High prevalence of BRAF V600E in patients with cholestasis, sclerosing cholangitis or liver fibrosis secondary to Langerhans cell histiocytosis

2021 ◽  
Author(s):  
Xiomara Carrere ◽  
Nicolas Pinto ◽  
Nagore Gene Olaciregui ◽  
Laura Galluzzo ◽  
Estefania Rossetti ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Sclerosing Cholangitis ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Braf V600e ◽  
High Prevalence

scholarly journals High prevalence of somatic MAP2K1 mutations in BRAF V600E–negative Langerhans cell histiocytosis

Blood ◽  
2014 ◽  
Vol 124 (10) ◽  
pp. 1655-1658 ◽  
Author(s):  
Noah A. Brown ◽  
Larissa V. Furtado ◽  
Bryan L. Betz ◽  
Mark J. Kiel ◽  
Helmut C. Weigelin ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Genome Sequencing ◽  
High Frequency ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Braf Mutations ◽  
Key Points ◽  
High Prevalence

Key Points Targeted genome sequencing reveals high-frequency somatic MAP2K1 mutations in Langerhans cell histiocytosis. MAP2K1 mutations are mutually exclusive with BRAF mutations and may have implications for the use of BRAF and MEK targeted therapy.

High Prevalence of BRAF V600E Mutations in Langerhans Cell Histiocytosis of Head and Neck in Chinese Patients

2019 ◽  
Vol 27 (8) ◽  
pp. 836-843
Author(s):  
Xiaoxiao Liu ◽  
Ye Zhang ◽  
Chuan-Xiang Zhou
Keyword(s):  
Head And Neck ◽  
Langerhans Cells ◽  
Langerhans Cell Histiocytosis ◽  
Neck Region ◽  
Braf V600e Mutation ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Chinese Patients ◽  
Clonal Proliferation ◽  
High Prevalence

Langerhans cell histiocytosis (LCH) is characterized by clonal proliferation of Langerhans cells and has been classified as a hematolymphoid tumor. BRAF V600E mutation was found to be frequent in LCH; however, it has also been reported that Asia patients with LCH tend to show a lower rate of BRAF V600E mutation. In this study, we found LCH from the head and neck region often involved bone especially the posterior of the mandible and presented a high prevalence of BRAF V600E mutation in Chinese patients. Our findings also showed immunohistochemical detection correlated very well to DNA sequencing of BRAF alterations, which may be useful in the diagnosis of LCH, especially in cases with a low proportion of Langerhans cells, and BRAF inhibitors might be a treatment option for patients with LCH harboring BRAF V600E mutation.

scholarly journals Liver transplantation in a child with liver cirrhosis caused by langerhans cell histiocytosis: a case report

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Qi Wang ◽  
Shuguang Jin ◽  
Bo Xiang ◽  
Jing Chen
Keyword(s):  
Liver Transplantation ◽  
Liver Cirrhosis ◽  
Sclerosing Cholangitis ◽  
Langerhans Cell Histiocytosis ◽  
Liver Enzymes ◽  
Perianal Abscess ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Hepatobiliary System ◽  
Elevated Liver Enzymes

Abstract Background Langerhans cell histiocytosis (LCH) is a rare condition that has a variety of clinical manifestations. But LCH in children localized only in the hepatobiliary system is unusual. Case presentation. Here we reported a rare case of a 2-year-old boy who was serendipitously found to have elevated liver enzymes while undergoing treatment of a perianal abscess. After a period of earlier conservative treatment in another hospital, the perianal abscess had resolved but the levels of liver enzymes were still rising slowly. The child was then referred to our institution for a definitive diagnosis. After laboratory tests, imaging and pathological examinations, a diagnosis of liver cirrhosis and sclerosing cholangitis was established, although the cause was unclear. Subsequently, living-donor liver transplantation was performed due to deterioration in liver function. Following successful liver transplantation, a diagnosis of LCH localized only within the hepatobiliary system was finally confirmed, based on additional pathological and imaging investigation. Additionally, the BRAF V600E mutation in this patient was also confirmed. The child has now recovered without evidence of LCH recurrence. Conclusions LCH localized only within the hepatobiliary system is unusual. The presence of unexplainable sclerosing cholangitis and liver cirrhosis in any child should raise the suspicion of LCH.

scholarly journals Frequency detection of BRAF V600E mutation in a cohort of pediatric langerhans cell histiocytosis patients by next-generation sequencing

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shunqiao Feng ◽  
Lin Han ◽  
Mei Yue ◽  
Dixiao Zhong ◽  
Jing Cao ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Langerhans Cell Histiocytosis ◽  
Mutation Screening ◽  
Langerhans Cell ◽  
Braf V600e ◽  
P Value ◽  
Type I ◽  
Next Generation ◽  
Mutation Status ◽  
Generation Sequencing

Abstract Background Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.

scholarly journals BRAF V600E-Positive Congenital Multisite Langerhans Cell Histiocytosis

Cureus ◽  
2020 ◽  
Author(s):  
Maria Camila Prada Avella ◽  
Amaranto Suárez ◽  
Sharon Contreras ◽  
Alejandra Calderon
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Braf V600e

scholarly journals Vemurafenib provides a rapid and robust clinical response in paediatric Langerhans cell histiocytosis with the BRAF V600E mutation but does not eliminate low-level minimal residual disease based on ddPCR using cell-free circulating DNA

2020 ◽  
Author(s):  
Dmitry Evseev ◽  
Irina Kalinina ◽  
Elena Raykina ◽  
Daria Osipova ◽  
Zalina Abashidze ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Residual Disease ◽  
Braf V600e Mutation ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Circulating Dna ◽  
Neutropenic Sepsis ◽  
Day Range ◽  
Droplet Pcr ◽  
Free Circulating Dna

Background Langerhans cell histiocytosis (LCH) involves abnormal proliferation of Langerhans cells (LC), which is typically driven by the BRAF V600E mutation. High-risk LCH has a poor prognosis. Procedure Fifteen children (5 girls, 10 boys) with BRAF V600E+ LCH received vemurafenib (initial dose median 40 mg/kg/day, range: 11–51.6 mg/kg/day) between March 2016 and February 2020. All patients had previous received LCH-directed chemotherapy. The median age at LCH onset was 2 months (range: 1–28 months) and the median age at the start of vemurafenib treatment was 22 months (range: 13–62 months). The median disease activity score (DAS) at the start of vemurafenib treatment was 12 points (range: 2–22 points). Results The median duration of vemurafenib therapy was 29 months (range: 2.4–45 months). All patients responded to treatment, with median DAS values of 4 points (range: 0–14 points) at week 4 and 1 point (range: 0–3 points) at week 26. Toxicities included skin/hair changes (93%) and non-significant QT prolongation (73%). Two patients died, including 1 patient who experienced hepatic failure after NSAID overdose and 1 patient who developed neutropenic sepsis. Electively stopping vemurafenib treatment resulted in relapse in 5 patients, and complete cessation was only possible for 1 patient. Digital droplet PCR for BRAF V600E using cell-free circulating DNA revealed that 7 patients had mutation statuses that fluctuated over time. Conclusion Our study confirms that vemurafenib treatment is safe and effective for young children with BRAF V600E+ multisystem LCH. However, treatment using vemurafenib does not completely eliminate the disease.

scholarly journals BRAF-V600E–mutated Rosai-Dorfman-Destombes disease and Langerhans cell histiocytosis with response to BRAF inhibitor

2019 ◽  
Vol 3 (12) ◽  
pp. 1848-1853 ◽  
Author(s):  
Rosemarie Mastropolo ◽  
Allison Close ◽  
Steven W. Allen ◽  
Kenneth L. McClain ◽  
Scott Maurer ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Braf Inhibitor ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Disease Monitoring ◽  
Blood Testing ◽  
Molecular Assays ◽  
Key Points ◽  
Treatment Plans ◽  
Inhibitor Treatment

Key Points Demonstration of BRAF-V600E in Rosai-Dorfman-Destombes disease requires sensitive molecular assays and molecular-based tissue immunostain. BRAF-V600E blood testing is important for disease-monitoring BRAF-mutated histiocytosis and can guide inhibitor treatment plans.

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