OBJECTIVES: To study the clinical characteristics, efficacy, and prognosis of pediatric Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis was conducted on 72 children with newly diagnosed LCH. RESULTS: The median age of the 72 children was 5 years (range: 0-14 years), with skull involvement being the most common (56 cases, 77.8%). The BRAF-V600E mutation was not associated with clinical characteristics, efficacy, or prognosis (P>0.05). The 5-year overall survival rate was 91.6%±4.2%, and the 5-year event-free survival (EFS) rate was 67.5%±5.8%. The 6-week chemotherapy response rate and 5-year EFS rate were lower in the risk organ involvement group compared to the no risk organ involvement group (P<0.05). The five-year overall survival rates for the group with multi-system involvement and the group with platelet count ≥450×10⁹/L were respectively lower than those for the single-system involvement group and the group with platelet count <450×10⁹/L (P<0.05). Risk organ involvement is an independent risk factor for 5-year EFS (P<0.05). CONCLUSIONS Skull is the most commonly affected site in pediatric LCH. The BRAF-V600E mutation is not related to clinical characteristics, efficacy, or prognosis. Elevated platelet count, risk organ involvement, and multisystem involvement are associated with poor prognosis, with risk organ involvement being an independent risk factor for 5-year EFS.
Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Child, Preschool ; Child ; Male ; Infant ; Female ; Adolescent ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/genetics* ; Prognosis ; Infant, Newborn ; Mutation

Langerhans cell histiocytosis of bone is a rare tumor disease characterized by the large accumulation of CD1a⁺ and CD207⁺ dendritic cells in tissues of unknown cause.It mainly occurs in children aged 1-4 years old,with incidences of 4-6 per million in children and 1-2 per million in adults.Due to its low incidence,diverse clinical manifestations,and no obvious specificity of imaging manifestations,the definitive diagnosis and early treatment of this type of tumor are challenging.In this paper,we report 8 cases of Langerhans cell histiocytosis of bone and review the relevant literature published in the past five years to summarize the clinical characteristics,pathological features,diagnosis,treatment,and prognosis of this disease.
Humans ; Bone Diseases/therapy* ; Histiocytosis, Langerhans-Cell/therapy*

Langerhans Cell Histiocytosis (LCH) is a rare disorder characterized by the abnormal proliferation of histiocytes, predominantly affecting the bones and skin. However, it can also involve the bone marrow, liver, spleen, lungs, pituitary gland, central nervous system, and other organs. The disorder is named for the neoplastic cells that resemble dendritic Langerhans cells found in the skin and mucosa.

We present the case of a 2-year-old Filipino female diagnosed with recurrent LCH, highlighting the diagnostic challenges and therapeutic interventions encountered. The patient initially presented with characteristic papules and plaques indicative of LCH. Initial treatment involved multi-agent chemotherapy, which resulted in significant clinical improvement. However, following the cessation of therapy, the patient experienced recurrence of symptoms, necessitating reevaluation. A skin punch biopsy confirmed the diagnosis of LCH, reinforcing the decision to reinitiate chemotherapy. Complications arose during treatment, including febrile neutropenia, which required hospitalization and adjustments to the management plan. After completing the chemotherapy cycles, the patient demonstrated marked clinical improvement, with the resolution of systemic symptoms and a reduction in the severity of cutaneous lesions.

This case underscores the complexities in managing recurrent LCH in pediatric patients. A comprehensive diagnostic evaluation, vigilant monitoring for treatment-related complications, and prompt therapeutic interventions are critical for achieving optimal outcomes. Effective management requires a multidisciplinary approach to address the unique challenges presented, ensuring timely interventions to improve patient outcomes.

Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m², twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.
Male ; Female ; Child ; Humans ; Cytarabine/adverse effects* ; Cladribine/adverse effects* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Histiocytosis, Langerhans-Cell/drug therapy* ; Prognosis

Langerhans cell histiocytosis (LCH) is a group of unexplainable abnormal proliferation and aggregation of Langerhans cell. LCH can be classified into four clinical variants: Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma, and congenital self-healing LCH. LCH is most prevalent in children. Lesions can be localized in a single system or multiple organs, and clinical manifestations vary depending on the affected organs. The skin and mucocutaneous tissues are the starting point of the affected tissue. This study presents a LCH case characterized by transient self-healing. This case can further provide references for the clinical diagnosis and treatment of LCH.
Child ; Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Diagnosis, Differential

OBJECTIVES: Pulmonary Langerhans cell histiocytosis (PLCH) is a clonal disease, characterized by proliferation of Langerhans cells that derived from bone marrow infiltrating the lungs and other organs. Due to the rarity of the disease, the current understanding of the disease is insufficient, often misdiagnosed or missed diagnosis. This study aims to raise clinicians' awareness for this disease via summarizing the clinical characteristics, imaging features, and treatment of PLCH. METHODS: We retrospectively analyzed clinical and follow-up data of 15 hospitalized cases of PLCH from September 2012 to June 2021 in the Second Xiangya Hospital of Central South University. RESULTS: The age of 15 patients (9 men and 6 women, with a sex ratio of 3 to 2) was 21-52 (median 33) years. Among them, 8 had a history of smoking and 5 suffered spontaneous pneumothorax during disease course. There were 3 patients with single system PLCH and 12 patients with multi-system PLCH, including 7 patients with pituitary involvement, 7 patients with lymph node involvement, 6 patients with bone involvement, 5 patients with liver involvement, 2 patients with skin involvement, 2 patients with thyroid involvement, and 1 patients with thymus involvement. The clinical manifestations were varied but non-specific. Respiratory symptoms mainly included dry cough, sputum expectoration, chest pain, etc. Constitutional symptoms included fever and weight loss. Patients with multi-system involvement experienced symptoms such as polyuria-polydipsia, bone pain, and skin rash. All patients were confirmed by pathology, including 6 by lung biopsy, 3 by bone biopsy, 2 by lymph node biopsy, and 4 by liver, skin, suprasternal fossa tumor, or pituitary stalk biopsy. The most common CT findings from this cohort of patients were nodules and/or cysts and nodular and cystic shadows were found in 7 patients. Three patients presented simple multiple cystic shadows, 3 patients presented multiple nodules, and 2 patients presented with single nodules and mass shadows. Pulmonary function tests were performed in 4 patients, ventilation dysfunction was showed in 2 patients at the first visit. Pulmonary diffusion function tests were performed in 4 patients and showed a decrease in 3 patients. Smoking cessation was recommended to PLCH patients with smoking history. Ten patients received chemotherapy while 2 patients received oral glucocorticoid therapy. Among the 11 patients with the long-term follow-up, 9 were in stable condition. CONCLUSIONS PLCH is a neoplastic disease closely related to smoking. The clinical manifestations and laboratory examination are not specific. Pneumothorax could be the first symptom which is very suggestive of the disease. Definitive diagnosis relies on histology. There is no unified treatment plan for PLCH, and individualized treatment should be carried out according to organ involvement. Early smoking cessation is essential. Chemotherapy is the main treatment for rapidly progressing PLCH involved multiple organs. All diagnosed patients can be considered for the detection of BRAF^V600E gene and relevant targeted therapies have been implemented recently.
Adult ; Cysts ; Female ; Histiocytosis, Langerhans-Cell/therapy* ; Humans ; Lung/pathology* ; Male ; Retrospective Studies ; Smoking/adverse effects* ; Smoking Cessation

OBJECTIVE: To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children. METHODS: Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae. RESULTS: Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus. CONCLUSION 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.
Child ; Cladribine/adverse effects* ; Cytarabine ; Histiocytosis, Langerhans-Cell/drug therapy* ; Humans ; Recurrence ; Retrospective Studies

Langerhans cell histiocytosis (LCH) is a rare proliferative disease dominated by the proliferation of Langerhans cells, which is inflammatory myeloid neoplasms. Its clinical manifestations are variable, occurring at any age and at any site, and it is rarer in adults than in children. The gold standard for diagnosis is histopathological biopsy. Due to the rarity of adult LCH and the heterogeneity of this disease, treatment of adult LCH should be developed according to the extent of the disease and risk stratification. With the discovery of MAPK, PI3K and c-KIT signaling pathway activation, especially BRAF V600E and MAP2K1 mutations, targeted therapy has become a hot spot for therapeutic research. Meanwhile, the discovery of high expression of M2-polarized macrophages and Foxp3⁺ regulatory T cells (Treg) in LCH has provided an important basis for the immunotherapy. In this article, we will focus on reviewing the latest research progress in the treatment of adult LCH in recent years, and provide a reference for clinical research on the treatment of adult LCH patients.
Adult ; Child ; Histiocytosis, Langerhans-Cell/therapy* ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf/metabolism* ; Signal Transduction ; T-Lymphocytes, Regulatory/pathology*

Child ; Endoscopy ; Histiocytosis, Langerhans-Cell/therapy* ; Humans ; Mandible ; Tongue

Currently, the World Health Organization classifies Langerhans cell tumors into Langerhans cell histiocytosis and Langerhans cell sarcoma (LCS). LCS is a neoplastic proliferation of Langerhans cells showing malignant cytological features and aggressive clinical behavior with grave prognosis. Only a few cases have been reported in the available literature; therefore, to date, no definitive treatment has been established. A 64-year-old woman presented with a 1-year history of an asymptomatic, slow-growing erythematous nodule measuring 0.7 cm on her scalp. The patient also reported a 3-month history of a painful swelling on the right side of her neck. Histopathological examination of a scalp biopsy specimen revealed sheets of atypical cells with hyperchromatic nucleoli and clear cytoplasm. Immunohistochemical studies revealed malignant cells positive for CD1a, CD31, CD68, and S-100 expression. Additionally, positron emission tomography–computed tomography and fine-needle aspiration revealed LCS of the cervical lymph nodes and surrounding soft tissue. We recommended surgical excision and adjunctive chemotherapy; however, the patient refused treatment and died of the disease 28 months later.
Biopsy ; Biopsy, Fine-Needle ; Cytoplasm ; Drug Therapy ; Electrons ; Female ; Histiocytosis, Langerhans-Cell ; Humans ; Langerhans Cell Sarcoma ; Langerhans Cells ; Lymph Nodes ; Middle Aged ; Neck ; Parotid Gland ; Prognosis ; Scalp ; World Health Organization