Standardized salvage treatments for refractory/relapse Langerhans cell histiocytosis (LCH) remain to be established. Trametinib (TRA) has shown marked efficacy in LCH, but cohort studies regarding efficacy and safety of TRA monotherapy in refractory/relapse LCH were scarce. We retrospectively analyzed 22 patients with refractory/relapse LCH treated with TRA monotherapy. Patients were treated for a median of 21.4 months (3.0-51.6 months). Nineteen (86.4%) of 22 of patients remained progression-free during TRA treatment. Sixteen patients stopped TRA (not due to progression or toxicity), of which 10 remained progression free, with median follow-up time of 28.7 months (1.5-44.6 months) after TRA withdrawal, and 6 patients experienced relapse, with median time to relapse from post-TRA withdrawal of 3.7 months (2.7-16.5 months). Two patients continued on TRA at last follow-up and one switched to chemotherapy due to toxicity. Three-year event-free survival was 50.7% (95% CI: 27.7-69.8), with a median follow-up time of 36.4 months (3.0-67.6 months). From TRA initiation to 12 months of treatment, cell-free BRAF/MAP2K1 mutation status in blood presented as negative to negative or positive to negative was correlated with superior event-free survival rate (EFS) rate. Toxicity was tolerable, and adverse events were predominantly skin rash (77.3%), paronychia (22.7%), and diarrhea (13.6%). Overall, TRA was effective and safe in the treatment of patients with refractory/relapse LCH, offering a convenient therapeutic alternative.

ABSTRACT Objectives Langerhans Cell Histiocytosis (LCH) is an inflammatory myeloid neoplasm with heterogeneous outcomes. This study aimed to identify independent risk factors influencing event-free survival (EFS) in pediatric LCH, focusing on initial white blood cell (WBC) counts and disease extent. Methods We retrospectively analyzed 67 pediatric LCH patients with bone involvement treated at Hebei Children's Hospital, Hebei Clinical Medicine Research Center for Children's Health and Diseases between 2013 and 2022. The primary endpoint was EFS. Cox proportional hazards regression models determined predictors of adverse outcomes. Results The 3-year EFS rate was 76.1% (median follow-up: 48 months). Univariate analysis linked multiple disease sites, risk-organ involvement, CNS risk site involvement, diabetes insipidus, and elevated WBC count to poor EFS. In multivariate analysis, only multiple site involvement (Hazard Ratio [HR] = 3.12, p = 0.025) and an elevated initial WBC count (>10 × 10⁹/L) (HR = 2.89, p = 0.034) remained independent predictors. Discussion While risk-organ involvement is a traditional stratifier, systemic inflammatory burden, reflected by leukocytosis, offers independent prognostic value. Patients with elevated WBC counts or multisite disease warrant intensive monitoring. Conclusion Elevated initial WBC count and multiple site involvement independently predict shorter EFS in pediatric LCH. Integrating these markers into risk stratification could optimize therapies.

Repurposing osteoporosis medications for other diseases: a narrative review by the European Calcified Tissue Society (ECTS).

Langerhans cell histiocytosis (LCH) occurring in a Pheochromocytoma in the adrenal gland is exceptionally rare and prone to misdiagnosis. The special coexistent tumors harbor distinct genetic mutations. This uncommon case could introduce novel considerations and a strong teaching message to all the clinicians and pathologists.

Cutaneous Histiocytoses.

Langerhans cell histiocytosis (LCH) is a rare clonal myeloid neoplasm with prominent inflammatory features and heterogeneous manifestations in adults, often leading to diagnostic delay. We report a 32-year-old man who presented with a two-year history of recurrent ulcerative intertriginous skin lesions refractory to empirical treatment for presumed inflammatory or infectious dermatoses. Biopsy from the ulcer edge showed atypical histiocytoid cells with characteristic nuclear grooves and numerous eosinophils; immunohistochemistry was positive for CD1a, S-100, and Langerin with a Ki-67 index of ~40%, confirming cutaneous LCH. Baseline 18 F-FDG PET/CT (August 2022) demonstrated multisystem disease with extensive cutaneous involvement and imaging-suggestive involvement of multiple extracutaneous sites, including multifocal osseous lesions, the thyroid, gastrointestinal tract, lymph nodes, lung (cystic lesions), and an intramuscular nodule. After six cycles of cytarabine-based induction chemotherapy, follow-up PET/CT (April 2023) showed near-complete metabolic remission with only residual low-grade uptake in the perineal skin and maxillomandibular/gingival region. In contrast, 99m Tc-MDP whole-body bone scintigraphy with SPECT/CT performed one year later (July 2024) revealed persistent multifocal tracer uptake, most prominent in the craniofacial skeleton and long bones, with corresponding CT changes suggestive of ongoing remodeling. This case highlights the importance of early biopsy of persistent unexplained ulcerative intertriginous lesions in adults to expedite systemic staging, and demonstrates the complementary roles of serial 18 F-FDG PET/CT and bone scintigraphy with SPECT/CT in longitudinal assessment of osseous disease in adult multisystem LCH.

The natural history of pulmonary Langerhans cell histiocytosis (PLCH) is unpredictable. Therefore, the identification of prognostic biomarkers for PLCH represents a major goal for better management of patients. The aim of this study was to evaluate the levels of various blood mediators in PLCH patients at diagnosis and explore their relationships with forced expiratory volume in one second (FEV1) outcomes. We used multiplex immunoassays to measure at diagnosis the serum concentrations of thirty mediators in patients with stable vs. declining FEV1. Multivariable-adjusted logistic regression models, accounting for matched variables (age, sex, and daily tobacco consumption), were used to compare concentrations between patients stratified on the basis of their FEV1 values. Nine patients with declining FEV1 profiles over time who had an available blood sample at the time of PLCH diagnosis were paired with 16 patients whose FEV1 profiles remained stable over a median follow-up of 3.6years [IQR 2.2-5.1]. The levels of two biomarkers, TNF-α and MMP-7, were significantly greater in patients with a decreased FEV1 than in those with a stable FEV1 in the univariable analysis after adjustment for matching variables. The median serum levels of TNF-α were 137 [75-358] pg/mL in the declining FEV1 group and 60 [45-92] pg/mL in the stable FEV1 group (p = 0.032). Similarly, the median MMP-7 levels were 16344 [13318-18000] pg/mL and 11555 [9796-12495] pg/mL, respectively (p = 0.047). There was a negative correlation between FEV1 values and MMP-7 levels (rho = -0.65, p = 0.001) but not with TNF-α levels (rho = -0.33, p = 0.14). TNF-α and MMP-7 levels are potential prognostic blood biomarkers in PLCH.

Guideline for the diagnosis and treatment of Langerhans cell histiocytosis in Chinese children (2026)

A Case of Multisystem Langerhans Cell Histiocytosis with Palmar Hyperkeratosis and Purpuric Nail Bands as the Initial Presentation: New Insights into An Old Disease.

Adult-onset Langerhans cell histiocytosis in an elderly female with cutaneous and nodal involvement: A case report

Neurodegeneration in Langerhans Cell Histiocytosis: beyond a Sequela.

Langerhans cell histiocytosis (LCH) is a rare clonal myeloid neoplasm with varied and often organ-specific manifestations. Hepatic involvement in adult LCH is rare and frequently results in delayed diagnosis due to its non-specific clinical and biochemical features. We describe the case of a woman in her late twenties who presented with intermittent upper abdominal discomfort, fatigue and weight loss. Despite extensive imaging, serological workup and initial liver biopsy, no definitive diagnosis could be established. Ultimately, diagnostic laparoscopy and histopathological examination with immunohistochemistry confirmed the diagnosis of multifocal hepatic LCH. This case highlights the importance of considering LCH in the differential diagnosis of unexplained hepatomegaly with cholestatic liver enzyme elevation and systemic symptoms. Early liver biopsy with appropriate immunophenotyping is critical for timely diagnosis and initiation of treatment.

Scalp swelling diagnosed as benign lymphadenopathy, later revealed to be invasive langerhans cell histiocytosis with nodal involvement in a pediatric patient: importance of broad differential for common problems

Choriocarcinoma is a highly aggressive malignant germ cell tumour containing syncytiotrophoblasts that secrete beta-human chorionic gonadotropin, and it has a poor prognosis, with a dismal 5-year survival rate of <5%. It generally affects young individuals. Cystic lesions in the lung are uncommon in malignancies that can predispose patients to spontaneous pneumothorax. Multiple cystic lesions are less commonly seen in metastatic disease. Diffuse cystic lung diseases (DCLD) are a group of diseases characterised by cysts in the bilateral lung fields that are not necessarily evenly distributed. The differential diagnosis is limited and typically includes lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis. Sometimes, metastatic malignancy can present as DCLD. Metastatic leiomyoma, endometrial stromal sarcoma and cellular fibrous histiocytic tumours have been reported as causes of lung cysts. We report a case of choriocarcinoma with cystic lung metastasis in a woman in her 30s.

Introduction: Langerhans cell histiocytosis (LCH) is a rare but potentially life-threatening hematologic disorder characterized by a wide spectrum of skin manifestations that may mimic a variety of common neonatal and pediatric diseases. Objectives: To raise awareness of the broad clinical spectrum of cutaneous manifestations important for early recognition. Methods: Herein, we present seven cases of LCH with diverse skin manifestations, disease type, and course of disease. Results: Dermatological examination was key in suspecting LCH in all cases, enabling prompt oncological evaluation with skin signs preceding other organ involvement. Skin manifestations ranged from isolated to widespread skin rashes. Common lesions included erythematous, reddish-brown, or skin-colored crusted or scaly papules or maculopapular lesions. However, plaques, patches, vesicles, and urticarial lesions may also occur. Conclusions: Timely dermatological consultation should be sought in cases of non-resolving, therapy-resistant skin lesions and an unclear diagnosis.

Lung cysts, a common feature found in patients with hairy cell leukemia and Langerhans cell histiocytosis

The efficacy of cladribine in treating pulmonary Langerhans cell histiocytosis (PLCH) has been suggested in select case reports. Treatment-related malignancies remain a concern. In this phase 2 trial, the efficacy and safety of cladribine was evaluated in symptomatic PLCH patients with airflow obstruction and/or a decrease in lung function within the previous year. Cladribine was administered for 4 monthly cycles combined with infectious prophylaxis. Patients were followed up every 3 months during the first year to assess efficacy and then until 48 months. The primary endpoint was the cumulative incidence of response to treatment at 6 months, defined as ≥10% improvement in forced vital capacity (FVC) and/or forced expiratory volume in 1 s (FEV1), with an increase of at least 200 mL in the absolute value of FEV1. The study was registered with www. gov: NCT01473797. Ten patients (6 men; median age, 37 years; IQR [33; 47.5]; 6 current smokers) were included. The cumulative incidence of response to treatment at 6 months was 70% (CI, 28.4-90.4). The response to cladribine was associated with a median decrease of 14.9 points (IQR [10.5; 23.5]) in the Saint George's Respiratory Questionnaire score. At 12 months, 5 patients were still responders. The duration of infection prophylaxis was 11.8 months [IQR 11.7; 29]. One patient died before the 12-month visit. The remaining patients were alive at 48 months. No, malignancies were detected. Cladribine improved lung function in half of the patients at one year of follow-up and was well tolerated overall.

Langerhans cell histiocytosis is a rare myeloid neoplasm that primarily affects children. Initial treatment depends on risk stratification, but overall survival is excellent. Patient with high-risk disease with risk organ involvement can experience disease reactivation or refractoriness to front-line therapy. A standard approach is not established in the literature, with different reported strategies, including conventional chemotherapy, MAPK-inhibitors and allogeneic hematopoietic (HCT). Allogeneic HCT is supported by retrospective studies with overall survival ranging from 56 to 77% in the largest series. Disease status at the time of HCT and the conditioning regimen (reduced-intensity conditioning versus myeloablative conditioning) correlates with survival and toxicity. Most recently, reduced-intensity conditioning modality has emerged as the preferred option for patients diagnosed with Langerhans cell histiocytosis who require allogeneic HCT.

Descriptive analysis of primary intermediate and benign spine tumors: A retrospective study using the Bone and Soft Tissue Tumor Registry in Japan.

ABSTRACTThis case report highlights that Langerhans cell histiocytosis should be suspected in the differential diagnosis for children who exhibit failure to thrive, diabetes insipidus, and skin lesions. Early recognition and timely management are crucial for preventing irreversible hypothalamic–pituitary damage and improving outcomes.