Search Results (74)

Background: Langerhans Cell Histiocytosis (LCH) is a rare histiocytic hematological disorder that frequently involves the lungs. Due to a lack of data about sex-related differences in LCH, the aim of this study is to evaluate sex-related differences in pulmonary function in a cohort of patients with LCH. Methods: We retrospectively analyzed data from 79 adult patients diagnosed with LCH. Demographic, clinical, and spirometric data were collected and compared by sex. Continuous variables were analyzed using the Mann–Whitney test and categorical variables were analyzed with the Chi-square test. Results: Out of 79 patients, 47 (59.5%) were females and 32 (40.5%) were males. Women showed significantly lower diffusing capacity of the lungs for carbon monoxide (DLCO%) and lower diffusing capacity of the lungs for carbon monoxide per unit of alveolar volume (DLCO/VA%) compared to men. Females showed a trend toward lower small airway indices, including maximal expiratory flow at 25 (MEF₂₅%) and forced expiratory flow at 25–75% (FEF_25–75%), though this was not statistically significant, while the residual volume-to-total lung capacity (RV/TLC) ratio was significantly higher in women. Among the functional parameters, DLCO% showed the highest accuracy (AUC 0.70) in the identification of lung involvement after multivariate regression analysis. Conclusions: Our findings suggest that the combination of lower gas exchange efficiency and increased peripheral air trapping secondary to small airway involvement in female patients may reflect the presence of a distinct functional LCH phenotype in women characterized by early small airway involvement and altered ventilation–perfusion dynamics, which may influence the clinical management of these patients. Furthermore, the moderate predictive value of DLCO% for lung involvement at baseline in LCH women suggests that DLCO may contribute to the detection of LCH women with lung involvement, although it should not be considered a definitive diagnostic test without a prospective and independent external validation. Full article

Langerhans cell sarcoma (LCS) is a rare and aggressive neoplasm characterized by a clonal proliferation of Langerhans cells (LCs), with multi-organ involvement and poor prognosis. Diagnostic challenges arise from its rarity and overlapping features with Langerhans cell histiocytosis (LCH), requiring immunophenotypic and histological analysis for differentiation. This case report discusses a 67-year-old male with multi-organ LCS involvement. Diagnosis was confirmed via liver biopsy and genetic analysis, revealing a MAP2K1 mutation. Treatment with subcutaneous cladribine and dexamethasone resulted in significant clinical and radiological improvement, despite hematological toxicity due to an underlying myelodysplastic neoplasm (MDS). This case proves the potential efficacy of cladribine for disseminated LCS and highlights the necessity for further research into optimal therapeutic approaches for this rare malignancy. Full article

Over the past decade, the field of childhood histiocytosis, particularly Langerhans cell histiocytosis (LCH), has undergone transformative changes. The integration of molecular genetics, targeted therapies, and refined diagnostic methodologies has revolutionized patient management and redefined disease classification. This editorial provides a comprehensive overview of the pivotal developments from 2015 to 2025, highlights ongoing challenges, and explores future directions in research and clinical care. Full article

Introduction: The group of so-called “sellar-region masses” consists of a heterogeneous group of neoplasms and tumor-mimicking lesions, whose differential diagnosis may be challenging due to the overlapping of clinical and radiological features, which can be found both in “common” and “uncommon” lesions. The choice of a correct treatment strategy is still arduous and requires histological analysis. Gamma Knife Radiosurgery (GKRS) has already been reported as a safe and effective treatment in these cases. The objective of this study is to evaluate single-center pre-operative data, post-operative outcomes, and long-term follow-up in patients treated with GKRS for unusual sellar tumors. Methods: We retrospectively identified and analyzed nine patients treated with GKRS from 2004 to 2015, according to a standard protocol. Lesions consist of hypothalamic hamartoma (HH), Rathke’s cleft cist (RCC), Langerhans cell histiocytosis (LCH), spindle cell oncocytoma (SCO), choroid plexus papilloma (CPP), and ossifying fibroma (OF). The diagnosis was histologically confirmed in six patients that underwent surgery, while in three patients, diagnosis was based on characteristic clinical and radiological findings (two HH and one RCC). Pre-operative and post-operative data were retrieved from medical archives, and long-term follow-up was obtained through clinical and neuroradiological periodic examination. Results: In our series, all the “rare” sellar lesions treated, had a successful radiographic and clinical response in a medium-long follow-up period. Conclusions: The long-term follow-up results suggest that GKRS is a safe and effective treatment in rare sellar lesions, with very low toxicity. To the best of our knowledge, this report represents the largest series of unusual sellar lesions treated with GKRS in a single high-volume center, suggesting that GKRS might be an effective non-invasive adjuvant treatment option. Further studies and a larger number of patients are needed to confirm if residuals of these rare sellar lesions might regress on their own without treatment or if other non-invasive treatments could be as effective as GKRS. Full article

Background and Clinical Significance: Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a relatively novel entity, affecting single or multiple organ systems; it is characterized by aggregates of neoplastic cells of the histiocytic lineage, harboring molecular alterations in the ALK gene and exhibiting excellent response to systemic tyrosine kinase inhibitors. Case presentation: Herein, we present a pediatric case with cutaneous-only involvement: the 6-month-old male patient presented with an elevated, tan-colored lesion on his left forearm. Following surgical excision, histopathological evaluation reported spindle cells with wide eosinophilic cytoplasm and Touton-type giant cells. The tumor cells were positive for CD163, ALK, phosphorylated ERK, and cyclin D1. Fluorescent in situ hybridization revealed ALK rearrangement, whereas, upon next-generation sequencing, a DCTN1::ALK fusion was identified. Conclusion: Our case serves as a great addition to the limited number of cases reported in the literature, and it represents the first published pediatric case with the rare DCTN1::ALK fusion. The novelty of this genetic alteration and the lack of knowledge about its potential effects on the clinical aspects of ALK-positive histiocytosis highlight the importance of ancillary molecular testing, when available. Full article

Interstitial lung diseases (ILD) represent a diverse group of disorders that primarily affect the pulmonary interstitium and, less commonly, involve the alveolar and vascular epithelium. Overlapping clinical, radiological and histopathological features make proper classification difficult, requiring multiple complementary methodologies, including flow cytometry of bronchoalveolar lavages (BAL). This retrospective study analyzed BAL flow cytometry data from 1074 real-life patients, quantifying alveolar macrophages, CD4/CD8 lymphocytes, neutrophils, eosinophils, and CD1a+ Langerhans cells, with the aim of evaluating its diagnostic utility in ILD and pulmonary infection. Clustering and logistic regression analyses identified seven distinct leukocyte profiles: lymphocytic (associated with hypersensitivity pneumonitis, cryptogenic organizing pneumonia, and lymphocytic interstitial pneumonia), sarcoidosis, macrophagic (including nonspecific interstitial pneumonia, desquamative interstitial pneumonitis, pneumoconiosis, and unclassifiable ILD), neutrophilic (including usual interstitial pneumonia, respiratory bronchiolitis ILD, and acute interstitial pneumonia), infectious diseases, eosinophilic ILD, and Langerhans cell histiocytosis. The estimated leukocyte profiles were associated with different overall survival (OS) outcomes. Neutrophilic profiles, both infectious and non-infectious, correlated with poorer OS, particularly in patients without pulmonary fibrosis. Furthermore, corticosteroids and other immunosuppressive therapies did not show significant OS differences across leukocyte profiles. Although the gold standard in BAL cytology continues to be cytopathology, these results support BAL flow cytometry as a rapid and reliable complementary tool to aid in the classification of interstitial lung diseases based on immune cell profiles, providing valuable predictive information and contributing to personalized therapeutic approaches. Full article

We present an ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) scan of a 27 y/o patient with long-standing significant B symptoms, diffuse bone pain, increased inflammation parameters, and polydipsia revealing multiple FDG-avid osteolytic lesions of the axial skeleton including a vertebra plana of T7 and paraosseous soft tissue lesions. A CT-guided biopsy confirmed the diagnosis of Langerhans cell histiocytosis (LCH). This case highlights the importance of considering LCH in young patients with vertebral collapse and underscores the role of PET/CT imaging in establishing an accurate diagnosis. Full article

Rosai–Dorfman disease (RDD) is a rare proliferative disorder characterized by an overproduction of a type of immune cell called histiocytes, with unknown etiology. Although extranodal involvement is not uncommon, it is rarely seen within the nose. The available data are limited, and currently, there are no established guidelines for managing RDD. Different therapeutic options have been described, including corticosteroids, surgery, radiotherapy, or chemotherapy. This study aims to evaluate the potential benefit of radiotherapy in patients with nasal Rosai–Dorfman disease to improve the current diagnostic and therapeutic management. Herein, we report the case of a 54-year-old female patient with nasal RDD refractory to systemic corticosteroid therapy and transnasal endoscopic resection. She received fractionated low-dose radiotherapy with a total dose of 30 cGy administered in 2 cGy daily fractions. Complete remission was achieved, highlighting the potential role of radiotherapy as an effective therapeutic option for relapsing or steroid-refractory cases. This is one of the few well-documented cases reported with nasal Rosai–Dorfman disease treated with radiotherapy. Ongoing research on novel therapies offers hope for improved outcomes in relapsing cases that fail to respond to conventional treatments. Full article

Purpose: Erdheim–Chester disease (ECD) is an L Group Langerhans histiocytosis associated with pathogenic variants within the MAPK pathways, most commonly the BRAF gene. We analyzed prevalence, genetic, biochemical, and pituitary imaging features associated with arginine vasopressin deficiency (AVP-D), one of the most common endocrinopathies in ECD. Methods: A cross-sectional descriptive study of 61 subjects with ECD was conducted at a clinical research center from January 2011 to December 2018, with molecular genetics, baseline biochemical and pituitary endocrine function studies, and dedicated pituitary MRI (or CT) studies. AVP-D and anterior pituitary endocrinopathies (hypothyroidism, hypogonadism, adrenal insufficiency and panhypopituitarism) were assessed. Students’ t-tests, nonparametric tests, Fisher’s exact tests, and logistic regression were employed for analysis. Results: In total, 22 out of 61 subjects (36%; 19 males and 3 females) had AVP-D; 18 subjects with AVP-D were in active treatment with desmopressin. Those with versus without AVP-D were younger [mean (±SD): 50.00 (±10.45) vs. 56.72 (±10.45) years], had higher prevalence of BRAF V600E pathogenic variants [68% vs. 43%], lower IGF-1 [mean (±SD): 137.05 (±67.97) vs. 175.92 (±61.89) ng/mL], lower urine osmolality [416.00 (250.00–690.00) vs. 644.50 (538.75–757.75)) mOsm/kg], and a higher burden of central hypogonadism [81.82% vs. 36.00%], central hypothyroidism [23% vs. 2.5%], panhypopituitarism [41% vs. 0%], anterior pituitary endocrine deficits, absent posterior pituitary bright spots [63.64% vs. 20.51%], and abnormal pituitary imaging. In adjusted models, [OR (95%CI)] BRAF V600E mutation [7.38 (1.84–39.01)], central hypogonadism [6.193 (1.44–34.80)], primary hypothyroidism [13.89 (1.401–406.5)], absent posterior pituitary bright spot [12.84 (3.275–65.04)], and abnormal pituitary imaging [10.60 (2.844–48.29)] were associated with higher odds of having AVP-D. Conclusions: AVP-D is common in ECD and accompanied by a higher burden of pituitary endocrinopathies, BRAF V600E pathogenic variants, abnormal pituitary imaging, and absent posterior pituitary bright spots. Full article

Interstitial lung diseases (ILDs) represent a heterogenous group of lung disorders marked by inflammation and/or fibrosis of the lung parenchyma, often leading to progressive shortness of breath and end-stage respiratory failure. In the U.S., ILDs affect approximately 650,000 individuals and cause approximately 25,000–30,000 deaths annually. Lung transplantation (LTx) offers definitive treatment for advanced ILD, with improved survival attributed to advancements in immunosuppression, organ preservation, surgical techniques, and postoperative care. However, disease recurrence in transplanted lungs remains a significant concern. Understanding the risk factors and mechanisms underlying recurrence is critical for refining recipient selection and improving outcomes. This review examines ILD recurrence post LTx and its implications for lung transplantation success. Full article

The soluble interleukin-2 receptor (sIL-2R) is a novel biomarker associated with a variety of immune-mediated diseases. It is produced through the proteolytic cleavage of the membrane-bound interleukin-2 receptor α-chain on activated T lymphocytes; hence, its increase reflects T-cell activation and immune dysregulation. Elevated sIL-2R levels are frequently documented in conditions such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, histiocytosis, hemophagocytic lymphohistiocytosis, lymphomas, and graft-versus-host disease, suggesting a potential role in monitoring disease activity and progression. However, sIL-2R levels may increase in the context of immune response to infections and malignancies, requiring careful interpretation. It is essential to determine whether elevated levels of this marker within specific ranges could suggest a specific entity, due to the implications this may have for the management of patients. This case-based review presents five patients with different immune-mediated diseases, highlighting how these different conditions can present with characteristic ranges of sIL-2R elevation. By integrating clinical findings with sIL-2R measurements, we emphasize the biomarker’s utility in guiding diagnosis, as well as monitoring disease activity and determining prognosis, which can enhance clinical decision-making and patient management in rheumatology and related fields. Full article

Evaluating altered mental status and suspected meningeal disorders in children often begins with imaging, typically before a lumbar puncture. The challenge is that meningeal enhancement is a common finding across a range of pathologies, making diagnosis complex. This review proposes a categorization of meningeal diseases based on their predominant imaging characteristics. It includes a detailed description of the clinical and imaging features of various conditions that lead to leptomeningeal or pachymeningeal enhancement in children and adolescents. These conditions encompass infectious meningitis (viral, bacterial, tuberculous, algal, and fungal), autoimmune diseases (such as anti-MOG demyelination, neurosarcoidosis, Guillain-Barré syndrome, idiopathic hypertrophic pachymeningitis, and NMDA-related encephalitis), primary and secondary tumors (including diffuse glioneuronal tumor of childhood, primary CNS rhabdomyosarcoma, primary CNS tumoral metastasis, extracranial tumor metastasis, and lymphoma), tumor-like diseases (Langerhans cell histiocytosis and ALK-positive histiocytosis), vascular causes (such as pial angiomatosis, ANCA-related vasculitis, and Moyamoya disease), and other disorders like spontaneous intracranial hypotension and posterior reversible encephalopathy syndrome. Despite the nonspecific nature of imaging findings associated with meningeal lesions, narrowing down the differential diagnoses is crucial, as each condition requires a tailored and specific treatment approach. Full article

Background: The detection of mutations from circulating tumor DNA (ctDNA) represents a promising enrichment technique. In this retrospective study, the significance of ctDNA and imaging in Langerhans cell histiocytosis (LCH) monitoring was first examined, and the broader role of ctDNA in monitoring LCH was additionally explored. Methods: First, data visualization and survival analysis models were used to generalize the concordance between cfBRAF^V600E molecular response and radiographic response on clinical outcomes. Next, the molecular response of cfBRAF^V600E was observed from a dynamic perspective. A comparative analysis was then conducted between cfBRAF^V600E and ltBRAF^V600E status, examining their relationship to clinical manifestations and prognosis of LCH. Results: Eventually, 119 participants were enrolled in this trial between 2019 and 2023. Progression-free survival (PFS) was significantly shorter in patients with both radiologic and cfDNA molecular progression (17.67 versus 24.67 months, p < 0.05) compared to those without. A critical cfBRAF^V600E value of 0.03% has been determined for the first time. Both cfBRAF^V600E and ltBRAF^V600E mutations were associated with a higher proportion of children under 3 years of age, skin and spleen involvement, and a lower 3-year PFS rate. In contrast to ltBRAF^V600E, cfBRAF^V600E was linked to a higher proportion of risk organ invasion LCH (52% vs. 27.9%, p < 0.05) and a better therapeutic response at the sixth week (24% vs. 4.7%, p < 0.05). Furthermore, in patients with risk organ invasion-LCH and multisystem-LCH subtypes, cfBRAF^V600E was associated with a significantly lower 3-year PFS. Conclusions: In summary, these findings enhanced and supplemented the implications of ctDNA and imaging analysis application in children with LCH. Full article

Objective: This study examines the association between major urban pollutants and the long-term decline of non-idiopathic pulmonary fibrosis interstitial lung disease [non-IPF ILD]. Materials and methods: A total of 41 patients with non-IPF ILD were analyzed from 2011 to 2020, correlating disease long-term decline with concentrations of key pollutants [SO₂, CO, NO₂, O₃, PM_2.5, and PM₁₀] in Madrid. The likelihood of meeting severity criteria was assessed using a generalized linear model, considering the average pollutant levels during severe episodes. Results: At diagnosis, the average age of patients was 62.95 ± 13.13 years, with 47.6% women. The study found no significant association between pollution levels and the probability of meeting severity criteria for non-IPF ILD. The odds ratios were as follows: OR SO₂ = 0.92 [0.82–1.03], p = 0.16; OR CO = 0.99 [0.97–1.05], p = 0.70; OR NO₂ = 0.97 [0.92–1.03], p = 0.38; OR PM_2.5 = 0.79 [0.54–1.17], p = 0.24; OR PM₁₀ = 1.1 [0.94–1.28], p = 0.21; OR O₃ = 0.97 [0.92–1.01], p = 0.20. Conclusions: Our study suggests that, within the cohort of 41 patients with non-IPF ILD enrolled in this study, urban air pollutants in Madrid are not significantly linked to increased long-term decline of non-IPF ILD. This is one of the first studies to explore the impact of various urban pollutants on a diverse cohort of non-IPF ILD patients, including rare conditions like LAM and histiocytosis X. Further research with larger sample sizes and comprehensive exposure assessments is recommended. Full article

Background: Cranial vault lesions are common in children, with dermoid and epidermoid cysts being the most frequent. Management is debated due to their slow growth, but early resection can prevent complications and provide a definitive histological diagnosis, which is sometimes linked to systemic diseases. Methods: A retrospective study of children treated surgically for cranial vault tumors from January 2011 to April 2023 was conducted. The data collected included age, gender, symptoms, comorbidities, lesion location, radiological features, surgical techniques, histopathology, and recurrence rates. Results: Eighty-eight children (mean age: 3.5 years, mean tumor size: 1.21 cm) underwent surgery. The most common locations were the frontal and occipital bones. The main diagnoses were dermoid cysts, myofibroma, and Langerhans cell histiocytosis. Gross total resection was achieved in 64 cases with simple skin incisions. In 13 cases, small cranioplasties with bone cement were used. Craniotomy and cranioplasty with autologous bone grafting were performed for 11 patients with lesions larger than 2 cm and full skull thickness erosion. Conclusions: Early resection is recommended for complete removal with minimally invasive surgery and to ensure histological diagnosis. For lesions larger than 2 cm with full skull erosion, cranioplasty with autologous bone is the preferred technique. Full article