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120 Cards in this Set

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Q: Describe myeloproliferative disorders.
-a group of clonal, neoplastic diseases that involve the pluripotent hematopoietic stem cells, in this condition there is unregulated and uncontrolled growth and proliferation of the ancestral progeny of multipotent cells that exhibit differing degrees of differentiation
-affects non-lymphocytes, RBCs and platelets
Q: Describe the classification of the myeloproliferative disorders.
-the acute myeloproliferative disorders are the acute nonlymphocytic leukemias and are characterized by unregulated growth with limited or no differentiation
-chronic myeloproliferative disease include a group of disorders causing unregulated and excessive proliferation of cells with substantial differentiation, usually produces an excess of mature, eifferentiated hematopoietic cells
Q: What are some examples of chronic myeloproliferative disorders?
-chronic myelogenous leukemia
-polycythemia rubra vera
-agnogenic myeloid metaplasia
-idiopathic (essential, primary) thrombocythemia
Q: What are some examples of predisposing factors for leukemia?
-Chromosomal abnormalities: Trisomy 21 in Downs (18-20x incidence) and many others.
-RNA oncogenic viruses: HTLV-1 in T cell leukemia and EB virus in African Burkitt’s lymphoma
-Chromosome mutations: Hereditary ataxia telangiectasia
-Ionizing radiation: Treatment for other tumors
Q: Describe the common clinical manifestations of both acute and chronic leukemia.
-fatigue and weakness due to anemia
-bleeding or bruising due to DEC platelets, abnormal thrombopoiesis
-infections secondary to impaired WBC function
-lymphadenopathy and organomegaly
-WBC is moderately elevated
Q: Describe the incidence of both acute and/or chronic leukemia.
-there are 8-10 new cases/100,000/year with an approx. = number of acute and chronic, more adults than children are affected (10:1) and more males than females (1-2:1)
Q: Describe the acute myeloproliferative disorders.
-they have an abrupt onset and if left untreated can be fatal in less than 6 months
-they are not acute lymphoblastic leukemias
-subdivided into 7 main types on the basis of morphology
Q: What are the hematologic findings associated with acute leukemias?
-INC, normal or (less commonly) DEC WBC
-thrombocytopenia is common
-variable levels of anemia, but consistently observed
-bone marrow failure more often initially, than in chronic
Q: Describe the classifications of acute nonlymphocytic leukemia (ANLL, AKA acute myelogenous leukemias (AML)).
-use the FAB classification, classified as M1-M7 based on morphology and cytochemical standards, classification depends on series of cells (myeloid, erythroid, monocytic, or megakaryocytic)
Q: What is the use of classifying these leukemias?
-allows for a means for separating them from the acute lymphoblastic leukemias, this differentiation is important since specific therapy and prognosis is different
Q: What are the different ANLL classifications?
-M1 or M2-acute myeloblastic leukemia
-M3-acute promyelocytic (progranulocytic) leukemia
-M4-myelomonoblastic or monomyeloblastic (Naegeli-type) leukemia
-M5-monoblastic leukemia (Schilling type)
-M6-erythroblastic leukemia (DiGugliemo’s disease, eyrhtremic myelosis)
-M7-megakaryoblastic leukemia
Q: Describe M0.
-blasts lack definitive cytologic and cytochemical markers of myeloblasts (e.g. myeloperoxidase negative) but express myeloid lineage antigens and resemble myeloblasts ultrastructurally
Q: Describe M1.
-very immature, but >= 3% of blasts are peroxidase positive, few granules or Auer rods and little maturation beyond the myelobalst stage, most common leukemia in ages 15-60, M2 more differentiated and more Auer rods than M1
Q: Describe M2.
-full range of myeloid maturation through granulocytes
Q: Describe M3.
-most cells are hypergranular promyelocytes, often with many Auer rods per cell, patients are younger (median age 35-40 years), high incidence of DIC and associated bleeding disorders, strong assocaiteion with the t(15:17)
-treat with all-trans-retinoic acid (vitamin A derivative that binds RARalpha which induces myeloid maturation)
Q: Describe M4.
-myelocytic and monocytic differentiation evident, myeloid elements (+ myeloperoxidase stain) show range of maturation
Q: Describe M5.
-in M5a subtype, monoblasts (peroxidase-negative, nonspecific esterase-positive) and promonocytes predominate in marrow and blood
Q: Describe M6.
-dysplastic erythroid precurose (some megaloblastoid, others with giant or multiple nuclei) predominate and within the non-erythroid cells, >30% are myeloblasts, seen in advanced age, makes up 1% of de novo AML and 20% of the therapy-related AML, bizarre PAS + erythroblasts (normal is -), abnormal WBC (progress to ANLL)
Q: Describe M7.
-blasts or megakaryocytic lineage predominate
Q: Describe the clinical presentation of acute leukemias.
-presents with varying degrees of bone marrow failure, symptoms include anemia, leucopenia and infection or thrombocytopenia
-fatigue and fever are nearly universal
-WBC is unpredictable
-newly diagnosed individuals may have INC serum uric acid and elevated LDH levels
Q: Describe the epidemiology of acute leukemias.
-ANLL is a disease of adults, ALL is a disease of children, more common in whites than in blacks, and in men rather than women (3:2)
Q: Describe the chronic leukemias.
-clonal disorders of the hematopoietic stem cell that are associated with unregulated growth and proliferation of multipotent cells that are capable of differentiation to maturity
-they normally have an insidious onset with a clinical course that lasts 2-6 years
-usually a disease of an adult or elderly
Q: Describe the hematologic findings associated with chronic leukemias.
-WBC is INC (almost always), normal or often INC platelet count, organomegaly is more prominent that in acute leukemia
Q: On physical examination of patients, what is expected to be found in pts. with chronic leukemias?
-patients present with symptoms of disturbed marrow functioning, including anemia and recurrent infections, bleeding, or thrombotic tendency
-enlarged spleen
Q: What is on the differential diagnosis with an enlarged spleen?
-chronic myelogenous leukemia
-agnogenic myeloid metaplasia
-lymphomas
-chronic lymphocytic leukemia
-visceral leishmanisis (kala-azar)
-Gaucher’s disease
-Schistosomiasis
-malaria
Q: What are the common lab findings associated with chronic leukemias?
-normochromic, normocytic anemia (except in polycythemia vera), diffuse polychromatophilia, teardrop poikilocytosis
-high blood uric acid levels, elevated LAP (except in CML, where it is DEC)
Q: What are the general steps needed to be taken to evaluate and diagnose the different types of leukemia?
-to diagnose leukemia do CBC (which is consistent with abnormal hematologic conditions) and bone marrow aspirations/studies (often essential for diagnosis, needed min. of 20% blasts to diagnose acute leukemia)
-to classify use morphologic evaluations including cytochemical stains, immunologic markers and cytogenetic markers
Q: What are the different cytochemical stains used to differentiate between subtypes of leukemia?
-meyloperoxidase
-sudan black B
-specific esterase
-nonspecific esterase
-PAS stain
Q: What are the different types of immunologic markders used to differentiate between subtypes of leukemia?
-lymphocytes-CD3, 4, 8, 19, 20 and 34 (34 is markder for immature AML subpopulations, the stem cells)
-monocytes-CD13 and 14
-myeloid precursors-CD33
-erythroid precursors-CD41
-cIgM, TdT are also used
Q: What are the differenty types of cytogenetic markers used to differentiate between subtypes of leukemia?
-AML (M2): t(8:21)
-AML (M2): t(8:21)
-APL (M3 and M3m): t(15:17)
-AMML with abnormal eosinophilia (M4E): Inv (16) or del (16)
-AMoL poorly differentiated (M5a): t(9:11)
-CML (Philadelphia Chromosome): t(9:22)
-ALL (pre-B cell phenotype): t(1:19)
-ALL (Burkitt’s leukemia): t(8:14), t(2:8) & t(8:22)
-ALL (T-cell phenotype): t(1:14)
Q: Diagnosis of acute leukemia is made on the basis of:
1. demonstration of immature cells in the peripheral blood with confirmation of immature cells in the bone marrow, usually the bone marrow contains greater than 20% blastic morphology
2. categorizing th eleukemic cells as acute nonlymphocytic leukemia or acute lymphoblastic leukemia
3. categorizing the cell type enables placement within the FAB classification
Q: In terms of morphology, what are the features that are useful in distinguishing ANLL from ALL?
1. cell size-AML is large, ALL is small
2. nuclear chromatin-AML diffuse, ALL some clumping
3. nucleoli-AML multiple, ALL one, often large
4. cytoplasm-AML moderate, ALL scanty
5. auer rods-AML sometimes present, ALL absent
Q: In terms of special stains, what are the features that are useful in distinguishing ANLL from ALL?
-AML stains + for esterases and myeloperosidase (PAS for M6), ALL stains + for PAS and TdT
Q: In terms of immunophenotyping, what are the features that are useful in distinguishing ANLL from ALL?
-AML is + for CD33, 13 and 14 (M4, M5), ALL is + for CD 7, 5 and 2 (for T cells), CD 19 (for B cells), CD19,10 and cytoplasmic mu and CD22 (for pre-B cells) and cytoplasmic CD3 (for pre-T cells)
Q: What are the immunophenotypes and cells assoacited with the different classes of acute leukemia?
-M0-CD13, 33, 34, HLA-DR
-M1-CD13, 14, 15, 33, 34
Q: Describe the treatment for ANLL.
-to eradicate the malignant clone and allow normal hematopoiesis to reestablish itself
-first objective is to induce remission with remission-induction chemotherapy
-once remission is induced, it is consolidated with further chemo (usually cytosine arabinoside and daunomycin)
Q: What effect does chemo have on RBC counts?
-suppresses total blood counts, which remain low for 2-3 weeks, patients require transfusion support with RBCs for severe symptomatic anemia and platelet transfusions for both prohylaxis against bleeding and treatment of thrombocytopenic bleeding, WBC transfusion is unhelpful
Q: What are some examples of chronic myeloproliferative disorders?
-chronic myelogenous leukemia
-polycythemia rubra vera
-agnogenic myeloid metaplasia (myelofibrosis)
-idiopathic (essential, primary) thrombocythemia
Q: Describe polycythemia rubra vera. (PV)
-AKA erythrocytosis or erythremia, refers to INC red cell mass and is associated with spontaneous and unprovoked INC in red cell production and blood volume
-other marrow elements may also be involved (75% have leukocytosis, 50% have thrombocytosis)
Q: What is secondary or reactive polycythemia?
-when red cells INC to meet a recognizable physiologic stimulus
Q: Describe the epidemiology of PV.
-occurs in older adults, slightly more often in men than in women
Q: Describe the clinical presentation of PV.
-4 H’s (hypervolemia, hyperviscosity, hyperuriemia, histaminemia)
-hyperviscosity is associated with headaches, visual disturbances and thrombotic events
-INC histamine is assoacited with itching
-have a plethoric cherub face and 75% have splenomegaly
Q: What labs are associated with PV?
-major criteria include INC red cell mass, normal arterial O2 saturation, splenomegaly (if no splenomegaly must meet two minor criteria), and erythropoietin
-minor criteria include INC platelets and WBCs, INC LAP, INC serum B12, INC uric acid
Q: What is on the differential for polycythemia?
-PRV, hypoxemia, ectopic erythropoietin, stress, dehydration
Q: What are the levels of RBC mass, plasma volume, Sa O2 and erythropoietine in PRV?
-INC RBC mass, INC plasma volume, normal Sa O2 and DECerythropoietin
Q: What are the levels of RBC mass, plasma volume, Sa O2 and erythropoietin in hypoxemia?
-INC RBC mass, normal plasma volume, DEC Sa O2 and INC erythropoietin
Q: What are the levels of RBC mass, plasma volume, Sa O2 and erythropoietin in ectopic erythropoietin?
-INC RBC mass, normal plasma volume, normal Sa O2 and INC erythropoietin
Q: What are the levels of RBC mass, plasma volume, Sa O2 and erythropoietin in stress?
-normal RBC mass, DEC plasma volume, normal Sa O2 and normal erythropoietin
Q: What are the levels of RBC mass, plasma volume, Sa O2 and erythropoietin in dehydration?
-normal RBC mass, DEC plasma volume, normal Sa O2 and normal erythropoietin
Q: Describe the blood smear morphology associated with PV.
-RBC, hb and hct are INC, unless there is iron deficiency, occasionally have myelocytes and metamyelocytes, INC basophil count, abnormal platelets
-hypercellular marrow w abundance of all cell lines
Q: Describe treatment for PV.
-aimed at reducing the red cell mass by frequent, therapeutic bloodletting (phlebotomy), this controls thrombotic and hemorrhagic complications
Q: What is the prognosis for PV patients after phlebotomy?
-they stay in a variable period for ~10 years, then enter spent phase, in 15-20%, have progressive anemia and INCing enlargement of spleen or liver, resembles agnogenic myeloid metaplasia, have marrow fibrosis
Q: Describe the myelofibrosis with extramedullary myeloid metaplasia (primary myelofibrosis).
-is a primary stem cell disorder with uncontrolled megakaryocytes secreting platelet derived growth factor, which stimulates marrow fibrosis and eventually marrow failure
-hallmark is rapid development of obliterative marrow fibrosis, suppressing bone marrow hematopoiesis, leading to peripheral blood cytopenias and extensive neoplastic extramedullary hematopoiesis in the spleen, liver and lymph nodes
Q: Describe the pathophysiology of primary myelofibrosis.
-pathologic features stem from collagen deposition by non-neoplastic fibroblasts in the marrow, fibrosis displaces hematopoietic elements (including stem cells) form the marrow leading to extramedullary hematopoeisis
-fibrosis likely due to inappropriate release of fibrogenic factors from neoplastic megakaryocytes (specifically platelet-derived growth factor (PDGF) and TGF-beta, which are fibroblast mitogens)
-hematopoietic stem cells take up residence else where
Q: Describe the morphology of primary myelofibrosis.
-erythroid and granulocytic precursors appear normal but megakaryoctyes are large, dysplastic and abnormally clustered, fibrosis is minimal in this phase
-as it progresses marrow befomes hypocellular and diffusely fibrotic, even later marrow space is convereted to almost all bone leading to extramedullary hematopoiesis
Q: Describe the laboratory findings associated with primary myelofibrosis.
-thrombocytosis > 1,000,000 bizarre forms rarely seeing megakaryocytes on peripheral smear
-teardrop RBCs (important), may see Howell-Jolly bodies
-bone marrow yields dry tap, INC LAP and immature neutrophils with eosinophilia and basophilia
-normally normochromic, normocytic anemia, may be macrocytic
-may see INC LDH, INC uric acid and INC vita B12
Q: How does primary myelofibrosis present clinically?
-found usually in patients >50, big big spleen with LUQ pain and fullness due to infarction of the spleen, usually present with fatigue and anemia and usually die in 5 years
-may be preceded by PV or CML
-may have weight loss and night sweats due to INC metabolism associated with expanded mass of hematopoietic cells
Q: Describe essential thrombocythemia.
-hematopoietic stem cell disorder with INC proliferation and production largely confined to the megakaryocytic elements, most patients having platetlet counts > 600,000, usually > 50 years old, compatible with a long life, commonly causes bleeding and mild splenomegaly (splenectomy is contra-indicated)
-since all chronic myeloproliferative disodres can be associated with thrombocytosis, essential thrombocytosis as a diagnosis of exclusion (is also more benign than the other ones)
Q: Describe the pathophysiology of essential thrombocytopenia.
-unknown, bears some resemblance to PV
Q: Describe the lab findings with essential thrombocythemia.
-dysplastic megakaryocyte in the marrow
-mild neutrophilia (10,000-15,000/uL)
-bone marrow examination is helpful in excluding other chronic myeloproliferative disorders (usually have abnormal large platelts w/ mild leukocytosis)
-may see erythromelalgia
Q: What is erythromelalgia?
-throbbing and burning of hands and feet caused by occlusion of small arterioles by platelet aggregates
-in essential thrombocythemia but may also be seen in PV patientw with high platelet counts
Q: What is a differential diagnosis for thrombocytosis?
-can be primarily due to chronic myeloproliferative syndromes (primary thrombocythemia, myelofibrosis, PV, CML and 5 q syndrome
-can be secondary to infections (acute (abscess) or chronic (bronchiectasis), injury, malignant solid tumors, inflammatory disorders (rheumatoid arthritis) and acute and chronic blood loss)
-may also be idiopathic
Q: Describe chronic myelogenous leukemia (CML).
-is a clonal disorder of pluripotential stem cells that show an INC ability to proliferate but maintain capability to also differentiate, is characterized by unregulated growth, proliferation and differentiation of myeloid precursors committed toward granulocytic development
Q: Describe the epidemiology of CML.
-common leukemia between 30-50, with the peak incidence in the fourth and fifth decades
Q: What distinguishes CML from other MPDs?
-CML is distinguished by the presence of a distinctive molecular abnormality, a translocation involving the BCR gene on chromosome 22 and the ABL gene one chromosome 9
Q: Describe the resultant BCR-ABL gene.
-AKA Philadelphia chromosome, directs the synthesis of a 210-kDa fusion protein with tyrosine kinase activity
-the activity of diverse tykrosine kinases is normally regulated by ligand-mediated dimerization, followed by the activation of multiple downstream pathways which control cell survival and proliferation
-with the BCR-ABL gene, the net effect is cell division and inhibition of apoptosis contributing to unregulated myeloproliferation
Q: Describe the morphology of CML patients.
-usually 100% cellular bone marrow (normal is 50% cellular, 50% fat) with maturing granulocytic precursors comprising most of the INC cellularity
-INC megakaryocytes, DEC or normal erythroid progenitors
-leukocytosis, predominantely neutrophils, metamyelocytes and myelocytes with < 10% blasts
Q: How does CML present clinically?
-is an insidious disease often demonstrating non-specific symptoms including fatigue, weight loss, INCing tiredness, splenomegaly (most common finding) due to hypermetabolism due to INC cell turnover
-slowly progresses through different stages
Q: What are the different phases of CML?
-chronic phase-lasts for years, medication is given to control WBC count
-transitional/accelerated phase-not all patients progress to this phase, lasts several months and patients in this survive for 1-1.5 years, it is very difficult to control blood counts, the peripheral blood has 7.5% blasts and platelet > 100,000/uL
-acute phase-similar to acute leukemia, has a 3-6 month survival, >30% blasts in bone marrow and peripheral blood, chloromas are present as well as abnormal cytogenic findings (another Ph-positive clone or trisomy 8, 9, 10, or 21)
Q: What causes the CML to progress to accelerated phase?
-unknown, may involve activation of the proto-oncogen sequences, may have an inciting stimulus that promotes the unregulated, undifferentiated growth
-get INCing spleen size, INCing bone pain and symptoms of anemia or hypermetabolism, cells become dedifferentiated and many more immature cells are seen
Q: Describe the histological changes that occur with progression of CML.
-INCing basophilia and blasts, and INC in LAP
Q: What are the lab findings associated with CML?
-leukocytosis (>50% with WBC counts between 50k and 100k WBC/uL, see all stages of maturation especially myelocytes, metamyelocytes and bands, basophilia is prominent as disease progress)
-normocytic, normochromic anemia
-thrombocytosis
-bone marrow is hypercellular with expansion of myeloid cell line and precursor cells
Q: What lab tests can be done to diagnose CML?
-test for Ph chromoseom (t(22:9)), there are two forms (70% have a 5’ DNA breakpoint, 30% have a 3’ DNA breakpoint)
-hyperuricemia and therefore possibly urate kidney stones or clinical gout
-elevated serum B12 binding protein (TC-1)
Q: What is the treatment for CML?
-drugs that inhibit BCR-ABL kinase which induce complete hematologic remission in more than 90% of patients, they do only suppress the CML clone so they may not prevent progression to blast crisis
-allogeneic bone marrow transplantion is the favored treatment for younger patients, of which about 75% are cured
Q: Describe acute myelogenous leukemia (M1 or M2).
-associated with arrested development of bone marrow cells due to acquired genetic alterations that inhibit terminal myeloid differenation
-leads to DEC production of normal cells and includes anemia, thrombocytopenia and neutropenia
-have rapid proliferation of precursors with DEC apoptosis
-results in accumulation of younger cells in organs and tissues, especially in liver and spleen
Q: What are some things that may cause AML?
-myelodysplastic syndrome, aplastic anemia, myelofribrosis, PNA, DML, polycythemia rubra vera
-congenital-Down’s, Fanconi anemia, neurofibromatosis
-environmental-radiation, benzene
-chemotherapeutic agents-alkylating agents, topoisomerase II inhibitors
Q: What are the lab tests associated with AML?
-anemia, thrombocytopenia and neutropenia
-blasts in peripheral blood
-elevated LDH and uric acid
-bone marrow hypercellular with >30% blasts
-cytogenic studies especially for diagnosis of promyelocytic leukemia (M3)
Q: Describe the lymphoproliferative disorders.
-there is unregulated growth and proliferation of cells of the lymphoid series
-classified into acute (there is little or no differentiation to terminal maturity) and chronic (there is an unregulated growth with differentiation and an abundance of mature cells
-clonal in origin, representing expansion of a single clone of cells all exhibiting the same phenotypic markers as the parental cell
-can be classified into leukemias (affecting bone marrow and peripheral blood) or lymphomas (affecting reticuloendothelial organs)
Q: Describe acute lymphocytic (lymphoblastic) leukemia (ALL).
-encompasses a group of neoplasms composed of immature, precursor (pre-B) or T (pre-T) lymphocytes referred to as lymphoblasts, can also be non-B and non-T cell
-features similar to AML but more acute onset
-the majority (85%) of ALLs are precursor B-cell tumors that typically manifest as childhood acute leukemias
-T cell ALLS tend to present in adolescent males as lymphomas ofeten with thymic involvement
Q: Describe the pathophysilogy of ALL.
-the chromosomal aberrations that are seen in ALL dysregulate the expression and function of transcription factors for normal hematopoietic cell development, this likely intereferes with normal lymphoblast maturation leading to arrested development and the accumulation of immature progenitors
Q: Is there a relationship between types of ALL that determine prognosis?
-YES, common ALL Antigen (CALLA) in 60%, best for a cure (pre-B cell leukemias), T cell is intermediate in prognosis, transformed B cell has the poorest prognosis
-there is FAB classification (L1-L3) but not as important as T cell markers
Q: Describe the epidemiology of ALL.
-80% children and 20% adults
-there are about 2500 new cases each year
-twice as common in whites as in nonwhites and is slightly more frequent in boys than in girls
Q: What are the clinical symptoms associated with ALL?
-anemia, fever w/o infection, bone pain, hepatosplenomegaly, generalized lymphadenopathy, ecchymoses due to thrombocytopenia
Q: How to differentiate between AML and ALL.
-compared to myeloblasts, lymphoblasts have condensed chromatin, inconspicuous nucleoli, and scant agranular cytoplasm
-but if want to differentiate between ALL and AML, need to used B and T lymphocyte-specific markers with Abs, histochemical stains can also be helpful
-lymphoblasts (in contrast to myeloblasts) lack peroxidase + granules and often contain cytoplasmic aggregates of PAS + material
Q: What are the lab findings associated with ALL?
-anemia, thrombocytopenia and neutropenia
-WBC and lymphocyte count is variable (but ther are lymphoblasts)
-INC LDH and uric acid
-bone aspiration shows morphology of cells and flow can be used for confirmation (marked CDC and CD19)
Q: What do genetic tests for ALL look for?
-15% of patients have t(22:9), also can find t(4:11), t(2:8), and t(8:14)
Q: Describe immunophenotype in ALL.
-immunostaining for TdT (DNA polyermase expressed by pre-b and pre-T lymphocytes) is + in >95% of cases
-can also differentiate between B- and T-cell origin: pre-B have CD19 and CD10, early pre-B ALL has IgM absent but late-pre-B has IgM, pre-T ALL are CD1+, CD2+, CD5+ and CD7+, early pre-T are negative for CD3, CD4, and CD8, while late are + for these
Q: Describe chronic lymphocytic leukemia (CLL).
-the most common leukemia in patient over 60
-in most CLLs, the proliferating cells are B lymphocytes, which have normal surface characteristics and no detectable immunologic activity but characteristically express the CD5 antigen
Q: Describe the pathophysiology of CLL.
-leukemic B cells survive as long as 5 eyars vs. 1 year survival for normal B lymphocytes
-INC in production rate of B lymphocytes leading to massive cellular accumulation crowding out normally reactive B cells, these even overrun spleen, lymph nodes and bone marrow interfering with the movement of normal granulocytes, monocytes and erythrocytes across vascular membrane
-the clonal B-cells morphologically resemble mature lymphocytes, they also hve arrested B-cell differentiation and are immunologically incompetent
Q: Describe the genetics concerning CLL.
-is an acquired genetic disease, have overexpression of bcl 2 gene
-have an abnormal karyotype with over 50% of patients having deletion of Bq, 15% have trisomy 12
Q: Describe the clinical findings associated with CLL.
-have generalized lymphadenopathy, hepatosplenomegaly, autoimmune hemolytic anemia, hypogammaglobulinemia with infections
-WBC between 10,000 and 100,000 /uL
-as lymphocytes overrun the marrow, platelet counts and RBC production may decline, but intrinsic erythropoietic and thrombopoietic capabilites are normal
Q: What are the lab findings associated with CLL?
-mature lymphocytosis 20,000-200,000/uL (smudge cells are a clue as the cells are malignant and disintegrate easily)
-anemia, thrombocytopenia, and neutropenia
Q: How is CLL confirmed?
-flow cytometry of peripheral blood, + for CD5, CD19, CD20 and CD23, - for FMC-7
Q: Describe adult T cell leukemia.
-neoplasm of CD4+ T cells, observed in adults infected by human T-cell leukemia virus type 1 (HTLV-1)
-leads to generalized lymphadenopathy and hepatosplenomegaly, skin lesions, may also have a role as a progressive demyelinating disease affecting the CNS and spinal cord
-poor pronosis
Q: Describe the epidemiology of adult T cell leukemia.
-common in Japan and Caribbean, not a problem in U.S. yet, majority are ment
-transmitted by blood transfusions and sex
Q: What are the lab findings for adult T cell leukemia?
-hypercalcemia
-malignant T cells produce osteoclast activating factor resulting in lytic bone lesions
-peripheral blood lymphocytosis, also see multilobated nuclei in cells called cloverleaf or flower cells
Q: Describe Hairy-cell leukemia.
-a chronic malignant B cell disease in middle-aged men (4:1 are male), a clonal proliferation of morphologically distinct cells that are characterized by the presence of fine, cytoplasmic projections, a distinctive nuclear pattern (salt and pepper chromatin) and the presence within the cells of a specific tartate-resistant isoenzyme of acid phosphatase (TRAP test)
Q: How does Hairy-cell leukemia present clinically?
-present with pancytopenia and splenomegaly (85%)
-leukemic form with WBC > 10,000 and >50% hairy cells (in 15% of patients)
-prone to autoimmune disease (skin nodes with vasculitis) and infections (atypical mycobacterial vasculitis
Q: What are the lab findings for Hairy cell leukemia?
-packed marrow (to be differentiated from myelofibrosis), hairy cells are + for tartrate-resistant acid phosphatase
Q: How is hairy cell diagnosed?
-in contrast to CLL, cells express CD25 antigen
-bone marrow aspirate is a dry tap, bone marrow biopsy shows a characteristic eosinophilic interdigitating material that looks very much like fibrous tissue but is negative for fibrous stains
-can be cured using 2CdA therapy
Q: What do hairy cells look like?
-have round, oblong or reniform nuclei and modest amounts of pale blue cytoplasm with thread-like extensions
Q: Describe the immunophenotyping of hairy cells.
-express the pan B-cell markers CD19 and CD20, surface IgH (IgG normally) and eiterh kappa or lambda light chain, CD11c, CD25 and CD103
Q: Describe myelodysplastic syndrome (MDS).
-a group of clonal stem cell disorders characterized by maturation defects associated with ineffective hematopoiesis and an INC risk of transformation to AML, affects RBCs, platelets and leukocytes
-the cause is unknown with 55% of patients having cytogenetic abnormalities
-a sig. number of patients develop leukemia
-there is less than 30% blasts in bone marrow (greater than 30% in leukemia)
Q: What happens to the bone marrow in MDS?
-marrow is partly or wholly replaced by the clonal progeny of a mutation mulipotent stem cell that retains the capacity to differentiate into red cells, granulocytes and platelts but in an ineffective and disordered fashion
Q: How can MDS arise?
1. idiopathic or primary MDS occurs mainly at ages over 50 and often develops insidiously
2. therapy-related MDS (t-MDS) is a complication of previous genotoxic drug or radiation therapy that appears 2 to 8 years after treatment
Q: Describe the pathogenesis of MDS.
-unknown, cellularity of marrow is variable, MDS bone marrow progenitors undergo apoptosis at an INC rate
Q: What is the classification of MDS by FAB?
1. refractory anemia (refracoty cytopenia)
2. refracotyr anemia with ringed sideroblasts
3. refractory anemia with excess blasts
4. refractory anemia excess blasts in transformation
5. chronic myelomonocytic leukemia
Q: Describe refractory anemia (refractory cytopenia).
-most benign of the MDS and has the least likelihood of transformation into acute leukemia (<10%)
-clinically see anemia and fatigue in patient
Q: What are the lab findings associated with refractory anemia (RA)?
-normochromic, macrocytic or dimorphic with hypochromia anemia, macrocytic anemia in the presence of a hypercellular marrow that shows megaloblastic features
-R/O vita B12, folic acid and iron deficiency or chronic disease
-less than 5% blasts in bone marrow
Q: Describe refractory anemia with ringed sideroblasts (RARS).
-similar to refractory anemia but has iron granules in more than 15% of the normoblasts cases
-associated with INC serum iron and %iron saturation
-pts present with hypochromic, microcytic anemia but a dimorphic blood picture
-marrow is hypercellular
Q: What is the diagnostic feature of refractory anemia with ringed sideroblasts?
-the presence of numerous + iron granules arranged in a ring or parital ring around the nucleus on an iron stain
-to be classified as such need >15% of developing erythroid cells to contain the rings, <5% blasts in marrow
Q: Describe refracotyr anemia with excess blasts (RAEB).
-hallmark is normochromic or macrocytic anemia in the presence of hypercellular marrow that shows 5-20% myeloblasts and no Auer rods
-erythrocytes and megakaryocytes have dysplastic features
Q: Describe refracotyr anemia with excess blasts (transformation).
-represents a more advanced stage of RAEB with a greater percentage of blasts (20-30%), greater than 30% blasts is acute leukemia
-features are intermediate between cells with normal differentiation and evolution into acute leukemia
Q: What is the prevalence, % that progress to leukemia and Med survival of RA?
-28% prevalence, 12% that progress to leukemia and 50 months Med survival
Q: What is the prevalence, % that progress to leukemia and Med survival of RARS?
-24% prevalence, 8% that progress to leukemia and 51 months Med survival
Q: What is the prevalence, % that progress to leukemia and Med survival of RAEB?
-23% prevalence, 44% that progress to leukemia and 11 months Med survival
Q: What is the prevalence, % that progress to leukemia and Med survival of RAEB in transformation?
-9% prevalence, 60% that progress to leukemia and 5 months Med survival
Q: What is the prevalence, % that progress to leukemia and Med survival in chronic myelomonocytic leukemia?
-16% prevalence, 14% that progress to leukemia and 11 months Med survival
Q: Describe chronic myelomonocytic leukemia.
-characterized by an INC absolute monocyte count in the peripheral blood without a secondary stimulus such as TB or chronic inflammation, monocytes are atypical or immature and may show nucleoli
-insidious onset in older person, slowly progressive
-marrow may show an abundance of cleaved and clefted cells
Q: What are the lab findings associated with myelomonocytic leukemia?
-abnormal monocytes and myelocytes with >5% blasts in blood (bone marrow has <20%)
-+ esterase stain of monos and precursors
-INC serum lysozyme and hyperuricemia
-some have polyclonal gammopathy