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
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
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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
- 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.