Follicular Lymphoma and Mantle Cell Lymphoma

Abstract

Abstract/Scope of Chapter This chapter covers the commonly-encountered follicular lymphoma and the more aggressive but rare mantle cell lymphoma. These two B-cell lymphomas are predominantly lymph node-based but show characteristic patterns of spread to the bone marrow and gastrointestinal tract. Both lymphomas progress through recognizable histologic stages that are characterized by increasing number of large tumor cells and accumulation of cell cycle genetic defects. Follicular lymphoma however shows a more clear requirement for stromalderived cytokine signals and B-cell receptor pathway dysregulation for full transformation. Keywords IntroductionFollicular lymphoma and mantle cell lymphoma represent paradigms of the initiation-progression histogenetic model of lymphomagenesis discussed in Chap. 1. Although these tumors are defined based on their histologic and immunophenotype features, they both have characteristic initiating chromosomal translocations, t(14;18)/IGH-BCL2 and t(11;14)/CCND1-IGH, respectively. Later stages of lymphoma progression in both lymphomas involve the activation of common growth pathways and loss of tumor suppressors that largely determine the outcome. Follicular Lymphoma Incidence and Clinical FeaturesFL is the most common low-grade lymphoma, although there are marked geographic differences with a high incidence in the United States and Europe, and an extremely low incidence in parts of Asia [1,2]. The basis for these marked geographic variations is not yet known but may be related to population-based differences in genetic polymorphisms in immune regulatory genes or in the age or prevalence in which common infections are acquired. In the United States, the median age at presentation for FL is 59 years, with roughly equal incidence in males and females. Rare cases presenting in childhood are thought to represent distinct variants with low rates of progression and frequent extranodal localization.FL is almost always a systemic disease with multi-compartment lymphadenopathy. Bone marrow infiltration is detectable histologically in approximately 50% of cases, but lowlevel involvement can be detected using flow cytometric or molecular methods in 60-70%. Staging is done using the Ann Arbor classification, with risk stratification most commonly done using the FLIPI score.As disease burden increases, extranodal spread is common, with FL often colonizing sites of chronic inflammation (e.g., folliculitis in skin) or involving body fluids. Transformation to diffuse large B-cell lymphoma can occur at a discrete nodal or extranodal site, which can sometimes be detected as an occult "hotspot" in nuclear medicine studies. A variant of FL largely restricted to the small bowel has an indolent course [3,4]. Conversely, a small cell blastoid variant that often shows high-level peripheral blood and bone marrow involvement has a worse outcome than typical small cleaved (grade 1) FL [5,6]. Diagnostic Features and SubcategoriesFL has a characteristic nodular growth pattern in lymph node due to its displacem...