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International Journal of Hematology Jan 2024Juvenile xanthogranuloma (JXG) is usually identified by Touton giant cells, so their absence can complicate diagnosis. We encountered a case of non-typical neonatal JXG...
Juvenile xanthogranuloma (JXG) is usually identified by Touton giant cells, so their absence can complicate diagnosis. We encountered a case of non-typical neonatal JXG lacking Touton giant cells, which was difficult to differentiate from aleukemic leukemia cutis because of overlapping histopathological characteristics. A 1 month-old girl presented with a blueberry muffin rash and multiple 1-2 cm nodules within the subcutaneous and deeper soft tissues. Blood tests revealed pancytopenia. The initial nodule biopsy showed mononuclear cell infiltration, suggestive of mature monocytes or histiocytes, but no Touton giant cells. Bone marrow examination showed no evidence of leukemia. Despite worsening of the rash, pancytopenia, and weight gain over the following month, the results of the second biopsy remained consistent with the initial findings. Consequently, we provisionally diagnosed aleukemic leukemia cutis and initiated chemotherapy. After two courses of chemotherapy, the pancytopenia improved, but the nodules only partially regressed. A third biopsy of the nodule was performed to evaluate the histological response, and revealed Touton giant cells, confirming the diagnosis of JXG. In conclusion, distinguishing non-typical JXG from aleukemic leukemia cutis is challenging. This case highlights the importance of multiple biopsies and the potential for histopathological maturation.
Topics: Female; Humans; Infant; Exanthema; Histiocytes; Leukemia; Pancytopenia; Skin Neoplasms; Xanthogranuloma, Juvenile
PubMed: 37989992
DOI: 10.1007/s12185-023-03675-y -
Andes Pediatrica : Revista Chilena de... Oct 2023Giant Juvenile Xanthogranuloma (GJXG) corresponds to an infrequent variant of Juvenile Xantho- granuloma (JXG) and is characterized by a lesion larger than 2 cm in...
UNLABELLED
Giant Juvenile Xanthogranuloma (GJXG) corresponds to an infrequent variant of Juvenile Xantho- granuloma (JXG) and is characterized by a lesion larger than 2 cm in diameter. It usually presents as a plaque but infrequently, presents as an ulcerated nodule.
OBJECTIVE
To report two cases of atypical presentation of GJXG, highlighting the importance of considering them in the differential diagnosis of large, ulcerated tumors in infants.
CLINICAL CASES
Case 1: A 4-month-old healthy male infant presented with a rapid and progressive growing left inguinal nodule, present since 2 months of age. At physical examination he presented with a 2.6 cm indurated erythematous nodule with central ulceration. Histological study of an incisional biopsy was compatible with JXG. Ophthalmologic involvement was ruled out. Because of functional impairment and parents worry complete surgical removal was performed. The patient had favorable evolution without local recurrence at 4 years of follow-up. Case 2: A 6-month-old healthy male infant presented with a 2.4 cm scapular crusted nodule of rapid and progressive growth, present since birth. Histological study of an incisional biopsy confirmed JXG. Ophthalmologic involvement was ruled out. After 18 months of periodic clinical follow-up, there was a progressive reduction in size of the lesion.
CONCLUSIONS
The cases presented highlight the importance of considering JXG in the differential diagnosis of large, ulcerated tumors in infants. When encountered to atypical JXG presentations, histologic studies help to confirm the diagnosis. Given the favorable prognosis of this diagnosis, periodic clinical follow-up is advised; in exceptional cases, surgical or ablative treatments may be considered.
Topics: Humans; Infant; Male; Xanthogranuloma, Juvenile; Biopsy; Diagnosis, Differential; Neoplasms
PubMed: 37975698
DOI: 10.32641/andespediatr.v94i5.4673 -
The British Journal of Dermatology Jan 2024
Topics: Humans; Xanthogranuloma, Juvenile; Receptor Protein-Tyrosine Kinases; Neoplasms; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Receptors, Amino Acid
PubMed: 37930319
DOI: 10.1093/bjd/ljad427 -
JAMA Dermatology Dec 2023
Topics: Humans; Lung Neoplasms; Piperidines; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases; Xanthogranuloma, Juvenile
PubMed: 37878279
DOI: 10.1001/jamadermatol.2023.4027 -
International Ophthalmology Dec 2023To describe the clinicopathological features of a large cohort of patients with orbital histiocytoses and fibrohistiocytosis, such as Langerhans cell histiocytosis (LCH)... (Review)
Review
PURPOSE
To describe the clinicopathological features of a large cohort of patients with orbital histiocytoses and fibrohistiocytosis, such as Langerhans cell histiocytosis (LCH) and non-LCH disorders, and correlate patients' clinical characteristics with their pathological diagnosis.
METHODS
In this retrospective study, medical records of patients presenting to Farabi Eye Hospital, a tertiary eye care center in Tehran, Iran, from 2010 until 2022, were reviewed. Patients' demographics, chief complaint, location and laterality of the tumor, best-corrected visual acuity, presence of bone erosion on imaging, and their pathological diagnosis were retrieved. Excisional biopsy was performed and evaluated through light microscopy and immunohistochemistry study for their respective markers, including CD1a, CD68, CD207, and S100.
RESULTS
A total of 117 patients with 11 pathological subtypes of histiocytoses and fibrohistiocyosis were identified, with 56.4% male and 43.6% female patients. The mean age at presentation was 23.4 years (range 1.5 months-73 years). Swelling and palpable mass were the most common chief complaints. LCH was the most common pathology (32.5%), followed by juvenile xanthogranuloma (26.5%) and adult xanthogranuloma (21.4%). Age, lesion location, and bone erosion had a statistically significant difference among the various diagnosed subtypes.
CONCLUSIONS
Histiocytoses and fibrohistiocytosis are diverse and rare disorders potentially involving multiple organ systems. Ophthalmic manifestations of these diseases are even more uncommon. We reviewed their orbital presentation along with their respective histopathological findings. Our results also suggested that an orbital CT scan can be of diagnostic value to discriminate LCH from other histiocytic pathologies.
Topics: Adult; Humans; Male; Female; Infant; Retrospective Studies; Iran; Histiocytosis, Langerhans-Cell; Immunohistochemistry; Biopsy
PubMed: 37840073
DOI: 10.1007/s10792-023-02903-y -
Journal of Cutaneous Medicine and... Nov 2023
Topics: Humans; Cicatrix; Xanthogranuloma, Juvenile; Connective Tissue Diseases; Xanthomatosis
PubMed: 37795963
DOI: 10.1177/12034754231194010 -
Genes Aug 2023The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that...
The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the gene. The second case involves a child with alveolar rhabdomyosarcoma, juvenile xanthogranuloma, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nephroblastoma, in whom a pathogenic variant in the gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play significant roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are important for improving outcomes in these individuals.
PubMed: 37761810
DOI: 10.3390/genes14091670 -
Pediatric Investigation Sep 2023
PubMed: 37736360
DOI: 10.1002/ped4.12398 -
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 -
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