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83 Cards in this Set
- Front
- Back
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What is the definition of normal hematopoiesis?
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Process of stem cell proliferation, differentiation, and maturation resulting in the prod of terminally differenticated blood cells
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What is the fn of hematopoietic growth factors?
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regulate commitment to a lineage, proliferation, differentiation, and fn of hematopoietic
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What are some examples of hematopoietic growth factors?
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erythropoietin, colony -stimulating factors (eg GM-CSF, thrombopoietin, IL-2, IL-3, IL-5) IL=interleukon
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Why can't manufactured growth factors for animals be human hormones?
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animals may develop antibodies against it.
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Describe disorders of stem cells.
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Maybe be reversible or irreversibe depending on cause.
Causes: viral infections, drugs/chemicals causing direct cytotoxic or immune-mediated injury, and intrinsic defects in regulation of cell proliferation and differentiation |
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What are some manifestations of disorders of stem cells?
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lack of production (aplasia/hypoplasia), abnormal prod (dysplasia) or uncontrolled prod (neoplasia)
1. aplasia/hypoplasia: hypocellular or acellular marrow 2. myelodysplasia: cytopenia of single line or combination of anemia, thrombocytopenia, and/or neutropenia; morphologic abnormalities in marrow cells (nuclear/cytoplasmic dysynchrony, giant bands); may be pre-neoplastic cond 3. neoplasia |
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Describe look of atypical lymphocytes/reactive lymphocytes in blood
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large lymphocytes; may bave basophilic cytoplasm and prominent nucleoli
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Describe significance of atypical lymphocytes/reactive lymphocytes in blood.
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must be interpreted in light of other information; could be antigenstimulated cells or neoplastic lymphocytes
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Describe atypical mononuclear cells
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in blood, large mononuclear cells, sometimes blastic, or unrecognizable lineage (could be lymphoblasts, myeloblasts, rubriblasts, etc)
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Describe leukemia
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neoplastic proliferation of bone marrow cells w/ over-accumulation of cells in bone marrow, blood, and other tissues. Literally means 'white blood'. Circulating tumor. Called 'circulating' or 'liquid' tumor.
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Describe lymphoproliferative disorders (LPD).
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neoplasms characterized by excessive proliferation of cells of lymphoid series, including B cells, T cells, and plasma cells
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What is lymphoma?
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Type of LPD. Solid tumor. Breaks thru capsule and takes over all node. Proliferation begins and predominates in lymphoid organs, such as lymph nodes, and spreads to other organs. Solid tumors are formed.
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What is leukemia?
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Type of LPD. separated into ALL (acute lympoblastic leukemia) or CLL (chronic lymphocytic leukemia) Lymphoma better prognosis than leukemia.
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How does leukemia proliferation begin?
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begins on bone marrow and predominates in bone marrow and blood with infiltration of other organs. Usually no solid tumors formed ('circulating tumor'
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What is chronic granulocytic leukemia?
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genetic defect. Philadelphia chromosome. Results in cont active tyrosine kinase causing over-proliferation
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What is myeloproliferative disorders (MPD)?
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Type of LPD. neoplastic diseases of bone marrow characterized by excessive proliferation of one or more of nonlymphoid hematopoietic cell lines (i.e. erythroid, granulocytic, monocytic, and megakaryocytic lines). Non-lymphoid
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What is paraneoplastic syndromes?
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Type of LPD. Neoplasm-associated alterations in structre/fn of body that occur distant to tumor
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What is the incidence of LPD?
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10 times more common than myeloproliferative diseases in animals
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What type of LPD is more common?
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solid tumors (lymphoma) more common than leukemia
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What are LPD classified?
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according to cytologic/histologic characteristics, clinical presentation, and anatomical location
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What is Bovine Lymphoproliferative Disorder? (BLV)
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etiologic agent of LPD in adult cattle is the bovine leukemia virus (BLV)--a virus, not a disease. It is a retrovirus
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How is BLV transmitted?
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horizontal and req transfer of whole cells. Transfer of infected lymphocytes present in blood, milk, or tumors to susceptible animal by vector. Close contact of infected and susceptible animals.
Fetus or neonate may be infected by passage of infected lymphocytes in utero or in milk |
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What is the incidence of BLV?
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50% of cattle and 75% of herds
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Describe the viral infection of BLV.
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1. infection permanent but non-productive (no viremia) Doesn't prod virus
2. BLV test detects antibodies to virus present in blood 3. small percent of animals infected w/ BLV dev lymphoma--req infection plus genetic predisposition, stress, immunosuppression or large dose of virus 4. exposure to BLV results in one: a. no infection b. infection plus antibodies, but no disease c. infection, antibodies, persistent lympocytosis d. infection, antibodies, lymphoma. |
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What is persistent lymphocytosis (PL) in in BLV? 2 things
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lymphocytosis that persists at least 3 months
benign proliferation of B cells: subclinical, polyclonal |
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What is the incidence of PL in cattle w/ BLV? 2 things
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10-30% of cattle w/ BLV dev PL
Most animals w/ PL do not go on to dev lymphoma but may be at greater risk |
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What are the lab feat of BLV induced persistant PL? 3 things
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Total WBC count increased up to 150,000 microL
Lymphocytes: increased above normal for age of animal Bone marrow: lymphocytic hyperplasia, but other elements normal |
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How do you diagnose BLV induced PL? 4 things
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Lymphocytosis (absolute) that is persistent
Absence of other causes of lymphocytosis Absence of clinical signs and tumors Positive for anibodies to BLV |
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Describe BLV-induced lymphoma.
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Enzootic (adult) form.
Common form of adults Multicentri: any organ may be involved Common sites: abomasum, heart, lymph nodes, spleen, liver |
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What is the incidence of BLV-induced lymphoma?
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<5% of cattle infected w/ BLV dev lymphoma
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What are the lab feat of BLV-induced lymphoma? 3
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hemogram variable: +/- anemia (if present, often due to blood loss from tumor in GI tract)
+/- atypical lymphocytes in circulation lymphocytic leukemia in 5-10% of cases |
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How do you diagnose BLV-induced lymphoma? 2
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1. histopathologic/cytologic evaluation of tumor
2. serology: positive for antibodies to BLV |
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What is the incidence of feline lymphoid neoplasms?
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highest of any mammalian species
1/3 of feline neoplams (FeLV) |
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Describe feline leukemia virus.
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May be etiologic agent of mediastinal or multicentric lymphoma, lymphoid leukemias or other disorders.
Horizontally transmitted retrovirus productive virus: infected cats are viremic FeLV test detects viral antigens |
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How does FeLV manifest itself in viremic cats? 6
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1. no deasease=asymptomatic carriers
2. nonregenerative anemia (RBC hypoplasia) 3. immune-mediated hemolysis 4. lymphoproliferative disorders 5. myeloproliferative disorders 6 other * a postive FeLV test is NOT a diagnosis. Req tissue diagnosis to figure out what/where disease is |
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What are the forms of lymphoproliferative disease in cats?
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1. lymphoma
-alimentary: most common form; cats are older and FeLV neg; not caused by FeLV -multicentri; used to be seen in younger FeLV-positive cats; now begin seen in older FeLV-neg cats -mediastinal: tumor in thymus or cranial mediastinal LN; usually unger FeLV pos cats -other locations: ocular, renal cutaneous, CNS 2. Large granular lymphocyte (LGL) lymphoma 3. Lymphoid leukemia |
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What are the lab feat of lymphoma in felines?
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1. dep on form of disease
2. hemogram: dep on degree of bone marrow involvement -+/- reduction in any cell line, e.g. anemia -+/- neoplastic cells in circulation 3. cytology: evaluation for presence of tumor cells -imprints, fine needle aspirates of involved sites -pleural fluid analysis (mediastinal lymphoma) -bone marrow -cerebrospinal fluid |
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How would you diagnose feline neoplasms? 2
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cytologic/histopathologic evaluation of involved site
-reactive hyperplasia in cats can mimic lymphoma cytologically and histologically Young cats w/ mediastinal or multicentric lymphoma usually positive for FeLV (uncommon form now) |
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Describe feline Large granular lymphocyte (LGL) lymphoma or leukemia
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special form of lymphoma or leukemia
1. tumors of T cells or NK cells often involving jejunum, ileum, or mesenteric LN 2. lymphocytes contain prominant granules |
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Describe feline lymphoid leukemia
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Bone marrow replaced by neoplastic lymphocytes, normal hematopoiesis is reduced, circulating neoplastic cells usually evident in peripheral blood, and other organs may be infiltrated. In cats, ALL is more common than CLL
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What is the etiology of canine lymphoid neoplasms?
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unknown
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What is the occurrence of canine lymphoid neoplasms?
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all breeds
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How would one classify canine lymphoid neoplasms? 3
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1. anatomical location
2. histologic/cytologic characteristics 3. clinical staging |
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What are the forms of canine lymphoid neoplasms? 2
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Lymphoma
-multicentric form (generalized lymphadenopathy) is most common -other forms include mediastinal, alimentary, cutaneous, renal, ocular, CNS, and hepatic Lymphoid leukemias |
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What are the clin and lab feat of lymphoma in canine?
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May vary w/ site and duration of disease
1. hemogram -anemia (often mild) and thrombocytopenia most common hematologic abnormalities in dogs w/ lymphoma 2. neutrophilia common 3. lymphocytes: most dogs w/ lymphoma do not have lymphocytosis. Often have lymphopenia from stress. Once lymphoma gets into bone marrow, can see in peripheral blood. 2. humoral hypercalcemia of malignancy (paraneoplastic syndrome) -only small percentage of dogs w/ lymphoma dev hypercalcemia, lymphoma is common cause when dev -pathogenesis: 1. secretion by tumor cells of PTH-RP (parathyroid hormone-related protein) 2. results in osteoclastic bone resporption and increased renal resorption of calcium 3. synergistic factors include IL-1, TNF, and viatmin D. -consequence: hypercalcemic nephropathy, renal failure |
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How would one diagnose canine lymphoma?
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histopathologic evaluation of tumor
cytological evaluation: LN effusions, bone marrow |
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Describe acute lymphoblastic leukemia (ALL). 5
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-predominance of lymphoblasts in bone marrow and peripheral blood with infiltration of other organs
-lymphocyte counts range from 30,000-300,000 -occurs less freq than lymphoma -aggressive, rapidly progressive disease: prognosis for dogs w/ ALL is worse than for those with lymphoma -enzyme cytochemistry and immunophenotypiding (immunocytochemistry, flow cytometry) used to dist lympoblasts from blast cells of other lineages; common markers are CD3 for T cells and CD79a for B cells |
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Describe chronic lymphocytic leukemia (CLL). 4
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-increased small, mature lymphocytes in bone marrow, blood, and other organs; in dogs usually T cells
-lymphocyte counts range from 5,000 to >100,000 -occurs less freq than ALL or lymphoma -slowly progressive disease: prognosis for animals w/ CLL is much better than for those w/ ALL |
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What happens in dogs w/ LGL lymphoma or leukemia?
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-neoplastic proliferation of lymphocytes containing granules (T cells or NK cells)
-note: non-neoplastic proliferation of LGL described in dogs w/ chronic ehrlichiosis |
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What is plasma cell myeloma (multiple myeloma)?
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neoplastic proliferation of plasma cells and precursors
-clonal disorder -usually begins in bone marrow, where tumor cells accumulate--get lysis and lesions. Lytic lesions on bone. -LN, spleen, and liver may also be infiltrated |
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What is the etiology of mult myeloma?
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unknown
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Which species are affected by mult myeloma?
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dogs-most common species affected
cats-uncommon rarelely reported in pags, calves, and horses |
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clinical and lab manifestations of plasma cell myeloma are which 2 major feat?
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-proliferation of plasma cells
-development of monoclonal gammopathy. |
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desc proliferation of plasma cells w/ mult myeloma (2 things)
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Proliferation of neoplastic cells
-pressure, bone destrction, pathologic feat LYTIC LESIONS ON BONE -impaired hematopoiesis leading to reduced prod of blood cells |
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describe monoclonal gammopathy in mult myeloma 5 things
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1. Tumor cells prod monoclonal immunoglobulin
-referred to as 'M protein' or paraprotein -Protein is IgG, igA, or light chains _if IgA, hyperviscosity syndrome can dev from high plasma concentration of large immunoglobulins _Light chain proteinuria (Bence Jones proteins) can cause renal tubular damage -Bleeding disorder may occur from interference by high protein concentration w/ platelet fn and factor interactions 2. Animals often have concurrent decrease in albumin levels and in normal immunoglobulin levels w/ increased susceptibility to infection |
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What does the hemogram of mult myeloma look like? (4 things)
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-mild to mod anemia
-rouleaux formation from increased plasma proteins -+/- mild neutropenia -+/- thrombocytopenia |
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What does the bone marrow look like w/ mult myeloma? 2 things
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-tumor can be focal: may need to sample mult sites to document myeloma
-increased numbers plasma cells (10-90%) w/ cluster or sheet formation _plasma cells often have normal morphology _other diseases may be accompanied by increased plasma cells in marrow like inflammatory and immune mediated diseases. Plasma cells increase w/ infection, too |
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What do serum proteins look like in mult myeloma? (5)
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-monoclonal gammopathy in most dogs w/ myeloma
-elevated total protein concentration: up to 16 g/dL -serum protein electrophoresis: monoclonal spike -Immunoelectrophoresis: IgG, IgA, or light chains -Albumin is often decreased |
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What do urine proteins look like w/ mult myeloma? 2
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-if paraproteins are light chains, they pass into urine
-not detected by routine urine protein tests; urine electrophoresis is req |
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What can happen w/ dogs calcium w/ mult myeloma?
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hypercalcemia from osteoclast-mediated bone resorption, stimulated by cytokines such as IL-1 and TNF
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How would one diagnose mult myeloma? 3
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-plasmacytosis in bone marrow
-osteolytic lesions::often present w/ pathogenic fractures!! -monoclonal gammopathy (serum or urine) |
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What are myeloproliferative disorders?
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neoplasms of the bone marrow characterized by excessive proliferation of one or more of the nonlymphoid hematopoietic lines
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How common are myeloproliferative disorders in species?
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Most common in cats
uncommon in dogs rare in other domestic species |
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What is the pathogenesis of myeloproliferatve disorders?
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1. Disturbance in stem cell pool, resulting in defective proliferation and maturation
2. in cats, often caused by feline leukemia virus |
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How does one callify myeloproliferative disorders? 2
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Based on degree of cellular differentiation. Chronic myeloproliferative disorders (Chronic MPD) or acute myeloproliferative disorder (acute MPD)
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Describe chronic MPD 4
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Must beware this may be inflammation, pyogenic infections, immune mediated disease
1. proliferation proceeds in uncontrolled manner 2. maturation of cells occurs 3. result is over-accumulation of differentiated cells in bone marrow and blood 4. specific disorders: -Polycythemia vera (way too many blood cells) -chronic granulocytic leukemia (too many granulocytes) -essential thrombocytopenia (can also be from Fe def anemia or chronic inflamatory disease. neoplastic form too many platelets) |
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Describe Acute MPD 4 things
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Proliferation of cells incapable of maturation occurs
-result is accumulation of blast cells in bone marrow and blood -ex: acute myeloblastic leukemia acute monoblastic leukemia -lineage of cells cannot be deterined using routine stains since blast cells of diff lineages have similar appearance. Characterization of cell surface markers by low cytometry or of cytoplasmic contents by cytochemical staining are req to identify cell lineage |
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What are history that you would look for in MPD? 3
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lethargy, inappetence, weakness
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What are clin features of MPD? 2
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fever, lymphadenopathy, hepatoplenomegaly
2. death usually from infection or hemorrhage secondary to quantitative and qualitative defects in neutrophils and platelets |
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What are the lab feat of MPD? 2
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1. non regenerative anemia and thrombocytopenia are common
2. leukogram is variable |
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What is the prognosis of acute and chronic MPD?
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acute: poor
chronic: fair |
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Describe polycythemia in MPD.
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Found in chronic MPD.
Polycythemia vera (p vera) or primary erythrocytosis -neoplasm of erythroid series i resulting in over-accumulation of mature erythrocytes; PCV often 65-85% (primary absolute polycythemia) -rule out other causes of polycythemia ~common causes: dehydration (relative polycythemis), pulmonary and cardiovascular diseases resulting in hypoxia (secondary absolute polycythemia) ~less common: erythropoietin-secreting tumors, renal disease w/ localized renal hypoxia -serum levels of EPO may not distinguish dogs w/ P vera, although in many animals w/ disease EPO levels are low or normal |
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Describe chronic granulocytic leukemia (CGL) in chronic MPD
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1. blood: marked leukocytosis (neutrophilia) w/ left shift
2. bone marrow: -hypercellular -granulocytic hyperlasia -reduction of erythroid series -+/- reduction in megakaryocytes -neoplastic granulocytes invade other organs, e.g. liver and spleen -essential to rule out other causes of marked leukocytosis (leukemoid rxn), such as pyogenic infections and immune mediated diseases. inflammatory diseases much more common than CGL |
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Describe essential thrombocythemia in MPD.
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blood: persistent and excessive thrombocytosis, sometimes w/ bizarre platelets, in absence of other causes of thrombocytosis ( iron def anemia), blasts cells, or other myeloproliferative disorders
bone marrow: megakaryocytic hyperplasia, sometimes w/ abnormal forms |
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What is the therapy of MPD?
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aimed at reducing number granulocyted (in CGL), erythrocytes (in P vera), or platelets (in ET) in the blood.
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How does one diagnose acute MPD?
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Diagnosis made on basis of finding >30% blasts in bone marrow and/or blood
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Describe cates w/ acute MPD caused by FeLV.
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1. severe nonregenerative anemia is common. In blood, metarubricytosis and macrocytosis w/o polychromasia are common findings
2. thrombocytopenia (from decreased production) or thrombocytosis w/ bizarre forms may be present |
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What is the prognosis of acute MPD?
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poor.
-normal hematopoiesis marked reduced -other organs invaded by neoplastic blasts -response to current therapeutic modalities is poor |
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What is myelofibrosis?
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replacement of developing hematopoietic cells in marrow space w/ fibrous tissue
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What causes myelofibrosis?
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-secondary to marrow damage from other causes
-FeLV infection -Some MPD terminate in myelofibrosis -idiopathic |
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What are lab feat of myelofibrosis?
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-non regenerative anemia w/ poikilocytosis, metarubricytosis
-eventually pancytopenia |
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What is the diagnosis of myelofibrosis?
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aspirates of bone marrow usually not productive; bone marrow biopsy is req
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What are clues in the blood that indicate bone marrow disease?
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-nonregenerative anemia
-unexplained leukopenia -unexplained thrombocytopenia -presence of abnormal cells |
