The Lymphomas

The Lymphomas Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / ONCOLOGY -- Slide 1 Lymphoma Dr Rose Munge Slide 2 Introduction Lymphoma is the third most common cancer among U.S. children (≤14 yr old) Annual incidence of 15 cases per 1 million children. \nIt is the most common cancer in adolescents, accounting for 25% of newly diagnosed cancers in those 15-19 yr old.\n The 2 broad categories of lymphoma, Hodgkin lymphoma and non-Hodgkin lymphoma, have different clinical manifestations and treatments. Slide 3 Hodgkin Lymphoma Hodgkin lymphoma (HL ) is a malignant process involving the lymphoreticular system that accounts for 6% of childhood cancers. \nIn the United States, HL accounts for approximately 5% of cancers in children ≤14 yr old; it accounts for approximately 15% of cancers in adolescents (15-19 yr), making HL the most common malignancy in this age-group. Slide 4 Epidemiology The worldwide incidence of HL is approximately 2-4 new cases/100,000 population/yr.\nBimodal age distribution, with peaks at 15-35 yr of age and again after 50 yr.\nHL is the most common cancer seen in adolescents and young adults, and the 3rd most common in children <15 yr old.\nIn developing countries, the early peak tends to occur before adolescence.\nA male predominance is found among young children but lessens with age.\nInfectious agents may be involved, such as human herpesvirus 6, cytomegalovirus, and Epstein-Barr virus (EBV). Infection with EBV confers a 4-fold higher risk of developing HL and may precede the diagnosis by years Slide 5 Pathogenesis The Reed-Sternberg (RS) cell, a pathognomonic feature of HL, is a large cell (15-45 μm in diameter) with multiple or multilobulated nuclei.\nThis cell type is considered the hallmark of HL, although similar cells are seen in infectious mononucleosis, non-Hodgkin lymphoma, and other conditions. The RS cell is clonal in origin and arises from the germinal center B cells but typically has lost most B-cell gene expression and function. There is no single simple genetic aberration that leads to malignant transformation of the RS cell; rather, a combination of somatic mutations, chromosomal instability, and complex chromosomal rearrangements has been reported with no particular pattern or frequency Slide 6 This typically leads to cell regulation defects such as constitutive activation of the nuclear factor (NF)-κB pathway or abnormal regulation of the Bcl-2 family of proteins.\nHL is characterized by a variable number of RS cells surrounded by an inflammatory infiltrate of lymphocytes, macrophages, plasma cells, and eosinophils in different proportions, depending on the HL histologic subtype.\nThe interaction between the RS cell and these background inflammatory cells with their associated cytokine release is important in the development and progression of HL. Slide 7 Reactive infiltration of eosinophils and CD68+ macrophages and increased concentrations of cytokines, such as interleukin (IL)-1 and IL-6 and tumor necrosis factor (TNF), are associated with an unfavorable prognosis.\nOther factors associated with a worse prognosis include advanced stage, the presence of “B” symptoms, decreased response to therapy, and slow response to therapy.\nIn addition, evidence of CD8+ T cells surrounding the RS cell offers evidence of an important role in T-cell promotion of malignant cell survival, perhaps through the CD30 and CD40 ligands found on RS cells as well as immune checkpoint inhibition pathways.\nOther features that distinguish the histologic subtypes include various degrees of fibrosis and the presence of collagen bands, necrosis, or malignant reticular cells. The distribution of subtypes varies with age. Slide 9 Clinical Manifestations Painless, nontender, firm, rubbery, cervical or supraclavicular lymphadenopathy and usually some degree of mediastinal involvement.\nClinically detectable hepatosplenomegaly may be encountered. Depending on the extent and location of nodal and extranodal disease, symptoms and signs of airway obstruction (dyspnea, hypoxia, cough), pleural or pericardial effusion, hepatocellular dysfunction, or bone marrow infiltration (anemia, neutropenia, or thrombocytopenia).\nB symptoms- important in staging are unexplained fever 38°C, weight loss 10% total body weight over 6 mo, and drenching night sweats.\nLess common and not considered of prognostic significance- pruritus, lethargy, anorexia, or pain. Also exhibit immune system deficiencies that often persist during and after therapy. Slide 10 Diagnosis Evaluation includes history, physical examination, and imaging studies Any patient with persistent, unexplained lymphadenopathy un-associated with an obvious underlying inflammatory or infectious process should undergo chest radiography to identify the presence of a large mediastinal mass before undergoing lymph node biopsy.\nFormal excisional biopsy is preferred over needle biopsy to ensure that adequate tissue is obtained, bo