Most common lymphoid neoplasm in African Americans, second most common lymphoid neoplasm in Caucasians. Median age of diagnosis = 70 yrs. Male to female ratio 1:1.

Malignant cells destroy normal marrow microenvironment. Trabecular destruction and osteoclast activation leads to hypercalcemia and marrow replacement leads to anemia. Renal failure also contribution to anemia via underproduction of RBCs due to insufficient EPO.

Variable course (one year to many years). Ultimately poor response to current therapies. Autotransplantation following an initial round of highly toxic therapy has been shown to prolong survival in MM, but is not curative. Current cytogenetics: deletions of 13q (more aggressive), translocations 14q32 (common).

Prognosis & Treatment: if intervention is swift with intensive chemotherapy Burkitt's can be cured. However, timing is critical.

Aggressive lymphomas represent ~50% of the NHLs diagnosed in Western countries with the most common subtype being DLBCL which accounts for ~31% of all NHLs, affecting both children and the elderly. Associated with being immunocompromised (EBV+).

Gross pathology: homogenous fish-flesh replacement of involved tissue. Hemorrhage, necrosis, fibrosis. DLBCLs are locally destructive lesions. The discohesive nature of the proliferating cells that make up these masses lead to a soft bland "fish-flesh" appearance.

Immunosuppression: a subset of DLBCLs are more commonly EBV positive due to lack of immune surveillance resulting in proliferation of EBV infected B cells. These EBV+ B cells then acquire genetic accidents that lead to neoplastic transformation, typically to an aggressive lesion.

Monotonous infiltrate of medium-sized cells, very high proliferative and apoptotic rates, "starry sky" pattern (numerous tingible body macrophages), round nuclei with multiple central nucleoli, cytoplasm deeply basophilic with lipid vacuoles.

Biological underpinnings for all three variants of Burkitt lymphoma. Translocation of the oncogene cMYC into the heavy or light Ig chain regulatory machinery results in overexpression.

Flame cells - morphologic variants due to the pink border of IgA expressing cells.

Mott cells - globules of intracytoplasmic monoclonal Ig.

More aggressive myeloma show marked cytologic "atypia" with large bizarre nuclei, prominent nucleoli, and pronounced mitotic activity.

MGUS: monoclonal gammopathy of uncertain significance. A plasma cell disorder with low grade asymptomatic proliferations that are not clearly neoplastic.

Precipitation of large Ig moieties at low temperatures can be a problem in the extremities (Raynaud's disease).

Bleeding phenomena due to interference of Ig with platelet function and clotting cascade proteins. Serum hyperviscosity also results from paraproteinemia and produces sluggish bloodflow and subsequent vascular complications.

Cast nephropathy due to excess light chain aggregates in distal nephron leading to obstruction, toxicity of light chains for proximal tubular epithelial cells, hypercalcemia leading to hypovolemia, light chains settling as amyloid deposits. [note: casts are physically composed of cells - RBC/WBC - and are a sign of inflammation].

Ig (most often lambda light chains) settle out in unique beta-pleated sheets to form acellular tissue deposits that interfere with organ function.

Decreased normal Ig production results in predisposition to recurrent bacterial infections. A leading cause of death for MM patients.

Multifocal, causes bone pain, osteolytic lesions, and pathologic fractures. Lytic bone lesions are found at most prominent at sites of active hematopoiesis in the axial skeleton (ribs, skull, vertebrae). Pathologic fracture of vertebrae can be an emergency due to potential spinal cord compression.

In MM the most common paraproteins are IgG (50%) and IgA (25%), both of which have greater kappa than lambda light chains. An M spike consists of increased monoclonal Ig >3 gm/dL serum and >6 gm/dL urine. This spike is detected through electrophoresis and immunofixation.

Rapidly enlarging symptomatic mass at a single nodal or extranodal (40%, typically GI tract) site (unlike indolent lymphomas). Can arise from (1) progression/transformation of an indolent lymphoma or (2) de novo. Primary presentation with BM or PBL involvement is rare.

Immunoblastic: large, single centrally located nucleolus, abundant cytoplasm (can be plasmacytoid in appearance). Lymphoblastic lymphomas have cells that vaguely resemble large transformed lymphocytes seen in the interfollicular areas in reactive lymph nodes. These mostly arise as EBV+ primary CNS lymphomas.

Centroblastic: (like centroblasts from follicular lymphoma) medium-saved to large cells, oval vesicular nuclei, multiple membrane bound nucleoli, scant cytoplasm. Centroblastic tumors are composed of cells that resemble the transformed cell seen in a germinal center. These lesions are far more common than immunoblastic lymphomas, which are seen mostly in states of immunosuppression.

International Prognostic Index (IPI): age > 60, elevated serum LDH (measure of cell death and thus tumor burden), poor performance status (how fit the patient is), extensive disease (both sides of diaphragm - Ann Arbor clinical stage III or IV), involvement of multiple extranodal sites.

Gene expression profile analysis (based on putative stages of B cell development): GCB phenotype has significantly better survival than ABC phenotype.

This is an emergency! Rapid doubling time, high tumor burden, bulky disease, tumor lysis syndrome, potentially curable and as such treatment should begin ASAP. Doubling rate makes Burkitt's lymphoma responsive to DNA damaging agents.

Facial bones 50% (jaws, orbit), less common: ileocecum, ovaries, kidneys, breast.

Abdominal (ileocecal) masses more common, less common: ovaries, kidneys, breasts. LN involvement rare (more common in adults).

Seen throughout the world (children and young adults). Low incidence (1-2%) of NHL in West. Makes up 30-50% of childhood lymphoma, rare in adults. Adult median age - young (30), M:F ratio 2-3:1. Associated with EBV in < 30% of cases.

Most common childhood malignancy in equatorial Africa (malaria belt). Incidence peaks at 4-7 years, M:F ratio 2:1. Associated with EBV in all cases.

Primarily seen in association with HIV infection. Often the initial manifestation of AIDS. Associated with EBV in 25-40% of cases.

Hodgkin's Lymphoma