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Heme and Lymph > Week 1 > Flashcards

Week 1 Flashcards

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
Q

Langerhans Cell Histiocytosis

A

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

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26
Q

Hemophagocytic lymphohistiocytosis / hemophagocytic syndrome

A

potentially fatal hyperinflammatory condition
Primary: genetic,, perforins and granzymes induce apoptosis
Secondary: infxns, rheumatoligic, malignant, metabolic
EBV infxn is assoc
very high ferritin

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27
Q

Hematopoietic growth factors

A

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

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28
Q

Flow cytometry

A

Forward scatter: more for bigger cells

Side scatter: more with morecomplex cytoplasm (granules)

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29
Q

CD markers

A

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
Q

Lymphocytosis

A

lymphocytes >4k/ul
can be reactive (benign) or neoplastic
reactive: transient, <10k/ul, heterogenous, from infxn, stress, EBV, mononucleosis, etc
neoplastic: chronic, monotonous

31
Q

Infectious Mononucleosis

A

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
Q

Neoplastic Lymphocytoses

A 
Chronic lymphocytic leukemia (CLL)
hairy cell leukemia
splenic marginal zone lymphoma
large granular lymphocytic leukemia
adult T-cell lymphoma (ATLL)
Sezary syndrome
33
Q

HTLV-1 and HTLV-2

A

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
Q

CDs in Lymphocytoses

A 
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
Q

B-cell lymphoblastic leukemia / lymphoma

A

cell origin: bone marrow precursor B-cell
diverse chromosomal translocations: t(12,21)
mostly kids, pancytopenia, aggressive

36
Q

T-cell acute lymphoblastic leukemia / lymphoma

A

cell origin: precursor T-cell (usually thymus)
diverse chromosomal translocations: NOTCH1 mutations
adolescent males, thymic masses, aggressive

37
Q

Hairy cell leukemia

A 
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
Q

Small lymphocytic lymphoma / Chronic lymphocytic leukemia

A

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
Q

Adult T-cell leukemia/lymphoma

A

cell origin: helper t-cell
HTLV-1 provirus in tumor cells
adults, cutaneous lesions, hypercalcemia, aggressive
less aggressive if only in skin

40
Q

Mycosis fungoides / Sezary syndrome

A

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
Q

Large granular lymphocytic leukemia

A

cell origin: cytotoxic T-cell or NK cell
no specific chromosomal abnormal
adults, splenomegaly, neutropenia, anemia, autoimmune disease sometimes (rheumatologic)

42
Q

Acute lymphoblastic leukemia/lymphoma (ALL)

A

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
Q

Plasma cell Dyscrasias

A

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
Q

Multiple Myeloma

A

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
Q

Monoclonal Gammopathy of Undetermined Significance (MGUS)

A

most common monoclonal gammopathy
criteria: <10% clonal plasma cells in bone marrow, no myeloma related organ damage
benign, but can transform into malignant

46
Q

Plasmacytomas

A

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
Q

Amyloidosis

A

protein misfolding, deposition
inherited and acquired
Congo red +
primary: multiple myeloma, other plasma cell dyscrasias
secondary: chronic inflammation, renal failure
usually light chains

48
Q

T and B cell Devo of receptors

A

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
Q

Lymph node histology

A

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
Q

Spleen Histology

A

white pulp= immune,, T-cell=PALS(arterioles), B-cell=follicles
Red pulp=filter RBCs

51
Q

Follicular Hyperplasia

A

benign prolif of B-cells in follicles
causes: RA, infxn, HIV
Similar in morphology to Follicular Lymphoma
Architecture is preserved

52
Q

Neoplasms of mature B-cells (Lymphomas)

A 
Burkitt
Diffuse large B-cell
Extranodal marginal zone
Follicular
Mantle cell
53
Q

Neoplasms of mature T/NK-cells (Lymphomas)

A

Peripheral T-cell / unspecified
Anaplastic large cell
Extranodal NK/T-cell

54
Q

Burkitt Lymphoma

A

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
Q

Diffuse large B-cell lymphoma

A 
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
Q

Extranodal marginal zone lymphoma

A

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
Q

Follicular Lymphoma

A

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
Q

Mantle Cell lymphoma

A 
NHL
Naive B-cell
t(11,14) - CyclinD1-IgH
older males, disseminated disease
CD19,20,5+ ,, CD23- (unlike CLL)
moderately aggressive
59
Q

Peripheral T-cell lymphoma, unspecified

A 
NHL
helper or cytotoxic T-cell
no specific chromosomal ab
older adults, lymphadenopathy,, pleomorphic
aggressive
60
Q

Anaplastic large-cell lymphoma

A 
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
Q

Extranodal NK/T-cell lymphoma

A 
NHL
NK-cell more common
EBV assoc
adults, destructive extranodal masses, sinonasal, nasopharyngeal
aggressive
62
Q

Hodgkin Lymphoma

A

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
Q

Hodgkin Lymphoma: Nodular Sclerosis

A

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
Q

Hodgkin Lymphoma: Luekocyte Predominance

A

Non-classical, more rare
lymphohistiocytic variant RS cells,, popcorn cells
cervical, axillary
CD15,30- ,, CD20,45+

65
Q

Reactive Lymphadenopathy

A

Generally smaller, tender, low fevers, NO night sweats
Infectious or autoimmune
infectious mononucleosis - paracortical hyperplasia

66
Q

Rituximab

A

CD20 antibody
causes induced cell death of B-cells
used for many lymphomas

67
Q

Architecture of B-NHLs

A

Nodular/Follicular: Follicular, Mantle, Marginal zone, CLL/SLL
Diffuse: diffuse large, Burkitt

68
Q

Tumor size of B-NHLs

A

Small: Follicular, Marginal zone, CLL/SLL
Large: Diffuse large B-cell, Burkitt
Any: Mantle

69
Q

CD5, CD23, CD10 status of small B-NHLs

A 
CD5+:
CD23-: Mantle cell
CD23+: CLL/SLL
CD5-:
CD10-: Marginal zone
CD10+: Follicular
70
Q

Lymphoma translocations

A

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

Heme and Lymph (3 decks)

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