received fees for lectures from Boehringer Ingelheim and declares a research contract with Boehringer Ingelheim (contract number 43099358). All other authors declare no existing conflicts of interest., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome and aplasia of lacrimal and salivary glands. Previous studies indicate that pathogenic variants in FGF10 can cause childhood Interstitial Lung Disease (chILD) due to severe diffuse developmental disorders of the lung, but detailed reports on clinical presentation and follow-up of affected children are lacking., Methods: We describe four children with postnatal onset of chILD and heterozygous variants in FGF10, each detected by exome or whole genome sequencing., Results: All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years due to right heart failure related to severe pulmonary hypertension (PH) and one patient is alive at age of 6 years, but still symptomatic. Histopathological analysis of lung biopsies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia and interstitial fibrosis. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis., Discussion: Our report extends the phenotype of FGF10-related disorders to early onset chILD with progressive interstitial lung fibrosis and PH. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints and PH., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Rationale: Variable disease course and outcomes have been reported in children's interstitial lung disease associated with FLNA (Filamin A gene) variants. Objectives: To further delineate long-term respiratory outcomes and identify potential contributing factors to severe disease course. Methods: We retrospectively collected longitudinal data from three centers on nine cases (one male) with FLNA variants and early respiratory disease onset (within the first 24 mo of life). Clinical, radiographic, and histopathologic data were analyzed, focusing on cardiorespiratory disease course. Results: All required early respiratory support (three invasive ventilation, three noninvasive ventilation, three supplemental oxygen), and all experienced frequent severe infective respiratory exacerbations. Three died in infancy from refractory respiratory failure and pulmonary hypertension (PH). The six surviving individuals were 3, 10, 11, 15, 18, and 33 years old at time of reporting. The extent of functional respiratory impairment decreased with age; at last follow-up, there were no individuals on home invasive ventilation, one on nocturnal noninvasive ventilation, four on oxygen, and one on no respiratory support. Spirometry consistently demonstrated moderate to severe obstructive defects (forced expiratory volume in 1 s/forced vital capacity [FVC] z -score, -3.76 to -1.77; percent predicted FVC, 31.5% to 92.1%). Seven required PH treatment in early childhood (7/9), and three of the survivors (3/6) still receive treatment. Radiologic and histopathologic findings were consistent among cases. Conclusions: Early mortality was common, but many survivors stabilized even after severe symptoms in infancy. All survivors had persistent obstructive defects on spirometry, and half have persistent or recurrent PH. These typical findings are suggestive of this rare diagnosis and should prompt consideration of genetic testing.

Alveolar capillary dysplasia (ACD) is a rare lung developmental disorder leading to persistent pulmonary arterial hypertension and fatal outcomes in newborns. The current study analyzed the microvascular morphology and the underlying molecular background of ACD. One ACD group (n = 7), one pulmonary arterial hypertension group (n = 20), and one healthy con1trol group (n = 16) were generated. Samples of histologically confirmed ACD were examined by exome sequencing and array-based comparative genomic hybridization. Vascular morphology was analyzed using scanning electron microscopy of microvascular corrosion casts. Gene expression and biological pathways were analyzed using two panels on inflammation/kinase-specific genes and a comparison analysis tool. Compartment-specific protein expression was analyzed using immunostaining. In ACD, there was an altered capillary network, a high prevalence of intussusceptive angiogenesis, and increased activity of C-X-C motif chemokine receptor 4 (CXCR4), hypoxia-inducible factor 1α (HIF1A), and angiopoietin signaling pathways compared with pulmonary arterial hypertension/healthy controls. Histologically, there was a markedly increased prevalence of endothelial tyrosine kinase receptor (TEK/TIE2) +  macrophages in ACD, compared with the other groups, whereas the CXCR4 ligand CXCL12 and HIF1A showed high expression in all groups. ACD is characterized by dysfunctional capillaries and a high prevalence of intussusceptive angiogenesis. The results indicate that endothelial CXCR4, HIF1A, and angiopoietin signaling as well as TIE2 + macrophages are crucial for the induction of intussusceptive angiogenesis and vascular remodeling. Future studies should address the use of anti-angiogenic agents in ACD, where TIE2 appears as a promising target., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Septic aneurysms of the pulmonary artery are rare conditions, with few cases having been reported worldwide. They are assumed to result from septic emboli that cause a local inflammatory reaction of the arterial wall, ultimately leading to degenerative changes. We report the case of a 63-year-old female patient presenting with Klebsiella pneumoniae urosepsis and first diagnosis of diabetes mellitus, who developed a life-threatening infectious pulmonary artery aneurysm secondary to bacteremia with Klebsiella pneumoniae . The patient required a lobectomy due to pulmonary hemorrhage. We review the clinical hallmarks of Klebsiella pneumoniae related septic pulmonary embolic disease and summarize currently known risk factors for the development of infectious aneurysmatic disease including diabetes mellitus and other states of immunosuppression. The featured case aims to increase the awareness for this seldom but life-threatening complication of infectious diseases such as Klebsiella pneumoniae urosepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruwisch, Fischer, Häbel, Laenger and Bollmann.)