mantle cell lymphoma

Definition: Mantle cell lymphoma (MCL) is characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in overexpression of cyclin-D1 (CCND1) in the vast majority of cases.

Images

 Mantle cell lymphoma with prominent nodular pattern

• https://twitter.com/DanBabuMD/status/759573102007234560
• https://twitter.com/KyleBradleyMD/status/855422646305124352

Localization

 nodal mantle cell lymphoma
 digestive mantle cell lymphoma

Digital cases

 HPC:286 : Nodal mantle cell lymphoma
 HPC:301 : Mantle cell lymphoma of the ocular conjunctiva
 HPC:345 : Mantle cell lymphoma (lymph node)
 HPC:353 : Mantle cell lymphoma (lymph node)

The variable morphology of mantle cell lymphoma (MCL) is assumed to reflect progression from an early form with classical cytology and mantle zone or nodular growth to a later, more aggressive variant of the disease with blastoid cytology and a diffuse growth pattern. (23240716)

In the majority of cases, the mantle zone growth pattern is lost, but it had been reacquired in a small subset of MCLs at relapse. (23240716)

Twenty-two per cent of MCLs with classical/small cell cytology acquire blastoid features during the course of the disease. (23240716)

However, 50% of MCLs with blastoid cytology at primary diagnosis recurred as a classical variant. (23240716)

Ki67

 Ki67

• The Ki67 index increases over time, and is associated with prognosis in the primary and the relapse biopsy specimens. (23240716)
• In a large cohort of MCLs, it has been showed that the Ki67 index increases over time in MCL. (23240716)
• Assessment of the Ki67 index is a useful prognostic tool if assessment is performed in the relapse situation. (23240716)

Immunophenotype

 CD20+, CD5+, CD23-, CD10-, BCL6-
 sIgM+ bright
 Pan-B + (CD20, CD19)
 Positive; BCL2, CyD1
 Usually positive: CD5+, FMC-7, CD43
 Negative: CD10-, BCL6-, CD23-
 CD10-/+
 Aberrant phenotype: CD5-, CD10+, BCL6+

Putative cell of origin: CD5+ B-cells of the follicle mantle having germline IgV gene sequences.

Differential diagnosis

 diffuse small B-cell lymphomas

• B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma CCL/SLL

Variants

 Burkitt lymphoma transformation of mantle cell lymphoma (15370262)
 Cyclin D1 and t(11;14)-mantle cell lymphoma resembling marginal zone B-cell lymphoma (17316759)
 composite splenic marginal zone lymphoma and mantle cell lymphoma (17134739)

Localization

 nodal mantle cell lymphoma

Cytogenetics

Mantle cell lymphoma (MCL) is characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in overexpression of cyclin-D1 (CCND1) in the vast majority of cases.

In addition, alterations of other cell-cycle-regulating signal pathways as CDKN2B/CDKN2A-CCND1 pathway or ARF-MDM2-TP53 pathway are frequently observed.

 translocation t(11;14)(q13;q32) with CCND1 rearrangement with cyclin-D1 overexpression (50-90%) (11q13 and 14q32)
 translocation t(1;12)(p21;q23)
 complex karyotype

• complex karyotype carries an unfavourable prognostic significance

 1p22.3 deletion (116830336)
 11q23 deletion (16382446)

Molecular biology

In addition, alterations of other cell-cycle-regulating signal pathways as CDKN2B/CDKN2A-CCND1 pathway or ARF-MDM2-TP53 pathway are frequently observed.

 epigenetic alterations and genomic deletions of CDK inhibitors (CDKIs) p16(INK4a), p15(INK4b), p14(ARF) (16258956)

 cyclin D1 overexpression by CCND1 gene secondary to the translocation t(11;14)(q13;q32) (11q13 and 14q32)

See also

 B-cell lymphomas

• lymphomas with nodular pattern / nodualr lymphomas

Reviews

 Jares P, Colomer D, Campo E. Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nat Rev Cancer. 2007 Oct;7(10):750-62. PMID: 17891190

 Kurtin PJ. Mantle cell lymphoma. Adv Anat Pathol. 1998 Nov;5(6):376-98. PMID: 10095879

References

 Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression. Vogt N, Klapper W. Histopathology. 2013 Jan;62(2):334-42. doi : 10.1111/his.12009 PMID: 23240716

 Pathway discovery in mantle cell lymphoma by integrated analysis of high resolution gene expression and copy number profiling. Hartmann EM, Campo E, Wright G, Lenz G, Salaverria I, Jares P, Xiao W, Braziel RM, Rimsza LM, Chan WC, Weisenburger DD, Delabie J, Jaffe ES, Gascoyne RD, Dave SS, Mueller-Hermelink HK, Staudt LM, Ott G, Beà S, Rosenwald A. Blood. 2010 Apr 26. PMID: 20421449

 Mansoor A, Akbari M, Auer I, Lai R. Cyclin D1 and t(11;14)-positive B-cell neoplasms resembling marginal zone B-cell lymphoma: a morphological variant of mantle cell lymphoma. Hum Pathol. 2007 Feb 19; PMID: 17316759

 Balakrishnan A, von Neuhoff N, Rudolph C, Kamphues K, Schraders M, Groenen P, van Krieken JH, Callet-Bauchu E, Schlegelberger B, Steinemann D. Quantitative microsatellite analysis to delineate the commonly deleted region 1p22.3 in mantle cell lymphomas. Genes Chromosomes Cancer. 2006 Oct;45(10):883-92. PMID: 16830336

 Hutter G, Scheubner M, Zimmermann Y, Kalla J, Katzenberger T, Hubler K, Roth S, Hiddemann W, Ott G, Dreyling M. Differential effect of epigenetic alterations and genomic deletions of CDK inhibitors [p16(INK4a), p15(INK4b), p14(ARF)] in mantle cell lymphoma. Genes Chromosomes Cancer. 2006 Feb;45(2):203-10. PMID: 16258956