topic 3 autoimmunity part 8 immunoproliferative diseases
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Topic 3 Autoimmunity Part 8 Immunoproliferative Diseases. Terry Kotrla, MS, MT(ASCP)BB. Immunoproliferative Diseases. Focus on malignancies of the immune system, lymphoid cell line. Broadly classified as lymphomas and leukemias. - PowerPoint PPT PresentationTRANSCRIPT
Terry Kotrla, MS, MT(ASCP)BB
Topic 3 AutoimmunityPart 8 Immunoproliferative
Diseases
Immunoproliferative DiseasesFocus on malignancies of the immune system,
lymphoid cell line.Broadly classified as lymphomas and leukemias.Leukemias malignant cells present in bone
marrow and peripheral blood.Lymphomas, malignant cells arise in lymphoid
tissues:Lymph nodesTonsilsSpleen
Classified according to site malignancy first arose.
Immunoproliferative DiseasesPlasma cell dyscrasias
Multiple myeloma (MM)Waldenstrom’s macroglobulinemia
Involve bone marrow, lymphoid organs and other non-lymphoid tissue.
Biologically distinct, NOT classified as either lymphoma or leukemia.
Plasma cells may be found in blood later in myeloma, then classified as plasma cell leukemia.
Malignant TransformationMalignancy characterized by excess accumulation
of cells.Rapidly proliferating cells.Normal proliferation but do not undergo apoptosis
(programmed cell death).Rapid cell proliferation normal process of the
immune system to respond to antigenic stimulus.Malignancy occurs when regulatory processes fail
or mutations occur.Malignant cells “stuck” at early stage of
differentiation.May require altered or abnormal genes.May be triggered by viral infection or other
stimulus.
Malignant TransformationMalignant and premalignant proliferation of
cells can occur at any stage of differentiation.
Malignant cells may retain some or all of morphological and functional characteristics.Cell surface antigensSecretion of antibodyUsed to classify
Malignant Transformation - LymphomaArise due to persistent immunostimulation
coincides with immune deficiency.Provokes continuous proliferation and
mutations in lymphoid precursors.Immune deficiencies play two roles:
Ineffective immune response causes persistent stimulation to clear infection.
Immune surveillance for malignancy fails, especially in response to viral infections.
Malignant TransformationImmune system has diverse response to antigenic
challenge, “polyclonal response”.Malignancy may arise from excessive proliferation of
SINGLE genetically identical cell line or CLONE of cells.Malignancy occurs with population of uniform cells.
Presence of a large amount of single immunoglobulin type.
Increase in total amount of immunoglobulin.Malignancy diagnosed when lymphocytic cells in
bloodstream, bone marrow or lymphoid tissues consist of a uniform population of cells.
Specific mutations not known for most malignancies but more are being identified every day, may lead to effective treatment.
Immunoproliferative DiseasesB-cell immunoproliferative disorders most
commonly evaluated.B-cell lineage develop into plasma cellsUrine antibodies used to diagnose and
evaluate certain B-cell proliferationsB-cells produce one antibody specificity
(monoclonal).Persistent presence of large amounts of a
single immunoglobulin suggests malignancy.Increase in total amount of one specific clone
characteristic of benign reactive immunoproliferative disease.
LymphomasLymphomas
Hodgkin’s lymphomaNon-Hodgkin’s lymphoma
Historically difficult to classify, no one gold standard.
Revised European-American Lymphoma (REAL) classification adopted by WHO.Cell originsMorphologyImmunophenotypeGenetic featuresClinical features
Hodgkin’s LymphomaHighly treatable and curable.Occurs in young adults (15-35) and elderly
(over 55).Characterized by orderly spread of disease from
one lymph node group to another.Symptoms
FeverNight sweatsWeight lossEnlarged lymph nodesHepatomegaly, splenomegaly or
hepatosplenomegaly
Hodgkin’s LymphomaCharacterized by presence of Reed-Sternberg
cells.Abnormal lymphocyte which contains more than one
nucleusFound in affected lymph nodes and lymphoid organsB-cell lineage
Hodgkin’s Lymphoma – Diagnosis and TreatmentIn some cases there appears to be a
correlation between HL and infection with Epstein-Barr virus (EBV) infectionDetermine EBV antibody levelTest for EBV virus
Histological examination of lymph node biopsyFour types of HL differentiation based on cell
determinants (CD) found on the affected cells.Treatment
Radiation therapyChemotherapyStem cell transplant
Non-Hodgkin’s Lymphoma - NHLWide range of neoplasms that can include
any type of lymphoma EXCEPT Hodgkin’sB-cell lymphomas – most prevalent type 85%T- cell lymphomas
Prognosis varies significantly in severity.Slow progression – long term survival goodHighly aggressive – fatal
Non-Hodgkin’s Lymphoma - NHLAs lymphoma progresses and cancerous
lymphs spread beyond lymphatics body loses ability to fight infection.
Symptoms depend on type of NHLLymphadenopathyFeverNight sweatsWeight lossLoss of apetiteRed patches on the skinSeverely itchy skin, often affecting legs/feet
Non-Hodgkin’s Lymphoma - NDiagnosis
Tissue biopsyFlow cytometryImaging tests to determine where tumors are
located.Treatment
Watch and waitRadiation therapyChemotherapyTargeted therapy – use monoclonal antibodies to
target specific marker on cells where cancer starts.
Lymphoblastic LeukemiasCovered in Hematology, will not be covered
in this course.No questions for exams.Expected to know the material for future
exams and exit exam.Use material in textbook to enhance review
of the material.
Plasma Cell DyscrasiasCharacteristic is over production of a single
immunoglobulin component.Paraprotein or myeloma protein.Diagnosis and monitoring dependent on detecting
and quantitating the paraprotein.Screening and confirmatory tests performed in
most clinical laboratories.
Plasma Cell DyscrasiasInclude several related syndromes:
Multiple myelomaWaldenstrom’s macroglobulinemiaLight-chain diseaseHeavy-chain diseaseMonoclonal gammopathy of undetermined
significance.
Multiple MyelomaMalignancy of mature plasma cells.
Most serious and common of plasma cell dyscrasias.
Age of diagnosis 40 to 70 years, found in blacks twice as frequently as whites, and men twice as likely as women.
Have excess of plasma cells in the bone marrow.
Level of normal immunoglobulin decreased in proportion to abnormal immunoglobulin.
Multiple MyelomaImmunoglobulin produced by malignant
clone, can be of any class, IgG most common.
Important diagnostic feature is presence of Bence Jones protein in the urine.Abnormal production of free immunoglobulin
light chains, kappa or lambda.Can be detected by immunoelectrophoresis
or heat precipitation.
Multiple Myeloma - SymptomsThe presence of unexplained
AnemiaKidney dysfunctionElevated ESRBroken bones -lytic lesions cause bone pain
and fractures.Hemorrhage can occur due to
thrombocytopenia and paraprotein interferes in normal hemostasis.
Deposition of antibody derived material leads to organ dysfunctions, with kidneys most commonly involved.
Laboratory 10% or higher plasma cells in bone marrow. High serum protein level
Bence-Jones proteins being present in 60-70% of the cases.
Hyperviscosity develops when protein levels are high, especially with IgM producing tumors.
High levels of immunoglobulins lead to rouleaux formation being noted on blood smear.
Failure of bone marrow to produce normal number of hematopoietic cells leads to: AnemiaThrombocytopeniaNeutropenia
Multiple MyelomaBone Marrow –
Malignant plasma cells
Peripheral smear – pathologic rouleaux
Waldenstrom’s MacroglobulinemiaMalignant proliferation of IgM producing
lymphocytesMalignant cells more immature than plasma cells,
with appearance being between small lymph and plasma cell.
Plasmacytoid lymphs infiltrate bone marrow, spleen and lymph nodes.
Some IgM paraproteins behave as cryoglobulins, precipitate at cold temperatures.Occlude small vessels in patient’s extremities in cold
weather.Leads to skin sores and necrosis of fingers and toes.
Waldenstrom’s MacroglobulinemiaPatients with stable production of
monoclonal IgM without infiltration of marrow or lymphoid tissue are considered to have cold agglutinin syndrome.
Waldenstrom’s MacroglobulinemiaSymptoms
AnemiaHyperviscosityFatigueMucosal or GI bleedingNausea
TreatmentPlasmapheresisChemotherapyStem cell transplantMedian survival 5 years versus multiple
myeloma, 3 years.
Waldenstrom’s Macroglobulinemia
Cryoglobulins detected in blood or plasma by placing the sample in a refrigerator in the clinical laboratory.Precipitate forms at low temperatures (4C).Dissolves upon rewarming.May be associated with a cold red cell autoantibody
directed against the I antigen on the patient’s own red blood cells, may result in hemolytic anemia.
Laboratory DiagnosisMeasurement of immunoglobulin levels in
serum.Serum protein electrophoresis to separate
and detect abnormal levels, myelomas which produce only light chains may be missed.
Laboratory DiagnosisImmunoelectrophoresis used to evaluate
monoclonal gammopathies detected by SPE.
Immunofixation electrophoresis also used to evaluate monoclonal gammopathies.
Serum viscosity measurements useful for Waldenstrom’s macroglobulinemia or high levels of IgG or IgA paraproteins.
Bone marrow biopsy to establish diagnosis of lymphoproliferative disorder and determine extent of bone marrow replacement by malignancy.
Laboratory RolePerform specialized tests such as
Immunophenotyping by flow cytometryEvaluation of immunoglobulinsSerum protein electrophoresisImmunofixation electrophoresisEvaluation of genetic and chromosomal
abnormalities.May require additional education to be
qualified to perform.
Referenceshttp://www.ucl.ac.uk/~regfjxe/Arthritis.htm http://www.haps.nsw.gov.au/edrsrch/edinfo/
lupus.html http://pathmicro.med.sc.edu/ghaffar/
tolerance2000.htmhttp://repro-med.net/info/cat4.phphttp://stemcells.nih.gov/info/scireport/
chapter6.asphttp://www-ermm.cbcu.cam.ac.uk/
04008427h.htm http://www.biotest.de/ww/en/pub/folder_pharma/fields_of_use/
autoimmune_disease.htm http://72.14.203.104/search?q=cache:H7KcpVQ4xkYJ:www.peppypaws.com/
Glossary.html+Forbidden+clone+theory&hl=en&client=firefox-a
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