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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…

Chronic Myeloid Leukemia

Introduction and Historical Perspective Chronic myeloid leukemia (CML), a rare condition, has had a profound impact on the development of hematology/oncology and modern medicine as a whole ( Fig. 69.1A and B ). The story started in the 1830s with Alfred Francois Donné of Paris, a remarkable innovator who pioneered the use of microscopy in medicine and was the first to describe the different types of…

Acute Lymphoblastic Leukemia in Adults

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of diseases characterized by clonal proliferation of lymphoid progenitors (lymphoblasts). Improved diagnostic tools permit accurate and prompt diagnosis and aid in evaluation of minimal residual disease (MRD). There have been significant advances in the past decade toward understanding disease pathogenesis, refinement of prognostic groups, and the development of exciting new therapies directed toward specific disease subsets. These molecular…

Clinical Manifestations and Treatment of Childhood Acute Lymphoblastic Leukemia

Serial risk-directed clinical trials have optimized the combination of chemotherapeutic agents and, along with advances in supportive care, have led to current cure rates of childhood acute lymphoblastic leukemia (ALL) exceeding 85% compared with those of less than 10% in the 1960s. However, because ALL is the most common cancer in children, relapsed ALL remains a leading cause of death from disease in this age group.…

Pathobiology of Acute Lymphoblastic Leukemia

Introduction Normal lymphoid precursors undergo somatic recombination at their immunoglobulin (Ig) or T-cell receptor (TCR) gene loci, and the successful completion of V(D)J recombination, with the resultant formation of a functional Ig or TCR, is required for the survival of lymphocyte precursors. Positive and negative selection steps ensure that only lymphocytes with Ig or TCRs that function appropriately within the context of an individual’s immune microenvironment…

Myelodysplastic Syndromes and Myeloproliferative Neoplasms in Children

Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal stem cell disorders that result in ineffective hematopoiesis and an increased risk of developing acute myeloid leukemia (AML). Whereas in MDS ineffective hematopoiesis results in progressive cytopenias, in MPN ineffective hematopoiesis leads to excessive proliferation frequently characterized by increased peripheral blood counts. MDS and MPN are rare in children, and the only malignancy…

Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematopoietic-derived malignancy thought to occur by transformation of plasmacytoid dendritic cells (pDCs) or pDC progenitors. Normal pDCs are immune cells that recognize microbes via Toll-like receptors and are the principal producers of type 1 interferons in the setting of infection. The disease was formally named BPDCN in 2008, based on recognition that the malignant cells shared features with…