Hematology/oncology Pathology

Front 1

Neoplastic Progression

Back 1

Normal --> Hyperplasia --> Carcinoma in situ/preinvasive --> Invasive carcinoma --> Metastatic focus

Front 2

NORMAL

Back 2

**Normal cells w/ basal --> apical differentiation

Front 3

Hyperplasia

Back 3

=Cells have increased in NUMBER (hyperplasia)
=Abnormal proliferation of cells w/ loss of size, shape, and orientation = DYSPLASIA

Front 4

In situ carcinoma

Back 4

=Neoplastic cells have NOT invaded basement membrane
=High NUCLEAR/CYTOPLASMIC ratio and clumped chromatin
=Neoplastic cells encompass entire thickness

Front 5

Invasive Carcinoma

Back 5

=Cells have invaded the basement membrane using collagenases + hydrolases
=Can metastasize IF they reach a blood or lymphatic vessel

Front 6

Metastasis

Back 6

=Spread to a distant organ
=Must survive immune attack

**"Seed and soil" theory of metastasis
=Seed --> tumor embolus
=Soil --> target organ (=liver, lungs, bone, brain)

Front 7

Hyperplasia

Back 7

**Increase in number of cells (=reversible)

Front 8

Metaplasia

Back 8

=One adult cell type is replaced by another (reversible)

=Often secondary to irritation and/or environmental exposure -->

i.e. squamous metaplasia in trachea and bronchi of smokers

Front 9

Dysplasia

Back 9

=Abnormal growth w/ loss of cellular orientation, shape, and size in comparison to normal tissue maturation

=Commonly preneoplastic (reversible)

Front 10

Anaplasia

Back 10

=Abnormal cells lacking differentiation --> like primitive cells of the same tissue

**Often equated w/ undifferentiated malignant neoplasms

**Tumor giant cells may be formed

Front 11

Neoplasia

Back 11

=A clonal proliferation of cells that is uncontrolled and excessive

Front 12

Tumor GRADE

Back 12

=Degree of cellular DIFFERENTIATION based on the histological apperance of the tumor

**Usually graded I - IV based on:
=the degree of differentiation
=number of mitoses per high power field
=character of the tumor itself

**SO:
=Grade I --> low grade, well-differentiated
=Grade III/IV --> high grade, poorly differentiated

Front 13

Tumor STAGE

Back 13

**Stage usually has more prognostic value than grade!

STAGE = SPREAD

TNM

T= Tumor Size
N = Node involvement
M = Metastases

Front 14

Tumor Nomenclature

Back 14

I will give you the cell type--you give me what a benign + malignant tumor would be called.

Front 15

Epithelium

Back 15

**"Carcinoma" = epithelial origin

Benign:
=Adenoma
=Papilloma

Malignant:
=Adenocarcinoma
=Papillary carcinoma

Front 16

Mesenchyme

Back 16

**"Sarcoma" = mesenchymal origin

Front 17

Blood Cells

Back 17

Malignant:
=Leukemia
=Lymphoma

Front 18

Blood Vessels

Back 18

Benign:
=Hemangioma

Malignant:
=Angiosarcoma

Front 19

Smooth Muscle

Back 19

Benign:
=Leiomyoma

Malignant:
=Leiomyosarcoma

Front 20

Skeletal Muscle

Back 20

Benign:
=Rhabdomyoma

Malignant:
=Rhabdomyosarcoma

Front 21

Bone

Back 21

Benign:
=Osteoma

Malignant:
=Osteosarcoma

Front 22

Fat

Back 22

Lipoma

Liposarcoma

Front 23

>1 cell type

Back 23

Benign:
=Mature teratoma

Malignant:
=Immature teratoma

Front 24

Diseases Associated w/ Neoplasms

Back 24

I will give you the condition--You name the neoplasm.

Front 25

Down Syndrome

Back 25

=ALL (**we ALL fall DOWN!)
=AML

Front 26

Xeroderma Pigmentosum, Albinism

Back 26

=Melanoma
=BCC
=Squamous cell carcinoma of skin

Front 27

Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants

Back 27

=Gastric adenocarcinoma

Front 28

Tuberous Sclerosis

Back 28

**1st, what the hell is tuberous sclerosis?
=facial angiofibroma + seizures + mental retardation

**Associated w/:
=Astrocytoma
=Cardiac rhabdomyoma

Front 29

Actinic keratosis

Back 29

Squamous cell carcinoma of skin

Front 30

Barrett's esophagus (=chronic GI reflux)

Back 30

Esophageal adenocarcinoma

Front 31

Plummer-Vinson Syndrome

Back 31

Disease:
=Atrophic glossitis
=Esophageal webs
=Anemia
(**all due to iron deficiency)

Can result in:
=Squamous cell carcinoma of the esophagus

Front 32

Cirrhosis (=Alcoholic, hepatitis B or C)

Back 32

Hepatocellular carcinoma

Front 33

Ulcerative Colitis

Back 33

Colonic adenocarcinoma

Front 34

Paget's Disease of Bone

Back 34

Secondary osteosarcoma and fibrosarcoma

Front 35

Immunodeficiency States

Back 35

=Malignant lymphoma

Front 36

AIDS

Back 36

=Aggressive malignant lymphomas (non-Hodgkin's)
=Kaposi's sarcoma

Front 37

Autoimmune Diseases (=i.e. Hashimoto's thyroiditis, myasthenia gravis)

Back 37

Benign and malignant thymomas

Front 38

Acanthosis nigricans

Back 38

=hyperpigmentation and epidermal thickening often under arms

**Associated with:
=Visceral malignancy (stomach, lung, breast, uterus)

Front 39

Dysplastic Nevus

Back 39

Malignant melanoma

Front 40

Oncogenes

Back 40

**GAIN OF FUNCTION --> cancer!!

Front 41

abl

Back 41

CML

Front 42

c-myc

Back 42

Burkitt's lymphoma

Front 43

bcl-2

Back 43

Follicular and undifferentiated lymphomas (=inhibits apoptosis)

Front 44

erb-B2

Back 44

Breast, ovarian, and gastric carcinoma

Front 45

ras

Back 45

Colon carcinoma

Front 46

L-myc

Back 46

Lung tumor

Front 47

N-myc

Back 47

Neuroblastoma

Front 48

ret

Back 48

MEN types II and III

Front 49

Tumor Suppressor Genes

Back 49

**Loss of function --> cancer

**BOTH alleles must be lost for expression of disease

Front 50

Rb

Back 50

13q

Retinoblastoma, osteosarcoma

Front 51

BRCA1 and BRCA2

Back 51

17q, 13q

Breast and ovarian cancer

Front 52

p53

Back 52

17p

Most human cancers, Li-Fraumeni syndrome

Front 53

p16

Back 53

9p

Melanoma

Front 54

APC

Back 54

5q

Colorectal cancer

Front 55

WT1

Back 55

11q

Wilm's Tumor

Front 56

NF1

Back 56

17q

Neurofibromatosis type I

Front 57

NF2

Back 57

22q

Neurofibromatosis type II

Front 58

DPC

Back 58

18q

Pancreatic cancer

Front 59

DCC

Back 59

18q

Colon Cancer

Front 60

Tumor Markers

Back 60

**Tumor markers should NOT be used as the primary tool for cancer diagnosis

=they may be used to CONFIRM the diagnosis,to MONITOR for tumor recurrence, and to MONITOR response to therapy

Front 61

PSA

Back 61

=Prostate-specific antigen

**Prostatic carcinoma
=used for screening

Front 62

CEA

Back 62

=Carcinoembryonic antigen

**Very nonspecific but produced by ~70% of colorectal and pancreatic cancers

**Also produced by gastric and breast carcinomas

Front 63

alpha-fetoprotein

Back 63

**Normally made by the fetus

=Hepatocellular carcinomas
=Nonseminomatous germ cell tumors of the testis (i.e. YOLK SAC TUMORS)

Front 64

B-hCG

Back 64

Spells HCG!

H = Hydatidiform moles
C = Choriocarcinomas
G = Gestational trophoblastic tumors

Front 65

CA-125

Back 65

Ovarian cancer, malignant epithelial tumors

Front 66

S-100

Back 66

=Melanoma
=Neural tumors
=Astrocytomas

Front 67

Alkaline Phosphatase

Back 67

=Metastases to bone
=Obstructive biliary disease
=Paget's disease of bone

Front 68

Bombesin

Back 68

=Neuroblastoma
=Lung and gastric cancer

Front 69

TRAP

Back 69

(=Tartrate-resistant acid phosphatase)

**Hairy cell leukemia**
(=a B-cell neoplasm)

Front 70

Psammoma Bodies

Back 70

Laminated, concentric, calcific spherules seen in:

1) Papillary adenocarcinoma of the thyroid

2) Serous papillary cystadenocarcinoma of the ovary

3) Meningioma

4) Malignant mesothelioma

PSaMMoma
=Papillary, serous, meningioma, mesothelioma

Front 71

HTLV-1

Back 71

Adult T-cell leukemia

Front 72

HBV, HCV

Back 72

Hepatocellular carcinoma

Front 73

EBV

Back 73

=Burkitt's lymphoma
=Nasopharyngeal carcinoma

Front 74

HPV

Back 74

=Cervical carcioma (16, 18)
=Penile/anal carcinoma

Front 75

HHV-8

Back 75

=Kaposi's sarcoma
=Body cavity fluid B-cell lympohoma

Front 76

Chemical Carcinogens

Back 76

Given = Toxin

Tell me the affected organ.

Front 77

Aflatoxins

Back 77

Liver
=Hepatocellular carcinoma

Front 78

Vinyl chloride

Back 78

Liver
=angiosarcoma

Front 79

CCl4

Back 79

Liver
=Centrilobular necrosis, fatty change

Front 80

Nitrosamines

Back 80

Esophagus, stomach

Front 81

Cigarette Smoke

Back 81

Larynx, lung

Front 82

Asbestos

Back 82

Lung
=Mesothelioma and bronchogenic carcinoma

Front 83

Arsenic

Back 83

Skin
=squamous cell carcinoma

Front 84

Naphthalene (aniline) Dyes

Back 84

Bladder
=transitional cell carcinoma

Front 85

Alkylating Agents

Back 85

Blood
=Leukemia

Front 86

Small Cell Lung Carcinoma

Back 86

Cause = ACTH or ACTH-like peptide

Effect = CUSHINGS SYNDROME

Front 87

Small Cell Lung Carcinoma and Intracranial Neoplasms

Back 87

Cause = ADH

Effect = SIADH

Front 88

=Squamous Cell Lung Carcinoma
=Renal Cell Carcinoma
=Breast Carcinoma
=Multiple Myeloma
=Bone Metastasis (lysed bone)

Back 88

Causes:
=PTH-related peptide
=TGF-B
=TNF-alpha
=IL-1

Effect = HYPERCALCEMIA

Front 89

Renal Cell Carcinoma, Hemangioblastoma

Back 89

Cause = Erythropoietin

Effect = Polycythemia

Front 90

Thymoma, Small Cell Lung Carcinoma

Back 90

Cause:
=Abs against presynaptic Ca channels at the neuromuscular junction

Effect = Lambert-Eaton Syndrome (muscle weakness)

Front 91

Leukemias and Lymphomas

Back 91

Cause:
=Hyperuricemia due to excess nucleic acid turnover (i.e. cytotoxic therapy)

Effect = Gout, urate nephropathy

Front 92

Metastasis to the Brain

Back 92

**Primary tumors that metastasize to the brain:
=Lung
=Breast
=Skin (melanoma)
=Kidney (renal cell carcinoma)
=GI

**Typically multiple, well-circumscribed tumors at the gray-white border.

**Overall, 50% of brain tumors are from metastases.

Front 93

Metastasis to the Liver

Back 93

**Liver and lung are the MOST common sites of metastasis after the regional lympth nodes.

**Metastases >> Primary liver tumors

**Primary tumors that metastasize to the liver:

Colon > Stomach > Pancreas > Breast > Lung

("Cancers Sometimes Penetrate Benign Liver")

Front 94

Metastasis to Bone

Back 94

**Primary tumors that metastasize to the bone:
=Prostate
=Thyroid
=Testes
=Breast
=Lung
=Kidney

**Metastases from the BREAST and PROSTATE are most common!

**Metastatic bone tumors are by FAR more comon than primary bone tumors.

NOTE:
- Lung = Lytic
- Prostate = BLASTIC
- Breast = BOTH lytic and blastic

Front 95

Cancer Epidemiology

Back 95

**Cancer is the 2nd leading cause of death in the US

(=heart disease is 1st)

Front 96

Top 3 Cancers Found in Males

Back 96

1) Prostate (32%)
2) Lung (16%)
3) Colon and rectum (12%)

Front 97

Top 2 Cancer KILLERS in Males
=Mortality

Back 97

1) Lung (33%)
2) Prostate (13%)

**Deaths from lung cancer hve plateaued in men but continue to increase in females.

Front 98

Top 3 Cancers Found in Females

Back 98

1) Breast (32%)
2) Lung (13%)
3) Colon and rectum (13%)

Front 99

Top 2 KILLERS in Females

Back 99

1) Lung (23%)
2) Breast (18%)

Front 100

Biconcave

Back 100

Normal

Front 101

Spherocytes

Back 101

=Hereditary spherocytosis
=Autoimmune hemolysis

Front 102

Elliptocyte

Back 102

=Hereditary elliptocytosis

Front 103

Macro-ovalocyte

Back 103

=Megaloblastic anemia (+ hypersegmented neutrophils!)

=Marrow failure

Front 104

Helmet cell/Schistocyte

Back 104

=DIC
=Traumatic hemolysis

Front 105

Sickle Cell

Back 105

=Sickle cell anemia

Front 106

Teardrop Cell

Back 106

=Myeloid metaplasia w/ myelofibrosis

Front 107

Acanthocyte

Back 107

=Spiny appearance in abetalipoproteinemia

Front 108

Target Cell

Back 108

=HbC diseasae
=Thalassemia
=Asplenia
=Liver disease

Front 109

Poikilocytes

Back 109

**Nonuniform shapes
=TTP/HUS
=Microvascular damage
=DIC

Front 110

Burr Cell

Back 110

=TTP/HUS

Front 111

Anemia

Back 111

**FIRST decide what the MCV is...that will help you classify the anemia!

Front 112

MICROCYTIC, hypochromic

Back 112

MCV < 80

1) Iron deficiency anemia
=Decreased serum iron, Increased TIBC, Decreased ferritin

COLOR IMAGE 20

2) Thalassemias
=TARGET CELLS
=COLOR image 18

3) Lead poisoning--can result in Sideroblastic anemia

Front 113

MACROCYTIC

Back 113

MCV > 100

=Megaloblastic anemia--Vitamin B12/folate deficiency
=Drugs that block DNA synthesis (i.e. sulfa drugs, AZT)

Front 114

What would also indicate that you were dealing w/ a macrocytic anemia?

Back 114

Marked reticulocytosis
=Bigger than mature RBCs

Front 115

Vitamin B12 and Folate Deficiencies

Back 115

=Associated w/ HYPERSEGMENTED NEUROTPHILS

**Unlike folate deficiency, vitamin B12 deficiency (=pernicious anemia) is associated w/ NEUROLOGICAL problems

Front 116

Normocytic, Normochromic

Back 116

MCV 80 - 100

1) Acute hemorrhage

2) Enzyme Defects
=G6PD Deficiency, PK deficiency

3) RBC Membrane Defects
=i.e. hereditary spherocytosis

4) BM Disorders
=aplastic anemia
=leukemia

5) Hemoglobinopathies
=Sickle Cell Disease

6) Autoimmune hemolytic anemia

7) Anemia of Chronic Disease (ACD)
=Decreased TIBC, Increased ferritin, Increased storage of iron in marrow macrophages

Front 117

What would indicate that you are dealing w/ RBC hemolysis?

Back 117

=Decreased serum haptoglobin
=Increased serum LDH

Front 118

How would you differentiate between Immune and Non-Immune mediated RBC hemolysis?

Back 118

DIRECT COOMB'S TEST

Front 119

Aplastic Anemia

Back 119

=Pancytopenia characterized by SEVERE anemia, neutropenia, and thrombocytopenina

=Caused by failture or destruction of multipotent myeloid stem cells --> inadequate production or release of differntiated cell lines

Front 120

Causes:

Back 120

1) Radiation
2) Benzene
3) Chloramphenicol
4) Alkylating agents
5) Antimetabolites
6) Viral agents
=Parvovirus B19
=EBV
=HIV
7) Fanconi's anemia
8) Idiopathic
=Immune-mediated primary stem-cell defect

**May follow acute hepatitis

Front 121

Symptoms:

Back 121

- Fatigue
- Malaise
- Pallor
- Purpura
- Mucosal bleeding
- Petechiae
- Infection

Front 122

Pathologic Features

Back 122

**Pancytopenia w/ normal cell morphology

**Hypocellular bone marrow w/ fatty infiltration

**Diagnose w/ BM biopsy

Front 123

Treatment:

Back 123

=Withdraw offending agent

=Allogenic BM transplantation

=RBC and platelet transfusion

=G-CSF or GM-CSF
(i.e. granulocyte/granulocyte-macrophage colony stimulating factor)

Front 124

Sickle Cell Anemia

Back 124

**HbS mutation = a single amino acid replacement in the B-chain
=Substitution of normal glutamic acid w/ VALINE

**8% of African-Americans carry the HbS trait--.2% have the disease

**Results in sickled cells = CRESCECNT-SHAPED RBCs
=cells sickle under conditions of low O2 or dehydration

Front 125

What are the Complications in Heterozygotes?

Back 125

=Sickle Cell TRAIT

**Relatively resistant to malaria = balanced polymorphism

Front 126

What are the Complications in Homozygotes?

Back 126

=Sickle Cell DISEASE

1) Aplastic Crisis
=Due to parvovirus B19 --> in normal people, this infection causes an arrest of erythropoeisis
=This is a HUGE problem in SSA patients bc they rely more heavily on erythropoeisis = RBCs have a shorter lifespan

2) Autosplenectomy
=Sickled cells repeatedly block off small vessels --> infarction of parts of the spleen = NONFUNCTIONAL

3) Increased risk of encapsulated organism infection
=due to functional asplenia
=Strep. pneumo + H.flu common

4) Salmonella osteomyelitis
=Staph. still most common cause, but you seen TONS of salmonella in SSA patients vs. normal population

5) Painful Crisis
=Vaso-occlusive --> sickled cells block capillaries --> restrict blood flow to an organ --> ischemia/pain --> possible organ damage

6) Splenic sequestration crisis

COlOR IMAGE 21

Front 127

Treatment of Sickle Cell

Back 127

=Hydroxyurea (=increases HbF)

=BM transplantation

Front 128

Characteristic X-ray Finding

Back 128

="Crew-cut" on skull X-ray due to marrow expanision from increased erythropoeisis

**Also see in thalassemias

Front 129

HbC Defect

Back 129

=a different B-chain mutation

**Patients w/ HbC or HbSC (=one of each mutant gene) have MILDER disease than do HbSS patients

Front 130

Alpha Thalassemia

Back 130

**In alpha thalassemia--the alpha-globin chain is UNDERPRODUCED

**There are 4 geneteic loci for alpha globin--2 from mom and 2 from dad:
=the more of these loci which are delected/affected by mutation--the more severe the disease!

**There is NO compensatory increase of any other chains

**Prevalent in Asia and Africa.

Front 131

HbH

Back 131

**3 loci are affected = Hemoglobin H Disease

**Unstable Hb in the blood = HbH = B4-tetramers

Front 132

Hb Barts

Back 132

**All 4 loci are affected
=Abnormal Hb = Hb Barts = Gamma-4 tetramers

=results in HYDROPS FETALIS and intrauterine fetal death

Front 133

What is Hydrops Fetalis?

Back 133

=blood condition in the fetus characterized by edema in the subcutaneous tissue --> can lead to spontaneous abortion

Front 134

B-Thalassemia

Back 134

**More prevalent in Mediterranean populations

**Can be minor or major:

=B-thalassemia MINOR --> heterozygote = B-chain is UNDERPRODUCED
=(more mild/moderate disease)

=B-thalassemia MAJOR --> homozygote = B-chain is ABSENT

Color Image 19

Front 135

Complications of B-Thalassemia

Back 135

**In BOTH cases, fetal Hb production is compensatorily increased BUT is inadequate

**B-thalassemia MAJOR results in:
=SEVERE anemia requiring blood transfusions
=Cardiac Failure due to secondary hemochromatosis
=Marrow expansion --> skeletal deformities

Front 136

Hemolytic Anemias

Back 136

1) Increased serum bilirubin
=Jaundice, pigment gallstones

2) Increased reticulocytes
=Marrow compensating for anemia

Front 137

Autoimmune Anemia

Back 137

**Mostly extravascular hemolysis
=accelerated RBC destruction in liver Kupffer cells + spleen

**Includes:
=Warm Agglutinin
=Cold Agglutinin
=Erythroblastosis Fetalis

**Autoimmune hemolytic anemias are COOMB'S TEST POSITIVE!
=i.e. an immune mechanism is attacking the patient's RBCs!

Front 138

What is the Coomb's Test?

Back 138

**DIRECT Coomb's Test (DAT):
=Anti-Ig Ab is added to the patient's RBCs
=They will agglutinate if RBCs are coated w/ Ig

**INDIRECT (IAT):
=Normal RBCs added to the patient's serum
=Will agglutinate IF serum has anti-RBC surface Ig

Front 139

WARM Agglutinin

Back 139

"Warm Weather is GGGreat!"
=IgG

**Chronic anemia seen in:
=SLE
=CLL
=Certain drugs (alpha-methyldopa)

Front 140

COLD Agglutinin

Back 140

**"COLD icecream! MMMMMmmm."
=IgM
=i.e. Destructive Abs bind RBCs at LOW temperatures

**ACUTE anemia triggered by COLD
=Seen also during recovery from Mycoplasma pneumoniae OR infectious mononucleosis

Front 141

Erythroblastosis Fetalis

Back 141

**Seen in newborns due to Rh or other blood antigen incompatibility --> mother's Abs attack fetal RBCs

Front 142

Recall: What is the difference between INTRAVASCULALR and EXTRAVASCULAR hemolysis?

Back 142

Intravascular
=RBC lysis occurs in the circulation as a result of activation of the complement system cascade

Extravascular
=RBCs that are coated w/ Abs are specifically recognized in the RES and destroyed by macrophages

Front 143

Hereditary Spherocytosis

Back 143

**Intrinsic, extravascular hemolysis due to SPECTRIN or ANKYRIN defect

**RBCs are small and round w/ NO central pallor
=i.e. have less membrane (spectrin + ankyrin defect) and thus can't maintain biconcave shape
=because of their sphere-shaped --> more prone to hemolysis!
=the spleen recognizes abnormally-shaped RBCs (which NORMALLY indicate they are older) and destroys them

=Increased MCHC (mean corpuscular Hb concentration --> roughly compatible to how "red" a RBC will be = LOW MCHC = pale RBC)
=Increased RDW

Front 144

Lab Tests performed on hereditary spherocytosis.

Back 144

=Coomb's Test NEGATIVE

=Osmotic fragility test used to confirm

(i.e. HIGH osmotic fragility--> when placed in water are likely to burst)

Front 145

Paroxysmal Nocturnal Hemoglobinuria

Back 145

**Intravascular hemolysis due to membrane defect:
=Increased sensitivity of RBCs to the lytic activity of complement

Labs:
=Increased urine hemosiderin (i.e. breakdown product of RBCs)

**Often also have RED URINE.

**Venous thrombosis is a possible complication.

Front 146

Microangiopathic Anemia

Back 146

**Intravascular hemolysis seen in DIC, TTP/HUS, SLE, or malignant hypertension

**You will see schistocytes (=helmet cells) on blood smear

**Schistocyte = RBC fragmentation
=these diseases produce fibrin strands --> severe RBCs as they try to move past a thrombus

Front 147

DIC

Back 147

=Activation of the coagulation cascade leading to microthrombi and global consumption of platelets, fibrin, and coagulation factors

Front 148

What are the causes of DIC?

Back 148

1) Obstetric Complications
=MOST COMMON CAUSE
2) Gram-negative sepsis
3) Transfusion
4) Trauma
5) Malignancy
6) Acute pancreatitis
7) Nephrotic syndrome

Front 149

What are the lab findings in DIC?

Back 149

1) Increased PT

2) Increased PTT

3) Increased fibrin split products (=D-dimers)

4) DECREASED platelet cocunt

**Helmet-shaped cells + schistocytes on blood smear

Front 150

Bleeding Disorders

Back 150

**Include:

1) Platelet abnormalities
**Cause MICROHEMORRHAGE:
=Mucuous membrane bleeding
=Epistaxis
=Petechiae
=Purpura
=INCREASED bleeding time

2) Coagulation factor defects
**Cause MACROHEMORRHAGE:
=Hemarthroses (=bleeding into joints)
=Easy bruising
=Increased PT and/or PTT

Front 151

Causes of Platelet Abnormalities:

Back 151

1) ITP
2) TTP
3) DIC
4) Aplastic Anemia
5) Drugs (=immunosuppressive agents)

Front 152

Idiopathic Thrombocytopenic Purpura

Back 152

=LOW platelet count of unknown cause
=Related to Anti-platelet antibodies (i.e. also called "IMMUNE" TP)
=Increased megakaryocytes

Front 153

Thrombotic Thrombocytopenic Purpura

Back 153

**A microangiopathic hemolytic anemia
=spontaneous aggregation of platelets and activation of coagulation in small blood vessels
=Platelets are consumed in the coagulation + fibrin mesh "tears" apart blood vessels

=Schistocytes
=Increased LDH
=Neurologic Symptoms (bizarre behavior, altered mental status, headaches)

Front 154

Disseminated Intravascular Coagulation

Back 154

=Blood starts to coagulate throughout the whole body

Findings:
=Schistocytes
=Increased fibrin split products

Front 155

Coagulation Factor Defects

Back 155

1) Hemophilia A
=Factor VIII deficiency

2) Hemophilia B
=Factor IX deficiency

3) von Willebrand's Disease
=Mild --> most common bleeding disorder
=Deficiency of von Willebrand factor --> leads to defect in platelet adhesion and DECREASED factor VIII survival

Front 156

Qualitative Platelet Defects

Back 156

1) Bernard-Soulier Disease
=Defefct of platelet adhesion
=DECREASED GP Ib

2) Glanzmann's Thrombasthenia
=Defect of platelet AGGREGATION
=Decreased GP IIb-IIIa

Front 157

How low must the platelet count get before generalized bleeding occurs?

Back 157

**VERY LOW
=15,000 - 20,000
=Normal: 150,000 - 400,000

**Thrombocytopenia = <100,000

Front 158

What does PT measure?

Back 158

EXTRINSIC Factors

=II, V, VII, and X

Front 159

What does PTT measure?

Back 159

INTRINSIC Factors

=ALL factors except VII

Front 160

Lymphomas

Back 160

**Hodgkin's vs. Non-Hodgkin's

Front 161

Etiology/Epidemiology of HL:

Back 161

**50% associated w/ EBV

**BIMODAL DISTRIBUTION
=Young and old
=MORE common in MEN except for NODULAR SCLEROSING type

**Good Prognosis:
=INCREASED LYMPHOCYTES + DECREASED Reed-Sternberg Cells

Front 162

What the hell are Reed-Sternberg Cells?

Back 162

**Distinctive tumor GIANT CELLS seen in HL
=Bilobed OR binucleate w/ the 2 halves as mirror images --> "OWL'S EYES"
=CD30+ and CD15+ B-cell origin

**Necessary but NOT sufficient for a diagnosis of HL.

**Variants include LACUNAR CELLS in the nodular sclerosis variant.


COLOR IMAGE 25

Front 163

Findings in HL:

Back 163

1) Reed-Sternberg Cells

2) Localized, single group of nodes involved w/ CONTIGUOUS SPREAD
=SO, you often have SWOLLEN PAINESS LYMPH NODES (=most often in neck)
=extranodal involvement rare

3) Often have MEDIASTINAL LYMPHADENOPATHY

4) Constitutional symptoms are known as "B" symptoms:
=Low-grade fever
=Night sweats
=Weight loss

Front 164

Types of HL:

Back 164

1) Nodular Sclerosing
=65-75%

2) Mixed Cellularity
=25%

3) Lymphocyte Predominant
=6%

4) Lymphocyte Depleted
=RARE

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Non-Hodgkin's Lymphoma Overview:

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**Associated w/ HIV and Immunosupression

**Peak incidence 20-40 y.o.

**Majority involve B-cells
=except those of lymphoblastic T-cell origin

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Findings in NHL:

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1) Multiple, peripheral nodes involved
=extranodal involvement COMMON
=NONCONTIGUOUS spread

2) NO hypergammaglobulinemia

3) Fewer constitutional signs/symptoms

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Types of NHL:

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1) Smalll Lymphocytic Lymphoma

2) Follicular Lymphoma
="small cleaved cell"

3) Diffuse Large Cell

4) Lymphoblastic Lymphoma

5) Burkitt's Lymphoma

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Small Lymphocytic Lymphoma

Back 168

**Occurs in ADULTS.

**Cell Type = B-cells

**Like CLL w/ BUT w/ a predominance in the lymph nodes vs. CLL in the blood
=Low-grade

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Follicular Lymphoma

Back 169

**Occurs in ADULTS

**Cell type = B-cells

**Genetics:
=t(14:18) --> results in bcl-2 OVER-expression
=OVER-expression causes a blockage in apoptosis

**MOST COMMON ADULT LYMPHOMA
=Difficult to cure
=Indolent course

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Diffuse Large Cell

Back 170

**Occurs in: Usually older adults, BUT 20% occur in children

**Cell Type:
=80% B-cells
=20% T-cells (mature)

**AGGRESSIVE but up to 50% are curable.

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Lymphoblastic Lymphoma

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**Most often in CHILDREN.

**Cell Type = T-cells (immature)

**MOST COMMON lymphoma in children
=Commonly presents w/ ALL and mediastinal mass
=VERY AGGRESSIVE T-cell lymphoma

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Burkitt's Lymphoma

Back 172

**Most often occurs in CHILDREN

**B-cells

**Genetics:
=t(8:14)--> c-myc gene moves next to heavy-chain Ig gene (14)

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What is Burkitt's Lymphoma associated with?

Back 173

**Associated w/ EBV

Front 174

Microscopic Apperance of Burkitt's Lymphoma:

Back 174

**"Starry-sky" appearance
=Sheets of lymphocytes w/ interspersed macrophages

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Forms of Burkitt's Lymphoma:

Back 175

**Endemic Form in Africa
=JAW LESION

**Sporadic Form
=Pelvis or Abdomen

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Front 176

Leukemias--General Findings:

Back 176

1) Increased number of circulating leukocytes in blood

2) BM infiltrates of leukemic cells

3) Marrow failure can cause:
=Anemia (dec. RBCs)
=Infections (dec. WBCs)
=Hemorrhage (dec. platelets)

4) Leukemic cell infiltrates in liver, spleen, and lymph nodes are common

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Front 177

ALL

Back 177

**Acute Lymphoblastic/ Lymphocytic Anemia

=Children

Features:
=lymphoblasts

**MOST responsive to therapy
=may spread to CNS and testes

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AML

Back 178

**Acute Myelogenous Leukemia

=ADULTS

**Findings:
=AUER RODS
=Myeloblasts

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CLL

Back 179

=Chronic Lymphocytic Leukemia

**OLDER adults

Findings:
=Lymphadenopathy
=Hepatosplenomegaly
=Few symptoms--indolent course

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Lab Findings in CLL

Back 180

1) Increased smudge cells in peripheral blood smear

2) Warm antibody autoimmune hemolytic anemia

**Very similar to SLL.

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CML

Back 181

**Chronic Myelogenous Leukemia

**MOST commonly associated w/ the PHILADELPHIA CHROMOSOME (t[9:22], bcr-abl)

=Myeloid stem cell proliferation

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Presentation + Lab Studies

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Presents w/:
=Increased neutrophils + metamyelocytes
=SPLENOMEGALY

**May accelerate to AML = "BLAST CRISIS"

**note: CML has a very low leukocyte alkaline phosphatase (vs. leukemoid reaction)

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What is a leukamoid reaction?

Back 183

=elevated WBC count = leukocytosis = that is a physiologic response to stress/infection

**SO, in CML you would find the following 2 things that would help you distinguish it from the leukmoid rxn:

1) Low alkaline phosphatase
2) BASOPHILIA

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Backing up--we said that we had Auer Rods in AML...what are Auer Rods?

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=Peroxidase-positive cytoplasmic inclusions in granulocytes + myeloblasts

**Typically seen in Acute Promyelocytic Leukemia (M3)

**Treatment of AML M3 can release Auer rods --> lead to DIC.

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Chromosomal Translocations

Back 185

Given = the translocation

Give the associated disorder.

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t(9;22)

Back 186

**Philadelphia chromosome

=CML (bcr-abl hybrid)

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t(8;14)

Back 187

Burkitt's lymphoma
=c-myc activation

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t(14;18)

Back 188

Follicular Lymphoma
=bcl-2 activation

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t(15;17)

Back 189

M3 Type of AML
=responsive to all-TRANS retinoic acid

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t(11;22)

Back 190

Ewing's Sarcoma

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t(11;14)

Back 191

Mantle Cell Lymphoma

Front 192

Multiple Myeloma

Back 192

**Monoclonal plasma cell cancer that arises in the marrow + produces large amounts of IgG (55%) OR IgA (25%)

**Most common primary tumor arising within bone in adults.
=Destructive bone lesions + resultant HYPERCALCEMIA

**Can be associated w/ PRIMARY AMYLOIDOSIS

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Symptoms/Complications of MM:

Back 193

1) Renal insufficiency
2) Increased susceptibility to infection
3) Anemia

Think CRAB:
=hyperCALCEMIA
=renal failure
=anemia
=bone lesions

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Lab/Imaging Results

Back 194

**"punched out" lytic bone lesions on x-ray

**"FRIED EGG" apperance of cancer

**Monoclonal immunoglobulin spike (M protein) on serum protein electrophoresis

**IgG light chains in urine = Bence Jones Protein

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What does the blood smear show?

Back 195

**RBCs stacked like poker chips (=ROULEAU FORMATION)

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How is it different from Waldenstrom's Macroglobinemia?

Back 196

**M spike = IgM
=thus often have hyperviscocity symptoms

**NO LYTIC BONE LESIONS

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