Langerhans Cell Sarcoma
editPREVIOUS EDITIONThis page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition Table of Contents.
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
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)
No recurrent chromosomal rearrangements have been identified.
Characteristic Chromosomal Patterns
Put your text here
| 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.
| 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[3]
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| BRAF and MAP2K1; Activating mutations | MAPK signaling | Increased cell growth and proliferation |
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
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