Early chemotherapeutic intervention to avoid thyroidectomy in pediatric Langerhans cell histiocytosis with thyroid involvement accompanying tracheal stenosis: a report of two cases.

Thyroid involvement is rare in pediatric Langerhans cell histiocytosis (LCH). It may cause airway narrowing, leading to acute-onset respiratory distress. Severe cases may require emergent surgical interventions such as thyroidectomy, which should be avoided in children due to higher rates of complication, particularly in infancy. There is currently no consensus on the indications for surgical treatment in LCH with thyroid involvement. In this report, we describe the cases of two children who presented with tracheal stenosis caused by thyroid LCH, both of which were successfully treated by early induction of chemotherapy, and one of which was also treated for a shorter duration. Mutation analysis detected in-frame deletions of BRAF exon 12 in both cases. These cases suggest that timely diagnosis and administration of chemotherapy may alleviate severe airway obstruction and reduce the need for thyroidectomy in pediatric patients with thyroid LCH.

Optimal timing of liver transplantation for liver cirrhosis caused by sclerosing cholangitis in a patient with Langerhans cell histiocytosis: a case report.

Liver cirrhosis due to secondary sclerosing cholangitis caused by Langerhans cell histiocytosis (LCH) has a poor prognosis, and liver transplantation is the definitive treatment. However, the optimal timing has not been established. We report a 2-year-old girl with LCH-related liver cirrhosis who successfully underwent liver transplantation before progressing to severe liver dysfunction. Physical examination revealed a tumor on her palate. Biopsy was performed, and a diagnosis of LCH was established, together with hepatomegaly, splenomegaly, and rashes. Percutaneous liver biopsy before treatment revealed extreme fibrosis and absence of LCH cells. After beginning chemotherapy, she experienced several delays in treatment and dose reductions because of unacceptable bone marrow suppression, worsening liver dysfunction, and cholangitis. However, tumor shrinkage was observed in both magnetic resonance imaging and BRAF V600E mutant allele titers in her plasma. Given the good treatment response, liver transplantation was conducted. The postoperative course was uneventful, and chemotherapy was resumed 34 days after liver transplantation. Subsequent maintenance treatment was completed with no severe adverse effects. To prevent perioperative complications due to exacerbation of liver dysfunction and possible discontinuation of chemotherapy, liver transplantation should be considered before development of end-stage liver failure, provided that the original disease is well controlled.

Optimal DNA quality preservation process for comprehensive genomic testing of pediatric clinical autopsy formalin-fixed, paraffin-embedded tissues.

Clinical autopsies are performed to reveal the process of the disease that caused patient death and validate the diagnosis and treatment decisions. In pediatric clinical autopsy, the feedback provided to bereaved families has a considerable social impact; however, pediatric diseases are diverse, which makes it difficult to elucidate them. Therefore, it is necessary to employ molecular biology techniques in addition to conventional methods. Formalin-fixed, paraffin-embedded (FFPE) tissues are routinely prepared. However, clinical autopsy FFPE tissue processing is not standardized, and it is unclear whether DNA from such tissues can be used for comprehensive genomic analysis. In this study, we evaluated the DNA quality of FFPE tissues from 15 recent autopsy cases at a single-center children's hospital using quantitative polymerase chain reaction [PCR (Q129/Q41)] and nanoelectrophoresis (DNA integrity number (DIN)). Good quality DNA was obtained from every organ type excluding bone marrow within 6 days of formalin fixation. Prolonged proteinase K digestion (48 h > 24 h > 1 h) and thicker tissue sections (10 µm > 1 µm) improved Q129/Q41; however, 24 h fixed FFPE tissues showed better DNA quality. We propose an optimal and feasible workflow for storing short-term fixed FFPE tissues as DNA-preserved FFPE tissues for future comprehensive genomic searches.