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Actas Dermo-sifiliograficas Mar 2023The neurofibromatosis 1 (NF1) diagnosis is challenging in young children without a family history of NF1. The aims of this study were to estimate diagnostic delays in... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
The neurofibromatosis 1 (NF1) diagnosis is challenging in young children without a family history of NF1. The aims of this study were to estimate diagnostic delays in children without a family history of NF1 and to examine the effects of using café au lait macules and skin fold freckling as a single diagnostic criterion.
PATIENTS AND METHODS
Retrospective, descriptive, observational study of all patients diagnosed with NF1 before the age of 18 years who were seen at our hospital. The medical records of those included were reviewed to identify the date on which the diagnostic criteria of NF1 were objectified. The patients were categorized into 2 groups: those with a known parental history of NF1 and those without. Café au lait macules and skin fold freckling were assessed as a single diagnostic criterion, and genetic evidence was considered to confirm highly suspicious cases.
RESULTS
We studied 108 patients younger than the age of 18 years with a diagnosis of NF1. Mean (SD) age at diagnosis was 3.94 (±3.8) years for the overall group, 1 year for patients with a parental history of NF1, and 4 years and 8 months for those without. Diagnosis was therefore delayed by 3 years and 8 months in patients without a family history.
CONCLUSION
Skin lesions were the first clinical manifestation of NF1 in most patients. We believe that the National Institutes of Health's diagnostic criteria for NF1 should be updated to aid diagnosis in young children.
Topics: Humans; Child; Child, Preschool; Adolescent; Neurofibromatosis 1; Retrospective Studies; Cafe-au-Lait Spots; Skin Diseases; Melanosis
PubMed: 36370836
DOI: 10.1016/j.ad.2022.10.036 -
HCA Healthcare Journal of Medicine 2022Description Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. JXGs are benign and have a self-limiting course generally lasting 6...
Description Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. JXGs are benign and have a self-limiting course generally lasting 6 months to 3 years, with some reported durations longer than 6 years. We present a rarer congenital giant variant, defined as lesions with a diameter larger than 2 cm. It is uncertain if the natural history of giant xanthogranulomas is similar to the usual JXG. We followed a 5-month-old patient with a 3.5 cm in diameter, histopathologically-confirmed, congenital, giant JXG located on the right side of her upper back. The patient was seen every 6 months for 2.5 years. At 1 year of age, the lesion had decreased in size, lightened in color, and was less firm. At 1.5 years old, the lesion had flattened. By 3 years old, the lesion had resolved but left a hyperpigmented patch with a scar at the punch biopsy site. Our case represents a congenital giant JXG that was biopsied to confirm the diagnosis and then monitored until resolution. This case supports the clinical course of giant JXG not being affected by the larger lesion size and that aggressive treatments or procedures are not warranted.
PubMed: 37427313
DOI: 10.36518/2689-0216.1333 -
Haematologica Apr 2024The standard treatment for Langerhans cell histiocytosis (LCH) is chemotherapy, although the failure rates are high. Since MAP-kinase activating mutations are found in...
The standard treatment for Langerhans cell histiocytosis (LCH) is chemotherapy, although the failure rates are high. Since MAP-kinase activating mutations are found in most cases, BRAF- and MEK-inhibitors have been used successfully to treat patients with refractory or relapsed disease. However, data on long-term responses in children are limited and there are no data on the use of these inhibitors as first-line therapy. We treated 34 patients (26 with LCH, 2 with juvenile xanthogranuloma, 2 with Rosai-Dorfman disease, and 4 with presumed single site-central nervous system histiocytosis) with dabrafenib and/or trametinib, either as first line or after relapse or failure of chemotherapy. Sixteen patients, aged 1.3-21 years, had disease that was recurrent or refractory to chemotherapy, nine of whom had multisystem LCH with risk-organ involvement. With a median treatment duration of 4.3 years, 15 (94%) patients have sustained favorable responses. Eighteen patients, aged 0.2-45 years, received an inhibitor as first-line treatment. All of these have had sustained favorable responses, with a median treatment duration of 2.5 years. Three patients with presumed isolated central nervous system/pituitary stalk histiocytosis had stabilization or improvement of their disease. Overall, inhibitors were well tolerated. Five patients with single-system LCH discontinued therapy and remain off therapy without recurrence. In contrast, all four patients with multisystem disease who discontinued therapy had to restart treatment. Our data suggest that children suffering from histiocytoses can be treated safely and effectively with dabrafenib or trametinib. Additional studies are, however, needed to determine the long-term safety and optimal duration of therapy.
Topics: Child; Humans; Histiocytosis, Langerhans-Cell; Imidazoles; Oximes; Mutation; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones
PubMed: 37731389
DOI: 10.3324/haematol.2023.283295 -
Child's Nervous System : ChNS :... Oct 2021Juvenile xanthogranuloma (JXG) is a type of non-Langerhans cell histiocytosis that most commonly manifests as a solitary cutaneous lesion of the head and neck in...
Juvenile xanthogranuloma (JXG) is a type of non-Langerhans cell histiocytosis that most commonly manifests as a solitary cutaneous lesion of the head and neck in children. Intracranial JXG is extremely rare. Although it is widely known that JXG skin lesions gradually disappear over time without treatment, treatment guidelines for intracranial JXG have not been established. It is very difficult to predict whether an intracranial lesion is JXG with only a pre-operative imaging work-up without pathologic confirmation. We report a case of the youngest, a 3-month-old male infant with an intracranial extra-axial mass with rapid growth for 2 months. Additionally, we suggest characteristic MRI findings for intracranial extra-axial JXG of a low T2 signal and a kidney bean shape.
Topics: Head; Humans; Infant; Magnetic Resonance Imaging; Male; Xanthogranuloma, Juvenile
PubMed: 33660104
DOI: 10.1007/s00381-021-05088-w -
Ophthalmic Plastic and Reconstructive... Apr 2024Juvenile xanthogranuloma (JXG) is a subtype of histiocytosis characterised histologically by foamy non-Langerhan cells with Touton giant cells. It typically manifests as...
PURPOSE
Juvenile xanthogranuloma (JXG) is a subtype of histiocytosis characterised histologically by foamy non-Langerhan cells with Touton giant cells. It typically manifests as a single self-limiting cutaneous nodule in the paediatric population. Orbital JXG is extremely rare, and its clinical course and management are not well understood or defined. Herein we present 3 cases of orbital JXG and provide a detailed literature review.
METHODS
Review of 3 cases with orbital JXG and literature review of all published cases.
RESULTS
Three presented cases demonstrate the heterogeneous clinical course of orbital JXG. Although centred around the use of steroids, there is neither robust evidence nor consensus on its management. The wider JXG literature is currently concentrated around the classification of JXG with respect to histiocytosis, especially the exclusion of extracutaneous JXG as separate diseases. This separation is based on clinical, histopathological, and molecular findings. It is unclear where orbital JXG best fits in this emerging classification of JXG.
CONCLUSION
Our review of the cases and literature on orbital JXG show that it may manifest with variable clinical course and its molecular pathogenic mechanism may be different to that of the cutaneous JXG.
PubMed: 38687290
DOI: 10.1097/IOP.0000000000002696 -
Radiology Case Reports May 2023Juvenile xanthogranuloma (JX) is a non-Langerhans cell histiocytosis. Although precipitating factors remain unclear, it has been described mainly in infancy and early...
Juvenile xanthogranuloma (JX) is a non-Langerhans cell histiocytosis. Although precipitating factors remain unclear, it has been described mainly in infancy and early childhood. The giant variant of JX is a rare form that presents in infancy, measures over 2 cm and tends to involute only partly. Herein, we report a very rare localization of a giant JX in the parotid gland, discovered at age 1 month in an infant of a twin pregnancy and studied with ultrasound and magnetic resonance imaging.
PubMed: 36923389
DOI: 10.1016/j.radcr.2023.01.103 -
BMC Pediatrics Apr 2021Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of... (Review)
Review
BACKGROUND
Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult.
CASE PRESENTATION
A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition.
CONCLUSIONS
This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.
Topics: Biopsy; Edema; Female; Humans; Infant, Newborn; Purpura; Skin; Xanthogranuloma, Juvenile
PubMed: 33823829
DOI: 10.1186/s12887-021-02632-0 -
Case Reports in Dermatology 2021Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis. JXG is a rare benign tumor, which may be present at birth or develop later....
Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis. JXG is a rare benign tumor, which may be present at birth or develop later. The classical form of JXG is characterized by a red-yellowish benign papule or nodule with predilection sites on the head, neck, and trunk, although lesions can appear on extremities or extracutaneous sites. In most cases there is only one lesion, whereas numerous papules or nodules may occur. Special forms of JXG such as mixed, giant, subcutaneous, eruptive, clustered, and plaque-like have been reported and associations between JXG and systemic diseases have been made. Diagnosis mainly relies on the clinical appearance, and histology usually can confirm the disease. Here we present a very rare case of symmetrical giant facial plaque-type juvenile xanthogranuloma (SGFP-JXG) and compare it with classical JXG, variations of JXG, and discuss the differential diagnosis. A 4-year-old Caucasian female presented with plaque-like lesions composed of yellowish confluent papules on both the cheeks. The histological evaluation revealed a histiocytic lesion with a formation of Touton giant cells and immunohistochemistry results confirmed the diagnosis of the SGFP-JXG. In comparison to classical JXG, the onset of SGFP-JXG sometimes occurs later and the spontaneous resolution period may be prolonged. No associated diseases and no systemic involvements were observed. Histopathology is required to differentiate this form of JXG from other histiocytosis. To the best of our knowledge, only four cases of SGFP-JXG have been reported in the literature so far.
PubMed: 34413740
DOI: 10.1159/000515151 -
Pediatric Neurosurgery 2021Xanthogranuloma of the sellar region is a rare benign lesion, and there are few cases reported in children. Its histogenesis is controversial, and it is difficult to... (Review)
Review
INTRODUCTION
Xanthogranuloma of the sellar region is a rare benign lesion, and there are few cases reported in children. Its histogenesis is controversial, and it is difficult to strictly differentiate it from craniopharyngioma (CP), Rathke's cleft cyst, or pituitary adenoma.
CASE PRESENTATION
A 16-year-old boy presented with a rare xanthogranuloma of the sellar region after complaining of retardation of growth 5 years previously. The ophthalmologic evaluation revealed no visual field disturbance. Endocrinological examination revealed hypopituitarism. Magnetic resonance imaging showed an intrasellar mass extending into the suprasellar region and compressing the optic chiasma, which appeared mixed signals on T1-weighted images. Endonasal transsphenoidal resection of the tumor was performed. Histological analysis of the tumor sections demonstrated granulomatous tissue with cholesterol clefts, hemosiderin deposits, fibrous tissues, multinucleated giant cells, and lymphocyte. Thus, the tumor was pathologically diagnosed as xanthogranuloma of the sellar region, which is different from adamantinomatous CP. There was no epithelial tissue in any part of the tumor including tumor capsule but have focal necrosis and calcification. His endocrinological dysfunction did not recover, so a hormonal replacement was continuously required.
CONCLUSION
Xanthogranuloma of the sellar region is a rare entity but must be considered in the differential diagnosis of lesions of the sellar region, even in pediatric population. We should think about this disease when dealing with children with stunted growth accompanied by a long medical history. Our case demonstrates the natural progression of the disease, suggesting that xanthogranuloma of the sellar region without epithelial components may be an independent disease.
Topics: Adolescent; Child; Craniopharyngioma; Humans; Hypopituitarism; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Sella Turcica; Xanthogranuloma, Juvenile
PubMed: 34192694
DOI: 10.1159/000515517 -
Journal of Cutaneous Pathology Nov 2023Previously identified mutually-exclusive driver genes in juvenile xanthogranuloma (JXG) and adult xanthogranuloma (AXG) include mutations in MAP kinase pathway genes...
BACKGROUND
Previously identified mutually-exclusive driver genes in juvenile xanthogranuloma (JXG) and adult xanthogranuloma (AXG) include mutations in MAP kinase pathway genes such as MAP2K1, BRAF, ARAF, KRAS, NRAS, PIK3CD as well as fusions in BRAF and ALK, with a subset of cases with no identified driver yet. NTRK fusion has been identified in rare cases.
METHODS
We identified two consecutive index cases of localized JXG or AXG with NTRK1 fusion by next-generation sequencing (NGS) and confirmed by pan-NTRK immunostain. We expanded the study to a total of 50 cases of JXG and AXG using screening by pan-NTRK immunostain. We confirmed the specificity of our approach with negative results in 5 cases of histiocytic neoplasia lacking an NTRK fusion by NGS and 14 cases of non-neoplastic histiocytic disease.
RESULTS
We found 23 cases of JXG or AXG with overexpression of NTRK by immunostain, and these cases were restricted to localized disease (23 of 43 cases, 53.5%) rather than disseminated disease (zero of seven cases).
CONCLUSIONS
NTRK expression is common in JXG or AXG and associated with localized rather than disseminated disease. We speculate that the potential importance of this in JXG and AXG has not been previously appreciated due to the tendency to focus sequencing studies on disseminated disease. We confirm the presence of an NTRK1 fusion in two positive cases by NGS, however, additional genetic studies are necessary to further explore this.
Topics: Adult; Humans; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Xanthomatosis; Granuloma; Histiocytosis; Hematologic Neoplasms; Xanthogranuloma, Juvenile; Oncogene Proteins, Fusion
PubMed: 37580954
DOI: 10.1111/cup.14510