Neoplastic Myeloid Disorders Flashcards

Question

AML with megakaryocytic maturation Prognosis FAB Subtype Morphology/Comments

Answer 1

Intermediate M7 Blasts of megakaryocytic lineage predominate; detected with antibodies against megakaryocyte-specific markers (GPIIb/IIIaor vWF); often associated with marrow fibrosis; most common AML in Down syndrome

Answer 2

Almost exclusively leukemic cells | Hematopoiesis reduced via replacement (myelophthisic) or stem cell supression

Answer 3

Myeloblastshave delicate nuclear chromatin, prominent nucleoli, and fine azurophilic granules in the cytoplasm.

Answer 4

express CD34, a marker of multipotent stem cells, but do not express CD64, a marker of mature myeloid cells The same myeloid blasts express CD33, a marker of immature myeloid cells, and a subset express CD15, a marker of more mature myeloid cells. Thus, these blasts are myeloid cells showing limited maturation

Answer 5

Bone marrow aspirate shows neoplastic promyelocyteswith abnormally coarse and numerous azurophilicgranules. Other characteristic findings include the presence of several cells with bilobednuclei and a cell in the center of the field that contains multiple needle-like Auer rods.

Answer 6

Peripheral smear shows one monoblastand five promonocyteswith folded nuclear membranes

Answer 7

* Presents with same acute onset and symptoms as ALL (anemia, infection, fever, bone pain, and bleeding) * DIC occurs in AML with t(15;17)(q22;11-12);RARα/PMLfusion gene * Neoplastic cells with monocytic differentiation infiltrate skin * Variable blast count 100,000/mm3

Answer 8

* Much poorer overall prognosis than ALL * 60% can achieve one complete remission, but only 15-30% remain disease free after 5 years. * Survival dependent specific subtype and cytogenetic findings * Pre-existing MyelodysplasticSyndrome (MDS) confers “Dismal Prognosis” * Increased incidence in Down Syndrome * Myeloid Leukemia is usually Acute MegakaryoblasticLeukemia * Not as common as Acute Lymphoblastic Leukemia in Down Syndrome

Answer 9

* Splenomegaly * Hepatomegaly * Gum swelling or skin nodules * Sternal tenderness * Petechiae

Answer 10

median age at diagnosis 67

Answer 11

MEDIAN AGE AT DEATH 72

Answer 12

* Refractory cytopeniawith unilineagedysplasia * Refractory anemia * Refractory neutropenia * Refractory thrombocytopenia * Refractory anemia with ring sideroblasts * Refractory cytopeniawith multilineagedysplasia * Refractory anemia with excess blasts * Myelodysplastic syndrome with isolated del(5q) * Myelodysplastic syndrome, unclassifiable * Childhood myelodysplastic syndrome * Provisional entity: refractory cytopeniaof childhood

Answer 13

A, Nucleated red cell progenitors with multilobatedor multiple nuclei. B, Ringed sideroblasts, with iron-laden mitochondria (blue granules) C, Pseudo-Pelger-Hüetcells, neutrophils with two nuclear lobes instead of three to four D, Megakaryocytes with multiple separate nuclei

Answer 14

Cytopenia | Blasts (

Answer 15

Anemia No blasts Monocytes≤1,000/μL Erythroid dysplasia only

Answer 16

Cytopenia(s) | Blasts (10% of the cells of ≥2 myeloid lineages

Answer 17

5-19% blasts +/-Auer rods 10%-19% blasts +/-Auer rods

Answer 18

Anemia | ↔or ↑platelets

Answer 19

Cytopenia(s) Monocytes≤1,000 Unilineage or multilineage dysplasia

Answer 20

Affects individuals older than 50 years (mean age of onset 70 years) Presents with weakness, infection and hemorrhage caused by bone marrow failure and peripheral pancytopenia ~ 50% discovered incidentally during routine blood testing for another reason Anemia that may be accompanied by monocytosis

Answer 21

* If it looks like myelodysplasia and has >1000 monocytes/uLin the blood than the patient has chronic myelomonocyticleukemia * If it looks like myelodysplasia or a myeloproliferative syndrome and there is more than 20% blasts in the bone marrow or blood than it is acute myeloid leukemia

Answer 22

Some good prognostic groups may live 5 years or more Median survival in primary MDS varies from 9-29 months t-MDS prognosis is 4-8 months MDS is serious disease in its own right without progression to AML Overall progression to AML occurs in 10-40% and in these patients the prognosis is “dismal”…..6 months or less

Answer 23

* Multipotent progenitor cell capable of giving rise to mature erythrocytes, platelets, granulocytes (except CML) * In chronic myelogenousleukemia (CML) pluripotent stem cell gives rise to myeloid cells and lymphocytes * The neoplastic cells displace normal bone marrow and suppress normal hematopoiesis * The terminal differentiation of the neoplastic clone is unaffectedand mature end-stage cells are increased in the peripheral blood in markedly increased numbers * Associated with an abnormal increase in the activity of mutated tyrosine kinases with growth factor independent proliferation and survival

Answer 24

BCR-ABLfusion gene 100% Constitutive ABL kinase activation

Answer 25

JAK2point mutations >95% Constitutive JAK2kinase activation

Answer 26

JAK2point muations 50% to 60% Constitutive JAK2kinase activation

Answer 27

MPLpoint mutations 5% to 10% Constitutive MPLkinase activation

Answer 28

c-KITpoint mutations >90% Constitutive KIT kinase activation

Answer 29

FIP1L1-PDGFRαfusion gene Common Constitutive PDGFRα kinase activationConstitutive PDE4DIP-PDGFRβfusion gene Rare Constitutive PDGFRβ kinase activation

Answer 30

VariousFGFR1fusion genes 100% Constitutive FGFR1 kinase activation

Answer 31

Chronic myelogenousleukemia Polycythemia vera Essential thrombocythemia Primary myelofibrosis Systemic mastocytosis Chronic eosinophilic leukemia4 Stem cell leukemia5

Answer 32

* Chronic myelogenousleukemia, BCR-ABL1–positive * Chronic neutrophilic leukemia * Polycythemia vera * Primary myelofibrosis * Essential thrombocythemia * Chronic eosinophilic leukemia, not otherwise specified * Mastocytosis * Myeloproliferativeneoplasms, unclassifiable

Answer 33

* Myeloid and lymphoid neoplasms associated with PDGFRArearrangement * Myeloid neoplasms associated with PDGFRBrearrangement * Myeloid and lymphoid neoplasms associated with FGFR1abnormalities

Answer 34

* Chronic myelomonocyticleukemia * Atypical chronic myeloid leukemia, BCR-ABL1–negative * Juvenile myelomonocyticleukemia * Myelodysplastic/myeloproliferativeneoplasm, unclassifiable * Provisional entity: refractory anemia with ring sideroblastsand thrombocytosis

Answer 35

CML is distinguished from other chronic MPDs by the presence of a chimeric BCR-ABL gene derived from portions of the BCR gene on chromosome 22 and the ABLgene on chromosome 9 ….in more than 90% of cases … (9;22)(q34;q11) .. Philadelphia Chromosome(Ph) t(9;22) is also seen in some ALL and AML patients

Answer 36

•100% cellular marrow (no fat) •Increased precursors of all cell lines, including megakaryocytes •Peripheral marked leukocytosis 50,000 or even 100,000 total granulocyte count with PMNs, bands, metamyelocytes, myelocytes, +/-basophilia, but

Answer 37

many mature neutrophils, some metamyelocytes, and a myelocyte

Answer 38

Breakage and joining of BCR and ABL creates a chimeric BCR-ABL fusion gene that encodes a constitutively active BCR-ABL tyrosine kinase. BCR-ABL activates multiple downstream pathways, which drive growth factor-independent proliferation and survival of bone marrow progenitors. Because BCR-ABL does not interfere with differentiation, the net result is an increase in mature elements in the peripheral blood, particularly granulocytes and platelets.

Answer 39

This translocation involves transfer of portion of q arm, C22, to q arm, C9, and is designated t(9:22). This translocation brings c-ablproto-oncogene on chromosome 9 in proximity with bcr(breakpoint cluster) gene on chromosome 22.

Answer 40

Useful adjunct to routine cytogenetics heat to relax dna,seperate strands add fluorescently tagged dna probe cool to allow annealing of probe and target

Answer 41

Because of the pairing of sister chromatids during mitosis, signals on metaphase chromosomes may be seen as a single dot or a pair of closely spaced dots. Two pairs of red signals and two green signals are seen on metaphase, while 2 red and 2green signals are present in interphase nucleus, indicating the presence of normal, spatially distant copies of ABLand BCR, respectively.With CML show one normal ABLsignal, one normal BCRsignal, and an abnormal yellow signal created by superimposition of one BCRand one ABLsign

Answer 42

•Natural history is one of slow progression with moderate anemia and hypermetabolism(high cell turnover) •Major symptoms are weakness, easy fatigability and weight loss……..markedly enlarged spleen is a constant finding •Massive splenomegaly may lead to splenic infarcts •3 years median survival without treatment •50% of patients enter an “accelerated” phase (worse anemia and thrombocytopenia) then enter after 6 to 12 months a “blast crisis”----development of acute leukemia •Other 50% eventually develop “blast crisis” without accelerated phase •70% develop myeloid leukemia and 30% pre-B leukemia Rx-Gleevac/imatinib(BCR-ABL kinase inhibitor)

Answer 43

Enlarged spleen (2630 gm; normal: 150 to 200 gm) with greatly expanded red pulp stemming from neoplastic hematopoiesis

Answer 44

median age at diagnosis

Answer 45

median age at death 76

Answer 46

* True polycythemia with panmyelosis(erythrocytosis, granulocytosis and thrombocytosis) +/-basophilia * Peripheral blood hematocrit around 60% * increases in red cell mass produces symptoms related to hyperviscositysyndromes with thromboses and infarcts * Bone marrow-all precursors increased * Progenitor erythroblasts in PV are hypersensitive to erythropoietin (usually due to JAK2 V617F mutation) and serum erythropoietin levels are suppressed * JAK2 mutation occurs in >95% of patients

Answer 47

Median age onset 60 years Plethoric and cyanotic Abnormal viscosity and perhaps increased, but abnormal platelets leads to increased major bleeding and thrombosis Patients develop massive splenomegaly Pruritis and peptic ulcers due to released histamine from increased basophils 5-10% develop gout (hyperuricemia from nuclei breakdown)

Answer 48

Hemoglobin usually 14-28 gm/dLand Hct> 60% WBC 12,000 -50 ,000 /mm3 Platelets >500,000/mm3common Treat with phlebotomy to control symptoms and avoid bleeding/thrombosis complications Untreated survival is months With extended survival by treatment, 15-20% tend to evolve to a “spent phase” during which clinical and anatomic features of primary myelofibrosis develop Occasionally (1-2%) can develop blast crisis (AML)

Answer 49

Massive splenomegaly (3020 gm; normal: 150 to 200 gm) largely due to extramedullary hematopoiesis occurring in the setting of advanced marrow myelofibrosis.

Answer 50

•Least common of chronic myeloproliferativedisorders •JAK2 (50%) and MPL (5-10%)tyrosine kinase mutations or calreticulinmutations •Increased proliferation confined to megakaryocytes with platelet counts of > 450,000 with megathrombocytes •Since all chronic myeloproliferative disorders may be associated with thrombocytosis, essential thrombocythemiais a diagnosis of exclusion- No polycythemia or progressive marrow fibrosis

Answer 51

* Bone marrow cellularity only mildly to moderately increased but megakaryocytes are substantially increased in number * Thromboses (erythromelalgia) and bleeding occur * Indolent clinical course with onset after age 60 and median survival of 12 to 15 years

Answer 52

-numerous megakaryocytes, some much larger than normal. Peripheral platelet counts can exceed 1,000,000/microliter.

Answer 53

Peripheral blood smear shows marked thrombocytosis, including giant platelets approximating the size of surrounding red cells

Answer 54

rapidly developing obliterativemarrow fibrosis caused by extensive collagen deposition by non-neoplastic fibroblasts •Stimulated by platelet derived growth factor and TGF-β

Answer 55

Early in progression of fibrosis, marrow is hypercellularand there may be transient leukocytosis and thrombocythemia Eventually the fibrosis obliterates much of the marrow space and abnormal dysplastic precursor forms are seen (large clustered megakaryocytes) and cytopeniasdevelop JAK2 (50-60%) and MPL (1-5%)tyrosine kinase mutations or calreticulinmutations

Answer 56

Onset after age 60 with initial symptoms of progressive anemia or marked splenomegaly (+/-infarcts) caused by extramedullary hematopoiesis May develop hyperuricemia and gout Exhibit “leukoerythroblastosis” in peripheral smear Anemia, megathrombocytes and basophilia Aggressive disease: Median survival is 3-5 years 5-20% may develop AML-like blast crisis

Answer 57

Two nucleated erythroid precursors and several teardrop-shaped red cells (dacryocytes) are evident. Immature myeloid cells were present in other fields. An identical picture can be seen in other diseases producing marrow distortion and fibrosis.

Answer 58

A.K.A. eosinophilic granuloma, Langerhans cell granulomatosis, histiocytosisX (“H-X”), Hand-Schuller-Christian disease, Letterer-Siwedisease Immature dendritic cell Vesicular nuclei with linear grooves or folds On EM has “Birbeck” granules (HX bodies) composed of pentalaminartubules with dilations BRAF, TP53, RAS and MET mutations seen S-100+ ; CD1+; CD207+ (langerin), CD1a+, HLA-DR+

Answer 59

Express CCR6 like in normal Langerhans cells (CCL20 ligand in skin and bone) Express CCR7 abnormally (CCL19 & CCL20 in lymphoid tissues)

Answer 60

Age: most cases occur in childhood Incidence: 5 per million population per year Race: Caucasian>>>African-American Survival: Unifocaldisease (>99% 5-year survival) Multisystem disease (66% mortality)

Answer 61

Most frequently before 2 years of age (occasionally affects adults) Cutaneous lesions resembling a seborrheic eruption (Langerhans cells infiltrate) Hepatosplenomegaly, lymphadenopathy, pulmonary lesions and bone lesions With chemotherapy, 50% 5 year survival, untreated disease is rapidly fatal

Answer 62

•Langerhans cells with mixed eosinophils, lymphocytes, plasma cells, and neutrophils Many patients experience spontaneous regression Treatment: Chemotherapy if multifocal Local excision or irradiation if unifocal

Answer 63

•Skeletal system in older children or adults (occasionally skin, lung, or stomach)

Answer 64

* Multiple erosive bony masses young children * 50% have diabetes insipidus (involve posterior pituitary stalk of hypothalamus) * Hand-Schuller-Christian triad: calvarialbone defects, diabetes insipidus, and exophthalmos

Answer 65

Bilateral interstitial disease (Multifocal unisystem) Multiple fine nodules and cysts in the middle and upper lung zones Represents an inflammatory immunologic disorder (usually polyclonal) strongly associated with cigarette smoking 40% are clonal with BRAFmutations indicative of neoplastic proliferation

Answer 66

Pulmonary Langerhans' cell Granulomatosis Pulmonary histiocytosisX Pulmonary eosinophilic granuloma Eosinophilic granuloma of the lung

Answer 67

Age of onset between ages 15 and 40 Can regress spontaneously on cessation of smoking

Answer 68

Eosinophilic Granuloma

Answer 69

A,Langerhans cells with folded or grooved nuclei and moderately abundant pale cytoplasm are mixed with a few eosinophils. B,An electron micrograph shows rodlike Birbeckgranules with characteristic periodicity and dilated terminal end.

Neoplastic Myeloid Disorders Flashcards

(96 cards)