Difference between revisions of "HAEM5:Langerhans cell histiocytosis"
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{{DISPLAYTITLE:Langerhans cell histiocytosis}} | {{DISPLAYTITLE:Langerhans cell histiocytosis}} | ||
| − | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]] | + | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] |
{{Under Construction}} | {{Under Construction}} | ||
| − | <blockquote class='blockedit'>{{Box-round|title= | + | <blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Langerhans Cell Histiocytosis]]. |
}}</blockquote> | }}</blockquote> | ||
| + | |||
| + | <span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ 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 </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span> | ||
| + | |||
==Primary Author(s)*== | ==Primary Author(s)*== | ||
| Line 12: | Line 15: | ||
__TOC__ | __TOC__ | ||
| − | == | + | ==WHO Classification of Disease== |
| − | Histiocytic and dendritic cell neoplasms | + | {| class="wikitable" |
| − | + | !Structure | |
| − | + | !Disease | |
| − | + | |- | |
| + | |Book | ||
| + | |Haematolymphoid Tumours (5th ed.) | ||
| + | |- | ||
| + | |Category | ||
| + | |Histiocytic/Dendritic cell neoplasms | ||
| + | |- | ||
| + | |Family | ||
| + | |Langerhans cell and other dendritic cell neoplasms | ||
| + | |- | ||
| + | |Type | ||
| + | |Langerhans cells neoplasms | ||
| + | |- | ||
| + | |Subtype(s) | ||
| + | |Langerhans cell histiocytosis | ||
| + | |} | ||
==Definition / Description of Disease== | ==Definition / Description of Disease== | ||
| Line 55: | Line 73: | ||
==Clinical Features== | ==Clinical Features== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span> |
{| class="wikitable" | {| class="wikitable" | ||
|'''Signs and Symptoms''' | |'''Signs and Symptoms''' | ||
| − | |EXAMPLE Asymptomatic (incidental finding on complete blood counts) | + | |<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts) |
| − | EXAMPLE B-symptoms (weight loss, fever, night sweats) | + | <span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats) |
| − | EXAMPLE Fatigue | + | <span class="blue-text">EXAMPLE:</span> Fatigue |
| − | EXAMPLE Lymphadenopathy (uncommon) | + | <span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon) |
|- | |- | ||
|'''Laboratory Findings''' | |'''Laboratory Findings''' | ||
| − | |EXAMPLE Cytopenias | + | |<span class="blue-text">EXAMPLE:</span> Cytopenias |
| − | EXAMPLE Lymphocytosis (low level) | + | <span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level) |
|} | |} | ||
| Line 166: | Line 184: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC) | + | |<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC) |
| − | EXAMPLE 30% (add reference) | + | <span class="blue-text">EXAMPLE:</span> 30% (add reference) |
|Yes | |Yes | ||
|No | |No | ||
|Yes | |Yes | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
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). | 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). | ||
| Line 184: | Line 202: | ||
</blockquote> | </blockquote> | ||
| − | ==Individual Region Genomic Gain/Loss/LOH== | + | ==Individual Region Genomic Gain / Loss / LOH== |
Recurrent regional losses, gains, or regions with loss of heterozygosity have not been identified in the context of Langerhans cell histiocytosis. | Recurrent regional losses, gains, or regions with loss of heterozygosity have not been identified in the context of Langerhans cell histiocytosis. | ||
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| | | | ||
|} | |} | ||
| − | ==Gene Mutations (SNV/INDEL)== | + | ==Gene Mutations (SNV / INDEL)== |
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
| Line 235: | Line 253: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE: TP53; Variable LOF mutations | + | |<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations |
| − | EXAMPLE: | + | <span class="blue-text">EXAMPLE:</span> |
EGFR; Exon 20 mutations | EGFR; Exon 20 mutations | ||
| − | EXAMPLE: BRAF; Activating mutations | + | <span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations |
| − | |EXAMPLE: TSG | + | |<span class="blue-text">EXAMPLE:</span> TSG |
| − | |EXAMPLE: 20% (COSMIC) | + | |<span class="blue-text">EXAMPLE:</span> 20% (COSMIC) |
| − | EXAMPLE: 30% (add Reference) | + | <span class="blue-text">EXAMPLE:</span> 30% (add Reference) |
| − | |EXAMPLE: IDH1 R123H | + | |<span class="blue-text">EXAMPLE:</span> IDH1 R123H |
| − | |EXAMPLE: EGFR amplification | + | |<span class="blue-text">EXAMPLE:</span> EGFR amplification |
| | | | ||
| | | | ||
| | | | ||
| − | |EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference). | + | |<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference). |
<br /> | <br /> | ||
|} | |} | ||
| Line 257: | Line 275: | ||
| − | <blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the previous version of the page. Please incorporate above.}} | + | <blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV / INDEL)|The content below was from the previous version of the page. Please incorporate above.}} |
More than half of LCH cases display a ''BRAF V600E'' variant. Approximately 25% of LCH cases have an associated somatic MAP2K1 mutation in parallel with a germline BRAF variant <ref name=":0" />. | More than half of LCH cases display a ''BRAF V600E'' variant. Approximately 25% of LCH cases have an associated somatic MAP2K1 mutation in parallel with a germline BRAF variant <ref name=":0" />. | ||
| Line 315: | Line 333: | ||
==Links== | ==Links== | ||
| − | [[Langerhans | + | [[HAEM5:Langerhans cell sarcoma]] |
==References== | ==References== | ||
| Line 327: | Line 345: | ||
| − | <nowiki>*</nowiki>''Citation of this Page'': “Langerhans cell histiocytosis”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Langerhans_cell_histiocytosis</nowiki>.[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases L]] | + | <nowiki>*</nowiki>''Citation of this Page'': “Langerhans cell histiocytosis”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Langerhans_cell_histiocytosis</nowiki>. |
| + | [[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases L]] | ||
Latest revision as of 17:23, 6 September 2024
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Langerhans Cell Histiocytosis.
(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)*
Dr Malaika Perchard BSci(MedSci), MBBS, FRACP, FRCPA, (Paediatric Haematologist) Pathology Queensland
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | Histiocytic/Dendritic cell neoplasms |
| Family | Langerhans cell and other dendritic cell neoplasms |
| Type | Langerhans cells neoplasms |
| Subtype(s) | Langerhans cell histiocytosis |
Definition / Description of Disease
Tumours derived from Langerhans cells (LCs) are rare disorders characterized by clonal proliferation of LCs that can be subdivided in to two groups based on severity of cytological atypia and clinical aggressiveness. These two groups are LC histiocytosis (LCH) and LC sarcoma. LCH does not display overt malignant cytological features and is less clinically aggressive. [1]
Synonyms / Terminology
Langerhans cell histiocytosis (LCH)
Obsolete terms:
· Langerhans cell histiocytosis; unifocal
· Langerhans cell histiocytosis; multifocal
· Langerhans cell histiocytosis; disseminated
· Langerhans cell granulomatosis
· Solitary lesions: Histiocytosis X, eosinophilic granuloma
· Multiple lesions/disseminated: Hand-Schuller-Christian disease, Letterer-Siwe disease
Epidemiology / Prevalence
Langerhans cell histiocytosis
· Rare, annual incidence ~5 per 1 million population
· More common in paediatric age group
· Male predilection M:F 3.7:1
· More common in Caucasian population of Northern European descent than Black population
Clinical Features
Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)
| Signs and Symptoms | EXAMPLE: Asymptomatic (incidental finding on complete blood counts)
EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon) |
| Laboratory Findings | EXAMPLE: Cytopenias
EXAMPLE: Lymphocytosis (low level) |
editv4:Clinical FeaturesThe content below was from the previous version of the page. Please incorporate above.Patients with unifocal disease often present with lytic bone lesions and are usually older children or adults.
Patients with single system disease are usually young children that present with a combination of destructive bone lesions and associated soft tissue masses. Commonly the destructive bone lesions involve the skull and mandible. If there is cranial involvement patients can present with diabetes insipidus.
Patients with multi-system disease are usually infants who present with fever, cytopenias, hepatosplenomegaly and/or skin and skeletal lesions. Pulmonary involvement is possible but less common and variable in severity.
A trans-differentiation phenomenon is recognized with an association between tumours derived from Langerhans cells and T-lymphoblastic leukaemia. The leukemia-associated TR gene rearrangement is present in the Langerhans Cell Histiocytosis cells [1].
Sites of Involvement
Solitary lesions most commonly involve:
· Skull
· Femur
· Vertebra
· Pelvic bones
· Ribs
Solitary lesions less commonly involve:
· Lymph node
· Skin
· Lung
Multifocal lesions most commonly involve:
· Skin
· Bones (as above)
· Liver
· Spleen
· Bone marrow
Gonadal tissue and kidneys are rarely involved, even in the context of disseminated disease.
Morphologic Features
The key feature to the diagnosis is the presence of the LCH cells. These cells are oval with distinctive nuclear features including a grooved, folded, indented or lobed nucleus with fine chromatin and inconspicuous nucleoli. Nuclear atypia is minimal. These cells have moderately abundant cytoplasm that is slightly eosinophilic. LCH cells are usually devoid of cytoplasmic processes. Ultrastructural assessment of LCH demonstrates the hallmark cytoplasmic Birbeck granules. Birbeck granules have a tennis-racket shape with a zipper-like appearance. Identification of LC’s can be confirmed by langerin (CD207) expression.
LCH often has characteristic LC’s (including multinucleate and osteoclast like forms) surrounded by a milieu of eosinophils, neutrophils and small lymphocytes. In early lesions the LC predominate, but as the disease progresses LC’s decrease and there is an increase in foamy macrophages and fibrosis [1].
Tissue specimens:
· Spleen – shows nodular red pulp involvement.
· Liver – strong preference for intrahepatic biliary involvement with progressive sclerosing cholangitis
· Bone marrow – trephine is preferred to aspirate to demonstrate involvement.
Immunophenotype
LCH consistently express CD1a, langerin (CD2017) and S100 which can be used to distinguish LCH from other histiocytic disorders and non-neoplastic macrophages.
| Finding | Marker |
|---|---|
| Positive (universal) | Langerin, CD1a, CD4, S100, HLA-DR |
| Positive (subset) | CD68, Lysozyme (low), CD45 (low)
Ki-67 highly variable. |
| Negative (universal) | B and T cell markers (except CD4), Factor XIIIa, CD21, CD35, CD123, CD162, Fascin, TCL1, Fc receptors |
| Negative (subset) | N/A |
Chromosomal Rearrangements (Gene Fusions)
Put your text here and fill in the table
| 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). |
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the previous version of the page. Please incorporate above.LCH has been shown to be clonal, using an X-linked androgen receptor gene assay in many cases (not seen in some adult pulmonary lesions).
About 30% of cases have a detectable clonal IGH, IGK or TR rearrangement [1].
Individual Region Genomic Gain / Loss / LOH
Recurrent regional losses, gains, or regions with loss of heterozygosity have not been identified in the context of Langerhans cell histiocytosis.
| 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 |
|---|---|---|---|---|---|---|---|
Characteristic Chromosomal Patterns
Recurrent chromosomal abnormalities have not been described in the context of Langerhans cell histiocytosis.
| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
Gene Mutations (SNV / INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.)
| 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.
editv4:Gene Mutations (SNV / INDEL)The content below was from the previous version of the page. Please incorporate above.More than half of LCH cases display a BRAF V600E variant. Approximately 25% of LCH cases have an associated somatic MAP2K1 mutation in parallel with a germline BRAF variant [1].
Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) BRAFV600E Oncogene ~50% Unknown No Yes 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
Epignomic alterations in the context of Langerhans cell histiocytosis are not described.
Genes and Main Pathways Involved
B-RAF encodes B-Raf, a cytoplasmic serine/threonine kinase that has a role in regulating the mitogen-activated protein kinase signal transduction pathway. V600E is an activating missense mutation in codon 600 of exon 15 that causes substitution of valine to glutamate. This causes independent activation of the RAS-RAF-MEK-ERK signalling pathway, leading to unregulated cell growth and proliferation [2].
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| BRAF and MAP2K1; Activating mutations | MAPK signaling | Increased cell growth and proliferation |
Genetic Diagnostic Testing Methods
PCR or sequencing for BRAF variants, X-linked androgen receptor gene assay.
Familial Forms
Familial forms of Langerhans cell histiocytosis have not been described
Additional Information
Links
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "Appendix II: World Health Organization Classification of Tumours of the Haematopoietic and Lymphoid Tissues". Postgraduate Haematology: 986–988. 2010-10-28. doi:10.1002/9781444323160.app2.
- ↑ Richtig, G.; et al. (2017-09-04). "Beyond the BRAF V 600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients". British Journal of Dermatology. 177 (4): 936–944. doi:10.1111/bjd.15436. ISSN 0007-0963. line feed character in
|title=at position 23 (help)
1) Arber DA, et al., (2017). Histocytic and dendriic cell neoplasms, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Pileris SA, Jaffe R, Facchettic F, Jones DM and Jaffe ES, Editors. IARC Press: Lyon, France, p466-472
2) Richtig G, Hoeller C, Kashofer K, Aigelsreiter A, Heinemann A, Kwong LN, et al.. Beyond the BRAF V 600E hotspot: biology and clinical implications of rare BRAF gene mutations in . British Journal of Dermatology. British Journal of Dermatology; 2017;177(4):936–44.
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: “Langerhans cell histiocytosis”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Langerhans_cell_histiocytosis.