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196 Cards in this Set

  • Front
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Neoplastic Progression
Normal --> Hyperplasia --> Carcinoma in situ/preinvasive --> Invasive carcinoma --> Metastatic focus
NORMAL
**Normal cells w/ basal --> apical differentiation
Hyperplasia
=Cells have increased in NUMBER (hyperplasia)
=Abnormal proliferation of cells w/ loss of size, shape, and orientation = DYSPLASIA
In situ carcinoma
=Neoplastic cells have NOT invaded basement membrane
=High NUCLEAR/CYTOPLASMIC ratio and clumped chromatin
=Neoplastic cells encompass entire thickness
Invasive Carcinoma
=Cells have invaded the basement membrane using collagenases + hydrolases
=Can metastasize IF they reach a blood or lymphatic vessel
Metastasis
=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)
Hyperplasia
**Increase in number of cells (=reversible)
Metaplasia
=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
Dysplasia
=Abnormal growth w/ loss of cellular orientation, shape, and size in comparison to normal tissue maturation

=Commonly preneoplastic (reversible)
Anaplasia
=Abnormal cells lacking differentiation --> like primitive cells of the same tissue

**Often equated w/ undifferentiated malignant neoplasms

**Tumor giant cells may be formed
Neoplasia
=A clonal proliferation of cells that is uncontrolled and excessive
Tumor GRADE
=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
Tumor STAGE
**Stage usually has more prognostic value than grade!

STAGE = SPREAD

TNM

T= Tumor Size
N = Node involvement
M = Metastases
Tumor Nomenclature
I will give you the cell type--you give me what a benign + malignant tumor would be called.
Epithelium
**"Carcinoma" = epithelial origin

Benign:
=Adenoma
=Papilloma

Malignant:
=Adenocarcinoma
=Papillary carcinoma
Mesenchyme
**"Sarcoma" = mesenchymal origin
Blood Cells
Malignant:
=Leukemia
=Lymphoma
Blood Vessels
Benign:
=Hemangioma

Malignant:
=Angiosarcoma
Smooth Muscle
Benign:
=Leiomyoma

Malignant:
=Leiomyosarcoma
Skeletal Muscle
Benign:
=Rhabdomyoma

Malignant:
=Rhabdomyosarcoma
Bone
Benign:
=Osteoma

Malignant:
=Osteosarcoma
Fat
Lipoma

Liposarcoma
>1 cell type
Benign:
=Mature teratoma

Malignant:
=Immature teratoma
Diseases Associated w/ Neoplasms
I will give you the condition--You name the neoplasm.
Down Syndrome
=ALL (**we ALL fall DOWN!)
=AML
Xeroderma Pigmentosum, Albinism
=Melanoma
=BCC
=Squamous cell carcinoma of skin
Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants
=Gastric adenocarcinoma
Tuberous Sclerosis
**1st, what the hell is tuberous sclerosis?
=facial angiofibroma + seizures + mental retardation

**Associated w/:
=Astrocytoma
=Cardiac rhabdomyoma
Actinic keratosis
Squamous cell carcinoma of skin
Barrett's esophagus (=chronic GI reflux)
Esophageal adenocarcinoma
Plummer-Vinson Syndrome
Disease:
=Atrophic glossitis
=Esophageal webs
=Anemia
(**all due to iron deficiency)

Can result in:
=Squamous cell carcinoma of the esophagus
Cirrhosis (=Alcoholic, hepatitis B or C)
Hepatocellular carcinoma
Ulcerative Colitis
Colonic adenocarcinoma
Paget's Disease of Bone
Secondary osteosarcoma and fibrosarcoma
Immunodeficiency States
=Malignant lymphoma
AIDS
=Aggressive malignant lymphomas (non-Hodgkin's)
=Kaposi's sarcoma
Autoimmune Diseases (=i.e. Hashimoto's thyroiditis, myasthenia gravis)
Benign and malignant thymomas
Acanthosis nigricans
=hyperpigmentation and epidermal thickening often under arms

**Associated with:
=Visceral malignancy (stomach, lung, breast, uterus)
Dysplastic Nevus
Malignant melanoma
Oncogenes
**GAIN OF FUNCTION --> cancer!!
abl
CML
c-myc
Burkitt's lymphoma
bcl-2
Follicular and undifferentiated lymphomas (=inhibits apoptosis)
erb-B2
Breast, ovarian, and gastric carcinoma
ras
Colon carcinoma
L-myc
Lung tumor
N-myc
Neuroblastoma
ret
MEN types II and III
Tumor Suppressor Genes
**Loss of function --> cancer

**BOTH alleles must be lost for expression of disease
Rb
13q

Retinoblastoma, osteosarcoma
BRCA1 and BRCA2
17q, 13q

Breast and ovarian cancer
p53
17p

Most human cancers, Li-Fraumeni syndrome
p16
9p

Melanoma
APC
5q

Colorectal cancer
WT1
11q

Wilm's Tumor
NF1
17q

Neurofibromatosis type I
NF2
22q

Neurofibromatosis type II
DPC
18q

Pancreatic cancer
DCC
18q

Colon Cancer
Tumor Markers
**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
PSA
=Prostate-specific antigen

**Prostatic carcinoma
=used for screening
CEA
=Carcinoembryonic antigen

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

**Also produced by gastric and breast carcinomas
alpha-fetoprotein
**Normally made by the fetus

=Hepatocellular carcinomas
=Nonseminomatous germ cell tumors of the testis (i.e. YOLK SAC TUMORS)
B-hCG
Spells HCG!

H = Hydatidiform moles
C = Choriocarcinomas
G = Gestational trophoblastic tumors
CA-125
Ovarian cancer, malignant epithelial tumors
S-100
=Melanoma
=Neural tumors
=Astrocytomas
Alkaline Phosphatase
=Metastases to bone
=Obstructive biliary disease
=Paget's disease of bone
Bombesin
=Neuroblastoma
=Lung and gastric cancer
TRAP
(=Tartrate-resistant acid phosphatase)

**Hairy cell leukemia**
(=a B-cell neoplasm)
Psammoma Bodies
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
HTLV-1
Adult T-cell leukemia
HBV, HCV
Hepatocellular carcinoma
EBV
=Burkitt's lymphoma
=Nasopharyngeal carcinoma
HPV
=Cervical carcioma (16, 18)
=Penile/anal carcinoma
HHV-8
=Kaposi's sarcoma
=Body cavity fluid B-cell lympohoma
Chemical Carcinogens
Given = Toxin

Tell me the affected organ.
Aflatoxins
Liver
=Hepatocellular carcinoma
Vinyl chloride
Liver
=angiosarcoma
CCl4
Liver
=Centrilobular necrosis, fatty change
Nitrosamines
Esophagus, stomach
Cigarette Smoke
Larynx, lung
Asbestos
Lung
=Mesothelioma and bronchogenic carcinoma
Arsenic
Skin
=squamous cell carcinoma
Naphthalene (aniline) Dyes
Bladder
=transitional cell carcinoma
Alkylating Agents
Blood
=Leukemia
Small Cell Lung Carcinoma
Cause = ACTH or ACTH-like peptide

Effect = CUSHINGS SYNDROME
Small Cell Lung Carcinoma and Intracranial Neoplasms
Cause = ADH

Effect = SIADH
=Squamous Cell Lung Carcinoma
=Renal Cell Carcinoma
=Breast Carcinoma
=Multiple Myeloma
=Bone Metastasis (lysed bone)
Causes:
=PTH-related peptide
=TGF-B
=TNF-alpha
=IL-1

Effect = HYPERCALCEMIA
Renal Cell Carcinoma, Hemangioblastoma
Cause = Erythropoietin

Effect = Polycythemia
Thymoma, Small Cell Lung Carcinoma
Cause:
=Abs against presynaptic Ca channels at the neuromuscular junction

Effect = Lambert-Eaton Syndrome (muscle weakness)
Leukemias and Lymphomas
Cause:
=Hyperuricemia due to excess nucleic acid turnover (i.e. cytotoxic therapy)

Effect = Gout, urate nephropathy
Metastasis to the Brain
**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.
Metastasis to the Liver
**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")
Metastasis to Bone
**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
Cancer Epidemiology
**Cancer is the 2nd leading cause of death in the US

(=heart disease is 1st)
Top 3 Cancers Found in Males
1) Prostate (32%)
2) Lung (16%)
3) Colon and rectum (12%)
Top 2 Cancer KILLERS in Males
=Mortality
1) Lung (33%)
2) Prostate (13%)

**Deaths from lung cancer hve plateaued in men but continue to increase in females.
Top 3 Cancers Found in Females
1) Breast (32%)
2) Lung (13%)
3) Colon and rectum (13%)
Top 2 KILLERS in Females
1) Lung (23%)
2) Breast (18%)
Biconcave
Normal
Spherocytes
=Hereditary spherocytosis
=Autoimmune hemolysis
Elliptocyte
=Hereditary elliptocytosis
Macro-ovalocyte
=Megaloblastic anemia (+ hypersegmented neutrophils!)

=Marrow failure
Helmet cell/Schistocyte
=DIC
=Traumatic hemolysis
Sickle Cell
=Sickle cell anemia
Teardrop Cell
=Myeloid metaplasia w/ myelofibrosis
Acanthocyte
=Spiny appearance in abetalipoproteinemia
Target Cell
=HbC diseasae
=Thalassemia
=Asplenia
=Liver disease
Poikilocytes
**Nonuniform shapes
=TTP/HUS
=Microvascular damage
=DIC
Burr Cell
=TTP/HUS
Anemia
**FIRST decide what the MCV is...that will help you classify the anemia!
MICROCYTIC, hypochromic
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
MACROCYTIC
MCV > 100

=Megaloblastic anemia--Vitamin B12/folate deficiency
=Drugs that block DNA synthesis (i.e. sulfa drugs, AZT)
What would also indicate that you were dealing w/ a macrocytic anemia?
Marked reticulocytosis
=Bigger than mature RBCs
Vitamin B12 and Folate Deficiencies
=Associated w/ HYPERSEGMENTED NEUROTPHILS

**Unlike folate deficiency, vitamin B12 deficiency (=pernicious anemia) is associated w/ NEUROLOGICAL problems
Normocytic, Normochromic
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
What would indicate that you are dealing w/ RBC hemolysis?
=Decreased serum haptoglobin
=Increased serum LDH
How would you differentiate between Immune and Non-Immune mediated RBC hemolysis?
DIRECT COOMB'S TEST
Aplastic Anemia
=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
Causes:
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
Symptoms:
- Fatigue
- Malaise
- Pallor
- Purpura
- Mucosal bleeding
- Petechiae
- Infection
Pathologic Features
**Pancytopenia w/ normal cell morphology

**Hypocellular bone marrow w/ fatty infiltration

**Diagnose w/ BM biopsy
Treatment:
=Withdraw offending agent

=Allogenic BM transplantation

=RBC and platelet transfusion

=G-CSF or GM-CSF
(i.e. granulocyte/granulocyte-macrophage colony stimulating factor)
Sickle Cell Anemia
**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
What are the Complications in Heterozygotes?
=Sickle Cell TRAIT

**Relatively resistant to malaria = balanced polymorphism
What are the Complications in Homozygotes?
=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
Treatment of Sickle Cell
=Hydroxyurea (=increases HbF)

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

**Also see in thalassemias
HbC Defect
=a different B-chain mutation

**Patients w/ HbC or HbSC (=one of each mutant gene) have MILDER disease than do HbSS patients
Alpha Thalassemia
**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.
HbH
**3 loci are affected = Hemoglobin H Disease

**Unstable Hb in the blood = HbH = B4-tetramers
Hb Barts
**All 4 loci are affected
=Abnormal Hb = Hb Barts = Gamma-4 tetramers

=results in HYDROPS FETALIS and intrauterine fetal death
What is Hydrops Fetalis?
=blood condition in the fetus characterized by edema in the subcutaneous tissue --> can lead to spontaneous abortion
B-Thalassemia
**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
Complications of B-Thalassemia
**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
Hemolytic Anemias
1) Increased serum bilirubin
=Jaundice, pigment gallstones

2) Increased reticulocytes
=Marrow compensating for anemia
Autoimmune Anemia
**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!
What is the Coomb's Test?
**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
WARM Agglutinin
"Warm Weather is GGGreat!"
=IgG

**Chronic anemia seen in:
=SLE
=CLL
=Certain drugs (alpha-methyldopa)
COLD Agglutinin
**"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
Erythroblastosis Fetalis
**Seen in newborns due to Rh or other blood antigen incompatibility --> mother's Abs attack fetal RBCs
Recall: What is the difference between INTRAVASCULALR and EXTRAVASCULAR hemolysis?
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
Hereditary Spherocytosis
**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
Lab Tests performed on hereditary spherocytosis.
=Coomb's Test NEGATIVE

=Osmotic fragility test used to confirm

(i.e. HIGH osmotic fragility--> when placed in water are likely to burst)
Paroxysmal Nocturnal Hemoglobinuria
**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.
Microangiopathic Anemia
**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
DIC
=Activation of the coagulation cascade leading to microthrombi and global consumption of platelets, fibrin, and coagulation factors
What are the causes of DIC?
1) Obstetric Complications
=MOST COMMON CAUSE
2) Gram-negative sepsis
3) Transfusion
4) Trauma
5) Malignancy
6) Acute pancreatitis
7) Nephrotic syndrome
What are the lab findings in DIC?
1) Increased PT

2) Increased PTT

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

4) DECREASED platelet cocunt

**Helmet-shaped cells + schistocytes on blood smear
Bleeding Disorders
**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
Causes of Platelet Abnormalities:
1) ITP
2) TTP
3) DIC
4) Aplastic Anemia
5) Drugs (=immunosuppressive agents)
Idiopathic Thrombocytopenic Purpura
=LOW platelet count of unknown cause
=Related to Anti-platelet antibodies (i.e. also called "IMMUNE" TP)
=Increased megakaryocytes
Thrombotic Thrombocytopenic Purpura
**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)
Disseminated Intravascular Coagulation
=Blood starts to coagulate throughout the whole body

Findings:
=Schistocytes
=Increased fibrin split products
Coagulation Factor Defects
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
Qualitative Platelet Defects
1) Bernard-Soulier Disease
=Defefct of platelet adhesion
=DECREASED GP Ib

2) Glanzmann's Thrombasthenia
=Defect of platelet AGGREGATION
=Decreased GP IIb-IIIa
How low must the platelet count get before generalized bleeding occurs?
**VERY LOW
=15,000 - 20,000
=Normal: 150,000 - 400,000

**Thrombocytopenia = <100,000
What does PT measure?
EXTRINSIC Factors

=II, V, VII, and X
What does PTT measure?
INTRINSIC Factors

=ALL factors except VII
Lymphomas
**Hodgkin's vs. Non-Hodgkin's
Etiology/Epidemiology of HL:
**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
What the hell are Reed-Sternberg Cells?
**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
Findings in HL:
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
Types of HL:
1) Nodular Sclerosing
=65-75%

2) Mixed Cellularity
=25%

3) Lymphocyte Predominant
=6%

4) Lymphocyte Depleted
=RARE
Non-Hodgkin's Lymphoma Overview:
**Associated w/ HIV and Immunosupression

**Peak incidence 20-40 y.o.

**Majority involve B-cells
=except those of lymphoblastic T-cell origin
Findings in NHL:
1) Multiple, peripheral nodes involved
=extranodal involvement COMMON
=NONCONTIGUOUS spread

2) NO hypergammaglobulinemia

3) Fewer constitutional signs/symptoms
Types of NHL:
1) Smalll Lymphocytic Lymphoma

2) Follicular Lymphoma
="small cleaved cell"

3) Diffuse Large Cell

4) Lymphoblastic Lymphoma

5) Burkitt's Lymphoma
Small Lymphocytic Lymphoma
**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
Follicular Lymphoma
**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
Diffuse Large Cell
**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.
Lymphoblastic Lymphoma
**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
Burkitt's Lymphoma
**Most often occurs in CHILDREN

**B-cells

**Genetics:
=t(8:14)--> c-myc gene moves next to heavy-chain Ig gene (14)
What is Burkitt's Lymphoma associated with?
**Associated w/ EBV
Microscopic Apperance of Burkitt's Lymphoma:
**"Starry-sky" appearance
=Sheets of lymphocytes w/ interspersed macrophages
Forms of Burkitt's Lymphoma:
**Endemic Form in Africa
=JAW LESION

**Sporadic Form
=Pelvis or Abdomen

COLOR IMAGE 24
Leukemias--General Findings:
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

COLOR IMAGE 22
ALL
**Acute Lymphoblastic/ Lymphocytic Anemia

=Children

Features:
=lymphoblasts

**MOST responsive to therapy
=may spread to CNS and testes
AML
**Acute Myelogenous Leukemia

=ADULTS

**Findings:
=AUER RODS
=Myeloblasts
CLL
=Chronic Lymphocytic Leukemia

**OLDER adults

Findings:
=Lymphadenopathy
=Hepatosplenomegaly
=Few symptoms--indolent course
Lab Findings in CLL
1) Increased smudge cells in peripheral blood smear

2) Warm antibody autoimmune hemolytic anemia

**Very similar to SLL.
CML
**Chronic Myelogenous Leukemia

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

=Myeloid stem cell proliferation
Presentation + Lab Studies
Presents w/:
=Increased neutrophils + metamyelocytes
=SPLENOMEGALY

**May accelerate to AML = "BLAST CRISIS"

**note: CML has a very low leukocyte alkaline phosphatase (vs. leukemoid reaction)
What is a leukamoid reaction?
=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
Backing up--we said that we had Auer Rods in AML...what are Auer Rods?
=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.
Chromosomal Translocations
Given = the translocation

Give the associated disorder.
t(9;22)
**Philadelphia chromosome

=CML (bcr-abl hybrid)
t(8;14)
Burkitt's lymphoma
=c-myc activation
t(14;18)
Follicular Lymphoma
=bcl-2 activation
t(15;17)
M3 Type of AML
=responsive to all-TRANS retinoic acid
t(11;22)
Ewing's Sarcoma
t(11;14)
Mantle Cell Lymphoma
Multiple Myeloma
**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
Symptoms/Complications of MM:
1) Renal insufficiency
2) Increased susceptibility to infection
3) Anemia

Think CRAB:
=hyperCALCEMIA
=renal failure
=anemia
=bone lesions
Lab/Imaging Results
**"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
What does the blood smear show?
**RBCs stacked like poker chips (=ROULEAU FORMATION)
How is it different from Waldenstrom's Macroglobinemia?
**M spike = IgM
=thus often have hyperviscocity symptoms

**NO LYTIC BONE LESIONS

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