Hematology Flashcards
(118 cards)
1
Q
Erythrocyte
A
- 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
Q
Anisocytosis
A
varying sizes
3
Q
Poikilocytosis
A
varying shapes
4
Q
Reticulocyte
A
immature erythrocyte, marker of erythroid proliferation
5
Q
Thrombocyte
A
(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
Q
Thrombocytopeia results in?
A
(platelet dysfunction), petechiae
7
Q
vWF receptor is?
A
GpIb
8
Q
Fibrinogen receptor is?
A
GpIIb/IIIa
9
Q
Leukocyte
A
- divided into granulocytes (neutrophil, eosinophil, basophil) & mononuclear cells (monocytes, lymphocytes)
- responsible for defense against infections
- normally 4,000-10,000cels/mm^3
10
Q
Blood Cell Differentiation
A
-WBC differential from highest to lowers Neutrophils (54-62%) Lymphocytes (25-33%) Monocytes (3-7%) Eosinophils (1-3%) Basophils (0-0.75%)
11
Q
Neutrophil
A
- 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
Q
Monocyte
A
- differentiates into macrophages in tissues
- large, kidney-shaped nulceus
- extensive “frosted glass” cytoplasm
13
Q
Macrophage
A
- 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
Q
Eosinophil
A
- 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
Q
Causes of Eosinophilia
A
NAACP
Neoplastic, Asthma, Allergic process, Collagen vascular diseases, Parasites (invasive)
16
Q
Basophil
A
-mediates allergic reaction, densely basophilic granules containing heparin (anticoag), histamine (vasodilator), & luekotrienes (LTD4)
17
Q
Mast Cell
A
- 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
Q
Dendritic Cells
A
- 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
Q
Lymphocyte
A
mediates adaptive immunity, divided into B cells & T cells, round, densely staining nucleus w/ small amount of pale cytoplasm
20
Q
B lymphocyte
A
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
Q
Plasma Cell
A
-produces large amounts of ab specific to a particular antigen. Off-center nucleus, clock face chromatin distribution, abundant RER, & well-developed Golgi apparatus
22
Q
T lymphocyte
A
- 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
Q
Blood Group A
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
Q
Blood Group B
A
-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
118
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
