scholarly journals Childhood Langerhans cell histiocytosis with severe lung involvement: a nationwide cohort study

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Solenne Le Louet ◽  
Mohamed-Aziz Barkaoui ◽  
Jean Miron ◽  
Claire Galambrun ◽  
Nathalie Aladjidi ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Langerhans Cell Histiocytosis ◽  
Treatment Guidelines ◽  
Langerhans Cell ◽  
Infection Prophylaxis ◽  
Lung Involvement ◽  
Multisystem Disease ◽  
Abnormal Chest ◽  
Life Threatening ◽  
Severe Lung

Abstract Background Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed. Methods Among 1482 children (< 15 years) registered in the French LCH registry (1994–2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure. Results The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine–corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging. Conclusions Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.

scholarly journals Skin-limited Langerhans cell histiocytosis in an adult: a case report

2021 ◽  
Author(s):  
Neringa Guobytė ◽  
Emilija Šerpytienė ◽  
Monika Macejevska ◽  
Milda Krivickaitė ◽  
Jūratė Grigaitienė
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Skin Lesions ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Multisystem Disease ◽  
Small Nodule ◽  
Systemic Spread ◽  
Life Threatening ◽  
History Of ◽  
Skin Surgery

Langerhans cell histiocytosis (LCH) is an idiopathic group of disorders characterized histologically by proliferation and infiltration of tissue by Langerhans cell-type histiocytes. This disease can affect various organs. Patients with single system lesion should be followed carefully. Detection of somatic BRAF-V600E mutation in circulating blood cells or in lesional biopsies has been associated with high-risk clinical characteristics. A 38-year old male presented to our Dermatology Centre with a 3 months history of small nodule on his right leg skin. Surgery to remove the lesion was performed. The diagnosis of skin-limited Langerhans cell histiocytosis was established. Due to possible systemic spread the patient was referred to a haematologist for further evaluation. Full body CT scan did not show any infiltrates in other organs. Bone marrow aspirate and biopsy was performed, no Langerhans cells were detected. Sometimes skin lesions may represent the most clinically evident manifestation of potentially life-threatening multisystem disease.

Lung Involvement in Langerhans' Cell Histiocytosis: Prevalence, Clinical Features, and Outcome

PEDIATRICS ◽  
1992 ◽  
Vol 89 (3) ◽  
pp. 466-469
Author(s):  
S. Y. Ha ◽  
P. Helms ◽  
M. Fletcher ◽  
V. Broadbent ◽  
J. Pritchard
Keyword(s):  
Lung Function ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Similar Proportion ◽  
Lung Pathology ◽  
Lung Involvement ◽  
Lung Function Tests ◽  
Multisystem Disease ◽  
Female Ratio ◽  
Function Tests

In Langerhans' cell histiocytosis, the prognostic significance of pulmonary disease is controversial. The clinical and radiological features and lung function tests of Langerhans' cell histiocytosis patients presenting to a single tertiary referral center between 1981 and 1987 were reviewed. Age at diagnosis ranged from 2 weeks to 16 years (median 1.7 years) and the male-female ratio was 2.4:1. No child presented with lung involvement alone. In 18 (40%) of 45 patients with multisystem disease there was clinical and/or radiological evidence of lung pathology. Another 6 children (13%) with normal chest roentgenograms had abnormal lung function tests, suggesting subclinical ("occult") involvement. Those with overt lung disease tended to present at a younger than average age (median 0.6 years). The most common functional disturbance was reduced lung or respiratory compliance with reduced lung volumes. Patients with and without lung involvement showed a similar pattern of involvement of other organs, with skin and bone most commonly affected. Of the 45 children with multisystem disease, 38 (84%) survived 2 to 7 years after diagnosis; there was a similar proportion of deaths in children with and without lung involvement. It is concluded that lung involvement occurs in nearly half of young children with multisystem Langerhans' cell histiocytosis but does not adversely affect outcome.

scholarly journals Paediatric Langerhans Cell Histiocytosis Disease: Long-Term Sequelae in the Hypothalamic Endocrine System

2021 ◽  
pp. 1-9
Author(s):  
Elisa Vaiani ◽  
Guido Felizzia ◽  
Fabiana Lubieniecki ◽  
Jorge Braier ◽  
Alicia Belgorosky
Keyword(s):  
Anterior Pituitary ◽  
Langerhans Cell Histiocytosis ◽  
Endocrine System ◽  
Langerhans Cell ◽  
Hormone Deficiency ◽  
Bone Lesions ◽  
Pituitary Hormone ◽  
Multisystem Disease ◽  
Anterior Pituitary Hormone

Langerhans cell histiocytosis (LCH) is a disorder of the mononuclear phagocyte system that can affect almost any organ and system. The most common central nervous system (CNS) manifestation in LCH is the infiltration of the hypothalamic-pituitary region leading to destruction and neurodegeneration of CNS tissue. The latter causes the most frequent endocrinological manifestation, that is, central diabetes insipidus (CDI), and less often anterior pituitary hormone deficiency (APD). The reported incidence of CDI is estimated between 11.5 and 24% and is considered a risk factor for neurodegenerative disease and APD. Three risk factors for development of CDI are recognized in the majority of the studies: (1) multisystem disease, (2) the occurrence of reactivations or active disease for a prolonged period, and (3) the presence of craniofacial bone lesions. Since CDI may occur as the first manifestation of LCH, differential diagnosis of malignant diseases like germ cell tumours must be made. APD is almost always associated with CDI and can appear several years after the diagnosis of CDI. Growth hormone is the most commonly affected anterior pituitary hormone. Despite significant advances in the knowledge of LCH in recent years, little progress has been made in preventing long-term sequelae such as those affecting the hypothalamic-pituitary system.

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.

Adult-onset Neurological Langerhans Cell histiocytosis and Response to Treatment

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Al-Hader R ◽  
◽  
Suneja A ◽  
Memon AB ◽  
Mukherje A ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Brain Magnetic Resonance Imaging ◽  
Langerhans Cell ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Adult Onset ◽  
Multisystem Disease ◽  
Clonal Proliferation ◽  
Magnetic Resonance Imaging Mri ◽  
Mass Lesions

Introduction: Langerhans Cell Histiocytosis (LCH) is a rare form of cancer that mostly affects children and rarely adults. LCH involves an abnormal clonal proliferation of Langerhans cells in the bone marrow. These cells are capable of migrating from the skin to lymph nodes. Therefore, it is characterized as a multisystem disease. Neurological manifestations are not common, and often patients’ present with endocrine dysfunction with neuroimaging findings of hypothalamic and pituitary masses can mimic pituitary adenoma. Here, we discuss two instances of unusual adult-onset, primary neurological LCH in patients with a positive response to therapy-these two patients presented with mass lesion and neurodegenerative form of LCH, respectively. LCH can manifest features of mass lesions or neurodegeneration on brain Magnetic Resonance Imaging (MRI). Since it is rare in adults, it is crucial to identify this condition as timely treatment can have a better prognosis.

Childhood Histiocytoses

2020 ◽  
pp. 162-168
Author(s):  
Maurizio Aricò ◽  
Cor van den Bos ◽  
Sheila Weitzman
Keyword(s):  
Targeted Therapy ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Clinical Spectrum ◽  
Juvenile Xanthogranuloma ◽  
Erk Pathway ◽  
Therapeutic Approaches ◽  
Activating Mutations ◽  
Rosai Dorfman Disease ◽  
Genetic Abnormalities

This chapter summarizes the clinical spectrum of the histiocytic disorders—Langerhans cell histiocytosis (LCH), haemophagocytic lymphohistiocytosis (HLH), and some uncommon histiocytic disorders, including juvenile xanthogranuloma (JXG) and Rosai–Dorfman disease—as well as the current diagnostic and therapeutic approaches in these diseases. Multiple activating mutations in the RAS–RAF–MEK–ERK pathway have recently been described in LCH. Their role in the pathophysiology of the disorder and in targeted therapy is reviewed. This chapter explains the differences between primary and secondary HLH, and reviews the genetic abnormalities playing a role in both forms of HLH.

scholarly journals Langerhans-Cell Histiocytoses - Epidemiology, Classification, Clinical Features, Diagnosis, Complications, Treatment and Prognosis

2016 ◽  
Vol 9 (1) ◽  
pp. 3-16 ◽  
Author(s):  
Vera E. Papochieva ◽  
Dimitrinka S. Miteva ◽  
Penka I. Perenovska ◽  
Guergana Petrova
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Eosinophilic Granuloma ◽  
Langerhans Cell ◽  
Unknown Etiology ◽  
Bone Lesions ◽  
Multisystem Disease ◽  
The Past ◽  
System Disease ◽  
Young Smokers ◽  
Underlying Pathology

Summary Histiocytoses comprise a group of diverse diseases of unknown etiology with various clinical presentation and evolution. The underlying pathology is characterised by accumulation and infiltration of variable numbers of cells of the monocyte-macrophage line in the affected tissues and organs. Histiocytoses are divided into three major classes: Langerhans cell histiocytosis (LCH), non- Langerhans cell histiocytosis, and malignant histiocytic disorders. The term LCH (also known in the past as histiocytosis X) encompasses the following rare diseases: Eosinophilic Granuloma, Hand-Schuller-Christian disease, Letterer-Siwe disease, Hashimoto-Pritzker disease, in which accumulation of pathologic Langerhans cells (LCs) leads to tissue damage. LCs usually reside in the skin and ensure protection against infections by destroying foreign substances. LC accumulation is caused by antigen stimulation and inadequate immune response. Thus, clinical LCH manifestations range from isolated disease with mono- or multifocal bone lesions to disseminated multisystem disease. LCH is a rare disease, affecting mainly children and young smokers, aged 20-50 years. Lung involvement in LCH usually presents as a mono-system disease and is characterized by Langerhans cell granulomas (LCG) infiltrating and impairing the distal bronchioles. The definite diagnosis is based on lung biopsy of CAT selected LCG areas. So far, there is no an effective treatment, but the better understanding of the mechanisms involved in the pathogenesis of the disease would help in the development of effective therapeutic strategies in the future.

scholarly journals High prevalence of myeloid neoplasms in adults with non–Langerhans cell histiocytosis

Blood ◽  
2017 ◽  
Vol 130 (8) ◽  
pp. 1007-1013 ◽  
Author(s):  
Matthias Papo ◽  
Eli L. Diamond ◽  
Fleur Cohen-Aubart ◽  
Jean-François Emile ◽  
Damien Roos-Weil ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Myeloid Neoplasm ◽  
Myeloid Neoplasms ◽  
Key Points ◽  
High Prevalence

Key Points Some 10.1% of adults with non–Langerhans cell histiocytosis have a concomitant myeloid neoplasm with each often harboring distinct mutations. The presence of distinct kinase mutations in histiocytosis and myeloid neoplasms resulted in discordant responses to targeted therapy.

Adult Langerhans cell histiocytosis: A contemporary single-institution series of 186 patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7018-7018
Author(s):  
Gaurav Goyal ◽  
Marie Hu ◽  
Jason R Young ◽  
Robert Vassallo ◽  
Jay H Ryu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Langerhans Cell Histiocytosis ◽  
Overall Response Rate ◽  
Langerhans Cell ◽  
Braf V600e ◽  
First Line ◽  
Multisystem Disease ◽  
Presenting Symptoms ◽  
Systemic Therapies

7018 Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm driven by MAPK-ERK mutations in majority of patients. Contemporary data on treatments and outcomes in adult LCH are lacking. Hence, we undertook this study to analyze a large cohort of adult LCH patients. Methods: This was a retrospective study of adult (≥18 years) LCH patients seen at our institution between 1998 and 2018. Results: We included 186 patients with adult LCH (median age 43; 19-88), and 54% were females. 70% of patients were diagnosed after 2007. Common presenting symptoms were cough/dyspnea (30%), rash (17%), pain/swelling in head (17%), and diabetes insipidus (10%). 70 (38%) patients had multisystem LCH, 62 (33%) had isolated pulmonary LCH, and 35 (19%) had unifocal LCH. Common sites of involvement included lung (59%), bone (37%), skin (21%), and nervous system (16%). 121 (65%) were smokers; 48% of these had lung disease, while 52% had multisystem disease. 18 of 31 tested (58%) patients had BRAF-V600E mutation. Most common first-line treatment was smoking cessation in 24 patients, and led to an overall response rate (ORR) of 83% in pulmonary lesions. Radiation therapy was used in 11 patients, and led to an ORR 82%. Surgical resection of lesion was done in 23 patients, with relapses in 24%. Systemic therapies were used in 78 (42%) patients (Table). Most common first-line systemic therapy was cladribine with ORR of 78%. Vemurafenib was used in 3 patients with BRAF-V600E, leading to an ORR of 67% . After a median follow-up of 23 months (0-261), 21 patients had died. Of these, 10 died of progressive LCH. Median OS was not reached, and mean OS was 196 months. Conclusions: This is the largest contemporary series of adult LCH. It shows that diverse clinical spectrum, ranging from benign course to a progressive multisystem disease. Although smoking cessation was an effective treatment for pulmonary LCH, a large subset required systemic chemotherapy. [Table: see text]

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