Juvenile xanthogranuloma mimicking malignancy at uncommon sites in children: five cases and a systematic review
- 1Department of Pathology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, Hunan, China
- 2Department of Radiology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, Hunan, China
- 3Department of Critical Care Medicine, Hunan Aerospace Hospital, Hunan Normal University, Changsha, Hunan, China
Abstract
IntroductionJuvenile xanthogranuloma (JXG) typically presents in childhood as self-limited cutaneous lesions, but extracutaneous involvement is uncommon and may raise concern for malignancy. Although previous reviews have summarized the clinical spectrum of extracutaneous JXG, to our knowledge no study has systematically applied predefined criteria to quantify malignancy-mimicking presentations before histopathological diagnosis, or their diagnostic and management consequences, at the patient level.MethodsWe retrospectively analyzed five pediatric patients with JXG at uncommon anatomical sites and conducted a PRISMA 2020-guided systematic review of PubMed/MEDLINE, Embase, and CNKI (January 2006–September 2026; no language restriction).ResultsThe five cases from our institution (three boys and two girls; age range, 4–12 years) involved the chest wall/pleural cavity, spinal epidural space, Meckel's cave, kidney, and pineal region. All lesions were mass-forming; three were initially radiologically suspicious for malignancy, whereas two showed other tumor-like growth patterns. Histopathology demonstrated histiocytic proliferations expressing CD68 and/or CD163; CD1a and langerin were negative in the cases tested. Targeted sequencing detected a PIK3CA p.H1047R variant in one case (variant allele frequency, 1.96%); given its low allele frequency and the absence of orthogonal validation, this finding was interpreted cautiously as supportive rather than diagnostic. After linking reports at the patient level, the systematic review included 150 reports corresponding to 147 unique patients. A malignancy-mimicking presentation before histopathological diagnosis was documented in 15 of 147 patients (10.2%; in sensitivity analysis, 17/147 [11.6%]). Diagnostic or management consequences were documented in 11 of 15 patients (73.3%), including enucleation for suspected retinoblastoma.DiscussionMajor diagnostic challenges included unusual anatomical sites, tumor-like imaging findings, variable histopathologic features, and overlap with other histiocytic disorders. Diagnosis requires integration of clinical, radiological, pathological, immunophenotypic, and selective molecular data. Molecular findings are supportive rather than diagnostic, and no known molecular alteration is specific to JXG. We propose a practical diagnostic framework for distinguishing uncommon-site JXG from malignancy and other tumor-like processes. This framework is based on evidence from small, heterogeneous case series and institutional experience and is not intended to serve as an evidence-based management standard.
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BibTeX
@article{zhang2026juvenile,
title = {{Juvenile xanthogranuloma mimicking malignancy at uncommon sites in children: five cases and a systematic review}},
author = {Shan Zhang and Weijian Chen and Haomiao Zhou and Qiuhong Ma and Rong Wen and Li Du},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1976218},
url = {https://doi.org/10.3389/fonc.2026.1976218},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Juvenile xanthogranuloma mimicking malignancy at uncommon sites in children: five cases and a systematic review
AU - Shan Zhang
AU - Weijian Chen
AU - Haomiao Zhou
AU - Qiuhong Ma
AU - Rong Wen
AU - Li Du
PY - 2026
DA - 2026/10/23
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1976218
UR - https://doi.org/10.3389/fonc.2026.1976218
AB - IntroductionJuvenile xanthogranuloma (JXG) typically presents in childhood as self-limited cutaneous lesions, but extracutaneous involvement is uncommon and may raise concern for malignancy. Although previous reviews have summarized the clinical spectrum of extracutaneous JXG, to our knowledge no study has systematically applied predefined criteria to quantify malignancy-mimicking presentations before histopathological diagnosis, or their diagnostic and management consequences, at the patient level.MethodsWe retrospectively analyzed five pediatric patients with JXG at uncommon anatomical sites and conducted a PRISMA 2020-guided systematic review of PubMed/MEDLINE, Embase, and CNKI (January 2006–September 2026; no language restriction).ResultsThe five cases from our institution (three boys and two girls; age range, 4–12 years) involved the chest wall/pleural cavity, spinal epidural space, Meckel's cave, kidney, and pineal region. All lesions were mass-forming; three were initially radiologically suspicious for malignancy, whereas two showed other tumor-like growth patterns. Histopathology demonstrated histiocytic proliferations expressing CD68 and/or CD163; CD1a and langerin were negative in the cases tested. Targeted sequencing detected a PIK3CA p.H1047R variant in one case (variant allele frequency, 1.96%); given its low allele frequency and the absence of orthogonal validation, this finding was interpreted cautiously as supportive rather than diagnostic. After linking reports at the patient level, the systematic review included 150 reports corresponding to 147 unique patients. A malignancy-mimicking presentation before histopathological diagnosis was documented in 15 of 147 patients (10.2%; in sensitivity analysis, 17/147 [11.6%]). Diagnostic or management consequences were documented in 11 of 15 patients (73.3%), including enucleation for suspected retinoblastoma.DiscussionMajor diagnostic challenges included unusual anatomical sites, tumor-like imaging findings, variable histopathologic features, and overlap with other histiocytic disorders. Diagnosis requires integration of clinical, radiological, pathological, immunophenotypic, and selective molecular data. Molecular findings are supportive rather than diagnostic, and no known molecular alteration is specific to JXG. We propose a practical diagnostic framework for distinguishing uncommon-site JXG from malignancy and other tumor-like processes. This framework is based on evidence from small, heterogeneous case series and institutional experience and is not intended to serve as an evidence-based management standard.
SN - 2234-943X
ER -