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Hemoglobinopathy

Key points Normal adult hemoglobins include hemoglobins A (97%), A 2 ( 2%–3%), and F (<1%). Trace quantities of nonfunctional hemoglobins (methemoglobin, carboxyhemoglobin, sulfhemoglobin, and nitrosohemoglobin) are present in normal blood. Specific inherited point mutations of the beta-globin gene lead to abnormal unstable hemoglobin and resultant hemolytic anemia (e.g., hemoglobins S, C, and E). The hemolysis seen with hemoglobins S and C is caused by intraerythrocytic…

Iron, heme, and hemoglobin

Key points Dietary iron is absorbed by duodenal enterocytes, transported in the blood bound to the iron carrier protein transferrin, and released to transferrin receptor-bearing hepatocytes and macrophages. Hereditary hemochromatosis is an iron-overload condition often caused by high iron (Fe) protein (HFE) mutations that lead to excess iron absorption by the duodenum. Heme synthesis in erythroid precursors occurs in mitochondria by incorporation of ferrous iron into…

Erythropoiesis and oxygen transport

Key points Red blood cell (RBCs) production is stimulated by erythropoietin (EPO), a secreted glycoprotein produced by renal peritubular cells in response to hypoxia. EPO binds to EPO receptor-bearing erythroid colony-forming unit cells in the marrow, inducing proliferation, maturation, and inhibition of apoptosis. EPO deficiency in renal disease is associated with a hypoproliferative anemia. EPO excess in patients with chronic hypoxia is associated with polycythemia. After…

Hematopoiesis

Key points Hematopoiesis begins in the embryonal yolk sac and aorto-gonado-mesonephros (AGM), migrates to the fetal liver and spleen, and then moves to the bone marrow by birth. The nonhematopoietic marrow stroma provides a microenvironment conducive to growth and differentiation of hematopoietic cells. Hematopoietic marrow stem cells are small undifferentiated cells capable of both self-renewal and pluripotential differentiation. Growth and differentiating signals to hematopoietic cells are…

Mycosis Fungoides

Key Points Incidence The age-adjusted incidence of mycosis fungoides (MF) is approximately 6.4 cases per million. Three thousand cases per year are diagnosed in the United States, representing 72% of cutaneous T-cell lymphomas. Biologic Characteristics Mycosis fungoides is a chronic malignant disease of the skin involving skin-homing CD4+ T cells. The classical immunophenotype is CD2 + CD3 + CD4 + CD5 + CD45RO + CLA +…

Multiple Myeloma and Other Plasma Cell Neoplasms

Key Points Incidence and Epidemiology More than 32,100 new cases of multiple myeloma (MM) are diagnosed annually in the United States. MM accounts for 1.8% of all new cancers and 2.1% of cancer-related deaths. The rate in blacks is twice that in whites. Agricultural workers, woodworkers, and paper mill workers have a higher risk than other occupational groups. Etiology and Biological Characteristics The etiology of MM…

Non-Hodgkin Lymphoma

Key Points Epidemiology and Incidence There were an estimated 74,680 new cases of lymphoma and 19,910 deaths in the United States in 2018. The incidence is increasing in many countries, including the United States. The most common types are diffuse large B-cell (~30%) and follicular lymphoma (~25%). The etiology is uncertain, but immunosuppression and infectious agents contribute—including Epstein-Barr virus (EBV), human T-lymphotrophic virus-1 (HTLV-1), and Helicobacter…

Hodgkin Lymphoma

Key Points Incidence There are approximately 8500 new cases of Hodgkin lymphoma in the United States each year. Biological Characteristics Hodgkin/Reed-Sternberg (HRS) cells are the malignant cells in Hodgkin lymphoma. Increasing epidemiological and molecular evidence supports that a combination of genetic susceptibility, immune response impairment and exposure to specific infectious agents may play a central role in the pathogenesis of the disease. Pathology Classical Hodgkin lymphoma…

Overview

Basic Issues in Lymphoma Significant progress has been made in recent years in the understanding of the molecular basis of lymphomagenesis, and in the diagnosis, staging, treatment, and follow-up of patients with lymphoid malignancies. The current pathological classification incorporates molecular characteristics in addition to morphological and clinical features in identifying distinctive subtypes of disease entities. Modern genome-wide molecular analysis has helped characterize pathways that play key…

Rare Pediatric Tumors

Key Points Incidence (1) Hepatic tumors: 1.6 per million; male predominance. (2) Juvenile nasopharyngeal angiofibroma: 0.05% of head and neck tumors. (3) Pleuropulmonary blastoma: Extremely rare. (4) Hemangioma/lymphangioma: Hemangiomas: 1% of infants; lymphangiomas: 0.01% of infants. (5) Desmoplastic small round cell tumor: Extremely rare; primarily affects young males. (6) Langerhans cell histiocytosis: 1 to 5 per million; slight male predominance. (7) Nasopharyngeal cancer: 1% of pediatric…

Pediatric Hodgkin Lymphoma

Key Points Epidemiology and Biological Characteristics Relative to adult Hodgkin lymphoma, pediatric Hodgkin lymphoma has (1) Distinct features in relation to geographic distribution, gender, association with Epstein-Barr virus (EBV), and histological subtype; (2) Relatively higher incidence in developing countries and in males; (3) Nodular lymphocyte-predominant and mixed cellularity subtypes are more frequent. Staging Evaluation (1) All patients should have a history and physical examination; complete blood…

Pediatric Leukemia and Lymphoma

Key Points Epidemiology Acute leukemias (acute lymphoblastic leukemia [ALL] and acute myeloid leukemia [AML]) and lymphomas (Hodgkin and non-Hodgkin lymphoma [NHL]) together represent approximately 40% of malignancies in children. Annual incidence of new cases in the United States in children less than 15 years: ALL 2500-3500; AML ~500; NHL ~500. Biology, Classification, and Staging ALL is classified by: Immunophenotype: B-cell progenitor, T-cell progenitor, non-B, non-T; Morphology,…

Neuroblastoma

Key Points Epidemiology Neuroblastoma comprises 8% to 10% of childhood cancers, with 650 cases reported annually in the United States. It is the most common extracranial solid tumor in children and the most common malignancy in infants. The tumor primarily occurs in neural crest-derived tissues, and the adrenal gland is its most common location. Early Detection Screening has not impacted on survival or detection of high-risk…

Retinoblastoma

Key Points Incidence Retinoblastoma accounts for 2.5% to 4% of all pediatric malignancies. Its incidence is two to five cases per million children per year amounting to approximately 300 new cases per year in the United States. Biologic Characteristics Retinoblastoma presents in two distinct clinical/genetic forms: (1) a bilateral or multifocal form in 25% of children, characterized by the presence of germline mutations of the RB1…

Wilms Tumor

Key Points Incidence Renal tumors are the fifth most common cancer in children younger than 15 years of age. It is estimated that 7.1 per million children are affected, and 500 new cases are reported each year in the United States. The median age at presentation is 3.5 years. Histology of Pediatric Renal Tumors Favorable histology Wilms tumor: 80% to 85%. Anaplastic Wilms tumor: 5% to…

Pediatric Sarcomas of Bone

Key Points Incidence The pediatric sarcomas of bone are osteosarcoma (5.6 cases per million children per year) and Ewing sarcoma (2.8 cases per million children per year). Biologic Characteristics Osteosarcoma is associated with inactivation of the retinoblastoma gene. Ewing sarcoma is characterized by a reciprocal translocation involving breakpoints on the EWSR1 gene on chromosome 22q12A. The most common chromosomal translocation, t11:22 (q24;q12), is present in 85%…

Pediatric Soft-Tissue Sarcomas

Key Points Incidence Annually, there are 350 cases of pediatric rhabdomyosarcoma (RMS) in the United States. Of those, embryonal rhabdomyosarcoma (ERMS) comprises 75% (260 cases), and alveolar rhabdomyosarcoma (ARMS) comprises 25% (90 cases). Annually, there are 500 cases of pediatric non-rhabdomyosarcoma soft-tissue sarcoma (NR-STS) in the United States. These are divided into high-grade (Pediatric Oncology Group [POG] grade III), 67% (335 cases), and low and intermediate…

Central Nervous System Tumors in Children

Key Points Incidence and Overall Survival The overall incidence of childhood brain tumors is 5.67 per 100,000 person-years for children. Brain tumors are the second-most common childhood malignancy and the most common primary solid tumor. Pediatric brain tumors are a diverse group of tumors and outcomes are dependent on histologic subtype and treatment. Approximately 75% of children diagnosed with pediatric brain will experience long-term disease-free survival…