Term
| T/F Myeloproliferative neoplasms are the same thing as myeloproliferative disorders. |
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Definition
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Term
| What do myelodysplastic and myeloproliferative disorders have in common? |
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Definition
| they are clonal stem cell disorders, quantitative, transform to acute leukemia |
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Term
| What are differences between myelodysplastic and myeloproliferative disorders? |
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Definition
MD= quantitative and qualitative, cytopenias/ineffective hematopoeisis, abnormal morphology, minimal organomegaly
MP= quantitative only, cytosis with effective hematopoiesis, normal morphology, organomegaly (commonly spleen) |
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Term
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Definition
| chronic myelogenous leukemia, polycythemia vera, essential thromocythemia, primary myelofibrosis, chronic eosinophilic leukemia, NOS, mastocytosis, chronic neutrophilic leukemia, myeloproliferative neoplasm, unclassifiable |
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Term
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Definition
| primarily in adults (CML and ET can occur in children) |
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Term
| What is the incidence of MPN? |
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Definition
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Term
| What are the phases of MPNs? |
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Definition
| cellular phase (hypercellular BM, peripheral blood cytosis), fibrotic (progressive BM fibrosis), leukemic (AML or ALL in 20%) |
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Term
| What causes myelofibrosis in MPN? |
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Definition
| its a secondary phenomenon because fibroblasts do not belong to the neoplastic clone. Fibrosis is induced by release of cytokines and growth factors like PDGF and TGF-beta. Megakaryocytes appear to be esp. important in inducing myelofibrosis |
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Term
| All MPNs are characterized by... |
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Definition
| proliferation of one or more myeloid lineages (granulocyte, erythroid, megakaryocyte, mast cell); hypercellular marrow with effective hematopoiesis |
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Term
| What types of mutations underly MPNs? |
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Definition
translocations or point mutations that lead to 1) activated tyrosine kinase receptors 2) abnormalities in proteins that are important in tyrosine kinase pathways
also, enhanced expression of antiapoptotic pathways |
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Term
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Definition
| a tyrosine kinase that plays an important role in normal hematopoietic growth factor signaling |
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Term
| Mutation of JAK2 results in.. |
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Definition
| activation of the kinase, deregulated intracellular signaling with cell proliferation; cell proliferation is independent of normal growth factor control |
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Term
| Which MPNs are notable for having JAK 2 mutations? |
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Definition
99% of polycythemia vera
70% of essential thrombocythemia
50% of primary myelofibrosis |
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Term
| Why is getting a JAK2 mutation lab helpful for MPN? |
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Definition
| can confirm diagnosis of PV, ET, or primary myelofibrosis or confirm the presence of a clonal stem cell disorder and ruling out reactive disorders |
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Term
| What is the typical patient population of polycythemia vera? |
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Definition
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Term
| Is polycythemia vera responsive to EPO? |
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Definition
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Term
| What is the pathophysiology that leads to symptoms in polycythemia vera? |
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Definition
| increased Hct, Hb, blood viscosity --> thrombotic and hemorrhagic problems |
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Term
| What are the symptoms of PV? |
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Definition
| headache, pruritis (esp after hot shower), gout, bruising/epistaxis (platelet dysfunction), transient neurologic complaints (h/a, tinnitus, dizzines, blurred vision, paresthesias), atypical chest pain, hemorrhagic or thrombotic events, eryhtromelalgia |
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Term
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Definition
| increased skin temp, burning sensation, redness esp. in distal extremities |
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Term
| What causes the bruising/epistaxis of polycythemia vera? |
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Definition
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Term
| What are the physical exam findings of PV? |
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Definition
| splenomegaly, hepatomegaly, plethora, weight loss, weakness, sweating, hypertension |
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Term
| What are the two phases of PV? |
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Definition
1)polycythemic stage
2) "spent" stage (post-polycythemic myelofibrosis) |
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Term
| What does the bone marrow look like the the polycythemic stage of PV? |
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Definition
| panhyperplasia, mod to marked hypercellularity, no dysplasia, decreased or absent iron stores |
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Term
| How high does the Hgb/Hct have to be for a pt to qualify for the diagnostic criteria of PV? |
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Definition
> 18.5 in men
16.5 in women |
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Term
| What is the pO2 in polycythemic stage of PV? |
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Definition
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Term
| What are the WBC and PLT in polycythemic stage of PV? |
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Definition
| both are increased (may see mild neutrophilia, basophilia) |
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Term
| Why do pts with PV get gout? |
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Definition
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Term
| What is the serum EPO in pts with polcythemic stage of PV? |
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Definition
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Term
| What is the RBC mass in PV? |
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Definition
| increased in polycythemic stage; normal to decreased in spent stage |
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Term
| Describe the PBS of pts with "spent stage" of PV. |
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Definition
| leukoerythroblastic (immature WBCs, NRBCs, poikilocytosis, teardrop cells |
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Term
| Describe the bone marrow of the spent stage of PV. |
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Definition
| reticulin fibrosis, clusters of megakaryocytes, decreased erythropoiesis and granulopoiesis |
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Term
| Why do patients in the spent stage of PV get splenomegaly and hepatomegaly? |
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Definition
| extramedulary hematopoeisis |
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Term
| What two types of polycythemias must be ruled out to come to dx of PV? |
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Definition
| secondary polycythemia and relative polycythemia |
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Term
| What could cause a physiologically appropriate secondary polycythemia? |
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Definition
| chronic pulmonary or cardiac disease, residence at high altitude, high oxygen affinity hemoglobinopathy, increased carboxyhemoglobin (in smokers) and methemoglobin |
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Term
| What could cause a physiologically inappropriate PV? |
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Definition
| adrenal cortical hypersecretion, hydronephrosis (increased EPO), tumors producing EPO or anabolic steroids |
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Term
| What would cause a relative polycythemia? |
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Definition
| normal or decreased RBC mass, decreased plasma volume, disorders associated with decreased plasma volume (diarrhea, emesis renal disease) |
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Term
| How do you tell the difference between PV and secondary? |
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Definition
| PV has splenomegaly, leukocytosis, thrombocytosis and panmyelosis on BMA. Also has decreased or normal EPO levels and abnormal cytogenetics (JAK2+) |
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Term
| What are the future complications of PV? |
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Definition
| hemorrhagic/thrombotic episodes; will progress to myelofibrosis; may transform into acute leukemia |
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Term
| What is the median survival of a patient with PV? |
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Definition
| 6-18 months in untreated symptomatic patients after diagnosis; > 10 years with treatment |
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|
Term
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Definition
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Term
| What are synonyms for primary myelofibrosis? |
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Definition
| chronic idiopathic myelofibrosis (CIMF), idiopathic myelofibrosis, myelosclerosis with myeloid metaplasia (MMM), chronic granulocytic-megakaryocytic myelosis, agnogenic myeloid metaplasia |
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Term
| What are the characteristics of primary myelofibrosis? |
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Definition
| chronic progressive panmyelosis, progressive bone marrow fibrosis, massive splenomegally, leukoerythroblastic anemia |
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Term
| Describe the patient population of primary myelofibrosis? |
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Definition
| middle age to elderly most common in 7th decade; M=F |
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Term
| What are teh symptoms of primary myelofibrosis? |
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Definition
| insidious onset; up to 30% asymptomatic at diagnosis; low-grade fever, night sweats, weight loss, weakness, fatigue, bleeding (platelet dysfunction) |
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Term
| What are the physical findings of primary myelofibrosis? |
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Definition
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Term
| What are the characteristics of PBS of primary myelofibrosis? |
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Definition
| leukoerythroblastosis, marked anemia, prominent poikilocytosis with NRBCs and teardrops, leukocytosis with left-shift, may see blasts; large/bizarre plaetlets, micromegakaryocytes, and megakaryocyte nuclei |
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Term
| What do you see on BM of primary myelofibrosis INITIALLY? |
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Definition
| hypercellular prefibrotic phase with megakaryocytic hyperplasia (clustering and abnormally lobulated nuclei) |
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Term
| What do you see during the fibrotic phase of primary myelofibrosis on BM? |
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Definition
| reticulin or collagen fibrosis, dry tap |
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Term
| How long do patients with primary myelofibrosis live? |
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Definition
| 3-5 year median survival (ranges from months to decades); <20% 10 year survival |
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Term
| What percent of primary myelofibrosis tranforms to AML? |
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Definition
| 20-30%; can occur without prior cytotoxic tx and is part of natural history of PMF |
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Term
| What is teh cause of death in primary myelofibrosis? |
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Definition
| bone marrow failure, thromboembolic phenomenon, portal hypertenison, cardiac failure, transformation to acute leukemia |
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Term
| Describe the BMA of essential thrombocythemia? |
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Definition
| megakaryocytic hyperplasia; large, deeply lobulated megakaryocytes |
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Term
| What is the patient population of essential thrombocythemia? |
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Definition
middle age to elderly (most 50-60) where M=F
peak at 30 yoa where F>M
can see this in children |
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Term
| What is the positive WHO criteria for essential thrombocythemia? |
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Definition
sustained platelet count of at least 450 X 10^9
bone marrow biopsy shows proliferation and deeply lobulated megakaryocytes
JAK2 may be positive |
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Term
| Essential thrombocythemia is essentially a diagnosis of exclusion where you must rule out... |
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Definition
| PV, CML, PMF, MDS and reactive thrombocytosis |
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Term
| What are teh clinical manifestations of essential thrombocythemia? |
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Definition
| >1/2 are asymptomatic; bleeding, thromboembolic episodes (splenic or haptic vein thrombosis), disturbances in microcirculation (TIAs, digital ischemia with paresthesias and gangrene) |
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Term
| What is the clinical course of ET? |
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Definition
| indolent; long symptom free intervals interrupted by occasional life-threatening thromboembolic or hemorrhagic episodes; transformation to MDS or acute leukemia in < 5% (usually related to previous cytotoxic tx); progression to marrow fibrosis uncommon |
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Term
| What is teh prognosis of ET? |
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Definition
| 80% survival at 5 years; median survival of 10-15 years |
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Term
| What age group gets chronic eosinophilic leukemia? |
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Definition
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Term
| What are teh clinical featuers of chronic eosinophilic leukemia? |
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Definition
| cytokine driven organ damage (heart, lungs, CNS, skin, GI); splenic and hepatic involvment in 30-50%, restrictive cardiomyopathy (d/t endomyocardial fibrosis) |
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Term
| What diseases must you exclude to make a diagnosis of chronic eosinophilic leukemia? |
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Definition
| abnormal T cell populations that cause cytokine driven eosinophilia, hodgkin, NHL, other MPNs, some acute leukemias with eosinophilia, parasites, collagen vascular diseases |
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Term
| Describe the mophology of the eosinophils in chronic eosinophilic leukemia? |
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Definition
| sparse granulation, vacuolization, enlarged size, and hypo or hypersegmentation |
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Term
| What do you see on BMA of chronic eosinophilic leukemia? |
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Definition
| hypercellular with increased eosinophils, sometimes fibrosis |
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Term
| While chronic eosinophilic leukemia is due to a clonal cytogenetic abnormality, it is NOT due to the following mutations: |
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Definition
| Bcr/Abl (ph chrom), no rearrangement of PDGFRB, PDGFRA, FGFR1 |
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Term
| What features of chronic eosinophilic leukemia are associated with an unfavorable prognosis? |
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Definition
| marked splenomegaly, blasts in the blood, increased number of blasts in teh marrow |
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Term
| What is the typical patient with myeloid and lymphoid neoplasm with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1? |
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Definition
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Term
| What causes myeloid and lymphoid neoplasm with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1? |
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Definition
| abnormalities in genes encoding above aberratn tyrosine kinase receptors; result in increased tyrosine kinase activity |
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Term
| Why is it important to differentiate between chronic eosinophilic leukemia and myeloid and lymphoid neoplasm with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1? |
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Definition
| myeloid and lymphoid neoplasm with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 may be responsive to gleevec |
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Term
| How do you diagnose idiopathic hypereosinophilic syndrome? |
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Definition
| if no underlying cause of eosinopihlia can be found and the clonality of eosinophils can not be proven |
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Term
| What are teh two major subtypes of mastocytosis? |
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Definition
| cutaneous mastocytosis and systemic mastocytosis |
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Term
| What causes mastocytosis? |
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Definition
| somatic point mutations in KIT protooncogene results in activation of tyrosine kinase; resistant to imatinib (gleevec) |
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Term
| Can you use imatinib to treat mastocytosis? |
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Definition
| no, even though its a tyrosine kinase mutation it is resistant to imatinib |
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Term
| What's teh generic name for gleevec? |
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Definition
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|
Term
| What age is characteristic of cutaneous mastocytosis? |
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Definition
| childhood (50% get skin lesions before 6 mos of age) |
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Term
| What physical exam sign is indicative of cutaneous mastocytosis? |
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Definition
| darier's sign (lesions urticate when stroked) |
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Term
| What is urticaria pigmentosa? |
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Definition
| pigmented macular and maculopapular lesions (occurs in cutaneous mastocytosis) |
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Term
| What is the pathophys of cutaneous mastocytosis? |
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Definition
| aggregates of mast cells fill the papillary dermis and extend into the reticular dermis; no evidence of systemic involvement |
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Term
| Name the skin lesions of cutaneous mastocytosis? |
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Definition
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|
Term
| What's the prognosis of cutaneous mastocytosis? |
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Definition
| usually good outcome (may spontaneously regress) |
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Term
| What age group gets systemic mastocytosis? |
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Definition
| diagnosed after 2nd decade |
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Term
| What are the symptoms of systemic mastocytosis? |
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Definition
| constitutional (fever, weight loss, fatigue), skin (pruritis, urticaria, dermatographism), mediator related, musculoskeletal (bone pain, fractures, myalgias), organomegally (esp splenomegaly) |
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Term
| What are the mediator related symptoms of systemic mastocytosis? |
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Definition
| abdominal pain, GI distress, flushing, syncope, headache, hypertension, tachycardia, respiratory symptoms |
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|
Term
| High serum tryptase levels is indicative of... |
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Definition
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|
Term
| What finding on physical exam is typical of essentially all MPNs? |
|
Definition
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