Multiple Myeloma and Lymphoid Leukemias Flashcards
B-lymphocyte general
Recognize epitopes of antigens by way of antibody molecues on their surface
First produce IgM
Isotype switching (IgG later)
Immunoglobulin structure
2 heavy chains - greater molecular weight, have Fc that is recognized
2 light chains - lighter
Define monoclonal gammopathy
Pathological clonal expansion of a single B or plasma cell leading to the excessive production of a homogeneous monoclonal immunoglobulin or a polypeptide subunit of the immunoglobulin
Define paraproteinemia
Implies that there is a structural abnormality in the immunoglobulin (ie incomplete Ig)
M-protein
Monoclonal protein
Does not imply anything structurally about the molecule other than its homogeneous nature
Cryoglobulins
Abnormal proteins that precipitate at temperatures below body temperature
Define multiple myeloma
Clonal origin: malignancy of B lymphocyte plasma cell lineage
Arises in bone marrow
Systemic disease
Production of immunoglobulin
Incidence and Signalment of Multiple myeloma
Rare in cats, not found in bone; usually liver and spleen
More common in dogs, tends to cause bone lesions and is found in marrow
Pathology and natural behavior of multiple myeloma
Immunoglobulin production - M component - Paraprotein - Usually complete Ig . Just light chains Bence Jones . Just heavy chains heavy chain disease - Cryoglobulins insoluble <37 degrees Celsius
Sequelae of M component
Infection - Decreased production of normal Ig - Immunologic cripples Hypersensitivity syndrome - Increased total protein - Hypervolemia Organ or bone infiltration with neoplastic cells
Hyperviscosity syndrome
Heart failure - Increased perfusion pressure and hypervolemia lead to cardiomyopathy - Myocardial hypoxia Neuro signs - Poor perfusion - Seizure, lethargy, abnormal mentation
Renal failure
High protein content in filtrate Tubular obstruction - Bence Jones proteinuria Amyloidosis Ascending pyelonephritis Tumor infiltration Decreased perfusion
Ophthalmic abnormalities
Dilated and tortuous retinal vessels
Retinal hemorrhage
- Acute hemorrhage
Hemorrhagic diathesis
Decreased platelet adhesion
Interference with coagulation cascade and fibrin polymerization
Consumption of coagulation factors
Myelophthisis and thrombocytopenia
Other signs of multiple myeloma
Severe skeletal pain Pathologic fracture Spinal cord compression Myeloma induced osteolysis - Osteoclast activation
Hx in MM
Nonspecific signs: weakness, PU/PD, pain, lethargy, inappetence
More specific signs: Epistaxis, gingival bleeding, blindness
- Compressive lesion/fracture
- Neuro abnormalities
MM Criteria
Hyperglobulinemia and monoclonal gammopathy (tick-borne diseases are polyclonal)
>10-20% plasma cells in bone marrow or >5% neoplastic cells
Immunoglobulin light chain (Bence-Jones) proteinuria (never done)
Radiographic evidence of multifocal osteolytic lesions
Diagnostic tests
CBC - Anemia, thrombocytopenia, leukopenia Chem panel - Hyperglobulinemia - Hypercalcemia - Renal failure Urinalysis and culture - UTI
Monoclonal gammopathies
Multiple myeloma Primary macroglobulinemia B cell chronic lymphocytic leukemia B cell lymphoma Extramedullary plasmacytoma Plasma cell leukemia Idiopathic of "of unknown significance" (MGUS)
Hyperglobulinemia
Elevation in globulins (not specific) - Divided into alpha 1, alpha 2, beta, and gamma . Acute phase proteins Separation of proteins - Molecular weight and charge - Gamma globulin peak . Immunoglobulins . Polyclonal versus monoclonal
Diagnostic tests
Bone marrow aspirate - 5% plasma cells normal - >10% plasma cells supports MM Urine - Bence Jones proteins . Dipstick NOT reliable Survey rads - Axial skeleton
Prognostic factors
Reported negative prognostic factors
- Hypercalcemia
- Bence Jones proteinuria
- Extensive osteolytic bone lesions
Don’t be a fortune teller
Therapies directed at complications
Hyperviscosity syndrome - Fluid therapy - Plasmapheresis Infections - Antimicrobials Malignant bone pain - Analgesics - Bisphosphonates - Fx stabilization - Coarse-fractionated radiation therapy
Conventional therapies
Alkylating agents - Cyclophosphamide - Melphalan Steroids - Prednisone - Dexamethasone
Felines
Myeloma related disorder
Survival not as good
Lymphocytosis
True lymphocytosis
- Chronic inflammation/infection
. Viral infection elicits transient lymphocytosis
- Neoplasia
. Lymphoid leukemias
PARR
- Polymerase chain reaction for antigen receptor rearrangements
- Diagnostic test to assess “clonality” of lymphocytes
Acute lymphoblastic leukemia
Associated with cytopenias Special stains to differentiate cell of origin - Lymphoid versus myeloid All w/ LN involvement vs LSA w/ leukemia - Which is bigger disease - Treat the same CD34+ is a negative prognostic factor Cell counts <30,000 do better
Acute vs chronic leukemia
Chronic: a lot of normal looking lymphocytes
Acute: crazsy cells
Chronic lymphocytic leukemia
Prolonged survival (>2 y) Usually incidental finding Start oral chlorambucil and pred - Organ involvement - Cytopenias - Lymphocytes >80,000
