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Chapter 81 Mantle Cell Lymphoma 1307

Pathogenesis • Staging procedure includes a bone marrow biopsy and CT or
• Mantle cell lymphoma (MCL) is characterized by alterations in PET-CT of chest, abdomen, and pelvis; however, lumbar puncture
proliferative, antiapoptotic and prosurvival pathways. is not routinely performed. Although endoscopies of upper and
• The vast majority of MCL have the reciprocal translocation, t(11;14) lower gastrointestinal tracts are frequently positive, such evaluation
(q13,q23), which juxtaposes the CCND1 gene to the immunoglobin may not change management.
heavy-chain locus. TP53 and ATM genes are other commonly Therapy and Prognosis
mutated genes.
• Aggressive cases, particularly the blastoid variant, have an • MCL combines the worst features of both indolent lymphoma
increased number of chromosomal abnormalities and complex (noncurability) and aggressive lymphoma (aggressive course).
karyotype. • Therapeutic strategy is not standardized and may include wait-and-
• Dysregulation of the B cell receptor has also been implicated in the watch strategy in select asymptomatic patients, rituximab-based
pathogenesis of MCL. immunochemotherapy (BR or R-CHOP) in older patients, and
intensified chemotherapy such as R-Hyper-CVAD followed by
Diagnosis upfront high-dose chemotherapy and autologous hematopoietic
• The majority of patients present at an advanced stage (III or stem cell transplant in young fit patients.
IV) with lymphadenopathy, hepatomegaly, splenomegaly, and • Recent studies have demonstrated improved response rate and less
involvement of bone marrow and extranodal sites, especially the toxicity with BR, as compared with R-CHOP.
gastrointestinal tract. • Ibrutinib has emerged as an excellent option for the management
• Morphologic findings include monomorphic proliferation of small of relapsed or refractory MCL. Other salvage therapy includes
to medium-sized lymphoid cells with irregular nuclear border, bortezomib, bendamustine, lenalidomide, or temsirolimus frequently
dispersed chromatin, and inconspicuous nucleoli. combined with rituximab.
• Histologic transformation to large B-cell lymphoma does not occur; • Ki-67 level and MIPI (based on age, ECOG PS, LDH and white
however, MCL can have several morphological variants such as blood cell count) are two of the most important prognostic factors
blastoid and pleomorphic variants. in MCL.
+
−
• The characteristic immunophenotypic features (CD5 , CD10 , • Recent advances in the therapy of MCL have improved the OS at
−
+
+
CD19 , CD23 , FMC ) and the identification of t(11;14)(q13;q32) or a population level, with approximately half of the patients in the
cyclin D1 overexpression improve diagnostic accuracy. United States surviving beyond 5 years in recent years.
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