Path 13 Wbc, Ln, Spleen, Thymus

Front 1

what are myeloid tissues?

Back 1

bone marrow and cells derived from it

RBCs, PLTs, granulocytes, monocytes

Front 2

what are lymphoid tissues?

Back 2

thymus, LNs, spleen

Front 3

which stages in hematopoesis are capable of self-renewal?

Back 3

the first (stem cell) stage only

Front 4

what stimulates the differentiation of hematopoetic stem cells?

Back 4

stem cell factor (SCF aka cKIT ligand)
IL-6
FLT3 ligand

Front 5

what stimulates the differentiation myeloid progenitor cells into CFU-GM?

Back 5

GM-CSF

Front 6

what stimulates the differentiation of myeloid progenitor cells to CFU-b/Mg and BFU-E?

Back 6

Thrombopoietin, IL-11

Front 7

what mediates the differentiation of CFU-GM?

Back 7

G-CSF --> CFU-G (myeloblast --> neutrophil)

M-CSF --> CFU-M (monoblast --> monocyte)

Front 8

what stimulates production of eosinophils?

from what progenitor are they derived?

Back 8

IL-5

common myeloid progenitor --> CFU-eo --> eosinophiloblast

Front 9

where in bone marrow are normal megakaryocytes located?

Back 9

next to sinusoids, extend cytoplasmic processes that bud off into blood as plts

Front 10

where in bone marrow are RBC precursors located?

Back 10

surround macrophages (nurse cells) that provide iron for Hb synthesis

Front 11

what generalized changes in bone marrow are seen in disease states?

Back 11

Increased fat: aplastic anemia

Decreased fat: hematopoietic tumors, dzs w/ compensatory hyperplasia, and leukemias

Local marrow fibrosis: metastatic cancers and granulomatous dzs

Front 12

MCC of agranulocytosis?

Back 12

drug toxicity

Front 13

Drugs implicated in agranulocytosis?

Back 13

aminopyrine
chloramphenicol
sulfonamides
chlorpromazine
thiouracil
phenylbutazone

Front 14

which drugs cause neutropenia thru a toxic effect on granulocytic precursors in marrow?

Back 14

chlorpromazine and thenothiazines

Front 15

what is the most common sign of agranulocytosis?

Back 15

ulcerating necrotizing lesions of the gingiva and oral cavity

Front 16

MCC of neutrophilic leukocytosis?

Back 16

infection

Front 17

which growth factor induces neutrophilia?

what are causes of its release?

Back 17

G-CSF

acute bact infxn (esp pyogenic bact); sterile inflammation (eg tissue necrosis)

Front 18

causes of eosinophilia?

Back 18

allergy (hay fever, asthma)
skin diseases
parasitic infxns
drug rxns
some malignancies (hodgkin & non-hodgkin lymphomas)
collagen vascular dzs and vasculitides
atheroembolic dz

Front 19

causes of basophilia?

Back 19

(Rare) myeloproliferative dzs (eg CML)

Front 20

causes of monocytosis?

Back 20

chronic infxn, bact endocarditis, rickettsiosis, malaria
collagen vascular dzs (eg SLE)
inflamm bowel dzs (eg UC)

Front 21

causes of lymphocytosis?

Back 21

comes w/ monocytosis in chronic immunological stimulation disorders (tb, brucellosis)
viral infxns
B. pertussis infxn

Front 22

difference between neutropenia from peripheral destruction and neutropenia from destruction of granulocytic precursors?

Back 22

bone marrow is hypercellular

bone marrow is hypocellular

Front 23

morphologic neutrophil chgs in sepsis or severe inflammatory disorders?

Back 23

toxic granules (abnormally coarse, dark granules)

Dohle bodies (blue cytoplasmic patches of dilated ER)

cytoplasmic vacuoles

Front 24

MCC of acute cervical lymphadenitis?

Back 24

infections of teeth or tonsils

Front 25

MCC of acute axillary or inguinal lymphadenitis?

Back 25

infections in extremities

Front 26

MCC of acute generalized lymphadenopathy?

Back 26

systemic viral infxns (esp in children), bacteremia

Front 27

when does scarring of LNs occur?

Back 27

after suppurative rxns to pyogenic organisms

Front 28

activation of humoral immune response results in what type of LN rxn?

Back 28

follicular hyperplasia

Front 29

activation of T cell mediated immune response results in what type of LN rxn?

Back 29

Paracortical hyperplasia

Front 30

How to differentiate between follicular hyperplasia and follicular lymphoma?

Back 30

Hyperplasia:
-maintains LN architecture
-has marked variation in shape/size of nodules
-has frequent mitotic figures, phagocytic macrophages, and recognizable light and dark zones

Front 31

MCCs of paracortical lymphoid hyperplasia?

Back 31

immunologic rxns induced by drugs (esp phenytoin)

acute viral infxn (esp EBV)

Front 32

LN changes seen especially in LNs draining cancers such as carcinoma of the breast?

Back 32

sinus histiocytosis (aka reticular hyperplasia):
increase in # and size of cells that line lymphatic sinusoids

Front 33

what are histiocytoses?

Back 33

uncommon proliferative lesions of macrophages and dendritic cells, esp Langerhans cells

Front 34

from what normal mechanism do most lymphoid neoplasms derive?

Back 34

B cell class switching and somatic hypermutations to generate Ab diversity; most commonly translocations

Front 35

t(9,22) is associated with what disease(s)?

Back 35

ALL, AML, CML

Front 36

what inherited genetic factors predispose to WBC neoplasias?

Back 36

Bloom syndrome, Fanconi anemia, ataxia telangiectasia = Acute leukemias

+21, NF-1 = childhood leukemias

Front 37

Which viruses predispose to WBC neoplasias?

Back 37

HTLV-1 = adult T cell leukemia/lymphoma

EBV = Burkitt lymphoma, Hodgkin lymphoma, other B cell lymphomas in setting of T-cell immunodeficiency and NK-cell lymphomas

KSHV = Kaposi sarcoma

Front 38

what environmental agent is associated with gastric B-cell lymphomas?

Back 38

H. pylori infection

Front 39

chronic immune stimulation in what disease is associated with intestinal T-cell lymphomas?

Back 39

gluten-sensitive enteropathy

Front 40

term used for neoplasms with widespread BM involvement and usually peripheral blood

Back 40

leukemia

Front 41

term used for WBC proliferations that arise as discrete tissue masses

Back 41

lymphoma

Front 42

2/3 of NHLs and almost all Hodgkin's lymphomas present with what symptom?

Back 42

enlarged, nontender LNs

Front 43

which plasma cell neoplasm often presents as pain d/t pathologic fractures?

Back 43

multiple myeloma

Front 44

which WBC neoplasms cause symptoms through the secretion of circulating factors?

Back 44

plasma cell tumors (secretion of antibodies or fragments)

Hodgkin lymphoma (fever d/t release of inflammatory cytokines)

Front 45

most common origin of lymphoid neoplasm?

Back 45

B-cell origin

Front 46

MCC of cancer in children?

Back 46

ALL

Front 47

which subset of ALL presents as childhood leukemia?

Back 47

B-ALL

Front 48

which lymphoid neoplasm presents in adolescent males as thymic lymphomas (mediastinal mass)?

Back 48

T-ALL

Front 49

characteristic cells of this neoplasm are positive for TdT, PAS and acid phosphatase

Back 49

ALL

Front 50

lymphoblasts express CD19 and karyotype shows hyperdiploidy and t(12,21)?

Back 50

B ALL

Front 51

lymphoblasts often express CD1a and gain-of-fxn mutations in NOTCH1?

Back 51

T ALL

Front 52

clinical features of ALLs?

Back 52

- abrupt, stormy onset
- sxs related to BMS (fatigue, fever, bleeding)
- mass effect (bone pain, organomegaly, lymphadenopathy, testicular enlargement)
- CNS (HA, vomiting, nerve palsies)

Front 53

which WBC neoplasm causes compression of large vessels and airways in the mediastinum?

Back 53

T-ALL

Front 54

what factors are associated with poorer prognosis in ALL?

Back 54

- age < 2 or > 10
- blast counts > 100,000
- t(9,22)

Front 55

what factors are associated with better prognosis in ALL?

Back 55

- age 2-10
- low WBC
- hyperploidy
- trisomy 4,7,10
- t(12,21)

Front 56

which drug is used in t(9,22)+ ALLs and inhibits BCR-ABL kinase?

Back 56

Imatinib (Gleevec)

Front 57

ALL responsiveness to aggressive chemo (including CNS prophylaxis)?

Back 57

CR in 90% of children, 2/3 cured

Front 58

MCC of leukemia of adults in Western world?

Back 58

CLL

Front 59

difference between CLL and SLL?

Back 59

degree of peripheral blood lymphocytosis

Front 60

WBC neoplasm in which abnml cells gather in LNs in proliferation centers; PBS contains smudge cells?

Back 60

CLL/SLL

Front 61

Neoplastic cells are positive for CD19, CD20, CD23, and CD5;
deletions in 13q, 11q, 17p, trisomy 12q?

Back 61

CLL/SLL

Front 62

poor prognosis in CLL/SLL is associated with what progression of disease?

Back 62

prolymphocytic transformation (worsening cytopenias, inc splenomegaly, inc # prolymphocytes)

Richter syndrome - transformation to diffuse large B-cell lymphoma (rapidly enlarging mass in LN or spleen)

Front 63

tumor that arises from germinal center B cells and is strongly assoc'd w/ translocations involving BCL2 [t(14,18)]?

Back 63

Follicular lymphoma

Front 64

LN findings in follicular lymphoma?

Back 64

centrocytes - small, cleaved cells
centroblasts - larger cells w/ open chromatin, several nucleoli, modest amts of cytoplasm

Front 65

what are the results of t(14,18) mutation?

Back 65

BCL2 and Ig heavy chain loci switch, BCL2 is overexpressed, promotes survival of follicular lymphoma cells by blocking bax channel

Front 66

MCC of NHL in United States?

Back 66

follicular lymphoma

Front 67

response of follicular lymphomas to chemo/rad?

Back 67

survival is not improved by aggressive therapy

Front 68

mature B-cell tumors that express CD19, CD20 and sometimes translocation of BCL6; typically present at extranodal sites (GI, skin, bone, brain); aggressive, rapidly proliferating; may respond to therapy?

Back 68

Diffuse large B-cell lymphoma

Front 69

what are special subsets of diffuse large B-cell lymphoma?

Back 69

- may occur in setting of severe T-cell immunodeficiency; cells are usually infected with EBV

- may present as malignant pleural or ascitic effusion; mostly in advanced HIV or elderly; always infected with KSHV/HHV-8

Front 70

neoplasm with medium sized lymphocytes, "starry-sky" appearance, c-MYC t(8,14)?

Back 70

Burkitt lymphoma

Front 71

B-cell neoplasm assoc'd with EBV, presents in maxilla or mandible, involves kidneys, ovaries, adrenal glands?

Back 71

African (endemic) Burkitt lymphoma

Front 72

B-cell neoplasm with high incidence in AIDS, presents as mass involving ileocecum or peritoneum?

Back 72

American (sporadic) Burkitt lymphoma

Front 73

neoplasm of older adults presenting with hypercalcemia, bone pain, pathologic fxrs; inc gamma proteins, Bence-Jones proteins, and "punched-out" lesions of skull?

Back 73

Multiple myeloma (plasma cell myeloma)

Front 74

what causes lytic bone lesions in multiple myeloma?

Back 74

inc osteoclast activating factor (OAF, IL-6)
MIP1a induces expression of RANKL which activates osteoclasts
Modulators of Wnt pathway inhibit osteoblasts

Front 75

Disorder in which protein casts in DCT and collecting ducts are surrounded by multinucleated giant cells?

Back 75

myeloma kidney

Front 76

MCC of death in multiple myeloma?

Back 76

infection (inc susceptibility d/t dec production of serum Ig's)

Front 77

most common plasma cell dyscrasia?

Back 77

monoclonal gammopathy of uncertain significance (MGUS)

Front 78

MCC of elevated serum M protein level (< 3gm/dL) in asymptomatic older patient?

Back 78

MGUS

Front 79

B-cell neoplasm that infiltrates many organs, has M spike (IgM), but no hypercalcemia, and no lytic bone lesions present?

Back 79

Lymphoplasmacytic lymphoma

Front 80

what are Russell bodies and Dutcher bodies?

Back 80

Russell bodies - cytoplasmic immunoglobulin
Dutcher bodies - intranuclear immunoglobulin

characteristic of lymphoplasmacytic lymphoma

Front 81

hyperviscosity syndrome, associated with lymphoplasmacytic lymphoma, causes what complications?

Back 81

vascular dilations and retinal hemorrhages --> visual problems
neuro sxs (HA, confusion)
abnml globulins cause bleeding and cryoglobulinemia (precipitate at low temp and cause Raynaud phenomenon)

Front 82

lymphoid neoplasm of older males consisting of small, cleaved lymphocytes, but no proliferation centers, no large centroblasts; t(11,14), high levels of cyclin D, CD5+, CD23-?

Back 82

Mantle cell lymphoma

Front 83

B-cell tumor that commonly occurs at sites of chronic immune or inflammatory reactions?

Back 83

marginal zone lymphomas (MALTomas)

Front 84

Disease of middle-aged white males, may cause "dry tap" BM aspirate, presents with red beefy splenomegaly d/t infiltration of red pulp; stains positive for tartrate-resistant acid phosphatase (TRAP)

Back 84

Hairy cell leukemia

Front 85

neoplasm of CD4+ T-cells in adults infected with HTLV-1, esp. in Japan, W Africa, Caribbean; presents w/ skin lesions, hypercalcemia, enlarged LN, liver, and spleen; cloverleaf nuclei?

Back 85

Adult T-cell Leukemia/Lymphoma (ATLL)

Front 86

tumor of CD4+ T-cells that causes generalized pruritic erythematous rash (w/o hypercalcemia); abnml cells have cerebriform nuclei?

Back 86

Mycosis fungoides/Sezary syndrome

Front 87

difference btwn MF and Sezary syndrome?

Back 87

skin lesions of sezary syndrome rarely become tumors

sezary cells (cerebriform nuclei) are found in peripheral blood in sezary syndrome, only found in epidermis/dermis in MF

Front 88

rare neoplasm of CD8 T-cells, lymphocytes have abundant cytoplasm with coarse azurophilic granules?

Back 88

Large granular lymphocytic leukemia

Front 89

neoplasm presenting as descructive midline mass involving nasopharynx, skin, or testes; highly associated with EBV?

Back 89

extranodal NK/T-cell lymphoma

Front 90

how is HD different from NHL?

Back 90

- presents with fever
- spread is to contiguous (adjacent) nodal groups
- characterization based on inflammatory response instead of malignant cell
- no leukemic state
- extranodal spread uncommon

Front 91

neoplastic cell of this disease has "owl eye" bilobed nucleus w/ central nucleoli surrounded by clear space

Back 91

Hodgkin lymphoma
(Reed-Sternberg cells)

Front 92

HL variant that has L&H "popcorn" cells and are negative for CD15 and CD30, but positive for B-cell markers CD20 and BCL6?

Back 92

lymphocyte predominance type

Front 93

most common type of HL; has lacunar variant Reed-Sternberg cells that are positive for PAX5, CD15 and CD30; nuclear deposition of collagen in bands?

Back 93

Nodular sclerosis type

Front 94

type of HL with infiltrate of T-cells, eosinophils, plasma cells, benign macrophages with Reed-Sternberg cells; RS cells often infected with EBV?

Back 94

Mixed-cellularity type

Front 95

type of HL with few lymphocytes, many RS cells?

Back 95

lymphocyte depleted type

Front 96

stereotyped progression of spread of HL?

Back 96

nodal dz --> splenic dz --> hepatic dz --> marrow and other tissues

Front 97

clinical presentations of HL?

Back 97

usually painless lymphadenopathy

disseminated dz, mixed-cellularity or LD types may have B-cell symptoms: waxing/waning fever, wt loss, night sweats

Front 98

population at risk for AML?

Back 98

adults

Front 99

dx of AML is based on what?

Back 99

>= 20% myeloid blasts in bone marrow

Front 100

many myeloblasts on PBS, auer rods, peroxidase+ azurophilic cytoplasmic granules - Dx?

Back 100

AML

Front 101

auer rods are especially pronounced in what neoplasia (specific translocation)?

Back 101

t(15,17) - acute promyelocytic leukemia

Front 102

treatment of M3 subtype AML?

Back 102

all-trans retinoic acid (ATRA) - induces differentiation of myeloblasts

Front 103

difference between acute leukemias and chronic leukemias?

Back 103

mostly blasts (acute), more mature cells (chronic)

children or elderly (acute), midlife (chronic)

short and drastic (acute), longer, less devastating (chronic)

Front 104

karyotypic abnormalities associated with AML?

Back 104

de novo: t(8;21), inv(16), t(15;17)

following MDS or exposure to DNA-damaging agents: del or monosomies of 5 & 7

after tx w/ topoisomerase II inhibitors: MLL chromosome (11q23)

Front 105

disorder associated with t(8;14)?

Back 105

burkitt lymphoma (c-myc activation)

Front 106

disorder associated with t(14;18)?

Back 106

follicular lymphomas (bcl-2 activation)

Front 107

disorder associated with t(15;17)?

Back 107

M3 type AML

Front 108

disorder associated with t(11;22)?

Back 108

Ewing's sarcoma

Front 109

disorder associated with t(11;14)?

Back 109

Mantle cell lymphoma

Front 110

most common presentation of AML?

Back 110

sxs related to anemia, neutropenia, TCpenia (fatigue, fever, spontaneous mucosal and cutaneous bleeding)

Front 111

what factors contribute to bleeding diathesis in AML?

Back 111

thrombocytopenia

procoagulants and fibrinolytic factors released by leukemic cells (esp in t[15;17])

Front 112

which types of AML are high-risk?

Back 112

those that follow MDS or genotoxic therapy or that occur in elderly

Front 113

primary and t-MDS are associated with what karyotypic abnormalities?

Back 113

monosomy 5 and 7
del 5q, 7q, 20q
trisomy 8

Front 114

most common finding in MDS?

Back 114

dysplastic differentiation affecting all three myeloid lineages (erythroid, granulocytic and megakaryocytic)

Front 115

morphological changes seen in MDS?

Back 115

erythroid: ringed sideroblasts, megaloblastoid maturation, nuclear budding abnormalities

granulocytic; neutrophils with dec or abnml/toxic granules, pseudo-Pelger-Huet cells

Megakaryocytic: pawn ball meg.cytes

Front 116

what are pseudo-Pelger-Huet cells?

Back 116

neutrophils with only two lobes (seen in MDS)

Front 117

primary MDS affects what age group?

Back 117

> 60 y

Front 118

what are the chronic myeloproliferative disorders?

Back 118

- CML
- polycythemia vera
- essential thrombocytosis
- myelofibrosis w/ myleoid metaplasia

Front 119

what features are common to all MPDs?

Back 119

- neoplastic stem cells home in to secondary hematopoietic organs, esp spleen, leading to splenomegaly

- terminal spent phase: marrow fibrosis and peripheral cytopenias

- progression to acute leukemia

Front 120

what is the biomechanical change that occurs in CML?

Back 120

BCR gene (22) fuses with ABL gene (9) and synthesizes a constitutively active tyr-kinase, stimulating proliferation and survival of marrow progenitors

does not interfere with differentiation --> increase in mature cells in blood, esp granulocytes and plts

Front 121

what lab finding helps differentiate between CML and other leukemoid reactions?

Back 121

absence of leukocyte alk phos in CML

Front 122

cell counts in CML - RBCs, WBCs, Plts?

Back 122

dec RBCs
inc WBCs
inc Plts

Front 123

pharm tx of CML?

Back 123

Imatinib (anti-bcr-abl antibody)

Front 124

disease characterized by increased marrow production of RBCs, granulocytes, and plts?

Back 124

polycythemia vera

Front 125

mutation implicated in polycythemia vera?

Back 125

activating point mutations in tyr-kinase JAK2

Front 126

difference between polycythemia vera and secondary absoulte polycythemia?

Back 126

PCV = low EPO

secondary polycythemias = high EPO

Front 127

symptoms of PCV?

Back 127

plethora and cyanosis (d/t stagnation and deox of blood in peripheral vessels),

HA, dizziness, HTN, GI sxs,

DVT, MI, stroke

Front 128

why do some pts w/ PCV have HCT within normal range?

Back 128

chronic bleeding leads to iron deficiency which suppresses erythropoiesis

Front 129

extended survival with PCV leads to what?

Back 129

"spent phase" clinically resembling myelofibrosis

Front 130

pathogenesis of essential thrombocytosis?

Back 130

same JAK2 point mutation as in PCV - receptor tyr-kinase activation makes progenitors thrombopoeitin-independent

Front 131

major manifestations of ET?

Back 131

thrombosis and hemorrhage

DVT, portal and hepatic vein thrombosis, MI, erythromelalgia

Front 132

what is erythromelalgia?

Back 132

throbbing and burning of hands and feet caused by occlusion of small arterioles by plt aggregates

seen in ET and PCV

Front 133

pathogenesis of primary myelofibrosis?

Back 133

inappropriate release of PDGF and TGF-beta from neoplastic megakaryocytes (fibrogenic factors)

Front 134

in what disease are large platelets and dacryocytes found?

Back 134

myelofibrosis

(dacryocytes = teardrop shaped RBCs damaged during birthing process in fibrotic marrow)

Front 135

cause of splenomegaly in primary myelofibrosis?

Back 135

circulating hematopoeitic stem cells home to secondary hematopoietic organs esp spleen, liver, LNs

Front 136

secondary disorder that can complicate the picture of MPDs?

Back 136

hyperuricemia and gout (from high cell turnover rate)

Front 137

infant develops cutaneous seborrheic-like eruption on chest, back, and scalp; also has hepatosplenomegaly, lymphadenopathy, pulmonary lesions. Dx?

Back 137

Letterer-Siwe disease
(Multifocal multisystem Langerhans cell histiocytosis)

Front 138

pathogenesis of primary myelofibrosis?

Back 138

inappropriate release of PDGF and TGF-beta from neoplastic megakaryocytes (fibrogenic factors)

Front 139

in what disease are large platelets and dacryocytes found?

Back 139

myelofibrosis

(dacryocytes = teardrop shaped RBCs damaged during birthing process in fibrotic marrow)

Front 140

cause of splenomegaly in primary myelofibrosis?

Back 140

circulating hematopoeitic stem cells home to secondary hematopoietic organs esp spleen, liver, LNs

Front 141

secondary disorder that can complicate the picture of MPDs?

Back 141

hyperuricemia and gout (from high cell turnover rate)

Front 142

infant develops cutaneous seborrheic-like eruption on chest, back, and scalp; also has hepatosplenomegaly, lymphadenopathy, pulmonary lesions. Dx?

Back 142

Letterer-Siwe disease
(Multifocal multisystem Langerhans cell histiocytosis)

Front 143

What is the Hand-Schuller-Christian triad?

Back 143

calvarial bone defects, diabetes insipidus, and exophthalmos

(multifocal unisystem Langerhans cell histiocytosis that involves the posterior pituitary stalk)

Front 144

causes of congestive splenomegaly?

Back 144

venous obstruction d/t intrahepatic disorders (esp. cirrhosis) that slow portal venous drainage or extrahepatic disorders that impinge upon portal or plenic veins (pylephlebitis, portal vein thrombosis)

Front 145

MCC of splenic infarctions?

Back 145

emboli arising from the heart

Front 146

MCC of thymic hypoplasia?

Back 146

DiGeorge syndrome

Front 147

MCC of thymic hyperplasia?

Back 147

myasthenia gravis

(also seen in other AI dz: Graves, SLE, scleroderma, RA)

Front 148

difference between invasive thymoma and thymic carcinoma?

Back 148

invasive thymoma is cytologically benign but locally invasive

thymic carcinoma is invasive, somtimes accompanied by metastases, usually squamous cell carcinoma