Chapter 63: Mantle Cell Lymphoma

DEFINITION

• Mantle cell lymphoma (MCL), in its classic form, is made up of a diffuse infiltrate of small- to intermediate-size cells with irregular cleaved nuclei, dense chromatin, and indistinct nucleoli.

• MCL cells display an immunophenotype similar to lymphocytes in the mantle zone of normal germinal follicles: surface immunoglobulin (sIg) M+, sIgD+, CD5+, CD20+, CD10–, CD43+, BCL2+. In contrast to chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), MCL cells typically do not express CD23. MCL cells do not express the germinal center markers CD10 and BCL6, which are present in follicular lymphoma.

• The hallmark of MCL, present in most patients, is cyclin D1 overexpression and a t(11;14)(q13;q32).

• A number of variants exist, including a leukemic nonnodal variant associated with absent SOX11 expression, a blastoid/blastic variant, and a pleomorphic variant.

EPIDEMIOLOGY

• MCL represents about 6% of all non-Hodgkin lymphomas (NHLs).

• The age-adjusted incidence is about 0.7/100,000 per year.

• The median age at diagnosis is 65 years.

PATHOPHYSIOLOGY

• MCL is characterized by cell cycle dysregulation.

• The t(11;14)(q13;q32) translocation results in overexpression of the cell cycle regulator cyclin D1, which is coded for on 11q13.

• Rare cases do not overexpress cyclin D1 and usually overexpress cyclin D2 or D3.

• Additional genetic events are required for the development of the fully transformed state. Low numbers of cells carrying the t(11;14) translocation have been found in the blood of 1% to 2% of healthy individuals without any evidence of disease.

• The ATM (ataxia-telangiectasia mutant) gene is mutated in approximately 40% of patients. ATM inactivation facilitates genomic instability in lymphoma cells through an impaired response to DNA damage.

• Additional genetic anomalies that could contribute to the disease include losses in chromosomes 1p13-p31, 2q13, 6q23-27, 8p21, 9p21, 10p14-15, 11q22-23, 13q11-13, 13q14-34, 17p13, and 22q12; gains in chromosomes 3q25, 4p12-13, 7p21-22, 8q21, 9q22, 10p11-12, 12q13, and 18q11q23; and high copy number amplifications of certain chromosomal regions.

• Expression of SOX11 is an event subsequent to the development of t(11;14) and may result in the conversion of in situ MCL neoplasia to classical MCL (Figure 63–1).

• Mutations in a number of genes are associated with blastoid transformation, including TP53.

CLINICAL FEATURES

• The typical presentation is that ...