Advancements in the understanding and management of histiocytic neoplasms.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature. This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in high-risk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects. MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults. Further research is required to determine the optimal treatment duration and strategies for managing therapy interruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histiocytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Ten-Year Trends of Hematopoietic Stem Cell Transplantation in Korean Pediatric Cancer from the National Health Insurance Claims Data.

PURPOSE: We aimed to determine the current application and survival trends of hematopoietic stem cell transplantation (HSCT) among Korean children and adolescents with cancer. MATERIALS AND METHODS: Data of patients aged < 20 years with KCD-10 (Korean Classifications of Diseases, 10th revision) C codes and specific designation codes were collected from the National Health Insurance Service database. Thirty claim codes for HSCT were included, and data from 2009 to 2019 were analyzed. RESULTS: The operational definition of pediatric cancer yielded an annual average of 2,000, with annual cases decreasing. In 2019, 221 HSCTs were performed, a decrease from the ten-year average of 276. Allografts outnumbered autografts with a ratio of 1.5:1. The source of allograft was bone marrow in 15% of patients in 2009; however, it substantially decreased to 3.3% in 2019. Furthermore, 70.5% of allogeneic HSCT used peripheral blood stem cell (PBSC) grafts, which increased to 89.3% by 2015. Cord blood utilization markedly decreased to 2.7% in 2018. The 5-year overall survival (OS) rate of all patients was 85.1%. Overall mortality decreased among patients who underwent recent HSCT, and they exhibited a higher 5-year OS rate. CONCLUSION: In Korea, the number of pediatric patients with cancer is declining; however, the ratio of transplants to all patients remains constant. Patients who recently underwent transplantation showed better survival rates, possibly due to HSCT optimization. Korea showed a substantially greater PBSC utilization in pediatric HSCT. An in-depth examination encompassing donor relations and cause of death with a prospective registry is required in future studies.

Severe neonatal Marfan syndrome with a novel mutation in the intron of the FBN1 gene: A case report.

RATIONALE: Marfan syndrome (MFS) has been defined as a genetic disorder that affects various systems such as the musculoskeletal, orbital, and cardiovascular systems. Neonatal MFS is considered rare and the most severe form of MFS is characterized by rapidly progressive atrioventricular valve dysfunction, often leading to death during early childhood due to congestive heart failure. PATIENT CONCERNS: A newborn with neonatal MFS and severe cardiac involvement. He presented various severe clinical features such as arachnodactyly, camptodactyly, elbow and knee joint contracture, senile facial appearance, and deep settling with down-slanting palpebral fissure, hypoplastic ear cartilage, sagging mouth, brachycephaly, and ectopia lentis. DIAGNOSIS: Genetic analysis revealed a novel mutation at nucleotide 3964 (c.3964 + 1 G > T) in intron 32 of the fibrillin-1 gene. This mutation is identified to be in the so-called neonatal region of fibrillin-1 exon 24 to 32, as reported previously. INTERVENTIONS: The patient was managed medically for improving the low cardiac output according to severe mitral regurgitation and aortic regurgitation. Afterload reduction, full sedation, and use of diuretic were attempted to improve the oliguria and heart failure. OUTCOMES: Despite the medical management, aortic regurgitation, mitral regurgitation, pulmonary hypertension, and cardiac contractility got worse. Surgical treatment is essential to prolong the patient's life, however, considerations for the grave progression of the disease make families decide to continue palliative care instead of surgical treatment. A few months after birth, he presented with rapidly progressive aortic regurgitation, mitral regurgitation, and congestive heart failure leading to death. CONCLUSIONS: This review demonstrated the prominent characteristics of neonatal MFS mutations, it would be helpful for the recognition of novel neonatal MFS variants and valuable for the understanding of the genotype-phenotype correlations and using the plans for managements and counseling in neonatal MFS.