-
Apoptosis
-pathways
-characteristics
- Programmed cell death
- -ATP dependent
- -single cells, or small groups
- -no inflammation
- Pathways:
- 1. Intrinsic
- 2. Extrinsic
- Common pathway:
- -activation of cytosolic caspases
- -caspases activate endonucleases and proteases
- Characteristics:
- -cell shrinkage
- -nuclear shrinkage (pyknosis)
- -nuclear fragmentation (karyorrhexis)
- -nuclear dissolution (karyolysis)
- -basophilia
- -membrane blebbing
- -formation of apoptotic bodies (which are then phagocytosed by macrophages)
-
Apoptosis: Intrinsic Pathway
Involved in tissue remodeling in embryogenesis
- Occurs when growth factor is withdrawn from a proliferating cell population
- -decreased IL2 after resolved immune reaction
- -loss of hormonal stimulation leads to endometrial shedding
- Occurs after exposure to injurious stimuli
- -radiation
- -toxins
- -hypoxia
- Mechanism:
- Changes in proportions of anti- and pro-apoptotic factors (decreased Bcl-2, increased Bax)
- -increased mitochondria permeability and release of cytochrome C
- -cytochrome C activates caspases in cytoplasm
-
Apoptosis: Extrinsic Pathway
- Ligand Receptor Interactions:
- -FasL binding Fas (CD95) (eg: negative selection)
- -TNF binds TNF Receptor
- Immune cell:
- -cytotoxic T cell release of perforin (creates pores) and granzyme B (activates caspases)
-
Necrosis
-background
-types
- Death of large groups of cells followed by acute inflammation
- -enzymatic degradation and protein denaturation of a cell resulting from exogenous injury
- Types:
- -Coagulative
- -Liquefactive
- -Caseous
- -Fatty
- -Fibrinoid
- -Gangrenous
-
Coagulative Necrosis
- Pathology:
- -tissue remains firm
- -cell shape and organ structure are preserved
- -nuclei disappear
- Characteristic of:
- -ischemic infarction
- -any organ except brain
- Location:
- -heart
- -liver
- -kidney
-
Liquefactive Necrosis
- Pathology:
- -liquefied (enzymatic lysis of cells and protein)
- Characteristic of:
- -brain infarction (microglial cells produce enzymes)
- -abscess (NPs produce enzymes)
- -pancreatitis (enzymes from pancreas)
- -pleural effusion
-
Caseous Necrosis
- Pathology:
- -soft friable necrotic tissue
- -"cottage cheese"
- Characteristic of:
- -TB
- -systemic fungi
-
Fatty Necrosis
- Pathology:
- -necrotic adipose tissue with chalky-white appearance (due to deposition of calcium)
- -saponification (dystrophic calcification)
- Characteristic of:
- -peripancreatic fat
- -trauma to breast
-
Fibrinoid Necrosis
- Pathology:
- -leakage of proteins into vessel wall results in bright pink staining of wall
- Characteristic of:
- -malignant hypertension
- -vasculitis
-
Gangrenous Necrosis
- Pathology:
- -Dry Gangrene: ischemic coagulative necrosis that resembles mummified tissue
- -Wet gangrene: bacterial infection superimposed
- Characteristic of:
- -limbs
- -GI tract
-
Reversible Cell Injury
- Hypoxia impairs oxidative phosphorylation → decreased ATP synthesis
- 1. Impaired Na+/K+ ATPase: sodium and water buildup in cell
- 2. Impaired Ca2+ pump: Ca2+ buildup in cytosol
- 3. Aerobic glycolysis: lactic acid production/low pH
- Features:
- -Hallmark = cellular swelling
- -ER swelling → dissociation of ribosomes and decreased protein synthesis
- -nuclear chromatin clumping
- -decreased glycogen
- -fatty change
-
Irreversible Cell Injury
Hallmark = membrane damage
- Plasma Membrane Damage:
- -cytosolic enzymes leak into serum (eg: cardiac troponin)
- -additional Ca2+ enter cells → caspase activation
- Mitochondrial Membrane Damage:
- -loss of ETC
- -Cytochrome c leaks into cytosol
- Lysosomal Membrane Damage:
- -hydrolytic enzymes leak into cytosol
- -activated by high levels of Ca2+
- Nuclear Damage:
- -pyknosis
- -karyloysis
- -karyorrhexis
-
Ischemia Susceptible Areas
- Brain:
- -ACA/MCA/PCA boundary areas (watershed areas)
- -Hypoxic Ischemic Encephalopathy: pyramidal cells of hippocampus and Purkinje cells
- Heart:
- -Subendocardium (LV)
- Kidney:
- -straight segment of proximal tubule (medulla)
- -thick ascending limb (medulla)
- Liver:
- -area around central vein (zone III)
- Colon:
- -splenic flexure
- -rectum
-
Red Infarct vs Pale Infarct
- Pale Infarct:
- -occur in solid tissues with a single blood supply
- -heart
- -kidney
- -spleen
- Red Infarct:
- -hemorrhagic, following reperfusion
- -reperfusion injury due to damage by free radicals
- -loose tissues with collaterals
- -liver
- -lungs
- -intestines
-
Hypovolemic/Cardiogenic Shock
- Low-output failure
- -↑ TPR
- -Low cardiac output
- -Cold, clammy patient (vasoconstriction)
-
Septic Shock
- High-output failure:
- -↓ TPR
- -Dilated arterioles, high venous return
- -hot patient (vasodilation)
-
Atrophy
- Reduction in the size or number of cells
Causes:- -↓ hormones (uterus/vagina)
- -↓ innervation (motor neuron damage)
- -↓ blood flow
- -↓ nutrients
- -↑ pressure (nephrolithiasis)
- -occlusion of secretory ducts (CF)
- Mechanism:
- -Decrease in cell number: apoptosis
- -Decrease in cell size: ubiquitin-proteosome degradation of cytoskeleton, autophagy of cellular components
-
Inflammation
-characteristics
-vascular components
-cellular components
- Characteristics:
- -Rubor (redness)
- -Dolor (pain)
- -Calor (heat)
- -tumor (swelling)
- -functio laesa (loss of function)
- Vascular Components:
- -increased vascular permeability
- -vasodilation
- -endothelial injury
- Cellular Components:
- -Neutrophils (extravasate from circulation to injured tissue)
-
Acute Inflammation
-basic principles
-time course
-mediators
-outcomes
- Characterized by:
- -edema
- -neutrophils
Arises in response to infection or tissue necrosis
- Rapid onset (sec - min)
- Lasts minutes to days
- Mediators:
- 1. TLRs (TLR4: LPS)
- 2. Arachadonic Acid metabolites
- -PGI2, PGD2, PGE2: vasodilation, increased vascular permeability
- -PGE2: pain and fever
- -LTB4: attracts and activates NPs
- -LTC4, LTD4, LTE4: vasoconstriction, bronchospasm, increased vascular permeability
- 3. Mast cells:
- -activated by trauma, C3a/C5a, IgE cross linking
- -immediate response: preformed histamine
- -delayed response: production of leukotrienes
- 4. Complement:
- -C3a/C5a: mast cell degranulation
- -C5a: chemotatic for NPs
- -C3b: opsonin for phagocytosis
- -MAC (C5a, C6-9): microbe lysis
- 5. Hageman Factor:
- -factor XII
- -activates: coagulation and fibrinolytic system, C', Kinin system (Bradykinin)
- 6. Neutrophils:
- -phagocytosis
- -degranulation
- -inflammatory mediator release
- Outcomes:
- -Complete resolution
- -abscess formation
- -progression to chronic inflammation
-
Chronic Inflammation
-basic principles
-stimuli
-mediators
-granuloma
-outcomes
- Characterized by:
- -lymphocytes and plasma cells
- -persistent destruction or repair
- -blood vessel proliferation, fibrosis
Delayed response but more specific
- Stimuli:
- -persistent infection
- -infection with viruses, mycobacteria, parasites, fungi
- -autoimmune disease
- -foreign material
- -some cancer
- Mediators:
- 1. CD4 T cells
- -Signal 1: MHC II and TCR
- -Signal 2: B7 on APC, CD28 on T cells
- -Th1: IL2 and IFNg (CD8s, MPs)
- -Th2: IL4 and IL5 (class switching, eosinophils)
- 2. CD8 T cells
- -Signal 1: MCH I and TCR
- -Signal 2: cytokines (IL2 from CD4)
- -killing via perforin/granzyme or Fas
- 3. B cells
- -Antigen binding to IgM and IgD
- -CD4 T cells: MCH II and TCR, CD40
- -class switching, hypermutation, plasma cells
- Granuloma:
- -defining feature = epitheloid histocytes
- -giant cells
- -MP present Ag to CD4 cells
- -MP secrete IL12 → Th1 differentiation
- -Th1 secrete IFNg
- -caseating or non-caseating
- Outcomes:
- -scarring
- -amyloidosis
-
Leukocyte extravasation
- Step 1 (Rolling):
- -Stroma: E-selectin (induced by TNF and IL1), P-selectin (Weibel-Palade bodies)
- -Leukocyte: Sialyl-LewisX
- -"selectin speed bump"
- Step 2 (Tight Binding):
- -Stroma: ICAM-1 (TNF and IL1)
- -Leukocytes: LFA1 Integrin (C5a, LTB4)
- Step 3 (Diapedesis):
- -leukocyte travels between endothelial cells and exits blood vessels
- -Stroma: PECAM-1
- -Leukocyte: PECAM-1
- Step 4 (Migration):
- -leukocyte travels through interstitium to site of injury or infection guided by chemotactic signals
- -Bacterial Products: C5a, IL8, LTB4, Kallikrein (CILK)
-
Free Radical Injury: Damages to cells
- Damage cells via:
- -membrane lipid peroxidation
- -protein modification
- -DNA breakage
-
Free Radical Injury: Pathologic Generation
- Ionizing radiation
- -water to hydroxyl radical
- Inflammation
- -leukocyte oxidative burst (NADPH oxidase)
- Metals
- -Fe2+: Fenton reaction
- -Cu
- Metabolism of Drugs
- -eg: acetaminophen
- -P450 system of liver
Nitric Oxide
-
Free Radical Injury: Mechanisms of Elimination
- Enzymes
- -Catalase: in peroxisomes, eliminates H2O2
- -Superoxide Dismutase: in mitochondria, converts superoxide to H2O2
- -Glutathione Peroxidase: in mitochondria
- Antioxidants
- -glutathione
- -Vitamins A, C, E
- Metal Carrier proteins
- -transferrin
- -ceruloplasmin
Spontaneous decay
-
Free Radical Injury: Pathologies
Retinopathy of prematurity
Bronchopulmonary dysplasia
- Carbon Tetrachloride:
- -organic solvent in drycleaning industry
- -converted to CCl3 free radical by P450 system
- -cellular swelling/swelling of RER → ribosomes detach (impair protein synthesis)
- -Decreased apolipoproteins leads to fatty change in liver
Acetaminophen Overdose:- -fulminant hepatitis
- Iron Overload
- -Hemochromatosis
- Reperfusion after anoxia
- -return of blood to ischemic tissues produces superoxide
- -especially after thrombolytic therapy
- -can see continued rise in cardiac enzymes after reperfusion of infarcted myocardial tissue
-
Wound Healing
-phases
-types of tissues
- Phases:
- 1. Inflammatory (immediate)
- 2. Proliferative (2-3 days after wound)
- 3. Remodeling (1 week after wound)
- Labile Tissue:
- -stem cells that continuously cycle
- -small and large bowel
- -skin
- -bone marrow
- -REGENERATE
- Stabile Tissue:
- -cells that are quiescent (G0) but can reenter cell cycle
- -liver
- -REGENERATE
- Permanent Tissue:
- -myocardium
- -skeletal muscle
- -neurons
- -can't regenerate, heal by REPAIR
-
Wound Healing: Inflammatory Phase
-mediators
-characteristics
- Mediators:
- -Platelets
- -Neutrophils
- -Macrophages
- Characteristics:
- -clot formation
- -increased vessel permeability and NP migration to tissue
- -MPs clear debris two days later
-
Wound Healing: Proliferative Phase
2-3 days after wound
- Mediators:
- -Fibroblasts (type III collagen)
- -Myofibroblasts
- -Endothelial cells
- -Keratinocytes
- -Macrophages
- Characteristics:
- -deposition of granulation tissue and collagen
- -angiogenesis
- -epithelial cell proliferation
- -dissolution of clot
- -wound contraction (myofibroblasts)
-
Wound Healing: Remodeling
1 week after wound
- Characteristics:
- -Remove Type III collagen by collagenase (zinc as cofactor)
- -Type III collagen replaced by type I collagen (less flexible, more tensile strength)
-
Abberant Wound Healing
- Vitamin C deficiency:
- -hydroxylation of proline and lysine on procollagen residues
- -necessary for collagen cross linking
- Copper deficiency:
- -cofactor for lysyl oxidase
- -cross links lysine and hydroxylysine to form stable collagen
- Zinc deficiency:
- -cofactor for collagenase
- -replaces type III collagen with type I collagen
-
Granulomatous Diseases
-granuloma formation
-diseases
- Granuloma Formation:
- -Th1 cells secrete IFNg, activating MPs
- -TNFa from MPs induce and maintain granuloma formation
- **anti-TNFa drugs can cause granuloma breakdown leading to disseminated disease
- Diseases:
- -Mycobacterium tuberculosis
- -Fungal Infections (histo, cocci)
- -Treponema pallidum (syphilis)
- -M. leprae (leprosy)
- -Bartonella henselae (stellate shaped cells)
- -Sarcoidosis
- -Crohn's Disease
- -Wegener's
- -Churg-Strauss
- -Berylliosis, Silicosis
-
Transudate vs Exudate
- Transudate:
- -increased hydrostatic pressure
- -decreased oncotic pressure
- -Na+ retention
- Exudate:
- -lymphatic obstruction
- -inflammation
-
Erythrocyte Sedimentation Rate
-Elevated
-Decreased
- -Products of inflammation (eg: fibrinogen) coat RBCs and cause aggregation
- -When aggregated, RBCs fall at a faster rate within the test tube
- Elevated ESR:
- -infections
- -inflammation (temporal arteritis)
- -cancer
- -pregnancy
- -SLE
- Decreased ESR:
- -Sickle cell (altered shape)
- -Polycythemia (too many)
- -CHF (unknown)
-
Iron Poisoning
-mechanism
-symptoms
-one of the leading causes of fatality from toxicologic agents in children
- Mechanism:
- -cell death due to peroxidation of membrane lipids
- Symptoms:
- -Acute: gastric bleeding
- -Chronic: metabolic acidosis, scarring leading to GI obstruction
-
Amyloidosis
-basic principles
-types
- Basic Principles:
- -abnormal aggregation of proteins or their fragments into β-pleated sheets (deposited in extracellular space)
- -can't be degraded
- -leads to cell damage and apoptosis
- -congo red staining and apple-green birefringence
- -can be systemic or localized
- Types:
- -AL (primary)
- -AA (secondary)
- -Dialysis-related
- -Heritable
- -Senile systemic
- -Organ specific
-
AL (primary) Amyloidosis
-pathophysiology
-presentation
- Pathophysiology:
- -deposition of proteins from Ig Light chain
- -associated with plasma cell dyscrasias (ie: multiple myeloma)
- Often multiple organ system impact:
- -Renal (nephrotic syndrome)
- -Cardiac (heart failure, arrhythmia)
- -Hematologic (easy bruising)
- -Hepatomegaly
- -Neuropathy
-
AA (secondary) Amyloidosis
-pathophysiology
-presentation
- Pathophysiology:
- -systemic deposition of AA amyloid
- -derived from SAA (acute phase reactant)
- -seen with chronic diseases: RA, IBD, Spondyloarthropathy, chronic infections, Familial Mediterranean Fever (dysfunction of neutrophils)
- Presentation:
- -often multisystem like AL amyloidosis
-
Dialysis Related Amyloidosis
- Pathophysiology:
- -fibrils composed of β2-microglobulin (MHC I)
- -not filtered well from blood during dialysis
- -patients with ESRD and long-term dialysis
- Presentation:
- -carpal tunnel syndrome
- -other joint issues
-
Heritable Amyloidosis
-pathophysiology
-presentation
- -heterogenous group of disorders
- -eg: "Familial Amyloid Cardiomyopathy"
- Pathophysiology:
- -mutated serum transthyretin (TTR)
- -deposits in heart → restrictive cardiomyopathy
-
Age-Related (Senile) Systemic Amyloidosis
- Pathophysiology:
- -deposition of wild-type transthyretin (TTR)
- -in myocardium and other sites
- Presentation:
- -slower progression of cardiac dysfunction vs AL amyloidosis
- -usually asymptomatic
-
Organ-Specific Amyloidosis
- Alzheimer's
- -deposition of amyloid-β protein cleaved from amyloid precursor protein (c 21)
-
Hallmarks of Cancer
- -evasion of apoptosis
- -self-sufficiency in growth signals
- -insensitivity to anti-growth signals
- -sustained angiogenesis
- -limitless replicative potential
- -tissue invasion
- -metastasis
-
Neoplasm Progression
- 1. Normal
- 2. Hyperplasia/Dysplasia
- 3. Carcinoma in situ/preinvasive
- 4. Invasive Carcinoma
- 5. Metastasis
-
Hyperplasia
- -increase in number of cells (production of new cells from stem cells)
- -abnormal proliferation of cells
- -reversible!
**BPH: does not increase risk of prostate cancer
-
Dysplasia
- -loss of size, shape and orientation
- -often arises from long-standing hyperplasia or metaplasia
- -reversible!
-
Carcinoma in situ
- -neoplastic cells have not invaded basement membrane
- -high nuclear/cytoplasmic ratio and clumped chromatin
- -neoplastic cells encompass entire thickness
-
Invasive Carcinoma
- -cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases)
- -can metastasize if they reach a blood or lymphatic vessel
-
Metastasis
- -spread to distant organ
- -must survive immune attack
- "Seed and Soil" theory of metastasis:
- -seed = tumor embolus
- -soil = target organ
-
Reversible -plasias
- Hyperplasia
- -increase in number of cells
- Metaplasia
- -change in stress leads to a change in cell type
- -often secondary to irritation and/or environmental exposure
- -squamous metaplasia in trachea and bronchi of smokers
- -Barrett's esophagus
- Dysplasia:
- -abnormal growth with loss of cellular orientation, shape, and size
- -commonly preneoplastic
-
Irreversible -plasias
- Anaplasia:
- -abnormal cells lacking differentiation
- -resemble primitive cells of same tissue
- -often equated with undifferentiated malignant neoplasms
- -little or no resemblance to tissue of origin
- Neoplasia:
- -clonal proliferation of cells that is uncontrolled and excessive
- -may be benign or malignant
- Desmoplasia:
- -fibrous tissue formation in response to neoplasm
-
Tumor Grade
- Microscopic assessment of differentiation
- -how much a cancer resembles the tissue in which it grows
- -graded 1-4
- 1: low grade, well differentiated
- 2: high grade, poorly differentiated, anaplastic
*less prognostic value than stage
-
Tumor Stage
- Degree of localization/spread
- -based on clinical (c) or pathology (p) findings
- TNM
- T: Tumor size
- N: Node involvement
- M: Metastases (most important prognostic factor)
-
-
Benign Tumor
-characteristics
- -well differentiated
- -slow growing
- -well demarcated
- -mobile
- -no potential for metastasis
-
Malignant Tumor
-characteristics
- -may be poorly differentiated (does not have to be)
- -erratic growth/fast growing
- -locally invasive/diffuse
- -may metastasize
-
Cachexia
-presentation
-caused by
-mediators
- Presentation:
- -weight loss
- -muscle atrophy
- -fatigue
- Occurs in chronic disease
- -cancer
- -AIDS-heart failure
- -TB
- Mediated by:
- -TNFa (cachectin)
- -IFNg
- -IL6
-
Down Syndrome
- ALL ("we ALL fall Down")
- AML
-
Xeroderma Pigmentosum
- Melanoma
- Basal cell carcinoma
- Squamous cell carcinoma (especially)
-
Albinism
- Melanoma
- Basal cell carcinoma
- Squamous cell carcinoma (especially)
-
Chronic atrophic gastritis
Gastric adenocarcinoma
-
Pernicious Anemia
Gastric adenocarcinoma
-
Postsurgical gastric remnants
Gastric adenocarcinoma
-
Tuberous Sclerosis
- Giant cell astrocytoma
- Renal angiomyolipoma
- Cardiac rhabdomyoma
-
Actinic Keratosis
Squamous cell carcinoma of skin
-
Barret's esophagus
Esophageal adenocarcinoma
-
Plummer-Vinson Syndrome (decreased iron)
Squamous cell carcinoma of esophagus
-
Cirrhosis
-alcoholic
-hep B or C
Hepatocellular carcinoma
-
Ulcerative Colitis
Colonic adenocarcinoma
-
Paget's Disease of Bone
- Secondary Osteosarcoma
- Secondary Fibrosarcoma
-
Immunodeficiency States
Malignant Lymphoma
-
AIDS
- Aggressive malignant lymphomas (Non-Hodgkins)
- Kaposi's Sarcoma
-
Autoimmune Diseases
Lymphoma
-
Acanthosis Nigricans
- Visceral malignancy (stomach, lung, uterus)
- -associated with gastric carcinoma
-
Dysplastic nevus
Malignant melanoma
-
Radiation Exposure
- Leukemia
- Sarcoma
- Papillary thyroid cancer
- Breast cancer
-
Oncogenes
-description
-examples
- -proto-oncogenes are essential for cell growth and proliferation
- -oncogenes lead to unregulated cellular growth
- -Gain of function leads to increased cancer risk
- -Need damage only one allele
- Examples:
- -abl
- -cmyc
- -bcl2
- -HER2/neu
- -ras
- -L-myc
- -N-myc
- -ret
- -c-kit
-
abl
- Gene Product:
- -tyrosine kinase
-
c-myc
- Associated Tumor:
- -Burkitt's lymphoma
- Gene Product:
- -transcription factor
-
bcl-2
- Associated Tumor:
- -Follicular and undifferentiated lymphoma
- Gene Product:
- -anti-apoptotic molecule
-
HER2/neu
- Associated Tumor:
- -breast carcinoma
- -ovarian carcinoma
- -gastric carcinoma
- Gene Product:
- -tyrosine kinase
- -epidermal growth factor receptor
-
ras
- Associated tumor:
- -colon cancer
- -mutated in 70-80% of human tumors
- Gene Product:
- -GTPase (signal transduction of growth signal)
-
L-myc
- Associated tumor:
- -Lung tumor
- Gene Product:
- -transcription factor
-
N-myc
- Associated tumor:
- -neuroblastoma
- Gene Product:
- -transcription factor
-
ret
- Associated Tumor:
- -MEN2A, MEN2B
- Gene Product:
- -tyrosine kinase
-
c-kit
- Associated tumor:
- -gastrointestinal stromal tumor (GIST)
- Gene Product:
- -cytokine receptor
-
Tumor Suppressor Genes
-description
-examples
-regulate cell growth
- -Loss of function increases cancer risk
- -both alleles must be lost for disease
- Examples:
- -Rb
- -p53
- -BRCA1
- -BRCA2
- -p16
- -BRAF
- -APC
- -WT1
- -NF1
- -NF2
- -DPC4
- -DCC
-
Rb
- Associated tumor:
- -Retinoblastoma
- -Osteosarcoma
- **non-familial: unilateral retinoblastoma
- Gene Product:
- -inhibits E2F
- -blocks G1 to S phase transition
-
p53
- Associated Tumor:
- -most human cancers
- -Li Fraumeni syndrome
- Gene Product:
- -transcription factor for p21
- -blocks G1 to S phase transition
-
BRCA1/2
- Associated tumor:
- -breast cancer
- -ovarian cancer
- Gene Product:
- -DNA repair protein
-
p16
- Associated tumor:
- -Melanoma
-
BRAF
- Associated Tumor:
- -Melanoma
-
APC
- Associated Tumor:
- -Colorectal cancer
- -associated with FAP
-
WT1
- Associated Tumor:
- -Wilm's Tumor (nephroblastoma)
-
NF1
- Associated Tumor:
- -NF type 1
- Gene Product:
- -RAS GTPase activating protein (RAS-GAP)
-
DPC4
- Associated tumor:
- -Pancreatic cancer
- Gene Product:
- -DPC: Deleted in Pancreatic Cancer
-
DCC
- Associated tumor:
- -colon cancer
- Gene Product:
- -DCC: Deleted in Colon Cancer
-
Tumor Markers
-use
-examples
- Use:
- -screening
- -monitor for recurrence
- -monitor response to therapy
- -should not be used as primary tool for cancer diagnosis
- Examples:
- -PSA
- -Prostatic acid phosphatase
- -CEA
- -α-fetoprotein
- -β-hCG
- -CA-125
- -S-100
- -Alkaline Phosphatase
- -Bombesin
- -TRAP
- -CA-19-9
- -Calcitonin
-
PSA
- -used to follow prostate carcinoma
- -can also be elevated in BPH and prostatis
- -questionable risk/benefit for screening
-
Prostatic acid phosphatase
-prostate carcinoma
-
CEA
CarcinoEmbryonic Antigen
- -very non-specific
- -produced by 70% of colorectal and pancreatic cancers
- -also produced by gastric, breast and medullary thyroid carcinomas
-
α-fetoprotein
-normally made by fetus
- -Hepatocellular carcinoma
- -non-seminomatous germ cell tumors (testis, ovary)
-
β-hCG
- Hydatidiform moles
- Choriocarcinoma
- (Gestational trophoblastic disease)
*commonly associated with pregnancy
-
-
S-100
- Melanoma
- Neural tumors
- Schwannomas
-
Alkaline Phosphatase
- -metastases to bone
- -Paget's disease of bone
-
Bombesin
- Neuroblastoma
- Lung cancer
- Gastric cancer
-
TRAP
Tartrate-Resistant Acid Phosphatase (TRAP)
-Hairy cell leukemia (B cell neoplasm)
"TRAP the Hairy animal!"
-
CA-19-9
Pancreatic adenocarcinom
-
Calcitonin
Medullary Thyroid Carcinoma
-
Oncogenic Microbes
- HTLV1
- HBV, HCV
- EBV
- HPV
- HHV-8
- H pylori
- Schistosoma haematobium
- Liver fluke (clonorchis sinesis)
-
HTLV1
Adult T cell leukemia/lymphoma
-
HBV, HCV
Hepatocellular carcinoma
-
EBV
- Burkitt's lymphoma
- Hodgkin's lympohoma
- Nasopharyngeal carcinoma (asian men)
- CNS lymphoma (in immunocompromised)
-
HPV
- Cervical Carcinoma
- Penile/Anal Carcinoma
- Upper respiratory SCC
-
HHV8
- Kaposi's sarcoma
- Body cavity fluid B cell lymphoma
-
H pylori
Gastric adenocarcinoma and lymphoma
-
Schistosoma haematobium
Bladder cancer (squamous cell)
-
Liver fluke (Clonorchis sinensis)
Cholangiocarcinoma
-
Chemical Carcinogens
- Aflatoxin
- Vinyl chloride
- Carbon tetrachloride
- Nitrosamines
- Cigarette smoke
- Asbestos
- Arsenic
- Napthalene (aniline) dyes
- Alkylating agents
-
Aflatoxin
-from aspergillus (can get into improperly stored grains)
- Associated Tumor:
- -hepatocellular carcinoma
-
Vinyl Chloride
- Associated Tumor:
- -hepatic angiosarcoma
-
Carbon Tetrachloride
- Centrilobular necrosis
- Fatty change
(decrease protein synthesis of apolipoproteins)
-
Nitrosamines
-from smoked foods
- Associated Tumor:
- -gastric cancer
-
Cigarette Smoke
- Carcinogens:
- -arsenic
- -polycyclic hydrocarbons
- -naphthylamine
- Associated tumors:
- -Squamous cell carcinoma of lung
- -Small cell carcinoma of lung
- -Renal cell carcinoma
- -Transitional cell carcinoma (bladder etc)
- -Pancreatic adenocarcinoma
-
Asbestos
- Associated Tumors:
- Bronchogenic carcinoma > Mesothelioma
-
Arsenic
- Associated Tumors:
- -Squamous cell carcinoma (keep skin fair)
- -Liver angiosarcoma
-
Naphthalene (aniline) dyes
-found in cigarette smoke
- Associated Tumors:
- -Transitional cell carcinoma
-
Alkylating dyes
-chemotherapeutics
- Associated tumors:
- -leukemia
-
Paraneoplastic Syndromes
- Ectopic Hormones:
- -ACTH
- -ADH
- -PTHrP
- -Calcitriol
- -Epo
- -Lambert-Eaton Syndrome
-
Paraneoplastic Syndromes: ACTH
- Effect:
- -Cushing's syndrome
- Neoplasms:
- -Small cell lung carcinoma
-
Paraneoplastic Syndromes: ADH
- Neoplasms:
- -Small cell lung carcinoma
- -intracranial neoplasms
-
Paraneoplastic Syndromes: PTHrP
- Neoplasms:
- -Squamous cell lung carcinoma
- -renal cell carcinoma
- -breast cancer
-
Paraneoplastic Syndromes: Calcitriol
1,25 (OH)2 Vitamin D
- Neoplasm:
- -Hodgkin's lymphoma
- -some non-Hodgkin's lymphomas
-
Paraneoplastic Syndromes: Epo
- Neoplasms:
- -Renal cell carcinoma
- -Hemangioblastoma
- -Heptatocellular carcinoma
- -pheochromocytoma
-
Paraneoplastic Syndromes: Lambert Eaton Syndrome
Antibodies against presynaptic Ca channels at NMJ
- Neoplasms:
- -Small cell lung carcinoma
-
Psammoma bodies
- Description:
- -laminated, concentric, calcific spherules
- Seen in:
- -Papillary adenocarcinoma of thyroid
- -Serous papillary cystadenocarcinoma of ovary
- -Meningioma
- -Malignant Mesothelioma
PSaMMoma
-
Cancer Incidence
- Male:
- 1. Prostate (32%)
- 2. Lung (16%)
- 3. Colon/rectum (12%)
- Female:
- 1. Breast (32%)
- 2. Lung (13%)
- 3. Colon/rectum (12%)
** lung cancer incidence has dropped in men but has not changed significantly in women
-
Cancer Mortality
- Male:
- 1. Lung (33%)
- 2. Prostate (13%)
- Female
- 1. Lung (23%)
- 2. Breast (18%)
**Cancer is the second leading cause of death in the US
-
Common Sites of Metastasis
Carcinomas tend to metastasize via lymphatics
Sarcomas tend to spread hematogenously
- Carcinomas that spread hematogenously:
- -Renal cell carcinoma
- -hepatocellular carcinoma
- -follicular carcinoma of thyroid
- -choriocarcinoma
-
Brain Metastases
Lung > Breast > GU > Osteosarcoma > Melanoma > GI
- 50% of brain tumors are from mets
- Typically multiple well-circumscribed tumors at gray/white matter junction
-
Liver Metastases
Colon >> stomach > pancreas
Liver and lung are the most common sites of metastasis after regional LNs
-
Bone Metastases
Prostate/breast > Lung > Thyroid, Testes
Bone mets > primary tumors
whole-body bone scan shows predilection for axial skeleton
- Lung = lytic
- Prostate = blastic
- Breast = lytic and blastic
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