week 8- blood malignancy Flashcards
• What are the 4 major subdivisions of hematologic malignancies?
o Myeloid d/os: acute myeloid leukemia, or chronic myeloid d/os
o Lymphoid d/os: acute lymphoid leukemia, chronic lymphoid d/o
• What are the further subdivisions of chronic myeloid disorders?
o Chronic myeloid leukemia
o Myelodysplastic syndrome
o Atypical chronic myeloid d/o
o Chronic myeloproliferative dzs
• What are myeloproliferative d/os?
o cause abnormal proliferation of a line of blood cells; often multiple (erythroid, myeloid, and megakaryocytic precursors in BM)
o =clonal expansion that arises from a pluripotent stem cell
o have appropriate cell differentiation and result in mostly mature blood cells (unlike other myelodysplastic syndromes and leukemias)
• what are the types of myeloproliferative d/os?
o PCV (RBCs) o Primary (essential) thrombocytopenia (platelets) o Chronic myelogenous leukemia (granulocytes) o Myelofibrosis (collagen or fibrous tissue)
• How are MPDs detected? Sxs?
o Reflected in peripheral blood smear & CBC results.
o Often caught on a CBC with irregular cell counts or by splenomegaly on physical exam
o Presenting: none, HTN, itching, burning feet, thrombosis, splenomegaly (fullness and discomfort
• What is PCV?
o Increased Hb conc and increased RBC mass
o Incidence about 0.1-1.6/per million people, mb more in males
o 60 yrs mean dx
o Environment: exposure to high levels of radiation may increase risk
o CBC and peripheral smear show panmyelosis: increased RBCs, WBCs, &Plts
• What are the 3 classes of polycythemia?
o Relative: Dt low plasma volume: dehydration, burns, diuretics; inc RBC only; normal EPO
o Secondary: “Reactive Polycythemia”, Hypoxia (smoking), high altitude, lung disease; inc RBC only; inc EPO
o Primary: PCV, “Malignant” hematologic disorder, not self-limiting. Tx with phlebotomy, anti-neoplastic drugs; Significant increases in all formed elements; dec EPO
• What are the stages of PCV?
o 1: uncomplicated erythrocythemia
o 2: erythrocythemia and thrombocythemia
o 3: myeloid metaplasia with overlap syndromes of different grades of reticulin and collagen fibrosis of BM, splenomegaly, leukocytosis
o 4: spent phase polycythemia with leukoerythroblastosis
o 5: acute myelocytic leukemia
• What are ssx of PCV?
o Expanded blood volume & hyperviscosity lead to: weakness, HA, light-headedness, visual disturbances, fatigue, SOB
o Bleeding tendency is common (epistaxis)
o Pruritus is frequent
o Face may be red, retinal veins engorged
o HTN
o Hepatomegaly frequent
o Splenomegaly in > 75% of patients (extramedullary hematopoiesis, in liver and spleen; splenic infarcts common)
• What are the blood O and viscosity problems with PCV?
o Blood O2 inc, but tissue O2 dec
o Tissue hypoxia dt inc blood viscosity, causing problems with tissue perfusion & vessel thrombosis
o Easy blood clotting; MI or stroke; heart failure or angina
o Raynaud’s phenomenon is common
o Chronic cases result in inc CO & increased capillary beds in an effort to dec tissue hypoxia
• What is the effect of HCT on blood viscosity?
o Blood viscosity increases exponentially with inc HCT
o =more blood in vessels; dec blood flow
• What signs help dx of PCV?
o Inc Uric acid levels dt inc nucleic acid turnover
o EPO is low or undetectable
o RBC count > 6,000,000 /mm3; RBC stacks on smear
o BM is usually hypercellular (all cell lines)
o RBC survival time decreases in 25% leading to anemia. Myelofibrosis may develop during this phase.
• What are other findings in peripheral blood with PCV?
o Immature WBCs
o Immature RBCs, with marked anisocytosis and poikilocytosis: microcytes, elliptocytes, and dacrocytes may be seen
o Neutrophilia with abnormal morphology
o Thrombocytosis with abnormal morphology & if function is also abnormal then increased bleeding
• What is essential (primary) thrombocythemia?
o Hi Idiopathic platelet count of 500,000-1,00,000/L,
o w/o features of the other myeloproliferative disorders: Normal RBC mass; Lack of BM fibrosis; No dacrocytes; No “philadelphia chromosome” (CML)
o BM megakaryocyte hyperplasia
o Either a hemorrhagic or thrombotic tendency.
o Seen in 50-70 year olds
• What is seen on peripheral blood smear of ETC?
o Platelet aggregates, Giant Platelets, and Megakaryocyte fragments
• What may appear with 2nd TC that is not seen in ETC?
o Acute infection o Chronic inflammatory dz (RA, TB) o Iron deficiency anemia o Hemolysis o Cancer o Lymphoma o Splenectomy o Plt Count usu. < 1,000,000; Hx; PE; no (normal) platelet aggregation
• What is myelofibrosis?
o BM becomes fibrotic
o Splenomegaly
o Myeloid metaplasia: Extramedullary hematopoiesis, cells formed in liver & spleen
o Hallmark: inc reticulin staining; also be seen in pts with acute leukemias, esp acute myeloid leukemia (AML).
o Peak incidence 50-70 years
o Median survival 10 years from onset
o Dx by BM biopsy showing fibrosis, marrow aspiration commonly dry
o WBC & platelet counts frequently high initially, become low as disease progresses
• What is found on CBC of MF?
o Leukoerythroblastic: immature WBCs and RBCs.
o RBCs: Normocytic normochromic anemia; mild poikilocytosis, polychromatophilia & NRBCs, Dacrocytes
o WBCs: Initial leukocytosis with immature neutrophils
o Platelets: eventually thrombocytopenia (occasionally abn giant platelets)
• What other conditions may manifest as a “2nd MF” as part of their dz course?
o PV: 15-30% of cases o Leukemias, lymphomas, multiple myeloma o TB and osteomyelitis o Myelodysplastic Syndrome MDS o Exposure to benzene, X-Rays, Gamma Rays
• What is myelodysplasia?
o An insufficient # of funny looking cells that don’t work well
o =ineffective hematopoiesis; usu all 3 cell lines
o -> cytopenias, w/ extramedullary hematopoiesis in liver and spleen ->SM and HM
o BM may be normal or hypercellular & contains < 30% blasts.
o MDS d/os considered “pre-leukemic” condition, meaning: predilection to evolve into acute nonlymphocytic leukemias ANLL/Acute Myelogenous Leukemia
• What are ssx of MDS? CBC?
o Fatigue, weakness, anorexia, weight loss, abdominal fullness.
o May have increased bleeding & infections.
o Macrocytic anemia with anisocytosis
o Thrombocytopenia with variations in PLT size.
o WBCs may be normal, high, or low
o May see monocytosis and up to 5% blasts in peripheral blood.
• What is the WHO classification of MDS?
o Refractory anemia (RA): w/ (RARS) or w/o ringed sideroblasts
o Refractory cytopenia (MDS) with multilineage dysplasia (RCMD)
o Refractory anemia with excess blasts (RAEB)
o 5q- syndrome
o unclassifiable
o Myelodysplastic/Myeloproliferative diseases
o Chronic myelomonocytic leukemia (CMML)
o Atypic chronic myelogenous leukemia (aCML)
• What are the types of hematologic cancers?
o Leukemias: ALL, AML, CLL, CML
o Hairy Cell Leukemia
o Lymphomas: Hodgkin’s dz, Non-Hodgkin’s, Burkitt’s
o Plasma Cell Dyscrasias: Multiple Myeloma; Waldenstrom’s Macroglobulinemia
• What is leukemia?
o uncontrolled, abnormal WBC growth in BM. Accumulation of cancerous cells interferes with production of RBCs, WBCs and platelets.
o arise from changes in chromosomes -> cell loses ability to control its growth and death (apoptosis)
o One of 10 most frequently occurring cancers; 5 year survival rate is ~55%
• What are ssx of leukemia?
o Weight loss, fever, infections, fatigue, loss of appetite
o SOB, weakness, bone pain
o LA, SM/HM
o Night sweats, easy bleed/bruise, purple spots/patches
• What is cause of leukemia?
• No known causes; implicated risk factors:
o Viruses (Hep B, EBV, HIV)
o Exposure to Radiation
o Environmental factors (smoking, benzenes (also MF), herbicides)
o Genetic disorders (Down syndrome)
o Age (most often after 60 years old)
• What are the 4 general classifications of leukemias?
o Acute: Immature cells (usually blasts) predominate. Disease progresses rapidly
o ALL acute lymphoblastic leukemia (B or T cells)
o AML acute myeloblastic leukemia (granulocytes)
o Chronic: More mature cells are present. May take years to develop
o CLL chronic lymphocytic leukemia (B or T cells)
o CML chronic myelogenous (granulocytes)
• What is acute lymphoblastic leukemia (ALL)?
o Most common malignancy in children
o Peak incidence 3-5 yrs. 80% of cases in children; Second, lower peak in adults.
o Prognosis depends on factors present at dx:
o T-cell, younger age, initial WBC counts below 50,000 and quick response to chemo all have a better prognosis
• What is acute myeloblastic leukemia (AML)?
o 80% of adult acute leukemias.
o Mean age: 65
o Poor prognosis, especially patients > 50 years
• What is chronic myelogenous leukemia (CML)?
o 20% of all leukemia, both sexes affected
o Common btw. ages of 20-50, rare in childhood
o Poor prognosis
• What is chronic lymphocytic leukemia (CLL)?
o 30% of all leukemia
o Usually middle age to elderly
o Twice as common in men than women
o Average survival of 3-7 years after dx
• How is CLL diagnosed?
o PLT Low in 20-30%; WBC 20-150,000/ml; Increased mature lymphocytes
o Smudge cells: immature lymphocytes with increased fragility partially broken down during slide preparation
o Dx is made from a sustained ABS lymphocytosis of > 5000/ml
o Bone Marrow infiltrated with small lymphocytes
• How is ALL diagnosed?
o Anemia in 90%; Thrombocytopenia in 80%; WBC variable, usually elevated
o Lymphoblasts common in peripheral smear
o BM has greater than 30% blasts, usu means leukemia; Suppression of normal hematopoiesis
o Strongly reactive to special stain: Periodic acid-Schiff
• How is AML diagnosed?
o 90% Anemia; Thrombocytopenia; WBC variable, usually increased
o Myeloblasts common in peripheral blood
o BM: Greater than 30% blasts
o Strongly reactive to special stain: Sudan black B
o Genetic studies are important in classification and prognosis
o Auer rods: Found in Blasts; Small, rod-shaped; cytoplasmic elements; Thought to be abnormal lysosomes.
o Increased segmented neutrophils, myelocytes and metamyelocytes are seen in the peripheral blood
• How is CML diagnosed?
o Asymptomatic WBC < 50,000; Symptomatic WBC 200,000-1,000,000
o PLT high in 60%; low in 10%
o Some Blast forms in peripheral blood
o Absolute eosinophil & basophil counts increased
o Absolute lymphocytes & monocytes may be normal
o Doesn’t stain with Leukocyte alkaline phosphatase (LAP stain)
o Philadelphia chromosome found in 95%
• What is prognosis for AML, ALL, CNML, CLL?
o AML: 10-35% 5 yr survival rate
o ALL: 25-35% 5 yr survival; much better for children
o CML: 5-6 years
o CLL: stage 3/4 =2 years
• What are the differences b/w MPD, MDS, and ALs?
o Blood counts: hi; lo; either o MB cellularity: hi; lo; hi o Dysplasia: min; major; min o Terminal differentiation: present; absent; absent o Blasts: 20%
• What is lymphoma?
o heterogeneous group of neoplasms that arise in the lymphatic and reticuloendothelial (RE) systems.
• What is hodgkin’s dz?
o Reed-Sternberg cells: Dx is by lymph node biopsy showing them
o There can be a slight-to-moderate neutrophilia
o Lymphocytopenia can occur early & become pronounced with advanced disease
o Eosinophilia is present in 20% of patients
o Thrombocytosis can be present
o Increased ESR reflect active disease
o Microcytic hypochromic anemia in advanced dz
o Bimodal age distribution, peaks age15-34 & after age 60
o Spreads to contiguous lymph nodes
o Etiology unknown, but twin studies have shown genetic component.
o Hx of EBV, HIV, occupations (woodworkers)
o Pain in affected areas after consuming alcohol; fever, night sweats; intense pruritis is an early sign
• What is non-hodgkin’s lymphoma?
o Clonal proliferation of lymphoid cells in lymph nodes, bone marrow, tonsils, spleen, liver, or GI
o Etiology unknown.
o May be due to HTLV-1 Human T-cell Lymphoma Virus 1
o Anemia present in 33% initially, most develop it as disease progresses with non-contiguous spread
o Leukemic phase develops in 20-40% of lymphocytic lymphomas
o Dx can only be made via lymph node biopsy
• What is diff b/w HD and NHL?
o Age: 15-24 & >55; 67
o Prevalence: less; more common
o Location: often supraclavicular nodes, chest cavity; often abdomen nodes, supraclavicular
o Sx: system, night sweats, fever; not usu systemic
o Progression: from node to node, downward; less predictable, dxed at stage 4
• What is the Ann Arbor Staging System for HD and NHL?
o Stage I: single LN region or single extralymphatic organ or site
o Stage II: > 2 LN regions on same side of diaphragm or with limited, contiguous extra lymphatic tissue involvement
o Stage III: both sides of diaphragm involved, may include spleen or local tissue involvement
o Stage IV: multiple/disseminated foci involved with > 1 extra-lymphatic organs (i.e. bone marrow)
• What is Burkitt’s lymphoma?
o Highly undifferentiated B cell lymphoma
o Can involve sites other than the lymph nodes & reticuloendothelial system
o Most common in Central Africa
o Epstein Bar Virus: Associated with history of infection
• What are plasma cell dyscrasias?
o Diverse group; proliferation of one clone of plasma cells normally engaged in immunoglobulin (Ig) production.
o typified by the presence of a monoclonal Ig or polypeptide subunit in serum or urine.
o 2 main types: Multiple Myeloma; Waldenstrom’s Macroglobulinemia
• What are the multiple myeloma sxs of PCDs?
o Unexplained bone pain (back, thorax), renal failure, & recurrent bacterial infections most common.
o May see pathological fractures in vertebrae & anemia.
• What are the sxs of Waldenstrom’s Macroglobulinemia (PCD)?
o Most are asymptomatic.
o May have indications of “hyperviscosity syndrome,” of fatigue, bleeding from skin and mucous membranes, weakness, visual disturbances & headaches.
o Also Raynaud’s phenomenon.
• What is multiple myeloma?
o Progressive neoplastic dz
o Plasma cell tumors in BM
o Increased production of Specific monoclonal Ig: G,A,D,E
o Urinary Bence Jones protein: Free monoclonal k or l light chains
o Light chain = higher bone lytic lesions and associated hypercalcemia & renal failure
• What is the mnemonic for MM symptoms?
o C= hypercalcemia
o R=renal failure
o A=anemia
o B= bone lesions
• How is MM diagnosed?
o Anemia: normocytic,normochromic
o RBCs form rouleaux due to increased viscosity from abnormal proteins
o WBC & platelets counts usually normal
o ESR: often markedly elevated, > 100 mm/hr
o 55% produce IgG and 20% produce IgA.
o Total protein, BUN, creatinine, uric acid elevated
o Hypercalcemia in 1/3 of patients
o 40% Bence Jones proteinuria, (K or L light chains) urine need sulfosalicylic acid test to detect.
o Serum protein electrophoresis: increased monoclonal Ig protein, or“M protein” in 80%
• How is M protein detected?
o Spike is separate from albumin on chromography -> measure A/M ratio. <1 has poorer px
• What is Waldenstrom’s Macroglobulinemia?
o Clonal expansion of plasma cells that normally synthesize & secrete IgM
o resembles lymphomas, many sxs due to large amounts of circulating macroglobulin
o Many patients have a hx of Raynaud’s phenomenon
o Recurrent bacterial infections are a major problem.
• What is macroglobulinemia?
o Moderate anemia
o Marked rouleaux formation & very high ESR
o Leukopenia, relative lymphocytosis and thrombocytopenia occasionally occur
o Cryoglobulins, rheumatoid factor, and cold agglutinins may be present.
o Relative serum viscosity is usually > 4.0 (normal 1.4-1.8)
• Polycythemia vera?
o Sx: HA and SM
o hemoglobin 18 g/dL (rr-12-15.5)
o red blood cells 7,000,000/mm3 (rr-6-16 years: 4.0-5.2 x 106/mm3)
o white blood cells 22,000/mm3 (rr-3.5-10.5)
o platelets 1,248,000/mm3 (rr-150-450)
o EPO: decreased
o Bone marrow aspirate: hypercellular with mature cells
o Bcr-Abl translocation: negative
o JAK2 V617F mutation: positive
