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

Abstract: 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.

Juvenile xanthogranulomas in Asian children.

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytic disorder. It can rarely be associated with systemic involvement. There is a paucity of literature on JXG in Asian children. We aim to describe the epidemiology, clinical features, systemic associations, histological features and outcome of a cohort of Asian children with JXG, and review the literature on the condition. We retrospectively reviewed the demographic, clinical and histological data of patients less than 16 years of age, diagnosed with JXG at our tertiary pediatric hospital between January 2002 and April 2019. A total of 147 children with JXG were identified, with a slight male preponderance of 53.1%. The median age of the onset was 15.5 months, with 69.4% presenting before 2 years of age. There was no racial predilection. The most frequently involved site was the head and neck region (44.2%). The majority of patients (76.2%) presented with a solitary lesion. Spontaneous resolution was documented in 57.7% of our patients with mean duration to resolution of 18.8 months. The proportion and speed of resolution did not differ in children with single or multiple lesions. No ophthalmologic complications were detected in our study cohort. JXG in children is generally limited to the skin and is rarely associated with systemic involvement, including the eye. Unless clinically indicated, the results from our study does not support routine screening for juvenile myelomonocytic leukemia, eye or systemic complications, even in the setting of multiple cutaneous JXGs.

Juvenile xanthogranuloma: retrospective analysis of 44 pediatric cases (single tertiary care center experience).

BACKGROUND/OBJECTIVE: Juvenile xanthogranuloma (JXG) is a rarely encountered skin disorder, which is characterized by the proliferation of non-Langerhans cell histiocytes. As JXG primarily affects infants and young children, this study aims to describe the epidemiologic, clinical, and histopathologic characteristics of 44 children diagnosed with JXG at a tertiary health care center. METHODS: Fourty-four children with a histopathologic diagnosis of JXG between January 2003 and January 2017 were retrospectively reviewed. Data related to epidemiologic, clinical, and histopathologic features were extracted from hospital records. RESULTS: The mean age of the affected patients was 4.6 years old (range: 0-17 years old) at the time of diagnosis. Twenty-five patients (56.8%) were male, and 19 patients were female (43.2%). Thirty-six children (81.8%) had solitary JXG, one of which was a giant congenital JXG; eight children (18.2%) had eruptive JXG. The heterozygote mutation associated with neurofibromatosis 1 gene was detected in one patient who had both eruptive JXG and numerous café-au-lait spots. Another patient with eruptive JXG was identified to have hypercholesterolemia. None of the children with eruptive JXG developed symptoms or signs of extracutaneous involvement during their clinical follow-up. CONCLUSION: Since JXG is rarely encountered, there may be a tendency toward over-treatment, given concerns for extracutaneous involvement. However, our review revealed no instances of extracutaneous involvement.

Xantogranuloma juvenil: una entidad con amplio espectro clínico / Juvenile Xanthogranuloma: An Entity With a Wide Clinical Spectrum

El xantogranuloma juvenil es un trastorno benigno poco frecuente, que pertenece al amplio grupo de las histiocitosis de células no Langerhans. Se presenta con uno o más nódulos eritematosos o amarillentos, ubicados preferentemente en la cabeza y el cuello. La mayoría de los casos se inician durante el primer año de vida, incluyendo lesiones congénitas. La afectación extracutánea es rara, sugiriéndose tradicionalmente en la literatura estudiar el compromiso ocular. El diagnóstico del xantogranuloma juvenil es fundamentalmente clínico, sin embargo, en ocasiones se requiere confirmarlo con biopsia de piel. Las lesiones cutáneas son autolimitadas, por lo que suelen no requerir tratamiento. En la presente revisión se describen los distintos aspectos clínicos y terapéuticos de esta enfermedad, resaltando la evidencia respecto al estudio diagnóstico del compromiso extracutáneo

Juvenile xanthogranulomas (JXGs) are rare, benign lesions that belong to the large group of non-Langerhans cell histiocytoses. JXG presents with 1 or more erythematous or yellowish nodules that are usually located on the head or neck. Most JXG lesions are congenital or appear during the first year of life. Extracutaneous involvement is rare, but the literature traditionally suggests investigating the possibility of ocular compromise. JXG is mainly a clinical diagnosis, but a skin biopsy may sometimes be needed for confirmation. JXGs on the skin are self-limiting and usually do not require treatment. This review describes the clinical and therapeutic aspects of JXG, emphasizing available evidence and the diagnosis of extracutaneous involvement

Descriptive Analysis of Histiocytic and Dendritic Cell Neoplasms: A Single-Institution Experience.

PURPOSE: Histiocytic and dendritic cell neoplasms are rare hematologic tumors. This study aimed to describe the epidemiologic features of the entire spectrum of histiocytic and dendritic cell neoplasms, including clinicopathological variables and patient outcomes. MATERIALS AND METHODS: We comprehensively reviewed 274 patients who were diagnosed with histiocytic and dendritic neoplasms at Severance Hospital, Seoul, South Korea between 1995 and 2018. RESULTS: The most common neoplasm was Langerhans cell histiocytosis (LCH), followed by dermal xanthogranuloma. Among non-LCH sarcomas, histiocytic sarcoma (HS) showed a relatively high prevalence, followed by follicular dendritic cell sarcoma (FDCS). Disseminated juvenile xanthogranuloma (DJG), Erdheim-Chester disease (ECD), indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) rarely occurred. Generally, these tumors presented in childhood, although the non-LCH sarcoma (HS/FDCS/IDCS/IDCT) group of tumors and ECD occurred in late adulthood. Multiorgan involvement and advanced Ann-Arbor stage, as well as recurrence and death of disease, were not uncommon. The non-LCH sarcoma group had the worst overall survival, compared to the DJG, ECD, and LCH groups. CONCLUSION: Our findings indicate that histiocytic and dendritic cell neoplasms exhibit heterogeneous epidemiologic characteristics and that some patients may have unfavorable outcomes, especially those with non-LCH sarcoma.

Variante extracutánea de xantogranuloma juvenil en un adulto asociado a linfoma folicular / Extracutaneous variant of juvenile xanthogranuloma associated to follicular lymphoma in an adult patient

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Granulomatous diseases: Kids are not just little people.

Granulomatous diseases represent a heterogeneous group of conditions characterized by histiocytic inflammation that affect patients of any age. These diseases differ widely in their pathogenesis and include infectious and noninfectious conditions. This review focuses on noninfectious granulomatous conditions, with particular emphasis on age-related differences in the onset, epidemiology, clinical manifestations, prognosis, and age-specific management of specific granulomatous disorders. Knowledge of age-specific aspects of granulomatous conditions in adults and children improves both the extent of the diagnostic workup and the management of these patients.

The epidemiology, clinical characteristics, histopathology and management of juvenile- and adult-onset corneoscleral limbus xanthogranuloma.

PURPOSE: Adult-onset xanthogranuloma (AOX) of the corneoscleral limbus is a rare inflammatory condition of unknown aetiology. Similar to limbal juvenile xanthogranuloma (JXG), it presents as a growing mass at the corneoscleral junction. Limbal AOX and JXG can lead to sight-threatening complications if not managed in a timely manner. This systematic review summarises the main clinical and histopathological features of limbal AOX/JXG and discusses the management of this uncommon disease. METHODS: We performed a literature search in the MEDLINE database for all historical entries, using the search terms "limbus", "limbal" and "xanthogranuloma", and retrieved all articles reporting on limbal xanthogranuloma. After refining the search to articles relevant to limbal AOX, we were able to identify ten adult cases of limbal AOX and compare those with all reported cases of limbal JXG. RESULTS: Clinically, AOX usually presents as an isolated smooth, yellowish, dome-shaped nodule at the corneoscleral junction, similar to an ocular presentation of JXG, with which it also shares similar histopathological features. CONCLUSION: Limbal JXG and AOX may represent the same disease entity. Diagnosis relies on the clinical presentation, pathology and immunohistochemical profile. Spontaneous regression is unlikely, and thus prompt surgical intervention should be considered to prevent sight-threatening complications. Xanthogranuloma should be included in the differential diagnosis of corneoscleral limbal masses in patients of all age groups.

Uncommon histiocytic disorders: Rosai-Dorfman, juvenile xanthogranuloma, and Erdheim-Chester disease.

Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and Erdheim-Chester disease (ECD) are non-Langerhans cell (non-LCH) disorders arising from either a dendritic or a macrophage cell. RDD is a benign disorder that presents with massive lymphadenopathy, but can have extranodal involvement. In most cases, RDD is self-limited and observation is the standard approach. Treatment is restricted to patients with life-threatening, multiple-relapsing, or autoimmune-associated disease. JXG is a pediatric histiocytosis characterized by xanthomatous skin lesions that usually resolve spontaneously. In a minority of cases, systemic disease can occur and can be life threatening. Juvenile myelomonocytic leukemia (JMML), as well as germline mutations in NF1 and NF2, have been reported in children with JXG. Recent whole-exome sequencing of JXG cases did not show the BRAF-V600E mutation, although 1 patient had PI3KCD mutation. ECD is an adult histiocytosis characterized by symmetrical long bone involvement, cardiovascular infiltration, a hairy kidney, and retroperitoneal fibrosis. Central nervous system involvement is a poor prognostic factor. Interferon-α is the standard as front-line therapy, although cladribine and anakinra can be effective in a few refractory cases. More than one-half of ECD patients carry the BRAF-V600E mutation. Currently, >40 patients worldwide with multisystemic, refractory BRAF-V600E(+) ECD have been treated with vemurafenib, a BRAF inhibitor, which was found to be highly effective. Other recurrent mutations of the MAP kinase and PI3K pathways have been described in ECD. These discoveries may redefine ECD, JXG, and LCH as inflammatory myeloid neoplasms, which may lead to new targeted therapies.

[Juvenile xanthogranuloma of the corneoscleral limbus in adults]. / Xantogranuloma juvenil en limbo corneoescleral en el adulto.

CASE REPORT: A 25-year-old woman noticed a painless yellow-orange mass on her right eye. Her visual acuity was 20/20 in both eyes, and a slit-lamp examination showed a yellow-orange mass located at the superior limbus of the right eye. No other ocular abnormalities were observed. DISCUSSION: Surgical excision was carried out and the lesion was sent for histological examination. This showed a granulomatous lesion, rich in Touton-type giant cells, features that are strongly suggestive of juvenile xanthogranuloma (JXG). Ocular involvement occurs in 10% of cases of JXG.

Thalidomide therapy for aggressive histiocytic lesions in the pediatric population.

Aggressive histiocytic lesions are uncommon in the pediatric population. These neoplasms occur in isolation or after therapy for other types of hematopoietic malignancy such as T-cell acute lymphoblastic leukemia. The etiology of these lesions is poorly understood, and no definitive standard of care has been established for patients with these diagnoses. Here, we report the success of thalidomide treatment for 2 subtypes of histiocytic proliferation--metastatic histiocytic sarcoma and extracutaneous juvenile xanthogranuloma--in pediatric patients. Our findings highlight the importance of considering thalidomide therapy in this unique and difficult to treat patient population.

Juvenile xanthogranuloma in childhood and adolescence: a clinicopathologic study of 129 patients from the kiel pediatric tumor registry.

Juvenile xanthogranuloma (JXG) is an uncommon non-Langerhans cell histiocytosis. We investigated 148 biopsy specimens from 129 patients collected in the Kiel Pediatric Tumor Registry (KPTR) between 1965 and 2001. The clinical, histologic, and immunohistochemical characteristics of JXG were evaluated to gain more and deeper insights into the morphology and clinical behavior of JXG. Conventionally stained lesions were classified into the following morphologic subtypes: early JXG (EJXG), classic JXG (CJXG), transitional JXG (TJXG), or combined lesions with more than one basic pattern (combined JXG). Immunohistochemistry included antibodies against macrophages (Ki-M1P), S-100 protein, CD1a, and factor XIIIa (FXIIIa). Clinical data were obtained by means of a standardized questionnaire. The relative incidence of JXG in the KPTR is 0.52%. The male/female ratio was 1.4:1. The mean age was 22.4 months (median, 5 months; range, 0-244 months). A total of 34.5% of the cases of JXG were congenital, and 71.0% of the lesions were diagnosed within the first year of life. Most cases of cutaneous JXG were solitary (81.0%). Five cases (3.9%) presented with visceral (systemic) involvement. Histologically, CJXG was most frequent (47.2%), followed by EJXG (27.1%) and TJXG (16.0%). A total of 9.7% of the lesions represented combined JXG. Histiocytes, including giant cells, were positive for Ki-M1P (100%) and in most cases for FXIIIa (99%). The CD1a and S-100 protein reactions were generally negative. Clinical and follow-up data showed a generally favorable prognosis with a low relapse rate (7.0%) and even complete involution after incomplete resection. Only 1 of 5 patients with widespread congenital systemic disease died after 34 days. JXG is an uncommon, mostly cutaneous, and prognostically favorable histiocytic tumor of infancy. Simple tumor excision is the therapy for choice except in the very rare systemic JXG, in which multimodal chemotherapy is indicated.

Clinicohistopathologic comparison of adult type and juvenile type xanthogranulomas in Korea.

Xanthogranuloma (XG) is an uncommon benign disorder characterized by solitary or multiple yellow-red papulonodules on the skin, and occasionally, in other organs. It is predominantly a disease of infancy or early childhood, although adults may rarely be affected. To compare the clinicohistopathological featues of juvenile-type xanthogranulomas UXGs) and adult-type xanthogranulomas (AXGs) (>14 years) in Korea, 30 cases of JXGs and 15 cases of AXGs were compared clinically and histopathologically. Except for the fact AXGs were more often solitary and larger and showed neither other associated systemic diseases nor spontaneous regression, the clinical features such as color, mean number, or site of the lesions in AXGs were not statistically different from JXGs. Histologically, AXCs were not significantly different in amounts of foamy cells, giant cells including Touton cells, and inflammatory cells, although subcutaneous involvement was seen only in the two infant cases. In conclusion, in contrast to AXGs, JXGs need special attention to accompanying systemic diseases and do not need excisional procedures, considering their frequent spontaneous regression.

[Juvenile xanthogranuloma with intraocular involvement. A case report]. / Xanthogranulome juvénile avec localisation intra-oculaire. A propos dún cas.

Juvenile xanthogranuloma (JXG) is a rare and usually benign disease occurring in early childhood. It causes skin and deep seated lesions, notably in the eye. We report a case of JXG in the iris of a 9-month-old infant. Examination under general anesthesia revealed megalocornea, iris xanthogranuloma occupying the entire anterior chamber and high intraocular pressure. Skin lesions on the left lid and on the back were also found. Ocular hypertension resisted medical and surgical treatment. Cyclodestruction was necessary. The incidence of JXG is low (0.4%). The iris is the most frequently affected ocular tissue. Early diagnosis is necessary to avoid complications. Moreover, JXG can be associated in rare cases with neurofibromatosis or leukemia which must be systematically searched for.

Juvenile xanthogranuloma, neurofibromatosis, and juvenile chronic myelogenous leukemia. World statistical analysis.

BACKGROUND AND DESIGN: The concurrent finding of neurofibromatosis type 1 (NF), juvenile chronic myelogenous leukemia (JCML), and juvenile xanthogranuloma (JXG) has been repeatedly reported. Juvenile chronic myelogenous leukemia has been found more frequently in patients with NF and may present with various cutaneous manifestations, including JXG. To our knowledge, the relationship among these three entities has never been explored. The purpose of the present study is to explore this relationship by using a systematic review of the literature. We present five demonstrative cases of various associations among NF, JCML, and JXG. RESULTS: A family history of NF was found in 85% to 95% of children with NF and JCML (with or without JXG), as compared with that found in 47% of children with NF and JXG. The observed frequency of the triple association is 30-fold to 40-fold higher than that expected. It is estimated that children with NF and JXG have a 20-fold to 32-fold higher risk for JCML than do patients with NF who do not have JXG. CONCLUSIONS: A concomitant finding of JCML and JXG in children with NF represents a true association, rather than a coincidence. A finding of JXG in an infant with NF should alert a physician to a possible development of JCML.

Juvenile xanthogranuloma of the pelvic origin: a case report.

A case of juvenile xanthogranuloma (JXG) originating from the pelvic cavity is reported. The patient, a 4-month-old girl, was referred to our department for the examination and treatment of her left abdominal mass. As radiological studies strongly suggested the possibility of a malignant tumor of muscular origin, tumor extirpation was performed. The tumor was buried in the left psoas muscle. Histological examination showed the tumor consisted of polygonal cells containing small vacuoles with scattered Touton giant cells, and the diagnosis of JXG was made. To our knowledge, this is the first case of a pelvic JXG.

Xanthogranuloma: report on clinical and histologic findings in 64 patients.

Although xanthogranulomas are frequently encountered by pediatricians and dermatologists, data on the course of this tumor are restricted to several series with limited follow-up. We report on our experience with 64 patients whom we were able to identify from the surgical files. Our data support the currently held view that xanthogranulomas are generally benign, self-limited lesions. They may persist or continue to erupt for years, however, particularly in individuals who develop the first lesion after age 20 years.