Week 1 Flashcards

(70 cards)

1
Q

Differential blood count normals

A
Neutrophils: 34-71
Lymphocytes: 19-53
Monocytes: 5-12
Eosinophils: 0-7
Basophils: 0-1
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2
Q

Granulocytes

A

Neutrophils: PMNs, kill bacteria via NADPH oxidase
Eosinophils: bi-lobed nucleus, red granules contain major basic protein (MBP), kill parasites, secrete leukotrienes
Basophils: contain histamine and heparin, similar to mast cells, invilved in allergy (IgE)

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3
Q

Agranulocytes

A

Monocytes: largest, horseshoe-nucleus, turn into macrophages, APCs
Lymphocytes: B and T, immune cells, viruses

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4
Q

Hematopoieses flow chart

A

Multipotent stem cell-> MSCs and hemangioblasts
Hemangioblasts-> endothelial progenitors and HSCs
HSCs(CD34,cKit)->myeloid and lymphoid progenitors
Lymphoid->B and T cells
Myeloid-> erythroblasts, myeloblasts, megakaryoblasts (all CD45)

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5
Q

Erythrocyte differentiation

A

Proerythroblast: large, blue cytoplasm, multiple nucleoli
Basophylic erythroblast: only one nucleoli, less cytoplasm, more blue
Polychromatic erythroblast: mottled nucleus/chromatin, more grey cytoplasm, smaller
Orthochromatic erythroblast/normoblast: grey cytoplasm, nucleus near edge of cell
Reticulocyte: nucleus extruded but still immature
Erythrocyte: no nucleus, red pale color

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6
Q

Myeloblast (Neutrophil) differentiation

A

Myeloblast: large, pale blue cytoplasm, multiple nucleoli
Promyelocyte: many blue granules, peripheral nucleus, large
Myelocyte: fewer blue granules, more pale cytoplasm
Metamyelocyte: slightly indented nucleus, no visible granules
Band: C or S shaped nucleus
Neutrophil: multi-lobulated nucleus

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7
Q

Leukomoid Reaction

A

High white count (leukocyte >50,000/uL)
reactive to infection, usually bacterial
NOT neoplastic

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8
Q

Leukoerythroblastic reaction

A

immature bone marrow cells in the peripheral blood

secondary to bone marrow fibrosis, metastatic cancer, or severe bone marrow stress

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9
Q

Neutrophilia

A

absolute neutrophils >7000/ul
due to infxn or drugs
in infxn, also undergo “toxic change” in which neutrophils have prominent blue primary granules

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10
Q

Neutropenia

A

absolute neutrophils <1500/ul

due to aplastic anemia, immune destruction, sepsis, chemotherapy, etc

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11
Q

Eosinophilia

A

eosinophils >700/ul

due to thype I hypersensitivity, parasites, addison’s, or neoplasms

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12
Q

Basophilia

A

basophils >200/ul

usually due to chronic myelogenous leukenia

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13
Q

Myeloproliferative Neoplasms (MPN)

A
chronic myelogenous leukemia (CML)
Polycythemia vera (PV)
Primary myelofibrosis (PMF)
Essential thrombocytopenia (ET)
more common in adults, rare
CLONAL Hypercellular bone marrow with EFFECTIVE hematopoisis-> increased peripheral counts
organomegaly, can progress to acute leukemia or fibrosis
often increased tyrosine kinase activity
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14
Q

Myelodysplastic Syndromes (MDS)

A

CLONAL Hypercellular bone marrow with DECREASED peripheral counts
increased risk of AML
myeloblasts may increase, but <20%
chromosomal abnormalities common
more common in elderly
Tx: hypomethylating agents, growth factors, blood, allogenic stem cell transplant

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15
Q

Chronic Myelogenous Leukemia (CML)

A

MPN (mature cells)
BCR-ABL fusion gene (t(9,22), philidelphia chromosime-> tyrosine kinase activity
high leukocytosis (>100,000/ul), with neutrophilia and immature myeloid cells
often basophilia and thrombocytosis
progressive if not treated to accelerated and then blast phase (acute leukemia)
Tx: tyrosine kinase inhibitors (Imatinib)

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16
Q

Polycythemia vera (PV)

A

MPN
increased red cell mass, hypercellular bone marrow
JAK2 gene mutation
decreased serum EPO, normal O2sat

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17
Q

Primary myelofibrosis (PMF)

A

MPN
rapid bone marrow fibrosis and extramedullary hematopoiesis
splenomegaly-> portal HTN
anemia, teardrop cells, leukoerythroblastic reaction
JAK2 mutation in 50%
May develop AML

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18
Q

Essential Thrombocythemia (ET)

A
MPN
proliferation of megakaryocytes
elevated platelet count, atypical morphology
hypercellular bone marrow
JAK2 mutation in 50%
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19
Q

Acute Myeloid Leukemia (AML)

A

Primarily adults, poor outcome
proliferation of immature myeloblasts (large and uniform)
Auer rods,, myeloperoxidase (MPO)+, non-specific esterase+
CD34+, CD117+
cytopenias,, >20% myeloid blasts,, hypercellular bone marrow
leukopenia or leukocytosis
AML with chromosomal abnormalities= favorable
AML with myelodysplastic changes= bad
mutations: FLT3=bad,,NPM1=good
Tx: “7+3”,, induction then consolidation

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20
Q

AML with recurrent cytogenetic abnormalities

A

t(15,17) = favorable
t(9,11)(MLL) = intermediate
11q23(MLL) = unfavorable
MLL types: infantile AML, monocytic

t(15,17) = acute promyelocytic leukemia (APL)– hypergranular– PML-RARa– assoc with disseminated intravascular coagulation (DIC)-> respondes to ATRA

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21
Q

AML with myelodysplasia-related changes

A

monosomy 7 / del(7q)
monosomy 5 / del(5q)
older folks, unfavorable

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22
Q

Therapy-related AML or MDS

A

from chemotherapy or radiation
alkylating agents or topoisomerase II inhibitors
poor prognosis

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23
Q

Myeloid Sarcoma

A

extramedullary tumor of immature myeloid cells
can be assoc with AML
usually treated like AML

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24
Q

Histiocytic neoplasms

A

Proliferations of macrophages, wide spectrum

Langerhans cell

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25
Langerhans Cell Histiocytosis
immature dendritic cells in epidermis express CD1a and langerin,, Birbeck granules,, "tennis racket" appearance Multisystem (etterer-Siwe): young children, fatal if untreated Unisystem (eosinophilic granuloma): can spontaneous resolve,, Hand-Schuller-Christian triad= calvarial bone defects, diabetes insipidus, exophthalmos BRAF mutations
26
Hemophagocytic lymphohistiocytosis / hemophagocytic syndrome
potentially fatal hyperinflammatory condition Primary: genetic,, perforins and granzymes induce apoptosis Secondary: infxns, rheumatoligic, malignant, metabolic EBV infxn is assoc *very high ferritin*
27
Hematopoietic growth factors
Erythropoietin (EPO): stimulates erythroid precursors to mature, produced in kidney response to hypoxia,, supplemented in kidney disease, chemotherapy, MDS, HIV, premature infants Thrombopoietin (TPO): enhances megakaryocyte prolif and matureation, made in liver, Mpl receptor,, supplemented in immune thrombocytopenia Granulocyte colony stimulating factor (GCSF/filgrastim): myeloid growth factor produced by monocytes, macrophages, endothelial cells,, increase with inflammation,, increase neutrophil production,, uses: neutropenia, prior to bone marrow txplant,, bone pain
28
Flow cytometry
Forward scatter: more for bigger cells | Side scatter: more with morecomplex cytoplasm (granules)
29
CD markers
3: T-cells 4: helper t-cells 8: cytotoxic t-cells 13: granulocytes, monocytes 14: monocytes 15: granulocytes, monocytes 19: B-cells 20: B-cells 34: blasts, stem cells 45: leukocytes
30
Lymphocytosis
lymphocytes >4k/ul can be reactive (benign) or neoplastic reactive: transient, <10k/ul, heterogenous, from infxn, stress, EBV, mononucleosis, etc neoplastic: chronic, monotonous
31
Infectious Mononucleosis
lymphocytosis, atypical morphology heterogenous, large, lightly basophilic cytoplasm, encroaches on neighboring RBCs T-cells responding to EBV-infected B-cells criteria: 1 >50% mononuclear cells (monocytes and lymphocytes) 2 marked lymphocyte heterogeneity 3 >10% reactive lymphocytes
32
Neoplastic Lymphocytoses
``` Chronic lymphocytic leukemia (CLL) hairy cell leukemia splenic marginal zone lymphoma large granular lymphocytic leukemia adult T-cell lymphoma (ATLL) Sezary syndrome ```
33
HTLV-1 and HTLV-2
HTLV-1: infective dermatitis in kids, adult T-cell lymphoma, tropical spastic paraparesis (TSP), risk for protozoal infxns HTLV-2: rare cases of CD8 leukemia, disease resembling TSP, risk for bacterial infxns Viral gene= Tax = lifelong-> activate host transcription factors, mod signal transduction, inhibit apoptosis
34
CDs in Lymphocytoses
``` T-cell: 3,4,5,8 B-cell: 10,19,20,21 Monocyte/macrophage: 11c(hairy cell),15(Reed-Sternberg) Progenitor cell: 34 Activation: 30(Reed-Sternberg) All leukocytes: 45 ```
35
B-cell lymphoblastic leukemia / lymphoma
cell origin: bone marrow precursor B-cell diverse chromosomal translocations: t(12,21) mostly kids, pancytopenia, aggressive
36
T-cell acute lymphoblastic leukemia / lymphoma
cell origin: precursor T-cell (usually thymus) diverse chromosomal translocations: NOTCH1 mutations adolescent males, thymic masses, aggressive
37
Hairy cell leukemia
``` cell origin: memory B-cell no specific chromosomal abnormalities pancytopenia, splenomegaly, indolent middle age white males hairlike projections on leukemic cells,, "dry tap" complication on biopsy Coexpression of CD11c and CD22 overall good prognosis ```
38
Small lymphocytic lymphoma / Chronic lymphocytic leukemia
cell origin: naive B-cell or memory B-cell trisomy 12, del(11q,13q,17p) bone, lymph node, spleen, liver disease autoimmune hemolysis, thrombocytopenia sometimes, indolent CLL is most common leukemia of adults lymphocyte count >5,000/ul proliferation centers,, smudge cells CD5, CD23, CD19, CD20 + worse outcome: unmutated Ig segments, 11q and 17p deletions, lack of hypermutation, ZAP-70+ Staged on Rai staging (0-IV)
39
Adult T-cell leukemia/lymphoma
cell origin: helper t-cell HTLV-1 provirus in tumor cells adults, cutaneous lesions, hypercalcemia, aggressive less aggressive if only in skin
40
Mycosis fungoides / Sezary syndrome
cell origin: helper T-cell no specific chromosome abnormal adult, cutaneous patches, erythema, indolent lymphocytes have "cerebriform" nuclei with multiple delicate folds, brain-like nucleus
41
Large granular lymphocytic leukemia
cell origin: cytotoxic T-cell or NK cell no specific chromosomal abnormal adults, splenomegaly, neutropenia, anemia, autoimmune disease sometimes (rheumatologic)
42
Acute lymphoblastic leukemia/lymphoma (ALL)
85% are B-cell ALLs, childhood, CD10, CD19 less common are T-ALLs, adolescent males, thymic lymphoma, CD3 similar signs and symptoms to AML Worse prognosis: age less than 2 or more than 10, white count more than 100,000, t(9,22), CSF involved Good prognosis: age 2-10, low white count, hyperploidy
43
Plasma cell Dyscrasias
plasma cells: clock-face chromatin Benign (reactive): chronic infxns (H pylori), autoimmune (lupus) Neoplastic (clonal, M-protein): Multiple myeloma, MGUS, plasmacytoma, amyloidosis Bence Jones Protein: free light chains (in urine)
44
Multiple Myeloma
most common plasma cell neoplasm, malignant criteria: clonal plasma cells, M-protein, end organ damage (hypercalcemia, renal prob, anemia, bone prob) Osteolytic,, immunosuppression Always get BOTH serum and urine M-protein analysis can progress to plasma cell leukemia if spills into blood
45
Monoclonal Gammopathy of Undetermined Significance (MGUS)
most common monoclonal gammopathy criteria: <10% clonal plasma cells in bone marrow, no myeloma related organ damage benign, but can transform into malignant
46
Plasmacytomas
localized growth of monoclonal plasma cells can be seen in conjunction with multiple myeloma when distinct: no clonal cells in bone marrow Tx: radiation usually extramedullary (upper resp tract),, can also be solitary
47
Amyloidosis
protein misfolding, deposition inherited and acquired Congo red + primary: multiple myeloma, other plasma cell dyscrasias secondary: chronic inflammation, renal failure usually light chains
48
T and B cell Devo of receptors
variable region of heavy chain recombines D with J, then V with DJ then VDJ with constant to make heavy chain VDJC light chain recombines V and J, then with C, to make VJC, then joins up with heavy chain Only one chromosoma is expressed via allelic exclusion to ensure clonality Then selection: if fail to express receptors-> death, if weak self-interaction then positive selection, if strong or none, then death T-cells are first double positive, then mature to either CD4 or 8 depending on weak recognition of MHC
49
Lymph node histology
Hilum: artery, vein, efferent lymphatic Capsule, subcapsular sinus, cortex, medulla, Follicles: B-cells,, Germinal center (prolif, has light (centrocytes, antigen exposure) and dark(centroblasts, prolif) zones), Mantle zone (naive), Marginal zone (spleen only) Paracortex: T-cells, high endothelial venules (traffic lymphocytes to/from blood), dendritic cells
50
Spleen Histology
white pulp= immune,, T-cell=PALS(arterioles), B-cell=follicles Red pulp=filter RBCs
51
Follicular Hyperplasia
benign prolif of B-cells in follicles causes: RA, infxn, HIV Similar in morphology to Follicular Lymphoma Architecture is preserved
52
Neoplasms of mature B-cells (Lymphomas)
``` Burkitt Diffuse large B-cell Extranodal marginal zone Follicular Mantle cell ```
53
Neoplasms of mature T/NK-cells (Lymphomas)
Peripheral T-cell / unspecified Anaplastic large cell Extranodal NK/T-cell
54
Burkitt Lymphoma
NHL germinal center B-cell t(8,14) - cMyc sometimes assoc EBV young adults, extranodal masses,, uncommonly leukemia 1 African/endemic(all EBV) 2 Sporatic 3 HIV-assoc diffuse growth, high mitotic/apoptotic index "starry sky" pattern predeliction for abdominal/visceral involvement CD19,20,10,BCL6+,, BCL2- aggressive
55
Diffuse large B-cell lymphoma
``` NHL (most common) Germinal center B-cell Diverse chromosomal rearrangements BCL6, BCL2, c-Myc all ages, usually adults, rapidly growing mass diffuse pattern of growth CD19,20+ aggressive,, curable ```
56
Extranodal marginal zone lymphoma
NHL Memory B-cell t(11,18), t(1,14), t(14,18) - MALT1 or BCL10 adults with chronic inflammatory diseases, may be localized,, may regress if inciting agent is cleared (eg H. pylori) indolent
57
Follicular Lymphoma
NHL (most common in US) germinal center B-cell t(14,18) - BCL2-IgH older adults with generalized lymphadenopathy, marrow involvement (paratrabecular lymphoid aggregates) CD19,20,10+ ,, CD5- indolent,, often watch first, then treat w/ rituximab Can transform into diffuse large cell, or Burkitt (cMyc)
58
Mantle Cell lymphoma
``` NHL Naive B-cell t(11,14) - CyclinD1-IgH older males, disseminated disease CD19,20,5+ ,, CD23- (unlike CLL) moderately aggressive ```
59
Peripheral T-cell lymphoma, unspecified
``` NHL helper or cytotoxic T-cell no specific chromosomal ab older adults, lymphadenopathy,, pleomorphic aggressive ```
60
Anaplastic large-cell lymphoma
``` NHL cytotoxic T-cell ALK rearrangements -->JAK/STAT kids and young adults, lymph node and soft tissue disease large anaplastic cells, hallmark cells aggressive, but good prognosis ```
61
Extranodal NK/T-cell lymphoma
``` NHL NK-cell more common EBV assoc adults, destructive extranodal masses, sinonasal, nasopharyngeal aggressive ```
62
Hodgkin Lymphoma
Tumor giant cell= Reed-Sternberg ("owl-eye") localized, spread contiguously B-cell origin Classical:Nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depletion Non-classical: lymphocyte predominance CD15,30+ ,, CD45-
63
Hodgkin Lymphoma: Nodular Sclerosis
Most common form propensity for cervical, mediastinal nodes adolescents or young adults good prognosis Lacunar cell: large cell, single multilobule nucleus, pale cytoplasm CD15,30+ ,, CD20,45- Collagen bands
64
Hodgkin Lymphoma: Luekocyte Predominance
Non-classical, more rare lymphohistiocytic variant RS cells,, popcorn cells cervical, axillary CD15,30- ,, CD20,45+
65
Reactive Lymphadenopathy
Generally smaller, tender, low fevers, NO night sweats Infectious or autoimmune infectious mononucleosis - paracortical hyperplasia
66
Rituximab
CD20 antibody causes induced cell death of B-cells used for many lymphomas
67
Architecture of B-NHLs
Nodular/Follicular: Follicular, Mantle, Marginal zone, CLL/SLL Diffuse: diffuse large, Burkitt
68
Tumor size of B-NHLs
Small: Follicular, Marginal zone, CLL/SLL Large: Diffuse large B-cell, Burkitt Any: Mantle
69
CD5, CD23, CD10 status of small B-NHLs
``` CD5+: CD23-: Mantle cell CD23+: CLL/SLL CD5-: CD10-: Marginal zone CD10+: Follicular ```
70
Lymphoma translocations
Follicular: t(14,18) - BCL2 Mantle: t(11,14) - CyclinD1 Burkitt: t(8,14) - cMyc Marginal zone: t(11,18) Chromosome 2=kappa, 22-lambda, 8=cMyc