HAEM5:Erdheim-Chester disease

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 (EXAMPLE: Jane Smith, 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)	Erdheim-Chester disease

Definition / Description of Disease

Erdheim–Chester disease (ECD) is a histiocytic neoplasm characterized by accumulation of mature histiocytes, associated with inflammation and fibrosis in many different organs . (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

Erdheim–Chester disease (ECD) (Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.)

Epidemiology / Prevalence

Rare histiocytic neoplasm with median age at diagnosis being 55 years, male predilection. Many cases might be underdiagnosed.

Clinical Features

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Signs and Symptoms	Asymptomatic or presents with fever, fatigue Site related symptoms like bone pain, exophthalmos, xanthelasma, diabetes insipidus CNS-mass effect or neurodegerative type symptoms Cardiac tamponade Painful abdominal mass
Laboratory and imaging Findings	Symmetrical osteosclerosis of the leg bones on PET with bilateral uptake of FDG Hairy-kidney appearance in cases of bilateral perinephric involvement Mass-like infiltration of the right atrium on MRI Sclerosis of sinuses of the face on CT May be associated with chronic myelomonocytic leukaemia, Langerhans cell histiocytosis

Sites of Involvement

ECD can involve any organ, mostly excludes lymph nodes, spleen and liver. In majority of cases (80-95%) involves long bones, bilaterally and symmetric. Perinephric, periaortic involvement also frequent. Pitutary, neurologic, pulmonary, cardiac, serosal and cutaneous involvement (manifesting as xanthelasma or papule) also noted. (Instruction: Indicate physical sites; EXAMPLE: nodal, extranodal, bone marrow)

Morphologic Features

Histopathology:

• Infiltration by foamy, lipid-laden, and/or small mononuclear histiocytes and variable proportions of Touton giant cells, small lymphocytes, plasma cells, and/or neutrophils.
• Fibrosis usually present
• Can be misdiagnosed as reactive fibroinflammatory process if there is extensive fibrosis or it may also show partial morphological and immunophenotypic overlap with Rosai–Dorfman disease or with reticulohistiocytosis or Langerhans cell histiocytosis.

Immunophenotype

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Finding	Marker
Positive (universal)	CD163, CD68, CD14, and CD4 Positive for factor XIIIa, fascin, and (less commonly) S100 Diffuse strong cytoplasmic staining with VE1 monoclonal antibody suggestive of BRAF p.V600E mutation, but should be confirmed with molecular analysis Expression of phosphorylated ERK also noted frequently
Positive (subset)	EXAMPLE: CD2
Negative (universal)	CD1a and CD207
Negative (subset)	EXAMPLE: CD4

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 cBioportal (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
Gain-of-function somatic alteration	MAPK cell signalling pathway	EXAMPLE: Increased cell growth and proliferation
BRAF p.V600E mutations or BRAF, ARAF, NRAS, KRAS, or MAP2K1	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
	PIK3CA	EXAMPLE:  Abnormal gene expression program

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., Erdheim–Chester disease 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: “Erdheim-Chester disease”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 10/9/2024, https://ccga.io/index.php/HAEM5:Erdheim-Chester_disease.