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Hodgkin lymphoma

Hodgkin lymphoma (HL) is characterized by progressive enlargement of lymph nodes. It is considered unicentric in origin and has a predictable pattern of spread by extension to contiguous nodes. Etiology and epidemiology 1. Specific etiology is unknown. 2. Overall there is a slight female predominance when considering all children less than 20 years (M:F=0.9). 3. The Caucasian:African-American ratio is 1.3:1. 4. Comprises 6.4% of all childhood…

Acute myeloid leukemia

Acute myeloid leukemia (AML) is characterized by the abnormal proliferation and differentiation of myeloid precursors in the bone marrow. While the etiology of primary AML is unknown, certain predisposing factors can lead to secondary AML as discussed next. While AML is the less common of the two acute leukemias of childhood, it is responsible for most acute leukemia deaths. Incidence and epidemiology Leukemia accounts for 25–30%…

Acute lymphoblastic leukemia

Acute leukemias represent a clonal expansion and arrest at a specific stage of myeloid or lymphoid hematopoiesis. They constitute 97% of all childhood leukemias and consist of the following types: Acute lymphoblastic leukemia (ALL)—80%: of which 85% are B-cell acute lymphoblastic leukemia (B-ALL) and 15% are T-cell acute lymphoblastic leukemia (T-ALL) Acute myeloblastic leukemia (AML), also known as acute nonlymphocytic leukemia—15% Acute leukemias of ambiguous lineage—<2%…

Myelodysplastic syndromes and myeloproliferative disorders

Myelodysplastic syndromes Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by varying degrees of cytopenias secondary to ineffective and dysplastic hematopoiesis and increased propensity to evolve into acute myeloid leukemia (AML). In contrast to adult MDS patients, who usually present with a hypercellular bone marrow (BM), the majority of pediatric MDS patients present with a hypocellular BM, making them difficult to distinguish from acquired…

Lymphoproliferative disorders

Lymphoproliferative disorders (LPDs) manifest with uncontrolled hyperplasia of lymphoid tissues (lymph nodes, spleen, bone marrow, liver). They are a heterogeneous group of diseases that range from reactive polyclonal hyperplasia (immunologic disorders) to true monoclonal (malignant) diseases. Angioimmunoblastic lymphadenopathy with dysproteinemia This monoclonal disorder is now recognized as a form of peripheral T-cell lymphoma. Manifestations of this clinicopathological syndrome include: 1. generalized lymphadenopathy (80%); 2. hepatosplenomegaly (70%);…

Histiocytic disorders

Introduction Langerhans cell histiocytosis and related neoplastic histiocytoses (Erdheim–Chester disease, juvenile xanthogranuloma, and Rosai–Dorfman disease) typically arise from clonal proliferation of myeloid precursor cells driven by pathologically activated MAPK signaling, where hemophagocytic lymphohistiocytosis is a heterogeneous syndrome characterized by excessive immune activation. A revised classification proposal organizes histiocytoses according to pathogenic mechanisms and distribution as well as histology ( Table 15.1 ) and ( Table 15.2…

Vascular anomalies

Introduction When a patient with a suspected vascular anomaly is referred for consultation, it is critical to establish the correct diagnosis. The classification of vascular anomalies from the International Society for the Study of Vascular Anomalies (ISSVA) updated in 2018 distinguishes the vascular tumors from the vascular malformations and clarifies much of the confusing terminology. There are important elements in the history, physical examination, and diagnostic…

Disorders of coagulation

Hemostatic disorders Physiology of hemostasis As a result of injury to the blood vessel endothelium, three events take place concurrently: 1. vasoconstriction (vascular phase), 2. platelet plug formation (primary hemostatic mechanism—platelet phase), and 3. fibrin thrombus formation (initiation, amplification, and propagation phases). There are three integral components to hemostasis: 1. endothelial cells 2. platelets 3. plasma coagulation factors Endothelial cells secrete substances that: repel platelets [prostaglandin…

Disorders of platelets

Platelets are an important component in primary hemostasis. Defects in platelet number or function may lead to bleeding and bruising. Bleeding due to platelet disorders usually involves skin and mucous membranes, presenting as petechiae, purpura, ecchymosis, epistaxis, hematuria, menorrhagia, as well as gastrointestinal or intracranial hemorrhage (ICH). Platelet characteristics include: 1. Size: a. 1–4 μm (younger platelets are larger) b. Mean platelet volume (MPV): 8.9±1.5 fL…

Disorders of white blood cells

The most inclusive term for white blood cells (WBCs), that is, leukocytes, refers to the colorless amoeboid blood cells of the immune system involved in counteracting foreign substances and disease. Among these cells are granulocytes, a term that most accurately denotes the presence of granules in their cytoplasm, that is, neutrophils, eosinophils, basophils, and mast cells. While often used interchangeably with granulocytes, the term phagocyte refers…

Primary and secondary erythrocytosis

The term “polycythemia,” particularly as it pertains to newborns and children, should be more accurately termed erythrocytosis because it generally refers to conditions in which only erythrocytes are increased in number. It is usually a response to tissue hypoxia from any disorder causing inadequate oxygen, the presence of high-oxygen-affinity hemoglobins or increased production of erythropoietin (EPO) or other circulating erythropoietic stimulating factors, or mutations making erythroid…

Hemoglobinopathies

Sickle cell disease Pathophysiology HbS arises as a result of a point mutation (A→T) in the sixth codon of the β-globin gene on chromosome 11, which causes a single amino acid substitution (glutamic acid to valine at position 6 of the β-globin chain). HbS is more positively charged than HbA and hence has a different electrophoretic mobility. Deoxygenated HbS polymerizes, leading to cellular alterations that distort…

Extracorpuscular hemolytic anemia

The causes of extracorpuscular hemolytic anemia are listed in Table 8.1 ; they may be immune or nonimmune. Table 8.1 Causes of hemolytic anemia due to extracorpuscular defects. Immune Isoimmune Hemolytic disease of the newborn Incompatible blood transfusion Autoimmune IgG only Complement only Mixed IgG and complement Other antibody-mediated mechanisms Idiopathic Warm antibody Cold antibody Cold–warm hemolysis (Donath–Landsteiner antibody) Secondary Viral infections with EBV, CMV, hepatitis,…

General considerations of hemolytic diseases, red cell membrane, and enzyme defects

Hemolysis is a reduction in the normal red cell survival of 120 days. A general approach to diagnosing hemolytic anemia in the context of other causes of anemia is described in Chapter 3 , Classification and Diagnosis of Anemia in Children and Neonates. It may result from corpuscular abnormalities such as membrane, cytoskeleton, enzyme, or hemoglobin (Hb) defects, or from extracorpuscular abnormalities involving immune or nonimmune…

Bone marrow failure

Bone marrow failure may manifest as a single cytopenia (e.g., erythroid, myeloid, or megakaryocytic) or as pancytopenia. It may present with a hypoplastic or aplastic marrow or result from invasion of the bone marrow by neoplastic or nonneoplastic (e.g., storage cells) cells. Bone marrow failure may be congenital (mostly inherited) or acquired ( Table 6.1 ). Table 6.2 lists the inherited bone marrow failure syndromes (IBMFSs)…

Lymphadenopathy and diseases of the spleen

Lymphadenopathy Enlarged lymph nodes are commonly found in children. Lymphadenopathy might be caused by proliferation of cells intrinsic to the node, such as lymphocytes, plasma cells, monocytes, or histiocytes, or by infiltration of cells extrinsic to the node, such as neutrophils and malignant cells. In most instances lymphadenopathy represents transient, self-limited proliferative responses to local or generalized infections. Reactive hyperplasia, defined as a polyclonal proliferation of…

Nutritional anemias

Overview Nutritional anemias result from deficiencies of micronutrients that are essential for hematopoiesis and clinically defined by the presence of anemia with an inappropriately low reticulocyte count response by the marrow to the degree of anemia. Nutritional anemias are often grouped by size or mean corpuscular volume (MCV), with microcytic most commonly resulting in iron-deficiency anemia (IDA) and macrocytic or megaloblastic anemia due to either vitamin…

Classification and diagnosis of anemia in children and neonates

Classification and diagnosis Anemia is defined as a reduction in hemoglobin concentration, hematocrit, or red cell mass by more than two standard deviations below the mean for age and sex for the normal population. The normal ranges are also affected by geographic ancestry; African Americans have lower hemoglobin concentration on average (by ~0.5 g/dL) than people of European ancestry. As a result, 2.5% of the general…

Hematologic manifestations of systemic illness

A variety of systemic illnesses, including acute and chronic infections, neoplastic diseases, connective tissue disorders, and storage diseases, are associated with hematologic manifestations. The hematologic manifestations are the result of the following mechanisms: bone marrow dysfunction, anemia or erythrocytosis, thrombocytopenia or thrombocytosis, leukopenia or leukocytosis, hemolysis, immune cytopenias, alterations in hemostasis, acquired inhibitors to coagulation factors, acquired von Willebrand disease, acquired platelet dysfunction, and alterations in…

Molecular and genomic methodologies for clinicians

Over the last decade, molecular diagnostic testing in patients with hematologic and oncologic disorders has become increasingly sophisticated and prevalent. While in the past focused genetic tests were performed, in recent years the widespread use of genomic and molecular approaches in both research and clinical settings has refined diagnostics and therapeutics for pediatric blood disorders and cancer. This chapter provides an overview of the currently used…