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Created page with "==Primary Author(s)*== Dr Malaika Perchard BSci(MedSci), MBBS, FRACP, FRCPA, (Paediatric Haematologist) Pathology Queensland __TOC__ ==Cancer Category/Type== Histiocytic a..."

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==Primary Author(s)*==

Dr Malaika Perchard BSci(MedSci), MBBS, FRACP, FRCPA, (Paediatric Haematologist) Pathology Queensland

__TOC__

==Cancer Category/Type==

Histiocytic and dendritic cell neoplasms

==Cancer Sub-Classification / Subtype==

Tumours derived from Langerhans cells

==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. LC sarcoma displays overt malignant cytological features and is more clinically aggressive. <ref name=":0">{{Cite journal|date=2016-07-21|title=Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.|url=http://dx.doi.org/10.1182/blood-2016-06-721662|journal=Blood|volume=128|issue=3|pages=462–463|doi=10.1182/blood-2016-06-721662|issn=0006-4971}}</ref>

==Synonyms / Terminology==

Langerhans cell sarcoma (LCS)

==Epidemiology / Prevalence==

Langerhans cell sarcoma<ref name=":0" />

*Extremely rare
*Essentially only seen in adults (mean age at diagnosis is 41)

*More common in females <ref>{{Cite journal|last=Nakamine|first=Hirokazu|last2=Yamakawa|first2=Mitsunori|last3=Yoshino|first3=Tadashi|last4=Fukumoto|first4=Takaya|last5=Enomoto|first5=Yasunori|last6=Matsumura|first6=Itaru|date=2016|title=Langerhans Cell Histiocytosis and Langerhans Cell Sarcoma: Current Understanding and Differential Diagnosis|url=https://www.jstage.jst.go.jp/article/jslrt/56/2/56_109/_article|journal=Journal of Clinical and Experimental Hematopathology|language=en|volume=56|issue=2|pages=109–118|doi=10.3960/jslrt.56.109|issn=1346-4280|pmc=PMC6144204|pmid=27980300}}</ref>
*In a subset of cases Merkel cell polyomavirus sequences have been identified

==Clinical Features==

Most cases are identified in adults with extra nodal and multifocal disease with skin and underlying soft tissue lesions as the most common sites of involvement. Patients can present with multiorgan involvement including lymph nodes, lung, liver, spleen and bone lesions. Grade III-IV disease is present in ~44% of patients with only 22% of cases presenting with primary nodal disease only. Hepatosplenomegaly and pancytopenia are seen in less than a quarter of patients <ref name=":0" />.

LCS is an aggressive high grade malignancy associated with progressive disease and a high (>50%) mortality rate <ref name=":0" />.
==Sites of Involvement==

Most common:<ref name=":0" />

· Extranodal

o Skin and underlying soft tissue

Less common:

· Nodal

o Lymph nodes

· Extranodal

o Lung

o Liver

o Spleen

o Bone

==Morphologic Features==

The key feature for the diagnosis is the presence of the LCH cells. Overtly malignant features of LC's include a high mitotic rate (usually >50 mitoses per 10 high powered fields), clumped chromatin and the presence of nucleoli. The LC cell morphology can be highly pleomorphic, potentially with the cellular ultrastructure or phenotype being the only indication of the LC derivation. Similar to LCH, the Birbeck granules can be detected by electron microscopy. Characteristic complex nuclear grooves may be present on histology <ref name=":0" />.
==Immunophenotype==

The immunophenotype is identical to LCH, cells consistently express CD1a, langerin (CD2017) and S100, which can be used to distinguish LCH from other histiocytic disorders and non-neoplastic macrophages<ref name=":0" />.

{| class="wikitable sortable"
|-
!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
|}

==Chromosomal Rearrangements (Gene Fusions)==

No recurrent chromosomal rearrangements have been identified.
==Characteristic Chromosomal Patterns==

Put your text here

{| class="wikitable sortable"
|-
!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)==

A ''BRAF V600E'' mutation has been detected in one case of LCS.

{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
|-
|''BRAFV600E''
|Oncogene
|Unknown
|Uknown
|Potential
|}
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.

==Genes and Main Pathways Involved==

BRAF encodes B-Raf, a cytoplasmic serine/threonine kinase and has a role in regulating the mitogen-activated protein kinase signal transduction pathway. V600E is an activating point missense mutation in codon 600 of exon 15 causing substitution of valine to glutamate. This causes independent activation of the RAS-RAF-MEK-ERK signalling pathway leading to unregulated cells growth and proliferation<ref>{{Cite journal|last=Richtig|first=G.|last2=Hoeller|first2=C.|last3=Kashofer|first3=K.|last4=Aigelsreiter|first4=A.|last5=Heinemann|first5=A.|last6=Kwong|first6=L.N.|last7=Pichler|first7=M.|last8=Richtig|first8=E.|date=2017-10|title=Beyond the BRAF V 600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients|url=https://onlinelibrary.wiley.com/doi/10.1111/bjd.15436|journal=British Journal of Dermatology|language=en|volume=177|issue=4|pages=936–944|doi=10.1111/bjd.15436}}</ref>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|BRAF and MAP2K1; Activating mutations
|MAPK signaling
|Increased cell growth and proliferation
|}
==Links==

[[Langerhans Cell Histiocytosis]]

==References==
<references />
==Notes==
<nowiki>*</nowiki>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.
<references />

HAEM4Backup:Langerhans Cell Sarcoma - Revision history

Bailey.Glen: Created page with "==Primary Author(s)*== Dr Malaika Perchard BSci(MedSci), MBBS, FRACP, FRCPA, (Paediatric Haematologist) Pathology Queensland __TOC__ ==Cancer Category/Type== Histiocytic a..."

Bailey.Glen: Created page with "==Primary Author(s)*== Dr Malaika Perchard BSci(MedSci), MBBS, FRACP, FRCPA, (Paediatric Haematologist) Pathology Queensland TOC ==Cancer Category/Type== Histiocytic a..."