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T-Cell Lymphomas

T-cell lymphomas are a highly heterogeneous group of diseases sharing common origin from mature T-lymphocytes. Heterogeneity is appreciated on biologic and clinical grounds, both in terms of presentation (leukemic, nodal, extranodal, and cutaneous forms) and clinical behavior (aggressive versus indolent). Historically, peripheral T-cell lymphomas (PTCL) have always been separated by cutaneous T-cell lymphomas (CTCL), mostly because the former has a nodal and aggressive presentation, while the…

Malignant Lymphomas in Childhood

Malignant lymphomas are the third most common malignancy among children and adolescents. Among children less than 15 years of age, non-Hodgkin Lymphoma (NHL) is more frequent; however, in patients up to 18 years of age, Hodgkin lymphoma (HL) is predominant. NHLs in children are usually extranodal diffuse high-grade tumors, whereas low- and intermediate-grade nodal lymphomas predominate in adults. These differences are speculated to reflect maturational changes…

Virus-Associated Lymphoma

There are five well-characterized human viruses that are generally accepted as important in lymphomagenesis ( Table 87.1 ). These viruses may infect tumor cells (or their progenitors) or may act at a distance. The genomes of Epstein-Barr virus (EBV), Kaposi sarcoma–associated herpesvirus (KSHV, also known as human herpesvirus 8 [HHV-8]), and human T-lymphotropic virus-1 (HTLV-1) are present in tumor cells. The viral genes expressed in tumor…

Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a distinct subtype of mature B-cell non-Hodgkin lymphoma (NHL) that accounts for 5% to 10% of all NHL. Although a subset of patients with MCL may have an indolent course, MCL is generally an aggressive NHL. In the 1970s, the Kiel classification used the terminology centrocytic lymphoma to describe MCL, whereas Berard and Dorfman categorized it as lymphocytic lymphoma of intermediate…

High-Grade B-Cell Lymphomas

High-grade lymphomas are aggressive hematopoietic malignancies derived predominantly from transformed B cells. Notable subtypes include diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL), and Burkitt lymphoma (BL). Although these entities share many clinical and biologic features, the approach to their management is different; therefore an accurate histologic diagnosis is of utmost importance. There have been several recent therapeutic…

Diffuse Large B-Cell Lymphoma of the Central Nervous System

Diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) accounts for an overwhelming majority (95%) of cases of primary CNS lymphoma (PCNSL). According to the 2016 report of the World Health Organization (WHO), it is defined as DLBCL arising within the brain, spinal cord, leptomeninges, or eye. The WHO definition excludes lymphomas of the dura, intravascular large B-cell lymphomas (IVLBL), secondary CNS lymphomas (SCNSLs),…

Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal)

The term marginal zone refers to a histologic compartment located at the periphery of lymphoid follicles immediately outside their mantle zone. The marginal zone is especially evident in the spleen, although identical areas have been observed in other lymphoid structures, including mesenteric lymph nodes and mucosa-associated lymphoid tissue (MALT) ( Fig. 83.1 ). Ordinarily, it is composed predominantly of B cells that are slightly larger than…

Clinical Manifestations, Staging, and Treatment of Follicular Lymphoma

Non-Hodgkin lymphoma (NHL) refers to all malignancies of the lymphoid system with the exception of Hodgkin lymphoma. Development of the lymphoid system is a highly regulated process, characterized by differential expression of a number of cell-surface and intracytoplasmic proteins and antigen receptor gene rearrangements, somatic hypermutation, and class switching. Dysregulation of this orderly process can result in humoral deficiency, autoimmunity, or malignancy. The indolent B-cell lymphomas…

Origin of Non-Hodgkin Lymphoma and Therapeutic Targets

Over the past two decades, discoveries in basic immunology and the pathogenesis of malignancies have significantly advanced our understanding of the origin of lymphoid neoplasms. These diseases have been reexamined and grouped based on recurrent chromosomal rearrangements, histologic patterns, gene expression profiles, and more recently by patterns of gene mutations, gene fusions, and epigenetic alterations. The multiple revisions to the World Health Organization’s classification schemes for…

Hodgkin Lymphoma

Hodgkin lymphoma (HL) is an uncommon lymphoproliferative malignancy arising from B cells. It can affect all age groups but is most common in young adults. HL is the first adult malignancy to demonstrate the curative potential of combination chemotherapy. Today, more than 80% of patients with newly diagnosed HL can now expect to be cured of their disease. The challenge now, particularly since many affected patients…

Origin of Hodgkin Lymphoma and Therapeutic Targets

More than 150 years ago, Thomas Hodgkin described several cases of a lymphoproliferative disease, later named Hodgkin disease. For a long time this malignancy, now called Hodgkin lymphoma (HL), has been one of the most enigmatic forms of lymphomas. This is due to several key features of the disease: First, the pathognomonic and suspected tumor cells of HL, the mononuclear Hodgkin and the bi- or multinucleated…

The Pathologic Basis for the Classification of Non-Hodgkin and Hodgkin Lymphomas

Introduction and Historical Background The classification of malignant lymphomas has undergone significant changes over the past 50 years. The current approach is based on the integration of morphologic, phenotypic, genetic, and clinical features that allows the identification of distinct disease entities (see box on Principles of the Classification of Lymphomas ). This practical approach to lymphoma categorization was initially proposed by the International Lymphoma Study Group…

Hairy Cell Leukemia

Hairy cell leukemia (HCL) is one of the diseases exemplifying the importance of the application of appropriate diagnostic techniques and the importance of treatment strategies to obtain the best treatment outcomes for the individual patient. The disease was first described by Bouroncle and colleagues in 1958. The term hairy cell leukemia was first used to describe the disorder by Schreck and Donnelly in 1966 and was…

Chronic Lymphocytic Leukemia

Over the past several years, major advances have been realized in terms of improved understanding of the pathophysiology and therapeutic options for chronic lymphocytic leukemia (CLL). The plethora of information about CLL has increased dramatically and made management of what was a relatively straightforward disease quite complex but more rewarding. This chapter provides a reference source focused on critical issues in routine clinical management of CLL.…

Mast Cells and Mastocytosis

Paul Ehrlich used his 1878 doctoral thesis to characterize a new cell type—the mast cell (MC)—based on its reactivity to aniline dyes and the metachromatic appearance of its cytoplasmic granules. He referred to MCs as Mastzellen and he speculated that their intracellular granules contained phagocytosed materials or nutrients. Ehrlich also described a close relationship in tissues between MCs and blood vessels, nerves, gland excretory ducts, as…

Eosinophilia, Eosinophilic Neoplasms, and the Hypereosinophilic Syndromes

Eosinophils are highly specialized granulocytic effector cells that produce and store numerous biologically active mediators, including cytotoxic proteins, lipid mediators, chemotactic peptides, and cytokines ( Table 74.1 ). Under various pathologic conditions, blood eosinophils transmigrate through the endothelial layer and invade various target organs, where these cells secrete their products into the surrounding tissues, thereby triggering inflammation, toxic damage, and tissue remodeling. Since their initial characterization…

Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes

Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are a group of rare myeloid malignancies that paradoxically exhibit both dysplastic and proliferative hematopoietic cell characteristics. They share phenotypic features of both MDS, such as dysplasia and cytopenias, and of MPNs, including constitutional symptoms, splenomegaly, and terminally differentiated blood cell expansion. There are four adult MDS/MPN overlap syndromes: chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN…

Primary Myelofibrosis and Chronic Neutrophilic Leukemia

Primary myelofibrosis (PMF) is a Philadelphia chromosome-negative, clonal, myeloproliferative neoplasm (MPN) that is often but not always accompanied by the driver mutations JAK2V617F , calreticulin exon 9 ( CALR ), and the thrombopoietin receptor, MPL515L/K . PMF is clinically characterized by progressive splenomegaly, cytopenias, and cytokine-driven constitutional symptoms with a propensity for leukemic transformation (20%). Pathologically, PMF is associated with megakaryocyte hyperplasia and atypia, reactive bone…

Essential Thrombocythemia

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by platelet counts in excess of 450 × 10 9 /L, profound bone marrow (BM) megakaryocyte hyperplasia, leukocytosis, splenomegaly, a clinical course punctuated by hemorrhagic and/ or thrombotic episodes, and a possible evolution to myelofibrosis (MF) and MPN blast phase (MPN-BP). ET is a clinically heterogeneous disorder, with more than half of patients meeting the criteria…

The Polycythemias

Under normal conditions, the red blood cell (RBC) mass in humans is tightly controlled and remains relatively constant in a given individual. The numbers of senescent RBCs lost daily are replaced by newly formed ones by a carefully controlled network of growth factors, progenitor and precursor cells. Erythropoiesis can be augmented by a variety of stimuli that increase the delivery of oxygen to tissues. This delicate…