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Virally Associated B-Cell Lymphoproliferative Disease

The spectrum of virally associated B-cell lymphoproliferative diseases is broad, ranging from reactive lymphadenitis to lymphomas. Often the reactive processes can be diagnostically challenging and mimic lymphomas due to a combination of direct viral effects and indirect ones mediated by the immune system. In this chapter, we focus on gamma herpesviruses, namely Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), also designated as human herpesvirus 4…

Classical Hodgkin’s Lymphoma and Related Lesions

Definition Classical Hodgkin's lymphoma (CHL) is a clonal, malignant lymphoproliferation originating from germinal-center B cells. In contrast to most other lymphomas, the malignant cells usually represent only a small minority (0.1% to 2%) of the total cellular population of involved tissues. A histopathologic diagnosis of CHL is based on the identification of diagnostic Reed-Sternberg (RS) cells in an appropriate inflammatory background. Although many cases of CHL…

Nodular Lymphocyte–Predominant Hodgkin’s Lymphoma

Definition The World Health Organization (WHO) recognizes nodular lymphocyte–predominant Hodgkin's lymphoma (NLPHL) as a separate entity distinct from classical Hodgkin's lymphoma (CHL) in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. This reflects the fact that there are clear and consistent histologic, epidemiologic, immunologic, and genetic differences between NLPHL and CHL. NLPHL is an indolent germinal-center (GC) B-cell malignancy, representing a nodular proliferation comprising…

Plasma Cell Neoplasms

Plasma Cell Neoplasms Definition The plasma cell neoplasms and related disorders are clonal proliferations of immunoglobulin (Ig)-producing plasma cells or lymphocytes that make and secrete a single class of Ig or a polypeptide subunit of a single Ig that is usually detectable as a monoclonal protein (M-protein) on serum or urine protein electrophoresis. These immunosecretory disorders may consist exclusively of plasma cells (plasma cell neoplasm) or…

Plasmablastic Neoplasms Other Than Plasma Cell Myeloma

This chapter reviews two aggressive large B-cell lymphomas composed of large cells with a predominant immunoblastic or plasmablastic morphology and the immunophenotype of plasma cells. Despite sharing these morphologic and immunophenotypical features, one of them, plasmablastic lymphoma (PBL), occurs in patients with different types of immunodeficiency or advanced age, and most of them are related to Epstein-Barr virus (EBV). However, the second type occurs in immunocompetent…

Burkitt’s Lymphoma and Its Mimics

Burkitt's Lymphoma Denis Burkitt is credited with the pioneering work that led in 1958 to the first description of the clinical features of this unique tumor, the delineation of its geographic distribution, and the introduction of novel treatment protocols with chemotherapy. The eponym Burkitt's lymphoma (BL) appropriately recognizes his enormous contributions. The initial descriptions of BL were of rapidly growing tumors in the jaws of children…

Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma. In contrast to indolent (low-grade) lymphoma, the survival curve typically shows an initial downward slope followed by a plateau, indicating the potential curability of a significant proportion of patients who achieve remission ( Fig. 23-1 ). Open full size image Figure 23-1 Idealized survival curve of diffuse large B-cell lymphoma. An initial downward slope is followed by…

Mantle Cell Lymphoma

Definition In the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, the World Health Organization defines mantle cell lymphoma (MCL) as a mature B-cell neoplasm generally composed of monomorphic small to medium-sized lymphoid cells with irregular nuclei that carries 11q13 translocations, leading to overexpression of cyclin D1. Neoplastic transformed cells (centroblasts), paraimmunoblasts, and pseudofollicles are absent. MCL includes the previously recognized centrocytic lymphoma in the…

Nodal Marginal Zone Lymphoma

Definition Nodal marginal zone lymphoma (NMZL) is a primary nodal B-cell neoplasm derived from post–germinal center B cells. This lymphoma shares morphologic and immunophenotypic similarities with other marginal zone lymphomas, particularly extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) type and splenic marginal zone lymphoma (SMZL). Thus, secondary lymph node involvement by EMZL and SMZL should be excluded to establish the diagnosis with certainty.…

Primary Cutaneous B-Cell Lymphomas

Primary cutaneous B-cell lymphomas (CBCLs) are a heterogeneous group of B-cell lymphomas that present in the skin without evidence of extracutaneous disease at the time of diagnosis. CBCLs are much less common than primary cutaneous T-cell lymphomas (CTCLs). In Western countries, CBCLs constitute approximately 20% to 25% of all primary cutaneous lymphomas, and their overall annual incidence rate is estimated at 3.1 cases per 1 million…

Extranodal Marginal Zone Lymphoma: MALT Lymphoma

In classifying non-Hodgkin's lymphomas, considerable attention has been paid to architectural, cytologic, and functional similarities among the various lymphomas and normal lymphoid tissue, exemplified by the peripheral lymph node. However, studies of extranodal lymphomas, particularly gastrointestinal lymphomas (accounting for the majority), suggest that their clinicopathologic features are related not to lymph nodes but to the structure and function of mucosa-associated lymphoid tissue (MALT). The anatomic distribution…

Follicular Lymphoma

Definition Follicular lymphoma (FL) is defined in fourth edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues as a neoplasm composed of follicle center (germinal center) B cells (typically both centrocytes and centroblasts) that usually has at least a partially follicular pattern. If diffuse areas of any size composed predominantly or entirely of blastic cells are present in any case of FL, a…

Splenic Marginal-Zone Lymphoma and Other Small B-Cell Neoplasms in the Spleen

Definition The term splenic marginal-zone lymphoma (SMZL) was coined by Schmid and colleagues in 1992 for a B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal-zone differentiation as a characteristic finding. SMZL is defined in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues as a B-cell neoplasm comprising small lymphocytes…

Hairy Cell Leukemia

Definition of Disease and Nomenclature Hairy cell leukemia (HCL) is a mature B-cell neoplasm that involves primarily the blood, bone marrow, and splenic red pulp. The neoplastic lymphocytes have surface “hairy” projections and express the B-cell–associated antigens CD19, CD20, and CD22; characteristically, they are also positive for CD103, CD25, CD11c, CD123, and annexin A1. The vast majority of HCL cases have a recurrent activating point mutation…

Lymphoplasmacytic Lymphoma and Waldenström Macroglobulinemia

Definition of Disease Lymphoplasmacytic lymphoma (LPL) is defined in the WHO Classification of Tumours of Haematopoetic and Lymphoid Tissues, fourth edition, as a small B-cell neoplasm composed of lymphocytes, plasma cells, and plasmacytoid lymphocytes, which does not meet criteria for any of the other small B-cell lymphomas that may also exhibit plasmacytic differentiation. It typically involves bone marrow, but peripheral blood, lymph nodes, and spleen may…

B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Monoclonal B-Cell Lymphocytosis, and B-Cell Prolymphocytic Leukemia

B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (B-CLL/SLL) Definition of Disease B-cell chronic lymphocytic leukemia (B-CLL) is a clonal disorder of mature B lymphocytes, which are characterized by small, round nuclei; highly condensed chromatin; inconspicuous nucleoli; scant cytoplasm; and unique immunophenotype. Admixed are occasional large prolymphocytes with prominent nucleoli, which usually account for less than 10% of leukemic cells in a typical CLL. CLL is heterogeneous and…

Principles of Classification of Lymphoid Neoplasms

Historical Background The classification of lymphoid neoplasms used in this text is the one published by the World Health Organization (WHO) in WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues . Initially published in 2008, the WHO's fourth edition was recently revised and updated. The fourth edition built on the success of the third edition (2001), defining new entities and proposing solutions for problematic categories.…

Bone Marrow Findings in Inflammatory, Infectious, and Metabolic Disorders

This chapter addresses the peripheral blood and bone marrow response to a variety of non-malignant conditions. A bone marrow examination may be performed to evaluate a fever of unknown origin, looking for a specific infectious cause. In inflammatory or metabolic disorders, the bone marrow findings may be consistent with the underlying disease, suggestive of a complication of the disease, or related to treatment. Reactive leukocytic proliferations…

Evaluation of Anemia, Leukopenia, and Thrombocytopenia

Quantitative and qualitative abnormalities of the peripheral blood are routinely detected with an automated complete blood count (CBC) and examination of a peripheral blood smear. The peripheral blood evaluation serves as a screening test for potential bone marrow abnormalities and diseases that affect bone marrow function. When peripheral blood abnormalities are identified, the decision to further assess hematopoiesis by performing an invasive bone marrow procedure is…

Normal Bone Marrow

Although hematopoietic stem cells circulate in small numbers, hematopoiesis, in steady-state conditions in adult life, is largely confined to the bone marrow. All lymphopoietic and hematopoietic cells are ultimately derived from pluripotent hematopoietic stem cells—slowly cycling cells with a capacity for self-renewal. Pluripotent stem cells give rise to common lymphoid stem cells and multipotent myeloid stem cells. The multipotent myeloid stem cells give rise to lineage-committed…