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Journal of the European Academy of... Aug 2020Reticulohistiocytoses (RH) are rare and clinically heterogeneous histiocytic disorders of dermatological interest. Three clinical entities with superimposable... (Review)
Review
Reticulohistiocytoses (RH) are rare and clinically heterogeneous histiocytic disorders of dermatological interest. Three clinical entities with superimposable histopathological features are currently considered, namely solitary reticulohistiocytoma, diffuse/generalized reticulohistiocytosis and multicentric reticulohistiocytosis. Although in the last decade, RH studies have only minimally progressed, histiocytosis research has advanced considerably: the prognostic and therapeutic importance of the clinical subclassification of histiocytosis patients as well as of the detection of genetic alterations in the genes of the ERK pathway has been highlighted. According to these insights, we previously reported the presence of molecular alteration RH and described a subset of patients with disseminated multisystem involvement lacking arthritis. In the present review, we aim to update and revise the knowledge regarding RH. We first reviewed their histopathological, immunophenotypical and ultrastructural features, discussed their histopathological differential diagnosis with other conditions characterized by infiltrates made of oncocytic or epithelioid cells (with special regard to Destombes-Rosai-Dorfman disease) and finally summarized the molecular landscape of RH. We therefore tried to adjust the clinical subclassification of Langerhans cell histiocytosis to the clinical phenotypes of RH, outlining five clinically different groups of patients. Finally, we reconsidered the clinical workflow to the evaluation of RH patients, in light of the 5 different clinical groups and discussed the different therapeutic approaches and the possible role of target inhibitors.
Topics: Diagnosis, Differential; Epithelioid Cells; Histiocytosis, Langerhans-Cell; Histiocytosis, Non-Langerhans-Cell; Histiocytosis, Sinus; Humans
PubMed: 31955466
DOI: 10.1111/jdv.16214 -
Respiratory Research Dec 2023Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease (ILD) associated with smoking, whose definitive diagnosis requires the exclusion of...
BACKGROUND
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease (ILD) associated with smoking, whose definitive diagnosis requires the exclusion of other forms of ILD and a compatible surgical lung biopsy. Bronchoalveolar lavage (BAL) is commonly proposed for the diagnosis of ILD, including PLCH, but the diagnostic value of this technique is limited. Here, we have analyzed the levels of a panel of cytokines and chemokines in BAL from PLCH patients, in order to identify a distinct immune profile to discriminate PLCH from other smoking related-ILD (SR-ILD), and comparing the results with idiopathic pulmonary fibrosis (IPF) as another disease in which smoking is considered a risk factor.
METHODS
BAL samples were collected from thirty-six patients with different ILD, including seven patients with PLCH, sixteen with SR-ILD and thirteen with IPF. Inflammatory profiles were analyzed using the Human Cytokine Membrane Antibody Array. Principal component analysis (PCA) was performed to reduce dimensionality and protein-protein interaction (PPI) network analysis using STRING 11.5 database were conducted. Finally, Random forest (RF) method was used to build a prediction model.
RESULTS
We have found significant differences (p < 0.05) on thirty-two cytokines/chemokines when comparing BAL from PLCH patients with at least one of the other ILD. Four main groups of similarly regulated cytokines were established, identifying distinct sets of markers for each cluster. Exploratory analysis using PCA (principal component analysis) showed clustering and separation of patients, with the two first components capturing 69.69% of the total variance. Levels of TARC/CCL17, leptin, oncostatin M (OSM) and IP-10/CXCL10 were associated with lung function parameters, showing positive correlation with FVC. Finally, random forest (RF) algorithm demonstrates that PLCH patients can be differentiated from the other ILDs based solely on inflammatory profile (accuracy 96.25%).
CONCLUSIONS
Our results show that patients with PLCH exhibit a distinct BAL immune profile to SR-ILD and IPF. PCA analysis and RF model identify a specific immune profile useful for discriminating PLCH.
Topics: Humans; Bronchoalveolar Lavage Fluid; Lung Diseases, Interstitial; Histiocytosis, Langerhans-Cell; Smoking; Idiopathic Pulmonary Fibrosis; Cytokines; Immunoglobulins; Chemokines
PubMed: 38111019
DOI: 10.1186/s12931-023-02622-z -
Medicina (Kaunas, Lithuania) Apr 2021: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells. LCH often...
: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells. LCH often involves the bone, and its clinical evidence is limited. The purpose of this study is to report on the treatment of LCH at our institution and to add to the evidence for LCH. : We reviewed six cases of LCH treated in our hospital between November 2005 and February 2016. Patient age at the first visit, sex, site of origin, symptoms, image tools used for diagnosis, biopsy site, complications, treatment, and final clinical outcome were evaluated. The median follow-up period was 41 months. : The median patient age at the first visit was 13.5 years. Three male and three female individuals were enrolled. Multiple lesions were observed in five cases, and a solitary lesion was observed in one case. Pain was the chief complaint in five cases. Radiography was the most commonly used imaging tool. Bone scintigraphy or magnetic resonance imaging and positron emission tomography-computed tomography were also used to diagnose systematic LCH. Biopsy of the femur was performed in two cases, and biopsy of the tibia, lumbar vertebrae, rib, and radius was performed in one case each. Regarding comorbidities, one case of hepatitis B and one case of autism were observed. Chemotherapy was initiated in two patients. The other four patients were observed naturally. Continuous disease-free survival was observed in five patients. One patient remained alive but not without disease during the final follow-up examination. : LCH should be diagnosed as early as possible to treat it appropriately.
Topics: Female; Histiocytosis, Langerhans-Cell; Humans; Male; Positron Emission Tomography Computed Tomography; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 33917120
DOI: 10.3390/medicina57040356 -
SAGE Open Medical Case Reports 2022The sequential occurrence of Langerhans cell histiocytosis and acute leukemia in only one individual has been reported previously; however, it is rarely observed that...
The sequential occurrence of Langerhans cell histiocytosis and acute leukemia in only one individual has been reported previously; however, it is rarely observed that Langerhans cell histiocytosis can transform into acute lymphoblastic leukemia, and the underlying mechanisms remain unclear. In this report, we have analyzed a case of acute lymphoblastic leukemia converted from Langerhans cell histiocytosis using high-throughput sequencing method, and found that mitogen-activated protein kinase gene mutation, which can act as a marker for poor prognosis, might be involved in disease transformation. This is the first description about acute lymphoblastic leukemia B-cell type after Langerhans cell histiocytosis diagnosis and therapy in China.
PubMed: 35237442
DOI: 10.1177/2050313X221080328 -
Haematologica Sep 2023Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to pediatric neurodegeneration, whereby transformed LCH cells...
Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to pediatric neurodegeneration, whereby transformed LCH cells form agglomerated lesions in various organs. Although MAP-kinase pathway mutations have been identified in LCH cells, the functional consequences of these mutations and the mechanisms that cause the pathogenic behavior of LCH cells are not well understood. In our study, we used an in vitro differentiation system and RNA-sequencing to compare monocyte-derived dendritic cells from LCH patients to those derived from healthy controls or patients with Crohn's disease, a non-histiocytic inflammatory disease. We observed that interferon-γ treatment exacerbated intrinsic differences between LCH patient and control cells, including strikingly increased endo- and exocytosis gene activity in LCH patients. We validated these transcriptional patterns in lesions and functionally confirmed that LCH cells exhibited increased endo- and exocytosis. Furthermore, RNA-sequencing of extracellular vesicles revealed the enrichment of pathological transcripts involved in cell adhesion, MAP-kinase pathway, vesicle trafficking and T-cell activation in LCH patients. Thus, we tested the effect of the LCH secretome on lymphocyte activity and found significant activation of NK cells. These findings implicate extracellular vesicles in the pathology of LCH for the first time, in line with their established roles in the formation of various other tumor niches. Thus, we describe novel traits of LCH patient cells and suggest a pathogenic mechanism of potential therapeutic and diagnostic importance.
Topics: Humans; Child; Secretome; Histiocytosis, Langerhans-Cell; Myeloid Cells; Killer Cells, Natural; Neoplasms
PubMed: 36924254
DOI: 10.3324/haematol.2022.282638 -
The European Respiratory Journal May 2022
Topics: Adult; Cohort Studies; Histiocytosis, Langerhans-Cell; Humans; Prognosis; Prospective Studies; Pulmonary Alveoli
PubMed: 35618281
DOI: 10.1183/13993003.00700-2022 -
Dermatology Practical & Conceptual Jul 2020
PubMed: 32642313
DOI: 10.5826/dpc.1003a63 -
The Indian Journal of Radiology &... Jul 2021Langerhans cell histiocytosis (LCH) is a rare group of disorder, due to clonal neoplastic proliferation of dendritic cells in the bone marrow expressing a Langerhans...
Langerhans cell histiocytosis (LCH) is a rare group of disorder, due to clonal neoplastic proliferation of dendritic cells in the bone marrow expressing a Langerhans cell phenotype. 1 This disease particularly affects the pediatric age group and young adults and often presents with skin rashes, lung infiltrates, and bone lesions. It can also manifest with endocrine dysfunction and hematopoietic disorders. Involvement of gastrointestinal tract is very rare. Herein, we present a spectrum of three cases with gastrointestinal involvement.
PubMed: 34790313
DOI: 10.1055/s-0041-1735505 -
Frontiers in Oncology 2021In this study, the immune microenvironment in Langerhans cell histiocytosis (LCH) was characterized to determine if immune indices are predictive of severity. Serum...
In this study, the immune microenvironment in Langerhans cell histiocytosis (LCH) was characterized to determine if immune indices are predictive of severity. Serum samples from 54 treatment-naïve patients were analyzed quantitatively for inflammatory cytokines and immunoglobulins before and after the induction of chemotherapy. The initial serum sIL-2R, TNF-α, and IL-10 of untreated LCH patients with risk organ involvement (RO+) were significantly higher than those with single-system (SS) involvement. LCH patients with hematologic involvement exhibited a significantly higher sIL-2R, TNF-α, IL-10, and IL-1β expression, as compared to the group without involvement. sIL-2R, TNF-α, and IL-10 were increased in patients with liver or spleen involvement. Th cells have decreased in the liver+ and spleen+ group, and Ts cells were significantly decreased in non-response group after induction chemotherapy. The serum level of immune indices represents, to some extent, the severity of the disease. Pertinent laboratory inspections can be used to improve risk stratification and guide immunotherapy.
PubMed: 34026610
DOI: 10.3389/fonc.2021.631682 -
The Journal of International Advanced... Jan 2023Langerhans cell histiocytosis is a rare condition affecting the temporal bone in up to 60% of cases. Symptoms are non-specific and the differential diagnosis includes...
Langerhans cell histiocytosis is a rare condition affecting the temporal bone in up to 60% of cases. Symptoms are non-specific and the differential diagnosis includes infection, benign lesions such as cholesteatoma, and malignant lesions of the skull base. Here, we report the case of a 14-yearold child referred with chronic ear discharge, and background of multifocal Langerhans cell histiocytosis 9 years prior. Recurrence of Langerhans cell histiocytosis was initially suspected and systemic treatment was considered. Further imaging workup and surgical exploration of the mastoid showed a secondary acquired cholesteatoma arising from a dehiscent posterior ear canal wall. Surgical removal of the cholesteatoma was performed with a canal wall down procedure. We review the presentation and management of temporal bone Langerhans cell histiocytosis. We recommend that cholesteatoma should be considered in case of recurrence of otological symptoms in patients with a background of Langerhans cell histiocytosis.
Topics: Adolescent; Humans; Cholesteatoma; Cholesteatoma, Middle Ear; Ear Canal; Ear Diseases; Histiocytosis, Langerhans-Cell; Mastoid; Recurrence; Retrospective Studies; Temporal Bone
PubMed: 36718041
DOI: 10.5152/iao.2023.22716