Nail Changes in Langerhans Cell Histiocytosis: A Possible Marker of Multisystem Disease

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.

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Adult-onset Neurological Langerhans Cell histiocytosis and Response to Treatment

Austin Journal of Clinical Neurology ◽

10.26420/austinjclinneurol.2021.1146 ◽

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.

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

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01495-5 ◽

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.

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

Journal of Biomedical and Clinical Research ◽

10.1515/jbcr-2016-0001 ◽

2016 ◽

Vol 9 (1) ◽

pp. 3-16 ◽

Cited By ~ 1

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.7018 ◽

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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Pediatric Langerhans Cell Histiocytosis (LCH) Clinical Outcome in Hospital Civil De Guadalajara, México

Blood ◽

10.1182/blood-2018-99-115794 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4951-4951 ◽

Cited By ~ 1

Author(s):

Katterine Rojas Rodríguez ◽

Veronica Soto ◽

Carlos Rodriguez-Galindo ◽

Paola M. Friedrich ◽

Edwin Guzmán ◽

...

Keyword(s):

Clinical Outcome ◽

Langerhans Cell Histiocytosis ◽

Disease Risk ◽

Conflicts Of Interest ◽

Systemic Disease ◽

Giant Cells ◽

Langerhans Cell ◽

Induction Treatment ◽

Multisystem Disease ◽

Clonal Proliferation

Abstract Pediatric Langerhans cell histiocytosis (LCH) clinical outcome in Hospital Civil de Guadalajara, México. Introduction : LCH results from clonal proliferation of functionally and immunophenotyped inmature round Langerhans cells along with eosinophiles, machrophages, lymphocytes and ocasionally multinucleated giant cells (1). Its incidence is 2-10 cases by million of children below 15 yr in US (2). Our objective was to describe the clinical characteristics and treatment outcome of patients with LCH at Departement of Hematology-Oncology of Hospital Civil de Guadalajara México. Methods: It was a retrospective design and 41 pediatric patients below 18 yr were included. The diagnosis was corroborated by pathology and immunohistochemistry. Variables as age, gender, localised vs systemic disease, risk organ commitment, global survival (GS) and event free survival (EFS) were analysed. We used descriptive and inferencial statistics with SPSS program. Results: There were included 41 patients from January 1st 2012 to December 31st 2017. Relation male:female was 1.1:1. Mean presentation was localised disease (58%). Bone was the principal affected structure (34%) and it was 71% to be combined with lung, lymph node and CNS compromise. Risk organ commitment was presented in 32%, being more frecquent bone marrow and liver in 22% each one. Time induction treatment was equal or below 12 weeks in 66% of patients. The 25% of patients had reactivation of LCH, with similar lesions to the beggining in 19.5%. We found statistically significant differences between dead patients (DP) (14.6%) and not dead patients (NDP) (85.4%) in clinical presentation: localised (0% in DP vs 69% in NDP) and systemic disease (100% vs 31%) (p=0,003) and risk organ commitment (100% in DP vs 20% in NDP) (p=0,000). Median age of 13 vs 24 months was for DP and NDP respectively. Conclusion: Dead patients were younger than 13 months old, with systemic disease, and risk organ commitment. We found a later asking of medical advice in DP (6 months) vs NDP (2 months). Keys words: langerhans cell histiocytosis, multisystem disease, risk organ Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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BRAF V600E Mutation: A Significant Biomarker for Prediction of Disease Relapse in Pediatric Langerhans Cell Histiocytosis

Pediatric and Developmental Pathology ◽

10.1177/1093526619847859 ◽

2019 ◽

Vol 22 (5) ◽

pp. 449-455 ◽

Cited By ~ 7

Author(s):

Erdener Ozer ◽

Akin Sevinc ◽

Dilek Ince ◽

Resmiye Yuzuguldu ◽

Nur Olgun

Keyword(s):

Langerhans Cell Histiocytosis ◽

Direct Sequencing ◽

Prognostic Significance ◽

Braf V600e Mutation ◽

Langerhans Cell ◽

Braf V600e ◽

Erk Pathway ◽

Disease Relapse ◽

Multisystem Disease ◽

Mutational Status

Langerhans cell histiocytosis (LCH) is a rare disease presenting with usually a localized disease but sometimes a widespread aggressive disorder especially in children. Among the somatic mutations in RAF-MEK-ERK pathway, especially BRAF mutation has been detected so far in LCH. We aimed in this study to investigate the prognostic significance of the mutations of target genes playing a role in the RAF-MEK-ERK pathway in pediatric LCH. Mutation analyses were performed on tumor DNA extracted from formalin-fixed paraffin-embedded biopsy specimens of 38 pediatric LCH cases using a direct sequencing technique for BRAF, ARAF, MAP2K1, and MAP3K1 genes. The mutational status was correlated statistically with survival, clinical progression (disease relapse), and the established clinical prognostic parameters of LCH such as age, gender, localization, multisystem disease, central nervous system risk lesions, and risk organ or special-site involvement. BRAF V600E mutation was detected in 14 cases (36.8%), whereas ARAF mutation was found in only 1 case. No mutations were identified for MAP2K1 and MAP3K1 genes. The association of BRAF V600E mutation was significant in children with multisystem disease, younger age (<2 years), skin, and special organ involvement. BRAF V600E mutation was an independent predictive parameter for disease relapse. We therefore conclude that BRAF V600E mutation may be a significant marker for predicting disease progression in LCH and a candidate for targeted therapy for children with disease relapse and multisystem disease.

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Histiocitose de Largerhans no Adulto: Experiência de Dois Hospitais Portugueses

Acta Médica Portuguesa ◽

10.20344/amp.5360 ◽

2014 ◽

Vol 27 (6) ◽

pp. 726 ◽

Cited By ~ 1

Author(s):

Margarida Dantas de Brito ◽

Ângelo Martins ◽

Joaquim Andrade ◽

José Guimarães ◽

José Mariz

Keyword(s):

Langerhans Cell Histiocytosis ◽

Langerhans Cell ◽

Adult Patients ◽

Diagnosis Delay ◽

Multisystem Disease ◽

Pulmonary Tissue ◽

Bone Changes ◽

Alive With Disease ◽

The Moment ◽

Clinical Records

Introduction: Langerhans cell histiocytosis is a heterogeneous disease, more frequently diagnosed during childhood. Between 1/2001 and 12/2013, 20 adult patients were admitted at both Hospitals. This work aimed at ccharacterizing this population. Material and Methods: Retrospective study, review of clinical records. Results: 16 patients were eligible to analysis. The median age at diagnosis was 34 years (15-48); 10 males and 6 females. The referral motive was: respiratory complaints – 37.5%; bone changes – 37.5%; dental complaints - 25%; constitutional symptoms - 19%; mucocutaneous lesions – 6% and one patient (6%) was accidentally diagnosed after a thyroidectomy. The tissue of histological diagnosis was: bone - 50%; pulmonary tissue – 37.5%; liver, genital mucosa and thyroid - 6%, respectively. Staging was: single organ involvement (uni/multifocal) - 69% and multisystem disease in 31%. Clinical re-evaluation of these cases is being done at the moment. The median follow up was 5 years (1 month – 11 years) and the overall survival was 92%. Currently 19% are alive without signs of disease; 44% are alive with disease; 25% are under treatment and 12% died. Discussion: These results agree with published literature. Considering the actual guidelines 56% patients were incompletely staged, which probably lead to suboptimal treatment. There is heterogeneity of clinical procedures aiming at staging and treatment of these patients. Conclusion: The diagnosis of adulthood Langerhans cell histiocytosis is difficult considering the diversity of clinical behavior. Frequently this also leads to diagnosis delay. Prospective international clinical trials enrolling adult patients are important. Keywords: Adult; Histiocytosis, Langerhans-Cell.

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Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

Case Reports in Radiology ◽

10.1155/2015/536328 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

Bruno Araujo ◽

Francisco Costa ◽

Joanne Lopes ◽

Ricardo Castro

Keyword(s):

Langerhans Cell Histiocytosis ◽

Early Stage ◽

Biliary Tree ◽

Pulmonary Involvement ◽

Multiple Organ ◽

Langerhans Cell ◽

Liver Involvement ◽

Unknown Etiology ◽

Multisystem Disease ◽

Organ Systems

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment.

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