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HEME II > Ch 13 Leukemia/Lymphoma > Flashcards

Ch 13 Leukemia/Lymphoma Flashcards

1
Q

leukierythroblastosis

A

abnormal release of immature precursors into peripheral blood

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2
Q

when is inadequate or ineffetive granulopoiesis observed

A

suppression of hematopoietic stem cells, suppression of committed granulocytic precursors via drug exposure, ineffective hematopoiesis, congenital conditions

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3
Q

examples of suppression of hematopoietic stem cells

A

aplastic anemia, infiltrative marrow disorders

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4
Q

examples of ineffective hematopoiesis

A

megaloblastic anemias and myelodysplastic syndromes-defective precursors die in marrow

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5
Q

accelerated removal or destruction of neutrophils occurs with

A

immuologically mediated injury, splenomegaly, increased peripheral utilization

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6
Q

most common cause of agranulocytosis

A

drug toxicity

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7
Q

neutropenia caused by chlorpromazine and related phenothiazines results from

A

toxic effect on granulocytic precursors in bone marrow

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8
Q

agranulocytosis following administration of aminopyrine, thiouracil, and certain sulfonamides stems from

A

antibody-mediated destruction of mature neutrophils through mechaisms similar to those in drug-induced immunohemolytic anemias

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9
Q

hypercellular bone marrow

A

compensatory due to high destruction in periphery; ineffective granulopoiesis

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10
Q

what is a neutropenic patient at particularly high risk for

A

deep fungal infections caused by Candida and Aspergillus

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11
Q

toxic granules

A

coarser and darker than normal neutrophilic granules; represent abnormal azurophilic (primary) granules

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12
Q

Dohle bodies

A

patches of dilated endoplasmic reticulum that appear as sky blue cytoplasmic ‘puddles’

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13
Q

neutrophilic leukocytosis causes

A

acute bacterial infections; sterile inflammation (MI, burns)

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14
Q

eosinophilic leukocytosis causes

A

allergic disorders; skin diseases; parasitic infections; drug rxns; certain malignancies; collagen vascular disorders and some vasculitides; atheroembolic disease transiently

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15
Q

Basophilic leukocytosis causes

A

rare; myeloproliferative disease

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16
Q

monocytosis leukocytosis causes

A

chronic infections, bacterial endocarditis, riskettsiosis, malaria, collagen vascular disease, IBS

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17
Q

lymphocytosis leukocytosis causes

A

accompanies monocytosis in many disorders associated with chronic immunological stimulation; viral infections; bordetella pertussis infection

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18
Q

morphology of lymphadenitis

A

nodes swollen, gray-red, and engorged; prominence of reactive germinal centers with numerous mitotic centers

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19
Q

follicular hyperplasia of nodes (chronic)

A

due to stimuli that activate humoral immune responses; large oblong germinal centers surrounded by a collar of small restinf naïve B cells

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20
Q

germinal centers in follicular hyperplasia

A

1) dark zone containing proliferating blastlike B cells

2) light zone composed of B cells with irregular or cleaved nuclear contours

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21
Q

tingible-body macrophages

A

interspersed btwn germinal B centers and form an inconspicuous network of antigen-presenting follicular dendritic cells and macrophages; contain nuclear debris of B cells that underwent apoptosis

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22
Q

causes of follicular hyperplasia

A

RA, toxoplasmosis, early HIV infection

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23
Q

Paracortical hyperplasia of nodes

A

stimuli that trigger T cell-mediated immune responses like acute viral infections

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24
Q

T-cells in paracortical hyperplasia

A

activated T cells 3-4 times size of resting lymphocytes, several prominent nucleoli, and moderate amounts of pale cytoplasm

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25
Q

sinus histiocytosis (aka reticular hyperplasia)

A

increase in number and size of cells that line lymphatic sinusoids; may be prominent in nodes draining cancers like breast

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26
Q

lymphotoxin

A

cytokine required for formation of normal Peyer’s patches; involved in establishment of extranodal inflammation-induced collections of lymphoid cells

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27
Q

lymphoid neoplasms

A

diverse group of tumors of B, T, and NK-cell origin

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28
Q

Myeloid neoplasms

A

arise from early hematopoietic progenitors

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29
Q

3 categories of myeloid neoplasms

A

acute myeloid leukemias, myelodysplastic syndromes, and chronic myeloproliferative disorders

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30
Q

acute myeloid leukemias

A

immature progenitor cells accumulate in bone marrow

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31
Q

myelodysplastic syndromes

A

associated with ineffective hematopoisis and resultant peripheral blood cytopenias

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32
Q

chronic myeloproliferative disorders

A

increased production of one or more terminally differentiated myeloid elements usually leading to elevated peripheral blood counts

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33
Q

histiocytes

A

uncommon proliferative lesions of macrophages and dendritic cells; ex Langerhan cells-immature dendritic

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34
Q

MALToma genetic aberrations

A

MALT1 or BCL10 gene=bind one another in protein complex that regulates NF-kB

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35
Q

BCL6

A

encodes transcription factor expressed in germinal center B cells-germinal B cells can’t form without; must be turned off for germinal B cells to mature into memory or plasma cells

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36
Q

what occurs once B cell has antigen stimulation

A

enter germinal centers and upregulate activation-induced cytosine deaminase (AID)

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37
Q

AID fxn

A

specialized DNA-modifying enzyme essential for 2 types of Ig gene modifications: class switching and somatic hypermutation

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38
Q

EBV cancer assocaition

A

subset of Burkett lymphoma; 30-40% Hodgkin lymphoma, many B-cell lymphomas in setting of T-cell immunodeficiency, and rare NK-cell lymphomas

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39
Q

HHV8 cancer associations

A

Kaposi sarcoma, unusual B-cell lymphoma that presents as malignant effusion often in pleural cavity

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40
Q

gluten-sensitive cancer assocaition

A

T-cell lymphomas

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41
Q

H pylori cancer association

A

B-cell lymphomas

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42
Q

most common plasma cell neoplasm and presentation

A

multiple myeloma-causes bony destruction of skeleton and often presents as pain due to pathologic fractures

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43
Q

5 broad categories of lymphoid neoplasms used by WHO

A

1) precursor B-cell neoplasms
2) peripheral B-cell neoplasms
3) precursor T-cell neoplasms
4) peripheral T cell and NK-cell neoplasms
5) Hadgkin lymphoma

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44
Q

Acute lymphoblastic Leukemia/lymphomas (ALLs)

A

neoplasms of immature B or T cells; 85% are B-ALLs as childhood acute leukemias

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45
Q

what occurs in 55-70% of all T-ALLs

A

mediastinal thymic masses-also more likely to be associated with lymphadenopathy and splenomegaly

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46
Q

B- and T-ALL morphology

A

tumor cells have scant basophilic cytoplasm and nuclei somewhat larger than those of small lymphocytes; nuclear chromatin delicate and finely stippled-nucleoli absent/inconspicuous; high mitotic rate

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47
Q

differentiating ALL from AML

A

lymphoblasts have more condensed chromatin, less conspicuous nuclei, and smaller amounts of cytoplasm that usually lacks granules; diffinitive differentiation must be done with stains on antibodies specific for B and T cell antigens

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48
Q

histochemical stains

A

lymphblasts are myeloperoxidase-neg and often contain periodic acid-Schiff pos cytoplasmic material

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49
Q

what is positive in more than 95% of B and T-ALLs

A

immunostaining for terminal TdT (specialized DNA polymerase expressed only in B and T pre-lymphblasts)

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50
Q

B-ALLs usually express

A

pan B-cell marker B19 and transcription factor PAX5 and CD10 (CD10 neg in very immature B cells)

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51
Q

more mature B-ALLs express (“late pre-B”)

A

CD10, CD19, CD20, and cytoplasmic IgM heavy chain

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52
Q

most cases of T-ALLs express

A

CD1, CD2, CD5, CD7

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53
Q

late pre-T cell tumors express

A

CD3, CD4, and CD8

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54
Q

70% T-ALLs have what genetic gain-of fxn mutation

A

NOTCH1

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55
Q

loss of fxn mutations in B-ALLs

A

PAX5, E2A, and EBF, or balanced (12;21) involving genes TEL and AML1

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56
Q

clinical characteristics of ALLs

A

abrupt stormy onset within days to few weeks of first symptoms; depression of marrow fxn; mass effects caused by neoplastic infiltration; CNS manifestations due to meningeal spread

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57
Q

pediatric ALL prognosis

A

95% obtain complete remission with aggressive chemo and 75-85% are cured; only 35-40% adults cured

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58
Q

what indicates worse prognosis with ALLs

A

age under 2 (translocations involving MLL gene); adolescence or adulthood; peripheral blood blasts >100,000; philadelphia chromosome (9;22)

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59
Q

favorable indicators of ALL prognosis

A

age 2-10; low white cell count; hyperploidy; trisomy of 4, 7, and 10; (12;21)

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60
Q

Chronic lymphocytic leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

A

differ only in degree of peripheral blood lymphocytosis; chronic is >4000 per mm^3

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61
Q

CLL and SLL morphology

A

lymph nodes diffusely effaced by infiltrate of predominately small lymphocytes 6-12 um with round to slightly irregular nuclei (condensed chromatin and scant cytoplasm)

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62
Q

proliferation centers of CLL/SLL

A

larger activated lymphocytes that often gather in loose aggregates = pathognomonic for CLL/SLL

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63
Q

immunophenotype of CLL/SLL

A

pan B-cell markers CD19 and 20 as well as CD23 and 5; low-level expression of surface Ig typical

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64
Q

where is growth of CLL/SLL

A

largely confined to proliferation centers-receive critical cues from microenvironment

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65
Q

leukocyte count in CLL/SLL

A

highly variable-leukopenia can be seen with SLL marrow displacement and counts in excess of 200,000 sometimes seen in CLL with heavy tumor burdens

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66
Q

CLL/SLL and immune fxn

A

disrupts normal fxn via uncertain mechanisms; hypogammaglobulinemia common

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67
Q

what correlates with worse outcomes for CLL/SLL

A

deletions of 11q and 17p; lack somatic hypermutation; expression of ZAP-70

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68
Q

ZAP-70

A

protein that augments signal produced by Ig receptor

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69
Q

Richer syndrome

A

CLL prolymphocytic transformation or transformation to diffuse large B-cell lymphoma (5-10% patients)

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70
Q

prolymphocytes

A

large cells with single prominent, centrally placed nucleolus

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71
Q

Follicular lymphoma

A

tumor arises from germinal center B cells and is strongly associated with chromosomal translocations involving BCL2

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72
Q

2 principle cell types in follicular lymphoma

A

1) small cells with irregular or cleaved nuclear contours and scant cytoplasm (centrocytes) 2) larger cells with open nuclear chromatin, several nucleoli, and modest amount of cytoplasm (centroblasts)

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73
Q

other sites involved in follicular lymphom

A

peripheral blood 10%, bone marrow 85%-paratrabecular lymphoid aggregates, splenic white pulp and hepatic portal triads

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74
Q

neoplastic cells in follicular lymphoma express

A

CD19, CD20, CD10, surface Ig, BCL6; CD5 NOT expressed; BCL2 in more than 90%

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75
Q

translocation in follicular lymphoma

A

(14;18) that juxtaposes IgH locus on chromosome 14 and BCL2 locus on chromosome 18

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76
Q

presentation of follicular lymphoma clinically

A

painless, generalized lymphadenopathy; incurable-waxing and waning course

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77
Q

histologic transformation of follicular lymphomas

A

30-50% occurance; usually to diffuse large B-cell lymphoma; survival less than 1 year

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78
Q

Diffuse large B-cell lymphoma (DLBCL)

A

most common NHL; relatively large cell size and diffuse pattern of growth

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79
Q

what do DLBCL express

A

CD19, CD20, variable expression of germinal center B-cell markers like CD10 and BCL6; most have surface Ig

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80
Q

BCL6

A

DNA-binding zinc finger transcriptional repressor that is required for the fomration of normal germinal centers; can suppress p53

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81
Q

immunodeficiency-associated large B-cell lymphomas

A

severe T-cell immunodeficiency; neoplastic B cells usually infected with EBV

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82
Q

primary effusion lymphoma

A

malignant pleural or ascitis effusion-mostly with HIV or elderly; anaplastic in appaearance and fail to express surface B or T-cell markers, clonal IgH rearrangements; HHV8 infected

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83
Q

presentation of DLBCL

A

rapidly enlarging mass at nodal or extranodal site, virtually anywhere in body; bone marrow involvement usually late in course

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84
Q

outcome of DLBCL

A

rapidly fatal without treatment; wth chemo 60-80% complete remission with 40-50% cured

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85
Q

Burkitt lymphoma morphology

A

diffuse infiltrate of intermediate-sized lymphoid cells with round/oval nuclei, coarse chromatin, several nucleoli, and moderate cytoplasm; high mitotic index with numerous apoptotic cells

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86
Q

immunophenotype of Burkitt lymphoma

A

mature B cells that express IgM, CD19, 20, 10, and BCL6; fails to express BCL2

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87
Q

translocations in Burkitt lymphoma

A

c-MYC gene on chromosome 8

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88
Q

endemic burkitt lymphoma common presentation

A

mass involving madible and shows unusual predilection for abdominal viscera, especially kidneys, ovaries, and adrenals

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89
Q

sporadic burkitt lymphoma common presentation

A

mass involving ileocecum and peritoneum; involvement of bone marrow and peripheral blood uncommon

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90
Q

M component

A

monoclonal Ig identified in blood-in reference to myeloma

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91
Q

Bence-Jones proteins

A

free light chains small enough to be excreted in urine

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92
Q

what are associated with monoclonal gammopathies

A

1) multiple myeloma
2) Waldenstrom macroglobulinemia
3) heavy-chain disease
4) primary or immunocyte-associated amyloidosis
5) monoclonal gammopathy of undetermined significance (MGUS)

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93
Q

multiple myeloma

A

presents as tumorous masses scattered throughout skeletal system

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94
Q

Waldenstrom macroglobulinemia

A

high IgM lead to symptoms related to hyperviscocity of blood; usually in older adults with lymphoplasmacytic lymphoma

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95
Q

Heavy-chain disease

A

rare; associated with lymphoplastic lymphoma and unusual small bowel marginal zone lymphoma in malnourished populations; synthesis and secretion of free heavy-chain segments

96
Q

Primary or immunocyte-associated amyloidosis

A

monoclonal proliferation of plasma cells secreting light chains deposited as amyloid; some due to overt multiple myeloma

97
Q

multiple myeloma molecular specs

A

Ig genes in myeloma cells show evidence of somatic hypermutation; post-germinal center B cell that homes to bone marrow and differentiates into plasma cell

98
Q

what cytokines is the proliferation and survival of myeloma cells dependent on

A

IL-6

99
Q

MIP1alpha

A

myeloma-derived; up-regulates expression of receptor activator NF-kB ligand (RANKL) by bone marrow stromal cells, thus activating osteoclasts

100
Q

common translocation in multiple myeloma

A

FGFR (chromosome 4-cellular proliferation) and cell cycle regulatory genes cyclin D1 (chromosome 11) and cyclin D3 (chromosome 6); among others

101
Q

where do multiple myeloma lesions begin

A

in medullary cavity, erode cancellous bone, and progressively destroy bone cortex

102
Q

appearance of bone lesions in multiple myeloma

A

punched-out defects usually 1-4 cm and grossly consist of soft, gelatinous, red tumor masses

103
Q

cell variants in multiple myeloma

A

flame cells, plasmablasts, Mott cells (multiple grapelike cytoplasmic droplets), other inclusions like fibrils, crystalline rods and globules

104
Q

Russell bodies (cytoplasmic) or Dutcher bodies (nuclear)

A

globular inclusions

105
Q

rouleaux formation

A

red cells in peripheral blood stick to one another in linear arrays on smears

106
Q

myeloma kidney

A

bence jones proteins excreted and contribute to this in multiple myeloma-toxic to renal tubular epithelial cells

107
Q

hypercalcemia from multiple myeloma can cause

A

neurologic manifestations-confusion, weakness, lethargy, constipation, polyuria; contributes to renal dysfunction

108
Q

most common Ig in multiple myeloma

A

IgG 55%, IgA 25%; 1% nonsecretory

109
Q

marrow involvement in multiple myeloma causes

A

normocytic and chromatic anemia, sometimes accompanied by moderate leukopenia and thrombocytopenia

110
Q

proteasome inhibitors as treatment in multiple mueloma

A

induce cell death by exacerbating inherent tendency of misfolded proteins

111
Q

solitary myeloma (plasmacytoma)

A

inevitably progresses to multiple myeloma-can take 10-20 yrs or longer; upper respiratory tract can be cured by recestion

112
Q

smoldering myeloma

A

middle ground btwn multiple myeloma and monoclonal gammoathy of uncertain significance; plasma cells 10-30% marrow cellularity, serum M protein elevated, patients asymptomatic; 75% progress to multiple myeloma over 15 yrs

113
Q

monoclonal gammopathy of uncertain significance (MGUS)

A

most common plasma cell dyscrasia; patients asymptomatic and serum M protein <3gm/dL; ~1% dvlp symptomatic plasma cell neoplasm per year

114
Q

lymphoplasmic lymphoma

A

B-cell neoplasm of older adults; bears special resemblance to CLL/SLL-differs due to small fraction of tumor cells undergo terminal differentiation into plasma cells (usually monoclonal IgM)

115
Q

what does hyperviscosity due to IgM in lymphplasmic lymphoma cause

A

Walden-Strom macroglobulinemia: visual impairment associated with venous congestion, neurologic problems, bleeding, cryglobulinemia

116
Q

immunophenotype of lymphoplasmacytic lymphoma

A

B cell markers like CD20 and surface Ig; plasma cell component secretes same Ig that is expressed on surface of lymphoid cells; usually lack translocations

117
Q

clinical presentation of lymphoplasmacytic lymphoma

A

nonspecific; half have lymphadenopathy, hepatomegaly, splenomegaly; anemia caused by marrow infiltration common; 10% autoimmune hemolysis caused by cold agglutinins

118
Q

cryglobulinemia

A

results from precipitation of macroglobulins at low temps-produces symptoms like Raynaud phenomenon and cold uticaria

119
Q

lymphoplasmacytic lymphoma prognosis

A

incurable progressive disease. Median survival 4 yrs

120
Q

Mantle cell lymphoma demographics

A

uncommon; 5th to 6th decades; male predominance; tumor cells resemble normal matle zone B cells that surround germinal center

121
Q

what distinguishes mantle cell lymphoma from follicular and CLL/SLL

A

large cells resembling centroblasts and proliferation centers are absent

122
Q

what form of lymphoma is most likely to have involvement of the small bowel or colon with polyp-like lesions (lymphomatoid polyposis)

A

mantle cell lymphoma

123
Q

immunophenotype of mantle cell lymphoma

A

high levels of cyclin D1; most also express CD19, 20 and moderately high levels of surface Ig; usually CD5+ and CD23- (helps distinguish from CLL/SLL)

124
Q

what causes cyclin D1 overexpression in mantle cell lymphoma

A

(11;14) translocation involving IgH locus (14) and cyclin D1 locus (11); promotes G1 to S phase progression

125
Q

mantle cell lymphoma prognosis

A

poor-median survival 3-4 yrs; not currently curable

126
Q

marginal zone lymphomas

A

heterogeneous group of B-cell tumors that arise within lymph nodes, spleen, or extranodal tissues (eg MALTomas); most of memory B-cell origin

127
Q

Hairy cell leukemia

A

rare, distinctive B-cell neoplasm; middle-age white males

128
Q

morphology of hairy cell leukemia

A

leukemic cells have hairlike projections that are best recognized under phase-contrast microscope

129
Q

hairy cell leukemia and aspirations

A

generally cannot be aspirated since enmeshed in ECM composed of reticulin fibers

130
Q

splenic red pulp in hairy cell leukemia

A

heavily infiltrated leading to obliteration of white pulp and beefy red gross appearance; hepatic portal triads also involved frequently

131
Q

immunophenotype of hairy cell leukemia

A

pan B-cell markers CD19 and 20, surface Ig (usually IgG), and certain relatively distinctive markers like CD11c, CD25, and CD103; somatic hypermutation (post-germinal center memory B-cell origin)

132
Q

clinical manifestation of hairy cell leukemia

A

infiltation of bone marrow, liver, and spleen; massive splenomegaly; 1/3 present with infection

133
Q

prognosis of hairy cell leukemia

A

excellent; sensitive to ‘gentle’ chemo drugs

134
Q

peripheral T-cell lymphoma, unspecified

A

tumors efface lymph nodes diffusely; typically composed of pleomorphic mixture of variably sized malignant T cells; prominent infiltrate of reactive cells; brisk neoangiogenesis may also be seen

135
Q

immunotype of peripheral T-cell lymphoma, unspecified

A

CD2, 3, 5, and either aB or gd T-cell receptors; some express CD4 or 8

136
Q

prognosis of peripheral T-cell lymphoma, unspecified

A

cures have been reported, but prognosis significantly worse than comparable aggressive mature B-cell neoplasms

137
Q

Anaplastic Large-cell lymphoma (ALK positive)

A

uncommon; rearrangements in ALK gene (chromosome 2)-fusion gene with constitutively active tyrosine kinases (trigger pathways like Jak/STAT); tend to occur in children or young adults; frequently involve soft tissues

138
Q

hallmark cells of Anaplastic Large-cell lymphoma

A

horseshoe-shaped nuclei and columinous cytoplasm; often cluster around cenules and infiltrate lymphoid sinuses (mimicking metastatic carcinoma)

139
Q

what is a reliable indicator of ALK gene rearrangement

A

detection of ALK protein in tumor cells, as it is not expressed in normal lymphocytes

140
Q

prognosis of Anaplastic Large-cell lymphoma

A

good; cure rate 75% with chemo

141
Q

Adult T-cell leukemia/lymphoma

A

neoplasm of CD4+ T cells; infection with HTLV-1; endemic in Hapan, west africa, caribbean basin

142
Q

common findings of Adult T-cell leukemia/lymphoma

A

skin lesions, generalized lymphadenopathy, hepatosplenomegaly, peripheral blood lymphocytosis, and hypercalcemia

143
Q

appearance of tumore cells in Adult T-cell leukemia/lymphoma

A

varies, but multilobed nuclei (cloverleaf or flower cells) frequently observed

144
Q

HTLV-1 and tumor pathogenesis

A

encodes a protein Tax, that is a potent activator of NF-kB, which enhances lymphocyte growth and survival

145
Q

presentation/prognosis of Adult T-cell leukemia/lymphoma

A

present with rapidly progressive disease fatal within months to 1 yr despite aggressive chemo; sometimes only invades skin

146
Q

Mycosis Fungoides/Sezary syndrome

A

manifestations of CD4+ tumor cells that home to skin; 3 somewhat distinct stages (premycotic, plaque, and tumor phases); indolent course survival 8-9 yrs

147
Q

sezary syndrome

A

skin involvement is manifested as generalized exfoliative erythroderma-skin lesions rarely progress to tumefaction

148
Q

what do tumor cells of Mycosis Fungoides express

A

adhesion molecule CLA and chemokine receptors CCR4 and CCR10-contribute to homing to skin

149
Q

Large granular lymphcytic leukemia

A

T and NK cell variants; mainly in adults; tumor cells large lymphocytes with abundant blue cytoplasm and few course azurophilic granules

150
Q

T cell and NK cell variants in Large granular lymphcytic leukemia

A

T cell: Cd3+; NK cell: CD3- and CD56+

151
Q

prognosis of Large granular lymphcytic leukemia

A

T cell origin indolent and NK variants more aggressive

152
Q

extranodal NK/T-cell lymphoma

A

destructive nasopharyngeal mass is most common presentation; infiltrate surrounds and invades small vessels leading to extensive ishemic necrosis; associated with EBV

153
Q

prognosis of extranodal NK/T-cell lymphoma

A

highly aggressive-respond well to radiation, resistant to chemo; poor prognosis with advanced disease

154
Q

Hodkin lymphoma (HL) progression

A

arises in single node/chain of nodes and spreads first to anatomically contiguous lymphoid tissues

155
Q

Reed-Sternberg cells

A

neoplastic giant cells; seen in HL; release factors that induce accumulation of reactive lymphocytes, macrophages, and granulocytes (make up >90% tumor cellularity); derived from germinal center or post-germinal center B cells

156
Q

5 subtypes of HL

A

1) nodular sclerosis
2) mixed cellularity
3) lymphcyte-rich
4) lymphocyte depletion
5) lymphocyte predominance;
First 4 reed-sternberg cells have similar immunophenotype=classical HL

157
Q

morphology of Reed-sternberg cells

A

> 45 um with multiple nuclei or single nucleus with multiple nuclear lobes-each with large inclusion-like nucleolus about size of small lymphocyte; abundant cytoplasm

158
Q

lacunar cells

A

seen in noduar sclerosis subtype; more delicate, folded, or multilobate nuclei and abundant pale cytoplasm often disrupted during cutting of sections (leaves empty hole = lacuna)

159
Q

diagnosis of HL

A

identification of Reed-Sternberg cells in a typical prominent background of non-neoplastic inflammatory cells

160
Q

nodular sclerosis type of HL

A

most common 65-70%; lacunar variant and deposition of collagen in bands that divide involved lymph nodes into circumscribed nodules’ associated with EBV; excellent prognosis

161
Q

immunophenotype of Reed-sternberg cells in nodular sclerosis type of HL

A

PAX5 (B-cell transcription factor), CD15, CD30, neg for other B cell markers, t-cell markers, and CD45

162
Q

Mixed cellularity type of HL

A

20-25% cases; involved nodes diffusely effaced by heterogeneous cellular infiltrate; EBV 70%

163
Q

Lymphocyte-rich type of HL

A

uncommon-reactive lymphocytes make up vast majority of cellular infiltrate; nodes usually diffusely effaced, but vague nodularity due to presence of residual B-cell follicles sometimes seen; EBV 40%

164
Q

lymphocyte depletion type of HL

A

least common 90%; less favorable outcome

165
Q

why is immunotypeing in lymphocyte depletion type important

A

most tumors suspected to be this type actually prove to be large cell NHLs

166
Q

lymphocyte predominance type of HL

A

uncommon nonclassical variant ~5%; effaced by nodular infiltrate of small lymphocytes admixed with variable # macrophages; L&H variants instead of Reed-sternberg cells

167
Q

L&H (lymphocytic and histocytic) variants

A

multilobed nucleus resembling popcorn kernal; express B-cell markers typical of germinal-center B cells (CD20, BCL 6, neg for CD15 and 30); no EBV association

168
Q

EBV and NF-kB

A

express latent membrane protein 1 (LMP-1) that transmits signals that upregulate NF-kB

169
Q

example of cross talk of Reed-sternberg cells with surrounding reactive cells

A

T cells express ligands that activate CD30 and CD40 receptors found on Reed-sternberg cells-produce signals that up-regulate NF-kB

170
Q

alkylating chemotherapeutics increase risk for

A

AML and myelodysplasia

171
Q

myeloid neoplasms

A

heterogeneous group with origin from hematopoietic progenitor cells; primarily involve marrow and lesser degree secondary hematopoietic organs

172
Q

3 broad categories of myeloid neoplasms

A

Acute Myeloid leukemias, myelodysplastic syndromes, and myeloproliferative disorders

173
Q

Acute Myeloid leukemia

A

accumulation of immature myeloid forms in bone marrow suppresses normal hematopoiesis

174
Q

myelodysplastic syndromes

A

ineffective hematopoiesis leads to cytopenias

175
Q

myeloproliferative disorders

A

usually increased production of one or more types of blood cells

176
Q

Acute Myeloid leukemia specs

A

tumor of hematopoietic progenitors caused by aquired oncogenic mutations that impede differentiation, leading to accumulation of immature myeloid blasts in marrow; occurs at all ages-rises throughout life

177
Q

4 subdivisions of AML

A

particular genetic abberations, arising after myelodysplastic disorder or with MDS-features, therapy -related AML, wastebasket category=lack other features

178
Q

diagnosis of AML

A

presence of at least 20% myeloid blasts in bone marrow

179
Q

myeloblasts in AML morphology

A

delicate nuclear chromatin, 2-4 nucleoli, and more voluminous cytoplasm than lymphoblasts; Auer rods in cytoplasm

180
Q

Auer rods

A

distinctive needle-like azurophilic granules

181
Q

Monoblasts in AML

A

folded/lobulated nuclei, lack auer rods, and are nonspecific esterase-positive

182
Q

number of leukemic cells in blood in AML

A

highly variable; blasts may be >10000/mm^3 but are <10000 in half ppl; occasionally blasts absent from blood

183
Q

AMLs arising de novo in younger adults are associated with

A

balanced chromosomal translocations (8;21), inv(6), and (15;17)

184
Q

AMLs following MDS or exposure to DNA damaging agents

A

deletions or monosomies involving chromosomes 5 and 7 and usually lack translocations

185
Q

AML occuring after treatment with topisomerase II inhibitors

A

translocations involving MLL gene on chromosome 11

186
Q

AML in elderly

A

bad’ aberrations like deletions of schomosomes 5 and 7

187
Q

what do (8;21) and inv(16) disrupt in AML

A

CBF1-alpha and CBF1-Beta genes; encode polypeptides that bind one another to form a transcription factor required for normal hematopoiesis

188
Q

t(15;17) in acute promyelocytic leukemia

A

creates fusion gene that encodes part of retinoic acid receptor-alpha (RARa) fused to protein called PML; results in inhibition of granulocytic maturation

189
Q

FLT3

A

receptor tyrosine kinase that transmites signals that increase cellular proliferation and survival; commonly occurs with t(15;17), also with NPM (nucleophosmin) and c-KIT mutations

190
Q

ATRA (all-trans retinoic acid)

A

bonds PML-RARa fusion protein and antagonizes inhibitory effect

191
Q

clinical presentation of AML

A

fatigue, fever, spontaneous mucosal and cutaneous bleeding (similar to ALL)

192
Q

good prognostic indicators in AML

A

(8; 21) or inv(6); absence of c-KIT mutations

193
Q

Myelodysplastic syndromes (MDS) specs

A

clonal stem cell disorders characterized by maturation defects associated with ineffective hematopoiesis and high risl of transformation into AML

194
Q

MDS chromosomal aberration associations

A

monosomies 5 and 7, deletions of 5, 7, and 20, and trisomy 8

195
Q

marrow in MDS

A

usually hypercellular at diagnosis, sometimes normocellular or less commonnly hypocellular; disordered differentiation affecting erythroid, granulocytic, monocytic, and megakaryocytic lineages

196
Q

erythroid series in MDS

A

ringed sideroblasts (iron-laden mitochondria); megaloblastoid maturation-resembles B12 and folate deficiencies; nuclear budding abnormalities

197
Q

neutrophils in MDS

A

decreased secondary granules, toxic granulations, and/or Dohle bodies; pseudo-pelger-huet cells

198
Q

pseudo-pelger-huet cells

A

neutrophils with only 2 nuclear lobes

199
Q

pawn ball megakaryocytes

A

single nuclear lobes or multiple separate nuclei

200
Q

myeloid blasts in MDS

A

may be increased, but <10% leukocytes in blood

201
Q

myeloproliferative disorders specs

A

presence of mutated, constitutively activated tyrosine kinases; GF independent proliferation and survival of marrow progenitors; don not impair differentiaton=increase production of one or more mature blood elements

202
Q

Chronic Myeloid leukemia (CML)

A

presence of chimeric BCR-ABL gene derived from portions of 22 (BCR) and 9 (ABL); 90% philadelphia chromosome

203
Q

morphology of CML

A

marrow markedly hypercellular-increased #maturing granulocytic precursors; megakaryocytes increased with small, dysplastic forms; scattered macrophages with abundant wrinkled, green-blue cytoplasm; increased deposition of reticulin

204
Q

blood in CML

A

leukocytosis often over 100,000 cells/mm^3: predominately neutrophils, band forms, metamyelocytes, myelocytes, eosinophils, and basophils; blasts <10% blood cells; platelets increased

205
Q

imatinib

A

BCR-ABL inhibitor; diminishes BCR-ABL pos cells in marrow and elsewhere, but does not extinguish hematopoietic stem cell

206
Q

polycythemia vera (PCV)

A

increased marrow production of RBCs, granulocytes, and platelets; RBC increase responsible for most symptoms; activating point mutations in tyrosine kinase JAK2

207
Q

2 mutated copies of JAK2 in PCV leads to

A

higher WBC counts, more significant splenomegaly, symptomatic pruritis, and greater rate of progression to the spent phase

208
Q

morphology of marrow in PCV

A

hypercellular, but residual fat usually present; moderate to marked increase in reticulin fibers in 10%

209
Q

why does intense pruritis and peptic ulceration occur in PCV

A

release of histamine from basophils

210
Q

what does high cell turnover cause in PCV

A

hyperuricemia-gout in 5-10% cases

211
Q

huge consequences of PCV

A

bleeding or thrombosis

212
Q

spent phase of PCV

A

obliterative fibrosis in marrow and extensive extramedullary hematopoiesis, especially spleen

213
Q

essential thrombocytosis (ET)

A

point mutations in JAK2 (50%) or MPL (5-10%); elevated platelets, absence of polycythemia and marrow fibrosis

214
Q

MPL

A

receptor tyrosine kinase that is normally activated by thrombopoietin

215
Q

what must be excluded before diagnosis of ET when JAK2 or MPL intact

A

reactive thrombocytosis (inflammatory disorders and iron deficiency)

216
Q

bone marrow in ET

A

cellularity only mildly increased; megakaryocytes increased and include abnormally large forms

217
Q

peripheral smears in ET

A

abnormally large platelets, often accompanied by mild leukocytosis

218
Q

erythromelalgia

A

throbbing and burning of hands and feet caused by occlusion of small arterioles by platelet aggregates; seen in PCV and ET

219
Q

primary myelofibrosis

A

dvlp obliterative marrow fibrosis; cytopenias and extensive neoplastic extramedullary hematopoiesis; histologically similar to spent phase of other myeloproliferative diseases

220
Q

molecular pathogenesis of primary myelofibrosis

A

JAK 2 (50-60%), activating MPL (1-5%)

221
Q

cause of primary myeloofibrosis

A

fibrogenic factors released from neoplastic megakaryocytes causing ectensive deposition of collagen by non-neoplastic fibroblasts

222
Q

what factors from megakaryocytes may be cause for fibrosis in primary myelofibrosis

A

PDGF and TBF-B

223
Q

Primary mylofibrosis vs PCV and ET

A

nor clear whether truly distinct or merely reflects unusually rapid progression to spent phase

224
Q

osteosclerosis

A

fibrotic marrow space converted into bone

225
Q

histiocytosis

A

umbrella’ designation for variety of proliferative disorders of dendritic cells or macrophages

226
Q

Langerhans cell histiocytosis

A

abundant, often vacuolated cytoplasm and vesicular nuclei containing linear grooves or folds; presence of Birbeck granules in cytoplasm

227
Q

birbeck granules

A

pentalaminar tubules, often with dilated terminal end producing a tennis racket-like appearance, which contain protein langerin

228
Q

what do langerhan cell histiocytes express

A

HLA-DR, S-100, and CD1a

229
Q

clinicopathological entities of langerhan cell histoicytes

A

1) multifocal multisystem (letterer-siwe disease)
2) unifocal and multifocal unisystem (eosinophilic granuloma)
3) pulmonary

230
Q

multifocal multisystem (letterer-siwe disease)

A

before 2 yrs age, occasionally adults; cutaneous lesions resembling seborrheic eruption; rapidly fatal, intensive chemo 50% survive 5 years

231
Q

unifocal and multifocal unisystem (eosinophilic granuloma)

A

eosinophils usually prominent infiltrate; arises in medullary cavity of bones (calvarium, ribs, femur)

232
Q

unifocal lesions

A

commonly affect skeletal system in older children/adults; may heal spontaneously or cured by excision/irradiation

233
Q

multifical unisystem disease

A

young children; present with multiple erosive bony masses that sometimes expand into adjacent soft tissue; posterior pit involvement 50%

234
Q

HandSchuller-Christian triad

A

calvarial bone defects, diabetes insipidus, and exophthalmos

235
Q

Pulmonary Langerhans cell histiocytosis

A

adult smokers; may regress spontaneously on smoking cessation; polyclonal population of langerhan cells-reactive hyperplasia rather than true neoplasm

HEME II (5 decks)

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