Pathobiology of mantle cell lymphoma
- Jennifer R Brown, MD, PhD
Jennifer R Brown, MD, PhD
- Associate Professor
- Harvard Medical School
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
Mantle cell lymphoma (MCL) is a mature B cell non-Hodgkin lymphoma (NHL) that accounts for approximately 7 percent of adult NHLs in the United States and Europe. While it is often discussed together with the indolent forms of NHL, its behavior is more often that of an aggressive lymphoma. (See "Classification of the hematopoietic neoplasms".)
MCL has been previously referred to as intermediate lymphocytic lymphoma, mantle zone lymphoma, centrocytic lymphoma, and lymphocytic lymphoma of intermediate differentiation [1,2].
The pathobiology of MCL will be reviewed here. Information regarding the epidemiology, clinical presentation, diagnosis and treatment of MCL is presented separately. (See "Clinical manifestations, pathologic features, and diagnosis of mantle cell lymphoma" and "Initial treatment of mantle cell lymphoma".)
CELL OF ORIGIN
Most mantle cell lymphoma (MCL) cases are postulated to derive from naïve pre-germinal center B cells of the mantle zone, while a subset of MCL may originate from marginal zone or peripheral blood memory B cells.
The pre-germinal center ancestry of most MCLs is principally supported by the absence of somatic mutations in the immunoglobulin heavy chain variable region (IgVH) genes, which serve as a marker of germinal center transit . However, several studies have found somatic hypermutation in approximately 20 to 30 percent of MCL cases [3-5]. IGHV3-21 and IGHV4-34 usage was significantly overrepresented in MCLs in these studies. The V3-21 expressing cases were highly associated with expression of the same light chain, IGLV3-19, suggesting that these tumor cells are stimulated by an autoantigen recognized by the Ig formed by pairing of these heavy and light chains .
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