CDU-CM LEVEL III BLOCK IV Module 1: HEMATOLOGY LYMPHOID NEOPLASMS Nomenclature Leukemia = primary involvement of bone marrow and

nd blood Lymphoma = solid tumors of the immune system Classification (ALL) L1 = lymphoid malignancies of small uniform blasts (typical childhood ALL) L2 = lymphoid malignancies with larger and more variable size cells L3 = lymphoid malignancies of uniform cells with basophilic and vacuolated cytoplasm (typical Burkitts lymphoma cells) Epidemiology Sex Age peak Race Comments Whites > Blacks; most prevalent CLL M > F older adults uncommon in Asia form children, ALL EBV, radiation young adults Hodgkins M > F bimodal (20 and 80) Whites > Blacks EBV, HIV Lymphoma T cell: Asia NHL M > F elderly chemical exposure B cell: Western countries Etiology Infectious agent Epstein-Barr virus

Lymphoid Malignancy Burkitts lymphoma Post organ transplant lymphoma Primary CNS diffuse large B cell lymphoma Hodgkins disease Extranodal NK/T cell lymphoma Adult T cell leukemia/lymphoma

Comments Central Africa Majority of 1 CNS lymphomas are associated with EBV Asia and South America Transmission: lactation, blood borne, sexual contact; HTLV-1 is also the cause of tropical spastic paraparasis Overexpression of IL-6

HTLV-1

HIV HCV H. pylori

Diffuse large B cell lymphoma Burkitts lymphoma Lymphoplasmacytic lymphoma Gastric MALT lymphoma

Bacterium does NOT transform lymphocytes to produce lymphoma; vigorous immune response leads to the neoplasia Diffuse lymphadenopathy associated with systemic symptoms

HHV-8

Primary effusion lymphoma Multicentric Castlemans disease MALT lymphoma of the skin

Borrelia sp

Immunology About 75% of all lymphoid leukemias and 90% of all lymphomas are of B cell origin. Clinically most aggressive lymphoid leukemia is Burkitts leukemia. Many lymphomas contain balanced chromosomal translocations involving the antigen receptor genes. B cells are even more susceptible to acquiring mutations during their maturation in germinal centers. No specific genetic abnormalities have identified in Hodgkins disease other than aneuploidy. Genetic Links trisomy 12 t(9;22) t(4;11) t(8;14) Comments conveys poorer prognosis much poorer outlook associated with younger age, female predominance, high white cell counts, L1 morphology associated with older age, male predominance, frequent CNS involvement, L3 morphology

CLL ALL

SELECTED LYMPHOID MALIGNANCIES Neoplasm

Precursor B Cell Lymphoblastic Leukemia/Lymphoma

Unique Properties
most common cancer in childhood

Presentation
BM failure (pallor, fatigue, bleeding, fever, infection); anemia & thrombocytopenia; extranodal involvement (lymphadenopathy, CNS disease, hepatosplenomegaly, testicular enlargement, cutaneous infiltration) lymphadenopathy 1 fatigue, frequent infections autoimmune hemolytic anemia autoimmune thrombocytopenia red cell aplasia

Diagnosis
BM biopsy: infiltration by malignant lymphoblast

Cytogenetics
t(9;22)(q34;q11) t(4;11)(q21;q23)

DDx

Treatment

Comments
Adverse prognosis: - very high WBC count - presence of symptomatic CNS disease - unfavorable cytogenetic abnormalities (t(9;22)) Patients with unmutated immunoglobulins tend to have a more aggressive clinical course and are less responsive to therapy.

B Cell CLL or SLL

most common lymphoid leukemia

Combination chemotx: a. Consolidation phase high-dose systemic therapy and treatment to eliminate dse in the CNS; b. Continuing therapy to cure & prevent relapse. increased number of circulating trisomy 12; Mantle Cell Rai stage O or Binet A: lymphocytes that are monoclonal B abnormalities in Lymphoma no specific tx (10 years) cells and display CD5 antigen; chromosome 13 Intermediate stage: PS: smudge or basket cells tx on follow-up (7 years) (nuclear remnants) Rai stage III or Binet C: initial tx (1.5 years)

Follicular Lymphoma

most responsive to chemotherapy and radiotherapy

new, painless lymphadenopathy most common presentation

BM biopsy: small cleaved and large cells in follicular pattern of growth

Burkitts Lymphoma/Leukemia

Precursor T Cell Lymphoblastic Leukemia/Lymphoma Mycosis Fungoides Adult T Cell Lymphoma/Leukemia

Classification: - Predominantly small cells - Mixture of small and large cells - Predominantly large cells (higher proliferative fraction; progress more rapidly; shorter survival with single tx) most rapidly progressive peripheral lymphadenopathy Lymphoma: cells are homogeneous human tumor intraabdominal mass in size and shape; metastasis to the CNS Leukemia: monotonous mass of medium-sized cells with round nuclei, multiple nucleoli, basophilic cytoplasm, cytoplasmic vacuoles BM failure, very high WBC counts, mediastinal mass, pleural effusions lymphadenopathy, hepatosplenomegaly, metastasis to the CNS Cutaneous T Cell eczematous or dermatitic skin lesions Lymphoma Sezarys syndrome (erythroderma) caused by HTLV-1 lymphadenopathy, hepatosplenomegaly, T cell immunophenotype (CD4 +); retrovirus skin infiltration, hypercalcemia, lytic antibodies to HTLV-1; bone lesions, elevated LDH flower cells (indented nuclei)

t(14;18); BCL-2 protein (abn expression)

Agents: Chlorambucil Fludarabine (only drug associated with significant incidence of complete remission) CVP / CHOP combination Allogeneic SCT Reactive Chlorambucil Complication: follicular Cyclophosphamide may evolve to Diffuse hyperplasia CVP / CHOP combination Large B Cell Lymphoma *50-75% of Px will achieve a complete remission Field radiotherapy for localized lymhoma Diffuse begin within 48 hours of Large B Cell diagnosis! Lymphoma Cyclophosphamide Prophylactic therapy to the CNS (mandatory) intensive remission induction and consolidation regimens; BM transplantation total skin electron beam irradiation; palliative tx combination median survival of 7 chemotherapy (true months remissions unusual)

t(8;14) t(2;8) t(8;22) *c-myc gene