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Anales de Pediatria Aug 2022Langerhans cell histiocytosis (LCH) is a type of myeloid neoplasia that can affect different organs or tissues and exhibits substantial variability in its clinical...
Langerhans cell histiocytosis (LCH) is a type of myeloid neoplasia that can affect different organs or tissues and exhibits substantial variability in its clinical presentation and biological behaviour, so it may mimic different diseases. Performance of different clinical assessments and laboratory and imaging tests is recommended to determine the extent of involvement, which may be of a single location or multisystemic, and the presence or absence of dysfunction in risk organs, such as the haematopoietic system, liver and spleen. The diagnosis must be confirmed by histological examination of a biopsy sample. Molecular tests have identified mutations in the mitogen-activated protein kinase (MAPK) pathway, which has expanded treatment options. The diagnosis is complex and there is controversy regarding the management of certain cases. Treatment recommendations depend on the location of the lesions and the extent of involvement. International collaborative studies have demonstrated the effectiveness of prolonged combination therapies such as vinblastine and prednisone in severe or multisystemic forms, and anti-inflammatory drugs such as indomethacin and other cytostatic combinations have proven beneficial. Langerhans cell histiocytosis is a good example of the importance of precision medicine and the benefit of identifying molecular targets, common to different neoplasms, to develop new therapies. MAPK pathway inhibitors offer an alternative treatment option in refractory cases and neurodegenerative forms of LCH. Molecular testing can contribute to the prognosis, treatment and follow-up of LCH, especially in severe forms of disease.
Topics: Combined Modality Therapy; Histiocytosis, Langerhans-Cell; Humans; Mutation; Neoplasms; Prognosis
PubMed: 35869015
DOI: 10.1016/j.anpede.2022.05.005 -
Journal of Oral Pathology & Medicine :... Jul 2021Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation and infiltration of histiocytic cells. (Review)
Review
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation and infiltration of histiocytic cells.
METHODS
This review focused on the main aspects associated with LCH.
RESULTS
LCH can involve single or multiple organs and systems, with bone and skin being the most commonly affected sites. Regarding skeletal manifestations, the jawbones are involved in about 20%-30% of all cases. Such lesions may present as unilocular or multilocular images mainly affecting the posterior mandible. Oral soft tissue lesions may also occur, with the gingiva and hard palate being the most frequently affected sites.
CONCLUSION
The diagnosis and management of LCH are challenging, requiring a multidisciplinary approach, with dentists playing a central role since oral manifestations can be the first sign of the condition.
Topics: Gingiva; Histiocytosis, Langerhans-Cell; Humans; Mandible; Skin
PubMed: 34091963
DOI: 10.1111/jop.13207 -
Journal of Pediatric Hematology/oncology Jan 2022Langerhans cell histiocytosis (LCH) is characterized pathologically by langerin-positive (CD207+) dendritic cell proliferation and is considered by some as a myeloid... (Review)
Review
Langerhans cell histiocytosis (LCH) is characterized pathologically by langerin-positive (CD207+) dendritic cell proliferation and is considered by some as a myeloid neoplastic disorder. Hemophagocytic lymphohistiocytosis (HLH) is associated with immune dysregulation characterized by the accumulation of activated macrophages and hypercytokinemia. However, these 2 histiocytosis rarely coexist. Currently, the etiology, risk factors, optimal therapy, and outcomes of LCH-HLH remain unclear. We reviewed the medical records of 7 LCH-HLH patients from our hospital and analyzed 50 LCH-HLH patients reported in scientific literature. The median age of LCH onset of these 57 LCH-HLH patients was 1 year, and 91% (52/57) of patients diagnosed as LCH were less than 2 years old. Fifty-six LCH-HLH patients belonged to the multisystem LCH category and 84% (47/56) patients had risk-organ involvement. Twenty-three LCH-HLH patients were complicated with infection and 3 patients had a primary pathogenic mutation of HLH. Overall, 90% of LCH patients developed HLH at the diagnosis or during chemotherapy. Of the 57 LCH-HLH patients, 15 died. Multisystem LCH patients with risk-organ involvement under 2 years old were most likely to develop HLH when complicated with infection at diagnosis or during chemotherapy. Identifying LCH-HLH patients during early stages and treating them with prompt chemotherapy, hematopoietic stem cell transplantation, or supportive therapies are important for better survival.
Topics: Allografts; Female; Hematopoietic Stem Cell Transplantation; Histiocytosis, Langerhans-Cell; Humans; Infant; Lymphohistiocytosis, Hemophagocytic; Male
PubMed: 34133378
DOI: 10.1097/MPH.0000000000002212 -
Current Opinion in Pulmonary Medicine Sep 2023Pulmonary Langerhans cell histiocytosis (PLCH) is a rare diffuse cystic lung disease that affects young to middle-aged smoking adults of both genders. The identification... (Review)
Review
PURPOSE OF REVIEW
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare diffuse cystic lung disease that affects young to middle-aged smoking adults of both genders. The identification of molecular alterations in the canonical mitogen-activated protein kinase (MAPK) signalling pathway in most specific lesions has demonstrated the clonal/neoplastic nature of PLCH. We will summarize the progress made in the understanding of the pathogenesis of adult PLCH, and briefly highlight the recent findings useful for the management of the patients.
RECENT FINDINGS
The MAPK pathway is constantly activated in PLCH lesions. Apart from the BRAFV600E mutation, other driver somatic genomic alterations in this pathway (mainly MAP2K1 mutations/deletions and BRAF deletions) have been identified in the lesions, paving the way for targeted treatment. Smoking appears to promote the recruitment of MAPK-activated circulating myeloid precursors to the lung. The long-term survival of PLCH is more favourable with a 10-year survival >90%. Lung cancer and chronic respiratory failure are the main causes of death. Few patients develop severe pulmonary complications within the 5 years after diagnosis, justifying a close longitudinal follow-up of the patients.
SUMMARY
PLCH is a MAPK driven neoplasia with inflammatory properties. The place of targeted therapies in severe forms of PLCH warrants further evaluation.
Topics: Adult; Middle Aged; Humans; Male; Female; Lung; Lung Diseases; Histiocytosis, Langerhans-Cell; Smoking; Lung Neoplasms; Mitogen-Activated Protein Kinases
PubMed: 37410483
DOI: 10.1097/MCP.0000000000000988 -
Archivos de Bronconeumologia Jun 2023
Topics: Humans; Histiocytosis, Langerhans-Cell; MAP Kinase Signaling System
PubMed: 35589455
DOI: 10.1016/j.arbres.2022.02.015 -
Hematology. American Society of... Dec 2023Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm driven by activating mutations in the MAPK pathway, most commonly BRAF-V600E and MAP2K1. It affects... (Review)
Review
Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm driven by activating mutations in the MAPK pathway, most commonly BRAF-V600E and MAP2K1. It affects children and adults, with a wide spectrum of clinical presentations ranging from self-limited to multisystem (MS) life-threatening forms. LCH is defined by the accumulation of CD1a+/CD207+ cells in different organs, and patients with liver, spleen, or hematopoietic system involvement have a higher risk of mortality. Patients with neurodegeneration (ND) have devastating outcomes and are resistant to systemic therapies. MS-LCH is treated with risk-adapted therapy, but many patients require multiple salvage regimens that are myelosuppressive and expensive. MAPK inhibitors are increasingly being used, but most patients relapse upon discontinuation of therapy. Here, we review the management of central nervous system disease and how novel cerebrospinal fluid biomarkers might predict patients at high risk of ND who could benefit from early MAPK inhibition. Further, we discuss treatment strategies for refractory/relapsed (R/R) LCH, with a focus on MAPK inhibitors' efficacy and challenges (ie, the unknown): long-term toxicity in children, optimal duration, if they are curative, whether it is safe to combine them with chemotherapy, and their high price tag. Lastly, emerging strategies, such as the new panRAF inhibitor (Day 101) in patients with R/R LCH, ERK1/2 or CSF1R inhibition in patients with MEK1/2 inhibitor resistance, and targeting the microenvironment (checkpoint plus MEK inhibition) or senescent cells (mTOR or BCL-XL inhibitors) in R/R patients, are also examined.
Topics: Child; Adult; Humans; Mutation; Proto-Oncogene Proteins B-raf; Histiocytosis, Langerhans-Cell; Protein Kinase Inhibitors; Central Nervous System Diseases
PubMed: 38066856
DOI: 10.1182/hematology.2023000439 -
Asian Journal of Surgery Jul 2022
Topics: Chest Pain; Histiocytosis, Langerhans-Cell; Humans; Sternum
PubMed: 35277320
DOI: 10.1016/j.asjsur.2022.02.038 -
Clinical Imaging Mar 2020Histiocytosis syndromes (HS) are group of heterogeneous disorders characterized by abnormal accumulation and infiltration of histiocytes, cells derived from... (Review)
Review
Histiocytosis syndromes (HS) are group of heterogeneous disorders characterized by abnormal accumulation and infiltration of histiocytes, cells derived from hematopoietic cells of monocyte/macrophage lineage. Overall these disorders are rare. When they do occur they involve many organ systems including the central nervous system (CNS). While imaging findings can provide important clues, diagnosis of this disorder is challenging and definitive diagnosis often necessitates pathologic examination. In this review, we describe imaging features of HS involving the CNS, with the aim to increase our understanding of these disorders. The entities discussed in this review will include: Langerhans cell histiocytosis (LCH), Rosai-Dorfman Disease (RDD), Erdheim Chester Disease (ECD), hemophagocytic lymphohistiocytosis (HLH), and crystal-storing histiocytosis (CSH).
Topics: Central Nervous System; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Neuroimaging; Syndrome
PubMed: 31874337
DOI: 10.1016/j.clinimag.2019.10.001 -
Balkan Medical Journal Jan 2022
Topics: Histiocytosis, Langerhans-Cell; Humans; Palatine Tonsil
PubMed: 35330544
DOI: 10.4274/balkanmedj.galenos.2021.2021-6-145 -
[Rinsho Ketsueki] the Japanese Journal... 2022Histiocytosis is classified based on proliferating histiocyte-like cells. Langerhans cell histiocytosis (LCH) has several subtypes with various outcomes, from...
Histiocytosis is classified based on proliferating histiocyte-like cells. Langerhans cell histiocytosis (LCH) has several subtypes with various outcomes, from spontaneous to fatal regression, and these subtypes had been managed as different diseases. However, these different names of disease were unified to one disease named histiocytosis X since they are pathologically identical. Presently, LCH has been used as a unified name because proliferating cells have the characteristics of Langerhans cells. Since then, clonality and BRAF mutations have been reported, and their neoplastic characteristics has become clear; however, explaining its various subtypes is difficult with only the neoplastic character. Various relationships/correlations are also known between inflammatory factors and LCH subtypes. We have pointed out that the Merkel cell polyomavirus may be involved in LCH development and LCH is a disease with both neoplastic and reactive characters, that is, "a disease in which abnormal Langerhans-like cells with neoplastic character overreact to some triggers."
Topics: Histiocytosis, Langerhans-Cell; Humans; Langerhans Cells; Merkel cell polyomavirus; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 35662161
DOI: 10.11406/rinketsu.63.383