Juvenile xanthogranuloma

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

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Primary Author(s)*

Mayuri Shende, MBBS, DCP, FCPS, DNB, ASCP-SH CM

Scott Turner, PhD

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Histiocytic/Dendritic cell neoplasms
Family Histiocyte/macrophage neoplasms
Type Histiocytic neoplasms
Subtype(s) Juvenile xanthogranuloma

Definition / Description of Disease

Juvenile Xanthogranuloma (JXG) is a clonal expansion of non–Langerhans cell histiocytes with dermal macrophage phenotype.(Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories, diagnostic criteria if applicable, and differential diagnosis if applicable. Other classifications can be referenced for comparison.)

Synonyms / Terminology

Juvenile xanthogranuloma (Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.)

Epidemiology / Prevalence

Juvenile Xanthogranuloma is a rare histiocytic neoplasm comprising about 0.5% of all pediatric tumors, seldom seen in in adults. 20-35% cases are congenital, shows male predilection and mostly (>70% cases) arise during the first year of life.

Clinical Features

JXG are generally asymptomatic. Infants may present with ≥1 cutaneous, pale yellow-tan, dome-shaped papulonodular lesions, approximately5% patients show multiple lesions. These lesions begin as raised, pink to dark brown lesions that might get flatten later and heal/ scar within few months or years. A clinical subtype of JXG- benign cephalic histiocytosis occurs in head and neck of young children, asymptomatic, self-healing papular lesions. The lesions are often large, solitary and persistent in adults which needs exclusion of Erdheim–Chester disease. JXG may occur in patients with neurofibromatosis type 1, also reported in Wiskott–Aldrich syndrome. (Instruction: Can include references in the table. Do not delete table.)

Signs and Symptoms Asymptomatic in the beginning

≥1 cutaneous papulonodular lesions

Rarely systemic involvement with abnormal labs, ophthalmologic exam findings, seizures, hydrocephalus, diabetes Insipidus

Laboratory Findings Abnormal blood count, liver enzymes, metabolic tests

Cytopenia if bone marrow involved

Sites of Involvement

JXG involves and is generally confined to skin, head and neck, upper trunk and proximal extremities. Rarely ocular involvement, solitary lesion noted. Other extracutaneous sites of involvement- visceral, spinal, or intracranial area also reported rarely. (Instruction: Indicate physical sites; EXAMPLE: nodal, extranodal, bone marrow)

Morphologic Features

Gross appearance:

Cutaneous JXGs: Early lesions are pink macules, later progress to form pale to tan, dome shaped lesions.

Visceral JXGs: Nodules with variable size and appearance.

Histopathology:

  • Unencapsulated, circumscribed lesions composed of classic histiocytes, large xanthomatous histiocytes, foamy histiocytes and Touton giant cells..
  • Variable numbers of lymphocytes, eosinophils, plasma cells, neutrophils, and mast cells are often intermixed along with epithelioid cells, spindle cells and oncocytic histiocytes.
  • These histiocytes should not show significant nuclear pleomorphism.

Cytology:

  • Mononuclear or multinucleated histiocytes with kidney shaped/oval nuclei, variable numbers of lymphocytes, neutrophils, and eosinophils.
  • Touton giant cells or foreign body giant cells may be present.

Immunophenotype

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Finding Marker
Positive (universal) CD68, CD163, CD4, CD14, factor XIIIa, and fascin
Positive (subset) S100 (light nuclear and cytoplasmic staining)
Negative (universal) CD1a and CD207 (langerin), ALK
Negative (subset) N/A

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: 3'ABL1 / 5'BCR EXAMPLE: der(22) EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add reference)

Yes No Yes EXAMPLE:

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

Individual Region Genomic Gain / Loss / LOH

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Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7:1- 159,335,973 [hg38]

EXAMPLE:

chr7

Yes Yes No EXAMPLE:

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

chr8:1-145,138,636 [hg38]

EXAMPLE:

chr8

No No No EXAMPLE:

Common recurrent secondary finding for t(8;21) (add reference).

Characteristic Chromosomal Patterns

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Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE:

Co-deletion of 1p and 18q

Yes No No EXAMPLE:

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

Gene Mutations (SNV / INDEL)

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Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).


Note: A more extensive list of mutations can be found in Bioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

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Genes and Main Pathways Involved

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Gene; Genetic Alteration Pathway Pathophysiologic Outcome
NRAS, KRAS, ARAF, MAP2K1, and CSF1R, NTRK1 and BRAF gene fusions MAPK/ERK pathway alterations EXAMPLE: Increased cell growth and proliferation
PIK3CD mutations PI3K pathway EXAMPLE: Unregulated cell division
NA NA NA

Genetic Diagnostic Testing Methods

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Familial Forms

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Additional Information

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Links

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References

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EXAMPLE Book

  1. John  Chan et al., Juvenile xanthogranuloma, in: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. Lyon (France): International Agency for Research on Cancer; 2024. . (WHO classification of tumours series, 5th ed.; vol. 11). https://publications.iarc.who.int/637.

Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome. *Citation of this Page: “Juvenile xanthogranuloma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 10/9/2024, https://ccga.io/index.php/HAEM5:Juvenile_xanthogranuloma.