Langerhans cell sarcoma
Haematolymphoid Tumours (5th ed.)
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editHAEM5 Conversion NotesThis page was converted to the new template on 2023-12-04. The original page can be found at HAEM4:Langerhans Cell Sarcoma.
Primary Author(s)*
Dr Malaika Perchard BSci(MedSci), MBBS, FRACP, FRCPA, (Paediatric Haematologist) Pathology Queensland
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. [1]
Synonyms / Terminology
Langerhans cell sarcoma (LCS)
Epidemiology / Prevalence
Langerhans cell sarcoma[1]
- Extremely rare
- Essentially only seen in adults (mean age at diagnosis is 41)
- More common in females [2]
- In a subset of cases Merkel cell polyomavirus sequences have been identified
Clinical Features
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| 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.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 [1].
LCS is an aggressive high grade malignancy associated with progressive disease and a high (>50%) mortality rate [1].
Sites of Involvement
Most common:[1]
· 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 [1].
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[1].
| 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)
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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). |
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the previous version of the page. Please incorporate above.No recurrent chromosomal rearrangements have been identified.
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
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| 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)
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 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.)
| 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.A BRAF V600E mutation has been detected in one case of LCS.
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.
Epigenomic Alterations
Put your text here
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[3]
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| BRAF and MAP2K1; Activating mutations | MAPK signaling | Increased cell growth and proliferation |
Genetic Diagnostic Testing Methods
Put your text here
Familial Forms
Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)
Additional Information
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Links
HAEM5:Langerhans cell histiocytosis
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "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". Blood. 128 (3): 462–463. 2016-07-21. doi:10.1182/blood-2016-06-721662. ISSN 0006-4971.
- ↑ Nakamine, Hirokazu; et al. (2016). "Langerhans Cell Histiocytosis and Langerhans Cell Sarcoma: Current Understanding and Differential Diagnosis". Journal of Clinical and Experimental Hematopathology. 56 (2): 109–118. doi:10.3960/jslrt.56.109. ISSN 1346-4280. PMC 6144204. PMID 27980300.CS1 maint: PMC format (link)
- ↑ Richtig, G.; et al. (2017-10). "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. Check date values in:
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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 sarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/4/2023, https://ccga.io/index.php/HAEM5:Langerhans_cell_sarcoma.