A neoplasm of monomorphous B-cells resembling centrocytes. They are thought to be pre-germinal centre B lymphocytes that home to primary lymphoid follicles and to the mantel zones of secondary follicles. Neoplastic follicles are lacking.
Histopathology
The architecture may be diffuse or nodular, with or without residual germinal centres, or in a mantle zone growth pattern. Follicular dendritic cells may be present in loose or tight aggregates. The neoplastic cells are small to medium sized with irregular nuclei, fine chromatin, small inconspicuous nucleoli and pale indistinct scant cytoplasm, resembling centrocytes. Blastic cells (cells resemble centroblasts, immunoblasts or paraimmunoblasts) are rare or absent. However, at relapse, some cases show enlarged nuclei as seen in the "blastoid variant" of MCL. Hyalinised vessels are common. Scattered epithelioid histiocytes may give a "starry sky" appearance. Non-neoplastic plasma cells may be present.
Variant
Predominance of small round cells, mimicking small lymphocytic lymphoma. Prominent foci of cells with abundant pale cytoplasm may resemble proliferation centres.
Mantle cell lymphoma with a follicular growth pattern. Mantle cell lymphoma is typically diffuse or vaguely nodular. However, there may rarely be colonisation and preservation of non-neoplastic follicles, giving an architecture which closely resembles follicular lymphoma. As a result, there may be surviving admixed follicle centre cells, including centroblasts.
Blastoid mantle cell lymphoma; arise de novo or by transformation15; may show cytogenetic abnormalities of p16 and p18
classical8; there is a close resemblance of lymphoblastic lymphoma with dispersed chromatin and a high mitotic rate (>10/10 HPF, usually at least 20-30/10HPF). However, the CD5 positivity / TdT negativity of mantle cell lymphoma is retained. (Many lymphoblastic lymphomas are distinguished by being of T cell immunophenotype.) The proliferation index using Ki67 or MIB-1 is somewhat lower (~50%) than that in lymphoblastic lymphoma (~90%). Many cases show Cyclin D1 gene rearrangement13, overexpression of p53 and show multiple chromosomal imbalances or are tetraploid4,5,13. Blastoid transformation is associated with a worse prognosis4.
pleomorphic8; cells have large cleaved to oval nuclei, usually with prominent nucleoli, and pale cytoplasm Giemsa (or MGP) stain. May be tetraploid. This variant may give rise to a leukaemic component resembling prolymphocytic leukaemia11 ("prolymphocytoid variant"). The presence of the t(11;14) translocation is useful in differentiating these cases from true prolymphocytic leukaemia17.
With clonal plasma cell differentiation: the plasma cells within the nodules or mantle zones show light chain restriction and harbour the t(11;14)(q13;q32) translocation; they are negative for cyclin D116.
There are variants resembling:
marginal zone9 / monocytoid B-cell lymphoma There are prominent foci of cells with abundant pale cytoplasm.
plasma cell type of Castleman's disease8.
Cyclin D1 negative patients have significantly better prognosis, suggesting that these patients probably have other low-grade lymphomas resembling mantle cell lymphoma3.
Immunohistochemistry
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negative15 |
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positive |
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positive15 |
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positive15 |
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positive15 |
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negative15 or weakly positive |
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negative |
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positive15 |
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70% to 100% of cases1,2, 16/1815 |
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negative: rare aberrant expression may occur14 |
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FMC7 |
positive |
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SIgM and SIgD |
positive |
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a4b7 homing receptor |
positive in gastrointestinal cases |
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14/1615 |
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CD21 and CD35 demonstrate loose meshworks of FDCs.
Cytogenetics
t(11;14)(q13;q32) in 95% of cases by FISH, although it may not be apparent by standard cytogenetics. This translocation juxtaposes the immunoglobulin heavy chain and the Cyclin D1 gene, resulting in overexpression of cyclin D1, overcoming the suppressor effects of pRB and KIP1 in the regulation of the cell cycle12. Cyclin D3 is downregulated12.
Blastoid variants also show tetraploidy, CCND1 amplification, p53 mutation and p16 deletions.
Differential diagnosis
follicular colonisation needs to be distinguished from progressive transformation of germinal centres10.
Prognosis
Mantle cell lymphoma has the worst 5-year survival (11%) among all lymphoma types2 and a median survival of only 3 to 4 years3. A more aggressive course is associated with:
increased mitotic activity
blastoid morphology4,6,15
peripheral blood involvement6,17
karyotypic complexity
trisomy 12
17p loss and associated p53 inactivation12 / overexpression4
9p loss associated with p16 gene laterations15.
INK4a inactivation occurs in approximately 50% of mantle cell lymphomas and is associated with greater cellular proliferation12.
CD5 negative cases may be more indolent
Transformation to typical large cell lymphoma does not occur.
References
World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.
Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas Current Diagnostic Pathology 2000;6:55-63.
10 Jones D. Dismantling the germinal center: comparing the processes of transformation, regression and fragmentation of the lymphoid follicle. Advances in Anatomic Pathology 2002;9:129-138.
This page last revised 17.11.2006.
©SMUHT/PW Bishop