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Flashcards in Hematology Deck (118):
1

Erythrocyte

-carries O2 to tissues, CO2 to lungs
-anucleate & biconcave w/large surface area-to-volume ratio for rapid gas exchange
-120 day lifespan, glucose is source of energy (90% glycolysis, 10% in HMP shunt)
-membrane has HCO3- antiporter, allows RBC to sequester HCO3- & transport CO2 from periphery to lungs for elimination
-polycthemia=inc. hematocrit

2

Anisocytosis

varying sizes

3

Poikilocytosis

varying shapes

4

Reticulocyte

immature erythrocyte, marker of erythroid proliferation

5

Thrombocyte

(Platelet), involved in primary hemostasis, small cytoplasmic fragment derived from megakaryocytes
-8-10 day lifespan, when activated by endothelial injury, aggregates with other platelets & interacts w/fibrin to form platelet plug. Contains dense granules (ADP, Ca) and alpha granules (vWF, fibrinogen)
-approx. 1/3 of platelet pool stored in spleen

6

Thrombocytopeia results in?

(platelet dysfunction), petechiae

7

vWF receptor is?

GpIb

8

Fibrinogen receptor is?

GpIIb/IIIa

9

Leukocyte

-divided into granulocytes (neutrophil, eosinophil, basophil) & mononuclear cells (monocytes, lymphocytes)
-responsible for defense against infections
-normally 4,000-10,000cels/mm^3

10

Blood Cell Differentiation

-WBC differential from highest to lowers
Neutrophils (54-62%)
Lymphocytes (25-33%)
Monocytes (3-7%)
Eosinophils (1-3%)
Basophils (0-0.75%)

11

Neutrophil

-acute inflammatory response cell, inc. in bacterial infections. Phagocytic. Multilobed nucleus. Small, more numerous specific granules contain alkaline phosphatase, collagenase, lysozyme, & lactoferrin
-larger, less numerous azurophilic granules (lysosomes) contain acid phosphatase, peroxidase, & B-glucuronidase
-Hypersegmented (5 or more) seen in vit. B12/folate deficiency
-inc. band cells reflect states of inc. myeloid proliferation (bacterial infection, CML)

12

Monocyte

-differentiates into macrophages in tissues
-large, kidney-shaped nulceus
-extensive "frosted glass" cytoplasm

13

Macrophage

-phagocytoses bacteria, cell debris, & senescent RBCs & scavenges damaged cells & tissues
-long life in tissues
-macrophages differentiate from circulating blood monocytes
-activated by gamma-interferon, can function as antigen-presenting cell via MHC II, CD14 is a cell surface marker for macrophages

14

Eosinophil

-defends against helminthic infections (major basic protein). Bilobate nucleus
-packed w/large eosinophilic granules of uniform size, highly phagocytic for antigen-antibody complexes
-produces histaminase & arylsulfatase (helps limit reaction following mast cell degranulation)

15

Causes of Eosinophilia

NAACP
Neoplastic, Asthma, Allergic process, Collagen vascular diseases, Parasites (invasive)

16

Basophil

-mediates allergic reaction, densely basophilic granules containing heparin (anticoag), histamine (vasodilator), & luekotrienes (LTD4)

17

Mast Cell

-mediates allergic rxn in local tissues, mast cells resemble basophils structurally & functionally but are not the same
-can bind the Fc portion of IgE to membrane
-IgE cross-links upon antigen binding, causing degranulation, which releases histamine, heparin, & eosinophil chemotactic factors
-involved in Type I Hypersensitivity rxns.
-Cromolyn sodium prevents mast cell degranulation (used for asthma prophylaxis)

18

Dendritic Cells

-highly phagocytic antigen-presenting cells (APCs)
-function as link b/w innate & adaptive immune system, express MHC class II & Fc receptor on surface
-called Langerhans cells in the skin

19

Lymphocyte

mediates adaptive immunity, divided into B cells & T cells, round, densely staining nucleus w/ small amount of pale cytoplasm

20

B lymphocyte

Part of humoral immune response, arises from stem cells in bone marrow. Migrates to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue)
-when antigen is encountered, B cells differentiate into plasma cells that produce abs, & memory cells
-can function as an APC via MHC II
(Bone Marrow)

21

Plasma Cell

-produces large amounts of ab specific to a particular antigen. Off-center nucleus, clock face chromatin distribution, abundant RER, & well-developed Golgi apparatus

22

T lymphocyte

-mediates cellular immune response, originates from stem cells in bone marrow, but matures in the thymus
-T cells differentiate into cytotoxic T cells (express CD8, recognize MHC I), helper T cells (CD4, MHCII), & regulatory T cells
-CD28 (costimulatory signal) necessary for T-cell activiation, majority of circulating lymphocytes are T cells (80%)

23

Blood Group A

-A antigen on RBC surface & anti-ab in plasma
-incompatible blood transfusion can cause immunologic response, hemolysis, renal failure, shock, death
***anti A & B ab (IgM) do not cross placenta***
***anti Rh IgG do cross placenta***

24

Blood Group B

-B antigen on RBC surface & anti A ab in plasma

25

Blood Group AB

A & B antigens on RBC surface, no abs
"universal recipient" of RBC
-universal donor of plasma

26

Blood Group O

Neither A or B antigen, both abs in plasma
-universal donor of RBCs
-universal recipient of plasma

27

Rh

-Rh antigen on RBC surface, Rh- mothers exposed to fetal Rh+ blood (often in delivery) may make anti Rh IgG. in subsequent pregnancies, anti-Rh IgG crosses placenta, causing hemolytic disease of newborn (erythroblastosis fetalis) in next fetus that is Rh+
-Treat: Rho(D) immine globulin for mother at first delivery to prevent initial sensitization of Rh- mother to Rh antigen

28

Acanthocyte (spur cell)

-liver disease, abetaliproteinemia (states of cholesterol dysregulation)
"spiny"

29

Basophilic Stippling

Thalassemias, Anemia of Chronic disease, Lead poisoning

30

Bite Cell

G6PD deficiency

31

Elliptocyte

hereditary elliptocytosis

32

Macro-ovalocyte

megaloblastic anemia (also hypersengmented PMNs), marrow failure

33

Ringed Sideroblasts

sideroblastic anemia
excess iron in mitochondria = pathologic

34

Schistocyte, helmet cell

DIC, TTP/HUS, traumatic hemolysis (metal heart valve prosthesis)

35

Sickle Cell

Sickle cell anemia

36

Spherocyte

hereditary shperocytosis, autoimmune hemolysis

37

Teardrop cell

bone marrow infiltration (myelofirbosis)

38

Target Cell

HbC disease, Asplenia, Liver disease, Thalassemia

39

Heinz bodies

-Oxidation of Fe from ferrous to ferric form leads to denatured hemoglobin precipitation & damage to RBC membrane- formation of bite cells
-seen in G6PD deficiency, heinz body-like inclusions seen in alpha-thalassemia

40

Howell-Holly Bodies

-basophilic nuclear remnants found in RBC
-normally removed by RBCs by splenic macrophages
-seen in patients w/functional hyposplenia or asplenia, or after mothball ingestion (naphthalene)

41

Iron Deficiency

Microcytic, hypochromic (MCV<80fL)
-dec. Fe due to chronic bleeding (GI loss, menorrhagia), malnutrition/absorption disorders or inc. demand (pregnancy), dec. final step in heme synthesis
-dec. Fe, inc. TIBC, dec. ferritin
-microcytosis & hypochromia, may manifest as Plummer-Vinson syndrome (triad of Fe deficiency anemia, esophageal webs, atrophic glossitis)

42

alpha-thalassemia

Microcytic, hypochromic (MCV<80fL)
Defect: alpha-globin gene mutations, dec. alpha-globin synthesis
-cis deletion prevalent in Asian populations; trans deletion prevalent in African populations
-4 gene deletion: No alpha-globin, excess gamma-globin forms gamma4 (Hb Barts). Incompatible with life (hydrops fetalis)
-3 gene deletion: HbH disease, very little alpha-globin, excess beta-globin forms beta4 (HbH)
-1-2 gene deletion: no clinically sig. anemia

43

beta-thalassemia

Microcytic, hypochromic (MCV3.5%) on electrophoresis
-Major, homozygote: beta chain absent, severe anemia requiring blood transfusion (secondary hemochromatosis), marrow expansion ("crew cut" on skull x-ray), chipmuck facies, inc. HbF (alpha2gamma2)
-HbS/beta-thalassemia heterozygote: mild to moderate sickle disease dep. on amount of beta-globin production

44

Lead Poisoning

Microcytic, hypochromic (MCVs Lines) & on metaphyses of long bones on x-ray
-Enchphalopahty & Erythrocyte basophilic stippling
-Abdominal colic & sideroblastic Anemia
-Drops-wrist & foot drop, Dimercaprol & EDTA are the 1st line of treatment
-Succimer used for chelation for kids

45

Sideroblastic Anemia

Microcytic, hypochromic (MCV<80fL)
-Defect in heme synthesis, heriditary x-linked defect in delta-ALA synthase gene, reversible etiologies (alcohol, lead, & isoniazid)
-ringed sideroblasts (with lead-laden mitochondria)
-inc. Fe, normal TIBC, inc. ferritin
Treatment: pyridoxine (B6, cofactor for delta-ALA synthase)

46

Megaloblastic Anemia

-impaired DNA synthesis, maturation of nucleus delayed relative to maturation of cytoplasm
-ineffective erythropoiesis, pancytopenia

47

Folate Deficiency

Macrocytic (MCV>100fL), Megaloblastic
etiologies: malnutrition (alcoholics), malabsorption , antifolates (methotrexate, trimethoprim, phenytoin), inc. requirement (hemolytic anemia, preg.)
-hypersegmented neutrophils, glossitis, dec. folate, inc. homocysteine but normal methylmalonic acid

48

B12 deficiency (cobalamin)

Macrocytic (MCV>100fL), Megaloblastic
Etiologies: insufficient intake (strict vegans), malabsorption (Crohn's disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), proton pump inhibitors

hypersegmented neutrophils, glossitis, dec. B12, inc. homocysteine, inc. methylmalonic acid
-neurologic symptoms: subacute combined degeneration (due to involvement of B12 in fatty acid pathways & myelin synthesis)
-peripheral neuropathy w/sensorimotor dysfunction, posterior columns (vibration/proprioception), lateral corticospinal (spasticity), dementia

49

Orotic Aciduria

Macrocytic (MCV>100fL), Megaloblastic
-genetic mutation in enzyme that synthesizes uridine from orotic acid, presents in children as megaloblastic anemia that can't be cured by folate or B12
-Hypersegmented neutrophils, glossitis, orotic acid in urine
-Treatment: uridine monophosphate to bypass mutated enzyme

50

Nonmegaloblastic macrocytic anemias

-macrocytic anemia in which DNA synthesis is unimpaired
-Causes: Liver disease; alcoholism; reticulocytosis, inc. MCV; drugs (5-FU, AZT, hydroxurea)
-macrocytosis & bone marrow suppression can occur in absence of folate/B12 deficiency

51

Normocytic, normochromic anemia

-normocytic, normochromic anemias are classified as nonhemolytic or hemolytic
-hemolytic are by cause of hemolysis (intrinsic vs. extrinsic to the RBC) & by the location of hemolysis (intravascular vs. extravascular)

52

Intravascular hemolysis

Normocytic, normochromic anemia
Findings: dec. haptoglobin, inc. LDH, hemoglobin in urine (paroxysmal nocturnal hemoglobinuria), mechanical destruction (aortic stenosis, prosthetic valve)

53

Extravascular Hemolysis

Normocytic, normochromic anemia
-Findings: macrophage in spleen clears RBC, inc. LDH plus inc. UCB, which causes jaundice (hereditary spherocytosis)

54

Anemia of Chronic Disease

Nonhemolytic, normocytic anemia
-Inflammation, inc. hepcidin (released by liver, binds ferroportin on intestinal mucosal cells & macrophages thus inhibiting Fe transport), dec. release of Fe from macrophages
-dec. Fe, dec. TIBC, inc. ferritin, can become microcytic, hypochromic

55

Aplastic Anemia

Nonhemolytic, normocytic anemia
-caused by failure or destruction of myeloid stem cells due to: 1) radiation/drugs (benzene, chloramphenicol, alkylating agents, antimetabolites) 2) viral agents (parvo B19, EBV, HIV, HCV) 3) Fanconi's anemia (DNA repair defect) 4) Idiopathic (immune mediated, primary stem cell defect), may follow acute hepatitis
-Pancytopenia characterized by severe anemia, leukopenia, & thrombocytopenia. Normal cell morphology, but hypocellular bone marrow w/fatty infiltration (dry bone marrow tap)
-Symptoms: fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection
-Treatment: withdrawal of offending agent, immunosuppressive regiment (antithymocyte globulin, cyclosporine), allogenic bone marrow transplant, RBC & platelet transfusion, G-CSF or GM-CSF

56

Chronic Kidney Disease

Nonhemolytic, normocytic anemia
-dec. erythropoietin, dec. hematopoiesis

57

Hereditary Spherocytosis

Extravascular, Intrinsic hemolytic normocytic anemia
-defect in proteins interacting w/RBC membrane skeleton & plasma membrane (ankyrin, band 3, protein 4.2, spectrin)
-Less membrane causes small & round RBCs w/no central pallor (inc. MCHC, inc. red cel distribution width), premature removal of RBCs by spleen
Findings: splenomegaly, aplastic crisis (Parvo B19, infection)
Labs: positive osmotic fragility test, normal to dec. MCV w/abundance of cells, masks microcytia
Treatment: splenectomy

58

G6PD Deficiency

Extra/Intravascular, Intrinsic hemolytic normocytic anemia
-X-linked, defect in G6PD, dec. glutathione, inc. RBC susceptibility to oxidant stress. Hemolytic anemia following oxidant stress (sulfa drugs, infections, fava beans) RBCs primarily destroyed extravascularly
Findings: back pain, hemoglobinuria a few days later
Labs: blood smear shows RBCs with Heinz bodie & bite cells

59

Pyruvate Kinase Deficiency

Extravascular, Intrinsic hemolytic normocytic anemia
-autosomal recessive, defect in pyruvate kinase, dec. ATP, rigid RBCs
-hemolytic anemia in a newborn

60

HbC Defect

Extravascular, Intrinsic hemolytic normocytic anemia
-Glutamic acid-to-lysine mutation at residue 6 in beta-globin
-patients w/HbSC (1 of each mutant gene) have milder disease than have HbSS patients

61

Paroxysmal Nocturnal Hemoglobinuria

Intravascular, Intrinsic hemolytic normocytic anemia
-inc. complement-mediated RBC lysis (impaired synthesis of GIP anchor or decaying-accelerating factor that protect RBC membrane from complement)
-acquired mutation in a hematopoietic stem cell
-PNH tirad: hemolytic anemia, pancytopenia, & venous thrombosis
Labs: CD55/59 - RBCs on flow cytometry
Treat: eculizumab

62

Sickle Cell Anemia

Extravasuclar, Intrinsic hemolytic normocytic anemia
-HbS point mutation causes a single aa replacement in beta chain (substiution of glutamic acid w/valine) at position 6
Pathogenesis: low O2 or dehydration precipitates sickling (deoxygenated HbS polymerizes), which results in anemia & vaso-occlusive disease
-newborns initially asymptomatic b/c of inc. HbF and dec. HbS
-heterozygotes (trait) have resistance to malaria
-8% of African Americans carry the HbS trait

63

Sickle Cell Anemia Findings

-crescent-shaped RBCs
-"crew cut" on skull x-ray due to marrow expansion from inc. erythropoiesis (thalassemias)
-complications in homozygous:
aplastic crisis (parvo B19)
autosplenoctomy (Howell-Jolly bodies), inc. risk of infection w/encapsulated organisms ; functional splenic dysfunction occurs in early childhood
splenic sequestration crisis
Salmonella osteomyelitis
Painful crisis (vaso-occlusive), dactylitis (hand swelling), acute chest syndrome, avascular necrosis
renal papillary necrosis (due to low O2 in papilla) & microhematuria (medullary infarcts)
Treatment: hydroxuxrea (inc. HbF) & bone marrow transplant

64

Autoimmune Hemolytic Anemia

Extrinsic Hemolytic Normocytic Anemia
-Warm agglutinin (IgG), chronic anemia seen in SLE, CLL or w/certain drugs (alpha-methyldopa)
(warm weather is GGGreat)
-Cold agglutinin (IgM), acute anemia triggered by cold, seen in CLL, mycoplasma pneumonia infections, or infectious mononucleosis
-many warm & cold AIHA are idiopathic

-Coombs' positive

65

Direct Coombs

anti-Ig ab added to patients serum. RBCs agglutinate if RBCs are coated with Ig

66

Indirect Coombs

normal RBCs added to patient's seurm agglutinate if serum has anti-RBC surface Ig

67

Microangiopathic Anemia

Extrinsic Hemolytic Normocytic Anemia
-Pathogenesis: RBCs are damaged when passing through obstructed or narrowed vessel lumina
-seen in DIC, TTP-HUS, SLE, & malignant hypertension
-Schistocytes (helmet cells) are seen on blood smear due to mechanical destruction of RBCs

68

Macroangiopathic Anemia

Extrinsic Hemolytic Normocytic Anemia
-prosthetic heart valves & aortic stenosis may also cause hemolytic anemia secondary to mechanical destruction
-Schistocytes on peripheral blood smear

69

Infections

Extrinsic Hemolytic Normocytic Anemia
-inc. destruction of RBCs (malaria, Babesia)

70

Lead Poisoning

-Affected Enzyme: Ferrochelatase & ALA dehydratase
-accumulated: protoporphyrin, delta-ALA
-symptoms: microcytic anemia, Gi & kidney disease
kids: exposure to lead paint, mental deteriration
adults: environmental exposure (battery/ammunition/radiator factory), headache, memory loss, demyelination

71

Acute Intermittent Porphyria

affected enzyme: porphobilinogen deaminase
accumulated: porphobilinogen, delta-ALA, uroporphyrin (urine)
symptoms: Painful abdomen, Port wine-colored urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs
Treatment: glucose & heme, which inhibit ALA synthase

72

Porphyria Cutanea Tarda

enzyme: uroporphyrinogen decarboxylase
accumulated: uroporphyrin (tea-colored urine)
symptoms: blistering cutaneous photosensitivity, most common porphyria

73

PT

tests function of common & extrinsic pathway (factors I, II, V, VII, & X)
-defect inc. PT

74

PTT

tests function of common and intrinsic pathway (all except VII & XIII)
-defect inc. PTT

75

Hemophilia A or B

-inc. PTT
-intrinsic pathway coagulation defect
-A: deficiency of factor VIII, inc. PTT
-B: deficiency of factor IX, inc. PTT
-Macrohemorrhage in hemophilia-hemarthroses (bleeding into joints) easy bruising, inc. PTT

76

Vit K Deficiency

-inc. PT
-inc. PTT
-general coagulation defect
-dec. synthesis of factors II, VII, IX, X, proteins C/S

77

Platelet Disorders

-defects in platelet plug formation, inc. bleeding time
-platelet abnormalities, microheorrhage; mucous membrane bleeding, epistaxis, petechiae, purpura, inc. bleeding time, possible dec. platelet count

78

Bernard-Soulier Syndrome

Platelet Disorders
-dec. platelet count
-inc. bleeding time
-defect in platelet plug formation
-dec. GpIb, defect in platelet-to-vWF adhesion

79

Glanzmann's Thrombasthenia

Platelet Disorders
-inc. bleeding time
-defect in platelet plug formation
-dec. GpIIb/IIIa, defect in platelet-to-platelet aggregation
-Labs: blood smear shows no platelet clumping

80

Idiopathic Thrombocytoppenic Purpura (ITP)

Platelet Disorders
-dec. platelet count
-inc. bleeding time
-defect: anti-GpIIb/IIIa abs, splenic macrophage consumption of platelet/ab complex
-dec. platelet survival
-Labs: inc. megakaryocytes

81

Thrombotic Thrombocytopenic Purpura (TTP)

Platelet Disorders
-dec. platelet count
-inc. bleeding time
-deficiency of ADAMS13 (vWF metalloprotease), dec. degradation of vWF multimers
-Pathogenesis: inc. large vWF multimers, inc. platelet aggregtion & thrombosis, dec. platelet survival
Labs: schistocytes, inc. LDH
Symptoms: pentad of neurologic & renal symptoms, fever, thrombocytopenia, & microangiopathic hemolytic anemia

82

von Willebrand's Disease

mixed platelet & coag disorders
-inc. bleeding time
-no change or inc. PTT
-intrinsic pathway coagulation defect, dec. vWF, normal or inc. PTT (depends on severity, vWF acts to carry/protect factor VIII)
-defect in platelet plug formation, dec. vWF, defect in platelet-to-vWF adhesion
-mild byt most common inherited bleeding disorder. Autosomal dominant. Diagnosed in most cases by ristocetin cofactor assay
-Treatment: DDAVP (desmopressin), which releases vWF stored in endothelium

83

DIC

mixed platelet & coag disorders
-dec. CP, inc. BT, inc. PT, inc. PTT
-widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state
-Causes: sepsis (gram-), Trauma, Obstretric Complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusions. (STOP Making New Thrombi)
Labs: schistocytes, inc. fibrin split products (D-dimers), dec. fibrinogen, dec. factor V & VIII

84

Factor V Leiden

Production of mutant factor V that is resistant to degradation by activated protein C. Most common cause of inherited hypercoaguability in whites

85

Prothrombin gene mutation

Mutation in 3' untranslated region, inc. production of prothrombin, inc. plasma levels & venous clots

86

Antithrombin Deficiency

Inherited deficiency of antithrombin, inc. in PTT is blunted after heparin administration

87

Protein C or S deficiency

-dec. ability to inactivate factors V and VII, inc. risk of thrombotic skin necrosis w/hemorrhage following administration of warfarin

88

Blood Transfusion: Packed RBCs

Inc. Hb & O2 carrying capacity
give in acute blood loss, severe anemia

89

Blood Transfusion: Platelets

inc. platelet count (inc. ~5,000/mm3)
give to stop significant bleeding (thrombocytopenia, qualitative platelet defects)

90

Blood Transfusion: Fresh Frozen Plasma

inc. coag factor levels
give in DIC, cirrhosis, warfarin overdose

91

Blood Transfusion: Cryoprecipitate

contains fibrinogen, factor VII, factor XIII, vWF, & fibronectin
give to treat coagulation factor deficiencies involving fibrinogen & factor VIII

92

Blood Transfusion Risks

infection transmission (low)
transfusion rxns
Fe overload
hypocalcemia (citrate is a clacium chelator)
hyperkalemia (RBCs may lyse in old blood units)

93

Leukemia

-lymphoid or myeloid neoplasm with widespread involvement of bone marrow
-tumor cells are usually found in peripheral blood
-unregulated growth of leukocytes in bone marrow, inc/dec # of circulating leukocytes in blood & marrow failure, anemia (dec. RBC), infections (dec. WBC), and hemorrhage (dec. platelets); leukemic cell infiltrates in liver, spleen, & lymph nodes are possible

94

Lymphoma

discrete tumor mass arising from lymph nodes
-presentations often blur definitions

95

Leukemoid Reaction

Acute inflammatory response to infection
-inc. WBC count with inc. neutrophils & neutrophil precursors such as band cells (left shift)
-inc. leukocyte alkaline phosphatase
-contrast with CML (also inc. WBC count with left shift, but dec. leukocyte alkaline phosphatase)

96

Hodgkin's Lymphoma

-localized, single group of nodes, extranodal rare, contiguous spread (stage is prognosis)
-characterized by Reed-Sternberg cells
-Bimodal distribution-young adulthood & >55 yrs, more common in men except for nodular sclerosing type
-50% associated with EBV
-Constitutional "B" signs/symptoms: low grade fever , night sweats, weight loss

97

Non-Hodgkin's Lymphoma

-multiple, peripheral nodes, extranodal involvement common, noncontiguous spread
-majority involve B cells (except those of lymphoblastic T-cell origin)
-Peak incidence for certain subtypes at 20-40 yrs
-May be associated with HIV & immunosuppression
-Fewer constitutional signs/symptoms

98

Reed-Sternberg Cells

-Distinctive tumor giant cell seen in Hodgkin's disease
-binucleate or bilobed with the 2 halves as mirror images "owls eyes"
-RS are CD30+ and CD15+ B-cell origin
-Necessary but not sufficient for a diagnosis of Hodgkin's disease, better prognosis with strong stromal or lymphocytic rxn against RS cells
-Nodular sclerosing form most common (affects women & men equally) with best prognosis
-Lymphocyte mixed or depleted forms have poor prognosis

99

Burkitt's Lymphoma

B-cell
-adolescents or young adults
t(8;14) - translocation of c-myc (8) and heavy-chain Ig(14)
-"starry sky" appearance, sheets of lymphocytes with interspersed macrophages
-associated with EBV
-Jaw lesion in endemic form in Africa, pelvis or abdomen in sporadic form

100

Diffuse large B-cell lymphoma

B-cell
-usually older adults, but 20% in children
-most common adult NHL
-may be mature T cell in origin (20%)

101

Mantle Cell Lymphoma

B-cell
Older males
-t(11;14)-translocation of cyclin D1 (11) and heavy chain Ig (14)
-Poor prognosis, CD5+

102

Follicular Lymphoma

B-cell
adults
-t(14;18)-translocation of heavy-chain Ig (14) and bcl-2 (18)
-difficult to cure, indolent course, bcl-2 inhibits apoptosis

103

Adult T-cell Lymphoma

adults
-caused by HTLV-1
-adults present with cutaneous lesions, especially affects Japan, West Africa, and Caribbean
-aggressive

104

Mycosis fungoides/ Sezary Syndrome

T-cell
adults
-adults present with cutaneous patches/nodules
-CD4+, indolent course

105

Multiple Myeloma

-monoclonal plasma cell "fried egg" appearance, cancer that arises in the marrow & produces large amounts of IgG (55%) or IgA (25%)
-most common primary tumor arising within bone in the elderly (>40-50 years)
Associated with:
-inc. susceptibility to infection
-primary amyloidosis (AL)
-punched-out lytic bone lesions on X-ray
-M spike on protein electrophoresis
-Ig light chains in urine (Bence Jones Protein)
-Rouleaux formation (RBCs stacked like poker chips in blood smear)
Numerous plasma cells with "Clock face" chromatin & intracytoplasmic inclusions containing immunoglobulin
CRAB (hyperCalcemia, Renal insufficiency, Anemia, Bone lytic lesions/Back pain)

106

Waldenstrom's Macroglobulinemia

M spike = IgM (hyperviscosity symptoms), no lytic bone lesions

107

MGUS

-monoclonal gammopathy of undetermined significance (MGUS), monoclonal expansion of plasma cells with M spike
-asymptomatic precursor to multiple myeloma
-patients develop multiple myeloma at a rate of 1-2% per year

108

Acute Lymphoblastic Luekemia/Lymphoma ALL

Lymphoid
<15 yrs. T-cell ALL can present as mediastinal mass (leukemic infiltration of thymus)
-peripheral blood & bone marrow have inc. lymphoblasts
-TdT+ (marker of pre-T and pre-B cells), CALLA+
-most responsive to therapy
-may spread to CNS & testes
-t(12;21) is better prognosis

109

Small Lymphocytic Lymphoma (SLL)/ Chronic Lymphocytic Leukemia (CLL)

Lymphoid
>60 yrs. often asymptomatic; smudge cells in peripheral blood smear; autoimmune hemolytic anemia
-SLL same as CLL except CLL has inc. peripheral blood lymphocytosis or bone marrow involvement

110

Hairy Cell Leukemia

Lymphoid
Adult, mature B-cell tumor in the elderly, cells have filamentous, hair-like projections
-stains TRAP (tartrate-resistant acid phosphatase)+
-Treatment: cladribine, an adenosine analog

111

Acute Myelogenous Leukemia (AML)

Myeloid
-median onset 65 yrs.
-Auer rods, inc. circulating myeloblasts on peripheral smear, adults
-t(15;17) M3 AML subtype responds to all-trans retinoic acid (vit A) inducing differentation of myeloblasts
-DIC is a common presentation in M3 AML

112

Chronic Myelogenous Leukemia (CML)

Myeloid
-highest incidence 30-60 yrs, defined by the Philadephia chromosome t(9;22), bcr-abl
-myeloid stem cell proliferation; present with inc. neutrophils, metamyelocytes, basophils, splenomegaly, may accelerate & transform to AML or ALL "blast crisis"
-Very low leukocyte alkaline phosphatase as a result of immature granulocytes (vs. leukemoid rxn-mature cells)
-Responds to imatinib (small molecule inhibitor of the bcr-abl tyrosine kindase)

113

Auer Bodies (rods)

-peroxidase-positive cytoplasmic inclusions in granulocytes & myeloblasts
-commonly seen in acute promyelocytic leukemia M3
-treatment of AML M3 can release Auer rods- DIC

114

Polycythemia Vera

inc. RBCs
inc. WBCs
inc. Platelets
- Philadephia chromosome
+ JAK 2 mutations
Abnormal clone of hematopoietic stem cell with constitutively active JAK 2 receptors, proliferate w/o EPO stimulation, often presents as intense itching after hot shower

115

Essential Thrombocytosis

no change RBCs
no change WBCs
inc. Platelets
- Philadephia chromosome
+ JAK 2 mutations (30-50%)
Similar to polycythemia vera, but specific for megakaryocytes

116

Myelofirbosis

dec. RBCs
variable WBCs
variable Platelets
- Philadephia chromosome
+ JAK 2 mutations (30-50%)
Fibrotic obliteration of bone marrow, tear drop cell

117

CML

dec. RBCs
inc. WBCs
inc. Platelets
+ Philadephia chromosome
- JAK 2 mutations
bcr-abl transformation leads to inc. cell division and inhibition of apoptosis

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Langerhans Cell Histiocytosis

-proliferative disorders of dendritic (langerhans) cells from monocyte lineage
-presents in a child as lytic bone lesions & skin rash
-cells are functionally immature & do not efficiently stimulate T lymphocytes via antigen presentation
-cells express S-100 (neural crest origin) & CD1a
-Birbeck granules "tennis rackets" on EM