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| {{DISPLAYTITLE:Langerhans cell histiocytosis}} | | {{DISPLAYTITLE:Langerhans cell histiocytosis}} |
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| [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] | | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] |
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| {{Under Construction}} | | {{Under Construction}} |
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| <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 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]]. |
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| |Subtype(s) | | |Subtype(s) |
| |Langerhans cell histiocytosis | | |Langerhans cell histiocytosis |
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| ==Definition / Description of Disease==
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| 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. <ref name=":0">{{Cite journal|date=2010-10-28|title=Appendix II: World Health Organization Classification of Tumours of the Haematopoietic and Lymphoid Tissues|url=http://dx.doi.org/10.1002/9781444323160.app2|journal=Postgraduate Haematology|pages=986–988|doi=10.1002/9781444323160.app2}}</ref>
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| ==Synonyms / Terminology==
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| Langerhans cell histiocytosis (LCH)
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| Obsolete terms:
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| · Langerhans cell histiocytosis; unifocal
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| · Langerhans cell histiocytosis; multifocal
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| · Langerhans cell histiocytosis; disseminated
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| · Langerhans cell granulomatosis
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| · Solitary lesions: Histiocytosis X, eosinophilic granuloma
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| · Multiple lesions/disseminated: Hand-Schuller-Christian disease, Letterer-Siwe disease
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| ==Epidemiology / Prevalence==
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| Langerhans cell histiocytosis
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| · Rare, annual incidence ~5 per 1 million population
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| · More common in paediatric age group
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| · Male predilection M:F 3.7:1
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| · More common in Caucasian population of Northern European descent than Black population
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| ==Clinical Features==
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| 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>
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| {| class="wikitable"
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| |'''Signs and Symptoms'''
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| |<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
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| <span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
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| <span class="blue-text">EXAMPLE:</span> Fatigue
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| <span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
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| |'''Laboratory Findings'''
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| |<span class="blue-text">EXAMPLE:</span> Cytopenias
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| <span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
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| <blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>
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| Patients with unifocal disease often present with lytic bone lesions and are usually older children or adults.
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| 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.
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| 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.
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| 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 <ref name=":0" />.
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| <blockquote class="blockedit">
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| <center><span style="color:Maroon">'''End of V4 Section'''</span>
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| ----
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| </blockquote>
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| ==Sites of Involvement==
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| Solitary lesions most commonly involve:
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| · Skull
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| · Femur
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| · Vertebra
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| · Pelvic bones
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| · Ribs
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| Solitary lesions less commonly involve:
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| · Lymph node
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| · Skin
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| · Lung
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| Multifocal lesions most commonly involve:
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| · Skin
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| · Bones (as above)
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| · Liver
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| · Spleen
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| · Bone marrow
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| Gonadal tissue and kidneys are rarely involved, even in the context of disseminated disease.
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| ==Morphologic Features==
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| 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.
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| 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 <ref name=":0" />.
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| Tissue specimens:
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| · Spleen – shows nodular red pulp involvement.
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| · Liver – strong preference for intrahepatic biliary involvement with progressive sclerosing cholangitis
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| · Bone marrow – trephine is preferred to aspirate to demonstrate involvement.
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| ==Immunophenotype==
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| LCH consistently express CD1a, langerin (CD2017) and S100 which can be used to distinguish LCH from other histiocytic disorders and non-neoplastic macrophages.
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| {| class="wikitable sortable"
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| !Finding!!Marker
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| |Positive (universal)||Langerin, CD1a, CD4, S100, HLA-DR
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| |Positive (subset)||CD68, Lysozyme (low), CD45 (low)
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| Ki-67 highly variable.
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| |Negative (universal)||B and T cell markers (except CD4), Factor XIIIa, CD21, CD35, CD123, CD162, Fascin, TCL1, Fc receptors
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| |Negative (subset)||N/A
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| |} | | |} |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> |
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| 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). | | 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). |
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| About 30% of cases have a detectable clonal IGH, IGK or TR rearrangement <ref name=":0" />. | | About 30% of cases have a detectable clonal IGH, IGK or TR rearrangement <ref name=":0">{{Cite journal|date=2010-10-28|title=Appendix II: World Health Organization Classification of Tumours of the Haematopoietic and Lymphoid Tissues|url=http://dx.doi.org/10.1002/9781444323160.app2|journal=Postgraduate Haematology|pages=986–988|doi=10.1002/9781444323160.app2}}</ref>. |
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| |}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | | |}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. |
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| <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> | | <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> |
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| 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" />. |
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| <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>. | | <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]] | | [[Category:HAEM5]] |
| | [[Category:DISEASE]] |
| | [[Category:Diseases L]] |
