Xanthogranuloma Research Articles

Solitary cutaneous nodule in a young boy: A diagnostic dilemma

Juvenile xanthogranuloma (JXG) is a type of benign histiocytic proliferative disorders seen in first two decades of life. It is a relatively uncommon benign cutaneous fibrohistiocytic lesion. Clinically, it presents as a papule or nodule which can either be solitary or can be yellow-brown in colour and firm in consistency. Usually, it is located in the face and neck. Sporadically, it can involve internal organs which can lead to serious complications. Differential diagnosis of this entity should be kept in mind whenever young patients presents with solitary nodule as it is a benign condition and only treatment warranted with local excision of the lesion.

In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy in children.

Molluscum contagiosum (MC), milia, keratosis pilaris (KP), verruca plana (VP), seborrheic keratosis (SK), and juvenile xanthogranuloma (JXG) are common papule dermatoses on the face of children that have a similar appearance. In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy (RCM) is helpful in the diagnosis of these ambiguous lesions in children. The purpose of this study was to clarify the RCM characteristics of MC, milia, KP, VP, SK, and JXG and explore the clinical application value of RCM for these common facial papule dermatoses. We recruited 113 patients referred for unequivocal facial papule dermatosis, including 21 patients with MC, 17 patients with milia, 19 patients with KP, 36 patients with VP, 8 patients with SK, and 12 patients with JXG. We evaluated the characteristics and distinguishing features of the six kinds of facial papule dermatoses using RCM. The main RCM features of the six dermatoses included a well-demarcated border of the lesion area. MC, milia and KP all manifested cyst-like structures, and their distinguishing features were the location of the cystic structures and the refractive index of the contents. Although VP, SK, and JXG did not have obvious cystoid structures, VP was typically characterized by uniformly distributed petal-like structures with a medium-to-high refractive index in the epidermis. With regard to SK, the characteristic features were an obviously thickened epidermis and cobblestone-like structures. JXG was mainly characterized by multiple large round and ovoid cells with a foamy cytoplasm, and discoid-shaped multinucleated large cells were diffusely distributed in the dermis. RCM allows the real-time visualization of major key diagnostic and distinguishing features of common facial papule dermatoses in children, including MC, milia, KP, VP, SK, and JXG.

Multiple papular xanthomas mimicking juvenile xanthogranulomas in an infant: A case report and review of the literature.

Multiple papular xanthomas mimicking juvenile xanthogranulomas in an infant: A case report and review of the literature.

Cutaneous Manifestations not Considered Diagnostic Criteria for Neurofibromatosis Type 1. A Case–Control Study

BackgroundThe diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. Patients and methodsCase–control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. ResultsThe prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.4–99.96%] and a positive predictive value (PPV) of 98.80% [92.54–99.94%] were estimated for NA and a specificity of 99.27% [95.4–99.96%] and a PPV of 92.86% [64.17–99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). ConclusionsNA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated.

Cyclin D1 Expression and Molecular Genetic Findings in Periocular Histiocytoses and Neoplasms of Macrophage-Dendritic Cell Lineage

Frequent activating mutations in the mitogen-activated protein kinase (MAPK) pathway genes have been identified in histiocytoses. MAPK signaling consistently upregulates cyclin D1. The goal of this study was to determine whether cyclin D1 expression by immunohistochemistry is a useful diagnostic marker for periocular histiocytoses and to further characterize their genetic basis. Retrospective observational case series. Pathology records were searched for all patients with histiocytoses diagnosed between 1995 and 2020. Eleven histiocyte-rich inflammatory lesions and 10 xanthelasma served as controls. Cyclin D1 immunohistochemistry was performed on all tissues. A subset of histiocytoses was evaluated by next-generation sequencing (NGS) and droplet digital PCR (ddPCR). There were 36 patients, 15 males (42%) and 21 females (58%), with histiocytoses: 9 juvenile xanthogranuloma (25%), 8 adult-onset asthma and periocular xanthogranuloma (22%), 7 Langerhans cell histiocytosis (19%), 5 Rosai-Dorfman disease (14%), 5 xanthogranuloma-not otherwise specified (14%), 1 Erdheim-Chester disease (3%), and 1 histiocytic sarcoma (3%). Moderate to strong nuclear cyclin D1 expression was present in ≥50% of lesional cells in histiocytoses (23/36, 64%), significantly more when compared to histiocyte-rich inflammatory lesions (0/11, 0%, P<.001) and xanthelasma (0/10, 0%, P<.001). Cyclin D1 was expressed in <10% of lesional cells in all 11 histiocyte-rich inflammatory lesions (P<.001) and all 10 xanthelasma lesions (P<.001). MAPK pathway gene mutations were detected in 12 of 14 (86%) histiocytoses successfully assayed by NGS and/or ddPCR. Our study confirms that the cyclin D1 immunohistochemical stain is a useful diagnostic marker for periocular histiocytoses, correlating with underlying mutations in MAPK pathway genes.

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

There are several activated forms of macrophages: 2 main groups are designated M1 and M2. While M1 macrophages have proinflammatory, bactericidal, and phagocytic functions and are the dominant phenotype observed in the early stages of inflammation, M2 macrophages are involved in constructive processes such as tissue repair; they play a role in wound healing and are required for revascularization and re-epithelialization. Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis. Its pathogenesis is not well understood, but it is not considered a neoplastic entity. JXGs possibly appear as a reaction to a nonspecific injury such as trauma or viral infection, although a genetic predisposition has been suggested in some cases. Tissue damage leads to a histiocytic response. JXGs appear, evolve toward maturation, and then most of them spontaneously regress. Young JXGs are characterized by small macrophages scattered in the dermis, in apposition close to the epidermis. As the lesion matures, the number of foamy macrophages and Touton cells increases and other cell types such as plasma cells, lymphocytes, and polymorphs are observed. Regressing xanthogranulomas will show numerous spindle cells in Significant values are in bold.a storiform distribution, interstitial fibrosis, and few foamy and Touton cells. In this study, we studied the immunophenotypic profile of macrophages found in cutaneous JXGs according to their stage of maturation. We examined the skin biopsies from 25 patients; all were embedded in paraffin and stained with hematoxylin and eosin and for immunohistochemistry. Typically, all JXGs were positive for factor XIIIa and CD4, and were negative for CD1a. The following histiocyte markers were used: CD68, CD204, CD163, MAC387, and HAM56. Images were analyzed by Image J software; data were statistically evaluated by SAS 9.0 software. The cases showed a slight predominance of males and the preference of the JXGs for the axial skin. Lesions occupied the papillary and reticular dermis in 85% of the cases and extended to the subcutaneous fat in the remainder. Compared with mature and regressing JXGs, younger lesions had a higher density of M1 macrophages, stained with MAC387. This antibody labels the histiocytes that have recently arrived in the areas of inflammation. As the lesions matured, there was an overwhelming predominance of M2 macrophages. These cells tended to cluster against the epidermis, except in the 2 cases in phase of regression. This suggests that there is a cross-talk between the epidermis and macrophages and that receptors, cytokines, chemokines, and adhesion molecules may play a role in the development and evolution of JXGs. These results indicate that, for most of their life, JXGs are formed by repairing M2 macrophages and are not just an M1 macrophagic response to a local antigen. The process appears to be influenced by chemical-mediator epidermal-macrophage cross-talking, considering the tendency of these cells to accumulate against the dermoepidermal junction.

Juvenile xanthogranuloma: A case report and literature review

Juvenile xanthogranuloma is a benign, self-limiting tumor that arises from histiocyte proliferation of unclear aetiology in children. Cutaneous manifestation is most common, and systemic involvement rarely occurs. Early diagnosis, on the other hand, is necessary for further evaluation in order to avoid disease complications later on. A four-month-old baby boy was referred to a dermatology clinic by the paediatric team because he had multiple skin lesions. Multiple well-defined borders, soft, non-fluctuant yellow and reddish papules or nodules ranging in size from 2.0 to 4.0 cm, have been seen over the scalp, face, chest, upper back, and upper limbs since birth. The examination of the eyes, heart, lungs, and abdomen is unremarkable. The results of additional imaging to test for systemic involvement were negative. A skin biopsy shows dense dermal infiltration by sheets of mononuclear histiocytes, from polygonal to spindle-shaped and plump, possessed of abundant pale eosinophilic cytoplasm with indistinct cytoplasmic borders. These lesion cells are diffusely positive for CD68 and negative for CD1a and S100. The features are consistent with juvenile xanthogranuloma. Following an 11-month follow-up, the skin lesion was much flatter and softer than before. Although systemic involvement with cutaneous juvenile xanthogranuloma is uncommon, a thorough examination is required to avoid conditions that are associated with high morbidity and mortality, such as hepatic failure, progressive central nervous system disease, and myeloid leukaemia.

Teaching NeuroImage: Intradural ALK-Positive Histiocytosis With Involvement of Nerve Roots and Spinal Dura.

A 3-year-old boy presented with progressive lower extremity weakness and difficulty walking for 2 months. Neurologic examination found the muscle strength of his left lower limb was grade 3 and tendon reflex was weakened. MRI demonstrated an intradural extramedullary mass between T10-11 with multiple and diffuse enhancement of thickened nerve roots and spinal dura (Figure). Juvenile xanthogranuloma was suspected as positive staining for CD68 and negative for S100 and CD1a, while immunoreactivity for ALK did not support it. The genetic test confirmed the diagnosis of ALK-positive histiocytosis with KIF5B-ALK fusion, which is a relatively new subtype of histiocytic disease.1,2

Juvenile and adult xanthogranuloma: A 30-year single-center experience and review of the disorder and its relationship to other histiocytoses

BackgroundJuvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis whose cell of origin, etiology and pathogenesis are not fully understood. We aimed to provide an update on histopathologic and immunophenotypic profile of this well-characterized entity whose relationship to the other histiocytoses has received renewed attention in light of recent molecular genetic studies. Materials and methodsA retrospective review of all the cases with the pathologic diagnosis of “xanthogranuloma” was performed on our archives from 1989 to 2019. ResultsA total of 525 patients with 547 lesions diagnosed as JXG were identified with the median age of 4.5 years, a male predominance (M:F ratio 1.3:1) and a predilection for the head and neck region (40.8%). Cutaneous lesions comprised 76.8% cases and another 15.7% presented within soft tissues. The most common non-soft tissue, extracutaneous lesions included the brain (2.6%), and lungs (1.8%). Three basic histopathologic patterns were identified: early classic (EJXG) (14.2%), classic (CJXG) (45.3%), and transitional JXG (TJXG) (40.5%). Multinucleated giant cells, either Touton or non-Touton, were most frequently present in CJXG followed by TJXG. Mitosis was rare (<1/10 high-power field) among different patterns. There was an association among the patterns and lymphocytic infiltrates (P = 0.036), and presence of Touton or non-Touton giant cells (P < 0.001 for both) but not for mitotic count (P = 0.105) or eosinophilic infiltrates (P = 0.465). Additionally, there was a correlation between age groups and presence of non-Touton giant cells (P = 0.012) but not for Touton cells (P = 0.127). We have demonstrated that immunophenotypic expression of the lesion was not associated with age at diagnosis nor morphologic pattern: factor XIIIa 192/204 (94.1%), CD11c 75/77 (97.4%), CD4 82/84 (97.6%), CD68 200/201 (99.5%), CD163 15/15 (100%), CD1a 1/110 (0.9%), S-100 48/152 (31.6%), CD31 15/21 (71.4%), and vimentin 104/105 (99.0%). ConclusionWe have documented in a substantial series of cases of JXG that there is a correlation between one of the three basic histopathologic patterns with age at diagnosis, but with a consistent immunophenotype among the three patterns. Considering sensitivity and specificity rates, we suggest that a combination of CD11c, CD4, CD1a and either CD163 (preferred) or CD68 stains provides more specific diagnostic yield in the differentiation of JXG from other histiocytic disorders. JXG is also discussed in terms of its relationship and distinction from other similar histiocytic disorders in the context of MAPK/ERK pathway mutations.

Adjunctive and Transformed Immunity: Histiocytic &amp; Dendritic Cell Neoplasm

Exceptional malignancies of the lymph nodes or soft tissue comprising of &lt; 1% of the tumour incidence are the Histiocytic and Dendritic cell neoplasm. A definitive appearance/biology/ Hematology/ histopathology / exclusive therapeutic options describe the condition. Morphology and Immune reactive appraisal may be mandated to distinguish the neoplasm. Preface: Histiocytic and Dendritic neoplasms are infrequent disorders which incriminate the accessory immune system or mesenchymal cells. Subject to the origin of the neoplasm, from the bone marrow precursors or the mesenchye, the lesions may be categorized as. i) The Histiocytic sarcoma (HS), Langerhans cell histiocytosis(LCH) and the Inter-digitizing dendritic cell sarcoma (IDCS) may commence from the bone marrow precursors and ii) The Follicular dendritic cell sarcoma (FDCS), Intermediate dendritic cell sarcoma (INDCS), Fibroblastic reticular cell tumour (FRCT) and Disseminated juvenile xanthogranuloma(DJX) may emanate from the Stromal or the mesenchymal cell. Divergent differentiation of the bone marrow precursors is a usual manifestation, though hybrid or trans-differentiating malignant lymphoid clones may also materialize in Inter-digitizing dendritic cell sarcoma (IDCS), Histolytic sarcoma (HS) and Follicular dendritic cell sarcoma (FDCS). Together, Histolytic and Dendritic cell tumors constitute &lt; 1% of the lymph node or soft tissue neoplasm. The tumors may be misinterpreted as Non Hodgkin’s Lymphoma or adjunct Lymph-Proliferative disorders. The rare malignancies may be a challenge to discern and medicate. Debatable Histolytic and Dendritic neoplasm mandate a referral. The disorder may be ascertained by the combined analysis on Histology and Immunehistochemistry

Juvenile Xanthogranuloma: A Comparative Immunohistochemical Study of Factor XIIIa, CD11c, and CD4.

Juvenile xanthogranuloma is a group C and L non-Langerhans cell histiocytosis, and its cell of origin is still debatable. The expression of CD11c, a more recently described macrophage marker, and CD4 have not been studied comprehensively. This study aimed to expand immunophenotypic profile and hence our understanding of the origin of these lesions. The surgical pathology archive was searched for the cases with the pathologic diagnosis of "xanthogranuloma" from 1995 to 2019. Immunohistochemical (IHC) stains were performed for factor XIIIa, CD11c, and CD4. Morphologically, each lesion was classified into early classic, classic, or transitional subtypes. Seventy-seven cases were included with the median age of 7.8 years (male:female 1.3:1). Uniform positivity was noticed for CD4 (n = 77), CD68 (n = 37), CD163 (n = 5), and vimentin (n = 4) stains. Other stains included CD11c 75/77 (97.4%), factor XIIIa 71/76 (93.4%), S-100 protein 4/23 (17.4%), and CD1a 0/18 (0%). Despite insignificant association between morphologic subtype and main studied IHC stains, factor XIIIa reactivity was highest in transitional lesions and CD11c showed higher reactivity in early classic lesions. CD11c and CD4 are sensitive markers and showed promising results in the diagnosis of juvenile xanthogranuloma compared with factor XIIIa. Despite different reactivity of factor XIIIa and CD11c in various morphologic subtypes, such association was statistically insignificant.

Juvenile xanthogranuloma in neurofibromatosis type 1. Prevalence and possible correlation with lymphoproliferative diseases: experience of a single center and review of the literature.

Neurofibromatosis type 1 (NF1), is a rare genetic disorder that may involve almost every organ system in the body such as cutaneous, ophthalmologic and central and peripheral nervous system. Cutaneous findings are usually the first sign of the disease. In this study, we investigate the real prevalence of xanthogranulomas juvenile (JXG) and possible correlation with lymphoproliferative diseases. This is a retrospective study conducted on a population with NF1 followed by February 1983 to February 2022 at the "Sapienza" University of Rome, Italy. We investigate the real prevalence of juvenile xanthogranuloma in NF1 and possible correlation with lymphoproliferative diseases. JXG was present in 39 cases (3.1%). JXG is more frequent in NF1 than in the general population while the possible association with lymphoproliferative diseases in NF1 remains controversial.

Histiocytic neoplasms: modern aspects of pathogenesis, classification, diagnosis and treatment

Histiocytic cell tumors present as a difficult group of diseases in terms of differential diagnosis due to their rare frequency, heterogeneous clinical manifestations and ambiguous clinical course. Considering MAPK-signaling pathway mutations role (including BRAFV600E) in the pathogenesis of histiocytic cell tumors the importance of genetic studies in the diagnosis and choice of therapeutic strategy in these diseases increases. In the current issue modern classifications of histiocytic cell tumors, morphological and immunophenotypic features of histiocytic and dendritic cells, and the role of recurrent somatic mutations of the MAPK signaling pathway in the pathological histiocytic proliferation are presented. Particular attention is given to Langerhans cell histiocytosis, Erdheim–Chester disease and juvenile xanthogranuloma. Clinical and diagnostic characteristics of these diseases and therapeutic approaches are presented.

On the knowledge of solitary juvenile xanthogranuloma of the eyelid: a case series and literature review

PurposeSolitary eyelid juvenile xanthogranuloma (JXG) is extremely rare, and there is limited literature on its clinical features and treatment outcomes. Here, we present a case series and comprehensive review of the literature on patients with isolated eyelid JXG.MethodsWe systematically extracted data from our institution’s records of isolated eyelid JXG cases and conducted a search for additional cases from the literature utilising the PubMed, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases. Patients with JXG were analysed with respect to age, sex, clinical presentation, therapy, and outcome. Group comparisons were performed.ResultsThirty-two patients (including 13 at our institution and 19 from prior publications) were identified. The median age at first presentation was higher in current patients than in the patients from the published cases (median 9 years, range 1.2 to 47.0 years; median 2 years, range 0.5 months to 46.0 years, respectively, P = 0.014). Of the patients who had known characteristics, no significant differences were observed between the two groups in terms of sex, affected eye, eyelid site, type of cutaneous involvement, or duration of symptoms (each P > 0.05). Seventeen (54.8%) patients were male. The most common lesion location was the upper eyelid (n = 10, 62.5%). Twenty-four (75.0%) cutaneous lesions had full-thickness skin involvement; 8 (25.0%) subcutaneous masses had a chalazion-like appearance. Histologically, the JXG masses were characterised by Touton giant cells with inflammatory cells. Additionally, there was no significant difference in treatment modalities between the two groups (P = 0.072), and 24 (75.0%) patients underwent surgical excision. The overall recurrence-free survival was 3.6 to 52.8 (median 27.0) months in the current patients. For published cases with available follow-up information, there was no recurrence in 10 cases and improvement in 1 case, with a median follow-up of 9.5 months.ConclusionSolitary eyelid JXG is a rare clinical entity and should be included in the differential diagnosis of eyelid mass lesions in patients of all age groups. Surgical excision is often selected for efficient treatment and to obtain an excisional biopsy.

The Importance of Clinicopathological Correlation: A Case of Xanthoma Disseminatum

Xanthoma disseminatum (XD) is a rare disease that presents with pruritic papules, classically involving the extensor surfaces and mucosal areas. We present a case of XD that was misdiagnosed as eruptive xanthomas and eventually self-resolved. Self-resolving XD may be within a spectrum of adult-onset juvenile xanthogranuloma. However, as there may be systemic consequences of XD, it is critical to ensure these patients obtain a complete evaluation and close follow-up.

Disseminated Juvenile Xanthogranuloma: A Case Report

Introduction: Histiocytoses are localized or systemic diseases that can broadly be classified into Langerhans cell histiocytosis and non-Langerhans cell histiocytosis. Juvenile Xanthogranuloma (JXG) belongs to the latter group, which occurs in around 0.5% population younger than 5 years, and presents as solitary or multiple lesions. Here, we present a case of disseminated JXG in an infant with the lesions regressing spontaneously. Case presentation: A 7-month-old boy presented with multiple erythematous nodular lesions over the body excluding limbs for 3 months. Initial laboratory work up was normal. Skin histopathology showed a dermal nodule with sheets of histiocytes exhibiting grooved vesicular nuclei and pale eosinophilic cytoplasm along with touton giant cells. Immunohistochemistry markers further confirmed the diagnosis. Lesions healed completely with symptomatic relief in 1.5 years and no recurrence occurred. Discussion: Disseminated JXG is a benign childhood disorder that can sometimes be associated with internal organs involvement mainly bones, eyes, and brain. Serious complications may follow in case of extracutaneous spread. Most frequently, JXG follows the occurrence of another neoplastic disorder but can sometimes appear de novo. Skin biopsy is required for the diagnosis and better education of the family. Conclusion: JXG in infancy is a rarity in South Asia. Therefore, along with the clinical judgment, clinicians must also get histological confirmation in order to manage this disorder successfully. Close surveillance for multiorgan involvement is also required to avoid any irreversible sequalae.

Juvenile Xanthogranuloma: A Case Report

Juvenile Xanthogranuloma (JXG) is a rare condition that can present as early as a neonate or develop later during paediatric age and adulthood. One should be aware of this entity as it can cause extreme anxiety to parents due to its variety of cutaneous features. Our case report details a JXG in an 11-month-old boy with a circumscribed nodule on his scalp, neck, and left arm. The nodule was histologically identified as a JXG following a skin punch biopsy.

JUVENILE XANTHOGRANULOMAS MASS CAUSED TESTICULAR TORSION A RARE OCCASION IN PEDIATRICS: A CASE REPORT

Background: Juvenile xanthogranulomas (JXG) is a histiocytic disorder, in a child below 5 years of age. Xanthogranulomatous orchitis (XGO) is a rare disease, it is an extremely rare inflammatory non-neoplastic destructive lesion of the testis, and a few cases have been reported to date. Aim: We reported a case of JXO presenting as a solitary mass in the left testicle causing testicular torsion in an 11-month-old child without manifestations of JXG elsewhere. Case presentation: the patient presented with an acute history of pain in his left hemi scrotum. An ultrasound study showed a 10 x 13 mm round tumor with a distinct boundary between the tumor and the irregular heterogeneous testicular tissue, Doppler ultrasound images submitted changes suggestive of testicular torsion. Surgery was performed that showed a necrotic left testicle, with and tumor-like lesion attached to the cord and overlapping the body of epididymis. A left orchiectomy was performed. Histopathology reported that the architecture of the testis was lost. Two cut sections in the mass nodular collections of abundant xanthomatous foamy macrophages. Xanthogranulomas was suggested. Conclusion: Because of the aggressive nature of this disease, curative treatment is by either radical or partial orchiectomy considered the goal standard for the final management outcome.

An overview of histiocytosis

Histiocytosis is a syndrome characterized by fever, pain, and other symptoms caused by the neoplastic proliferation of atypical cells of the macrophage-dendritic cell lineage and surrounding inflammatory cell infiltration. The diagnosis is confirmed by the immune-histological features of biopsied specimens. From this viewpoint, histiocytosis is divided into Langerhans cell histiocytosis (LCH) (CD1a+/CD207+/CD14±/CD68±) and non-LCH, including Erdheim-Chester disease (ECD), juvenile xanthogranuloma, and Rosai-Dorfman disease (CD1a-/CD207-/CD14++/CD68++). Genetic alterations occur at the cellular level in hematopoietic progenitor cells, and environmental factors are assumed to influence tumor development. The genomic analysis of the lesions involved revealed driver mutations primarily in the MAPK pathway, including BRAF-V600E, and the PI3K pathway. This strongly suggests that abnormalities in these signaling pathways play a role in pathogenesis. Steroids, vinca alkaloids, cytarabine, and cladribine are commonly used to treat histiocytosis. However, efficacy has not been fully confirmed in any of them. In recent years, the efficacy of BRAF inhibitors and MEK inhibitors has been reported mainly in therapy-resistant and refractory cases of LCH and ECD.

Cutaneous histiocytoses in children.

Cutaneous histiocytoses constitute a heterogeneous group of diseases characterised by the cutaneous accumulation of cells with the cytological and phenotypic features of macrophages or dendritic cells. The clinical spectrum ranges from self-resolving, skin-limited conditions to severe, multiorgan disease with a high morbidity rate. Until recently, cutaneous histiocytoses were classified according to the immunophenotype of the pathological cells, with differentiation between Langerhans cell histiocytosis (LCH) [CD1a+, CD207 (langerin)+] and non-Langerhans cell histiocytosis (CD68+, CD163+, CD1a-, CD207-). Over the last 12 years, a number of new pathophysiological findings (in particular, molecular pathology results) regarding histiocytoses have contributed to a new classification based on molecular alterations, as well as on clinical and imaging characteristics and the phenotype. The most frequent entities in children are juvenile xanthogranuloma and LCH.