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Diffuse Aggressive B-Cell Lymphomas

■ Introduction This chapter covers diffuse aggressive B-cell lymphomas in immunocompetent patients. In the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms concepts regarding diffuse and aggressive B-cell lymphomas have been further revised to reflect the current understanding of these diseases. Box 8.1 shows the current entities considered under this topic, most of which will be covered in this chapter. The immunodeficiency-related…

Small B-Cell Lymphomas

▪ Introduction This chapter covers the lymphomas of small B lymphocytes: small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT), splenic marginal zone lymphoma (SMZL), nodal marginal zone lymphoma (NMZL), and LPL. Though morphologically somewhat similar to one another, these tumors are characterized by wide differences in clinical presentation, phenotype, genetic features, and…

Benign Causes of Bone Marrow Abnormalities Including Infections, Storage Diseases, Systemic Disorders, and Stromal Changes

▪ Introduction A wide variety of benign conditions can be encountered in the bone marrow, and their clinical and morphologic findings are quite broad. A bone marrow biopsy may provide diagnostic answers to hematologic or systemic problems that have not been diagnosed previously. Often the differential diagnosis of these conditions includes both primary hematopoietic and non-hematopoietic malignancies. This chapter gives the reader an overview of this…

Bone Marrow Failure Syndromes

■ Introduction Bone marrow failure syndromes, defined as peripheral cytopenias due to decreased hematopoiesis in the bone marrow, may be divided into acquired and inherited conditions and further divided into disorders that alter only one hematopoietic lineage (erythroids, myeloids, or platelets) and those that involve all three lineages. This chapter contains detailed discussion of the two major entities leading to acquired pancytopenia (aplastic anemia and paroxysmal…

Reactive Lymph Nodes and Castleman Disease

■ Normal Lymph Node Anatomy Normal lymph nodes are typically bean shaped. They have, beginning at their periphery and moving centrally, a fibrous capsule, a cortex, a paracortex, a medulla, and a hilus. The cortex, a B-cell–predominant area, contains follicles. When inactive, follicles are composed of a uniform population of small lymphoid cells (primary follicles). Hyperplastic follicles have a germinal center surrounded by a mantle of…

Non-Neoplastic Morphologic Abnormalities of White Blood Cells and Macrophages

■ Introduction A variety of morphologic changes can occur in non-neoplastic white blood cells (WBCs). Some reflect nonspecific reactive changes, whereas others are specific and are associated with clinically significant disorders. In this chapter we review non-neoplastic changes representing a spectrum of morphologic abnormalities of leukocytes and macrophages seen in congenital or acquired disorders. The standard organization seen in other chapters will not be followed here,…

Hemostasis and Thrombosis

Basic Physiology of Hemostasis and Fibrinolysis Physiologic hemostasis is initiated with injury to a blood vessel wall. This triggers a sequence of reactions involving plasma proteins, platelets, extracellular membrane components, and the vascular smooth muscle to ultimately form a stable fibrin plug blocking the defect. Simultaneously, inhibitors of hemostasis and the fibrinolytic system are initiated to limit the size of the clot and ultimately clear it…

Red Blood Cell/Hemoglobin Disorders

■ Introduction The disorders of red blood cells can be divided into those of decreased red blood cell (RBC) mass (anemias) and those of increased RBC mass (erythrocytoses). Most of this chapter is devoted to various types of anemias, with only a short discussion of erythrocytosis. From the pathophysiologic standpoint, anemias can be divided into three categories ( Box 1.1 ): anemias of blood loss, anemias…

Diagnosis of Lymphoma in Extranodal Sites Other Than Skin

The spectrum of lymphomas encountered in extranodal sites differ from those encountered in lymph nodes ( Tables 61-1 and 61-2 ). Many of the lymphomas that involve extranodal sites are described as specific pathologic entities in other chapters. This chapter emphasizes the types of lymphomas encountered in extranodal sites and the site-specific differences in their clinical and pathologic features. Table 61-1 Extranodal Sites Involved by Lymphoma…

Spleen: Normal Architecture and Neoplastic and Non-neoplastic Lesions

Few hematologic malignancies arise primarily in the spleen; most conditions occurring at this site represent secondary involvement by diseases originating elsewhere in the body. The role of the pathologist in most cases is to confirm the known or suspected diagnosis and to exclude unsuspected pathology. Careful gross evaluation of the organ and optimal tissue fixation are essential for the successful interpretation of splenic pathology. Because of…

Non-lymphoid Lesions of the Lymph Nodes

Non-lymphoid elements are frequently present in surgically excised lymph nodes. This chapter reviews the most commonly encountered tumors and non-neoplastic lesions, especially those that can mimic lymphoma, and provides an update on studies useful in distinguishing them. The chapter begins with lymph node metastases because they can present the most diagnostic difficulty and also describes the range of non-neoplastic inclusions included in the differential diagnosis of…

Non-hematopoietic Neoplasms of the Bone Marrow

Definition The bone marrow, the primary site of hematopoiesis, may contain hematopoietic or non-hematopoietic tumors and also frequently reflects metabolic disturbances. The occurrence of bone marrow metastases is strongly influenced by microenvironmental factors that favor the engraftment of certain malignancies. Bone marrow involvement by metastatic tumor is often referred to as myelopthisis and presents in the blood, usually subtly, as microangiopathic leukoerythroblastic anemia ( Fig. 58-1…

Evaluation of the Bone Marrow After Therapy

General Approach A great number of changes occur in the bone marrow during and after therapy for malignancy. Although proper interpretation of these changes requires knowledge of the patient's original disease process, some general features are common to all cases. It may be assumed that the purpose of bone marrow studies performed during or after therapy is to evaluate disease involvement; however, other important information can…

Bone Marrow Evaluation for Lymphoma

Bone marrow examination is an important part of the workup of patients with lymphoma. It is often performed for staging purposes as well as for follow-up to evaluate for response to therapy or recurrence. In some patients, a diagnosis of lymphoma is initially made on a bone marrow biopsy obtained for evaluation of unexplained cytopenias, fevers of unknown origin, unexplained organomegaly, or mass lesions difficult to…

Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders

Definition Lymphoproliferative disorders (LPDs) associated with iatrogenic immunodeficiency constitute a spectrum of lymphoid or plasmacytic proliferations, including a major subset that occurs after solid organ, stem cell, or bone marrow trans­plantation (post-transplant lymphoproliferative disorders [PTLDs]). A smaller number of cases occur in other situations, such as in patients with rheumatoid arthritis treated with methotrexate or in young patients with Crohn's disease treated with tumor necrosis factor-α…

The Pathology of Primary Immunodeficiencies

Human primary immunodeficiencies (PIDs) are inborn errors of the immune system and comprise over 260 different genetic disorders. PIDs often result in predisposition to infection and tend to present early in life, with high morbidity and high mortality if left untreated. In recent years, it has become apparent that PIDs are no longer restricted to the risk for developing infections, but increasingly they are associated with…

Histiocytic and Dendritic Cell Neoplasms Including Langerhans Cell Histiocytosis and Langerhans Cell Sarcoma

The Histiocytes This chapter reviews aspects of Langerhans cell histiocytosis as a prototypical representative of the condition, and this is followed by consideration of the histiocytic and dendritic cell sarcomas and disseminated juvenile xanthogranuloma. Advances in these conditions since the previous edition are emphasized and the differential diagnostic points are highlighted. The nomenclature of the histiocytes is in a state of flux, and phenotypic distinctions between…

Non-neoplastic Histiocytic Proliferations of Lymph Nodes and Bone Marrow

The histiocytoses are a group of disorders characterized by the proliferation of macrophages and dendritic cells. The contemporary classification of histiocytic disorders (a classification proposed by the Reclassification Working Group of the Histiocyte Society and the World Health Organization Committee on Histiocytic/Reticulum Cell Proliferations) divides them into three groups: dendritic cell–related disorders, macrophage-related disorders, and malignant disorders. In 2008, the World Health Organization classified neoplasms of…

Blastic Plasmacytoid Dendritic Cell Neoplasm

Definition Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignant neoplasm characterized by the clonal proliferation of immature plasmacytoid dendritic cells (PDCs), also known as professional type I interferon-producing cells, or their precursors. Previously known under different names reflecting the uncertainty of its histogenesis (e.g., agranular CD4 + natural killer [NK] cell leukemia, blastic NK cell leukemia/lymphoma, agranular CD4 + CD56 + hematodermic neoplasm…

Eosinophilia and Chronic Eosinophilic Leukemia, Including Myeloid/Lymphoid Neoplasms with Eosinophilia and Rearrangement of PDGFRA, PDGFRB, FGFR1 , or JAK2

Eosinophilia is an increase in the number of circulating eosinophils accompanied by an increase of eosinophils and precursors in the bone marrow and often in other tissues as well. The upper limit of normal for the eosinophil count, if subjects with trivial allergic conditions are excluded, is about 0.46 × 10 9 /L; however, 0.5 × 10 9 /L is a practical working limit. The eosinophilia…