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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 -
The American Journal of Surgical... Oct 2023The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and...
The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC :: SYK fusion in 3 cases of a histopathologically distinct histiocytic neoplasm arising as solitary soft tissue lesions in children identified by next-generation sequencing and fluorescence in situ hybridization is described. Morphologically, all 3 neoplasms were composed of sheets of cells with round-oval nuclei and vacuolated eosinophilic cytoplasm but, in contrast to classic juvenile xanthogranuloma (JXG), Touton giant cells were absent. A separate cohort of classic JXG cases subsequently profiled by fluorescence in situ hybridization were negative for the presence of a CLTC::SYK fusion suggesting that CLTC::SYK fusion-positive histiocytoma is genetically and histologically distinct from JXG. We postulate that the CLTC::SYK fusion leads to aberrant activation of the SYK kinase, which is involved in variable pathways, including mitogen-activated protein kinase. The identification of a novel CLTC::SYK fusion may pave the way for the development of targeted therapeutic options for aggressive disease.
Topics: Child; Humans; In Situ Hybridization, Fluorescence; Xanthogranuloma, Juvenile; Histiocytoma; Mitogen-Activated Protein Kinases; Syk Kinase; Clathrin Heavy Chains
PubMed: 37522373
DOI: 10.1097/PAS.0000000000002102 -
Neuro-Chirurgie Sep 2023Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. Its systemic form affects 4% of patients. Lesions in the Central Nervous System (CNS)... (Review)
Review
Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. Its systemic form affects 4% of patients. Lesions in the Central Nervous System (CNS) occur in 2% of systemic cases. Sellar JXG should be one of the differential diagnoses for sellar lesions in young. This is a 15-year-old patient with non-specific headache, progressive visual loss and magnetic resonance imaging showing sellar lesion with suprasellar extension. The patient underwent microsurgery by pterional craniotomy with partial resection of the tumor. Pathology evidenced JXG. It progressively evolved with impairment of neuroendocrine functions, new lesions in different CNS locations and death two years after diagnosis. Sellar JXG without cutaneous manifestations is rare. There are no specific findings of the disease. Diagnosis requires additional tests, being defined by pathological analysis. Total resection presents a greater potential control comparing to partial resection. Even so, some patients may have progressive disease with poor clinical outcome.
Topics: Adolescent; Humans; Diagnosis, Differential; Headache; Magnetic Resonance Imaging; Xanthogranuloma, Juvenile
PubMed: 37482184
DOI: 10.1016/j.neuchi.2023.101472 -
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 -
Journal of the European Academy of... Dec 2023
Topics: Humans; Neurofibromatosis 1; Xanthogranuloma, Juvenile; Leukemia
PubMed: 37422708
DOI: 10.1111/jdv.19321 -
American Journal of Ophthalmology Case... Sep 2023To report a case of diffuse xanthogranuloma presenting as bilateral anterior uveitis in a neonate.
PURPOSE
To report a case of diffuse xanthogranuloma presenting as bilateral anterior uveitis in a neonate.
OBSERVATIONS
A neonate was brought by the parents with complaints of redness, watering, and photophobia in both eyes for 10 days. Examination under anesthesia revealed the presence of bilateral hyphema, fibrinous membrane, corneal haze, and raised intraocular pressure (IOP). Ultrasound Biomicroscopy revealed diffuse bilateral iris thickening. The child was managed medically with topical glaucoma medications, topical steroids, and cycloplegics. The child responded well with the resolution of hyphema, anterior chamber inflammation, and reduction of IOP.
CONCLUSION AND IMPORTANCE
In neonates and infants presenting with bilateral uveitis, spontaneous hyphema, and secondary glaucoma, even in the absence of a well-defined iris lesion, diffuse juvenile xanthogranuloma should be considered as a differential diagnosis.
PubMed: 37323587
DOI: 10.1016/j.ajoc.2023.101867 -
Brain Pathology (Zurich, Switzerland) Nov 2023
Topics: Child, Preschool; Humans; Male; Spinal Cord Neoplasms
PubMed: 37285582
DOI: 10.1111/bpa.13174 -
Paediatric Drugs Jul 2023Histiocytic disorders are rare diseases defined by the clonal accumulation of a macrophage or dendritic cell origin. These disorders include Langerhans cell... (Review)
Review
Histiocytic disorders are rare diseases defined by the clonal accumulation of a macrophage or dendritic cell origin. These disorders include Langerhans cell histiocytosis, Erdheim-Chester disease, juvenile xanthogranuloma, malignant histiocytoses, and Rosai-Dorfman-Destombes disease. These histiocytic disorders are a diverse group of disorders with different presentations, management, and prognosis. This review focuses on these histiocytic disorders and the role of pathological ERK signaling due to somatic mutations in the mitogen--activated protein kinase (MAPK) pathway. Over the last decade, there has been growing awareness of the MAPK pathway being a key driver in many histiocytic disorders, which has led to successful treatment with targeted therapies, in particular, BRAF inhibitors and MEK inhibitors.
Topics: Humans; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Mutation; Prognosis; Protein Kinase Inhibitors
PubMed: 37204611
DOI: 10.1007/s40272-023-00569-8 -
Cureus Apr 2023Juvenile xanthogranuloma (JXG) is an uncommon benign skin disorder of infants and young children characterized by dermal proliferation and infiltration of dendrocytes....
Juvenile xanthogranuloma (JXG) is an uncommon benign skin disorder of infants and young children characterized by dermal proliferation and infiltration of dendrocytes. We present a unique case of giant congenital JXG with a mixed presentation of macules, papules, nodules, and ulcerations in a neonatal male who was observed until the age of 23 months, by which time all lesions had spontaneously self-involuted. Prior to complete resolution, some lesions took the form of pedunculated protrusions. To our knowledge, this is the first of this atypical case to be presented in the literature.
PubMed: 37200655
DOI: 10.7759/cureus.37644