HAEM5:Erdheim-Chester disease

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

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

Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.)

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

Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

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.