Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is an aggressive and rare type of non-Hodgkin lymphoma (NHL) that develops from malignant B lymphocytes originating in the outer edge of the lymph node follicle, known as the mantle zone. MCL comprises 5-7 % of all NHL cases with an annual incidence rate of 1 in every 200,000 individuals in the US, the large majority of whom are men aged between 60 and 70.1
There are two types of MCL with different clinical presentations:2
- Classical or nodal MCL accounts for most cases, and usually begins with lymph node enlargement before spreading to other parts of the body via the lymphatic channels or blood;
- Leukemic non-nodal MCL is typically indolent and can result in a swollen spleen and lymphoma cells in the bloodstream and bone marrow.
Formation
MCL is characterized by the production of abnormal B cells in the mantle zone, however, the exact underlying cause is unknown. Researchers have identified an acquired genetic change that is shared by 85% of patients with MCL,3 in which translocation occurs between chromosomes 11 and 14. This genetic abnormality leads to the rearrangement of the bcl-1 gene locus and the dysregulation of the gene CCND1, resulting in the overexpression of the cell growth promoting protein cyclin D1 in the lymphoma cells.4 This is believed to contribute to the excessive growth of malignant B lymphocytes in the lymph nodes, but is likely to not be the only cause. SOX-11 has also emerged as a key oncogenic transcription factor in the pathogenesis of classical MCL, where it is overexpressed in a large majority of patients, even in cyclin D1 negative cases. This transcription factor is believed to promote tumor growth of MCL cells, as well as preventing cellular maturation, and regulating signaling and transcriptional pathways.5
Diagnosis and treatment assessment
Most individuals with MCL are diagnosed after the disease has progressed to stage III or IV. An excisional biopsy of the lymph node or affected area is used to differentiate MCL from other NHLs using immunohistochemical staining of cyclin D1, SOX-11, Ki-67 index of CCND1, and other B cell markers. There are also several morphological variations that can help identify MCL, including the effacement of the lymph node or the expansion of the mantle zone.6
Figure 1. Example micrograph of a Mantle cell lymphoma.9
The MCL international prognostic index (MIPI) is used to stratify patients into low, intermediate, and high prognostic groupings with a five year survival rate of 60%, based on age, disease progression with ECOG performance status, lactase dehydrogenase, white blood cell count, and Ki-67 positivity.7 Based on these results, symptoms are either actively monitored or treated with proteosome inhibitors; younger patients may be given combination chemotherapy or an allogeneic stem cell transplantation.
Cell markers
MCL is characterized by the expression of a mature B cell phenotype with intense CD19, CD20, CD22, PAX5, and CD79a. In the majority of cases, tumor cells co-express CD5 and are positive for BCL-2, CD43, and FMC7, but negative for CD23, CD10, BCL-6, CD200, and LEF1.8
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References
- Mantle Cell Lymphoma, National Organization for Rare Disorders. (2021). Retrieved 21 October 2021, from https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/
- Swerdlow, S. H., Campo, E., et al (2016). The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 127(20): 2375–2390. https://doi.org/10.1182/blood-2016-01-643569
- Leukemia and Lymphoma Society. (2014). Mantle Cell Lymphoma Facts [pdf] (4th ed., pp. 1-9). Retrieved from https://www.lls.org/sites/default/files/file_assets/mantlecelllymphoma.pdf
- R Rimokh, F Berger,. et al (1993). Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias. Blood. 81 (11): 3063–3067. doi: https://doi.org/10.1182/blood.V81.11.3063.3063
- Beekman R, Amador V, Campo E (2018). SOX11, a key oncogenic factor in mantle cell lymphoma. Current Opinion Hematology. 25(4):299-306. doi: 10.1097/MOH.0000000000000434. PMID: 29738333.
- Lynch DT, Koya S, Acharya U. (2021). Mantle Cell Lymphoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID: 30725670.
- Hoster E, Dreyling M, et al. (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 111(2):558–65. doi: https://doi.org/10.1182/blood-2007-06-095331
- Veloza L, Ribera-Cortada I., et al. (2019) Mantle cell lymphoma pathology update in the 2016 WHO classification. Annals of Lymphoma. 3:3
- https://www.shutterstock.com/de/image-photo/pleural-fluid-cytology-showing-involvement-by-1665700435
