Pathology

• 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)

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• Occurs when growth factor is withdrawn from a proliferating cell population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

• 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)

• 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

• 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

• 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

• Pathology:
• -soft friable necrotic tissue
• -"cottage cheese"

• Characteristic of:
• -TB
• -systemic fungi

• Pathology:
• -necrotic adipose tissue with chalky-white appearance (due to deposition of calcium)
• -saponification (dystrophic calcification)

• Characteristic of:
• -peripancreatic fat
• -trauma to breast

• Pathology:
• -leakage of proteins into vessel wall results in bright pink staining of wall

• Characteristic of:
• -malignant hypertension
• -vasculitis

• Pathology:
• -Dry Gangrene: ischemic coagulative necrosis that resembles mummified tissue
• -Wet gangrene: bacterial infection superimposed

• Characteristic of:
• -limbs
• -GI tract

• 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

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

• 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

• 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

• Low-output failure
• -↑ TPR
• -Low cardiac output
• -Cold, clammy patient (vasoconstriction)

• High-output failure:
• -↓ TPR
• -Dilated arterioles, high venous return
• -hot patient (vasodilation)

• 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

• 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)

• 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

• 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

• 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)

• Damage cells via:
• -membrane lipid peroxidation
• -protein modification
• -DNA breakage

• 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

• 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

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

• 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

• Mediators:
• -Platelets
• -Neutrophils
• -Macrophages

• Characteristics:
• -clot formation
• -increased vessel permeability and NP migration to tissue
• -MPs clear debris two days later

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)

1 week after wound

• Mediators:
• -fibroblasts

• Characteristics:
• -Remove Type III collagen by collagenase (zinc as cofactor)
• -Type III collagen replaced by type I collagen (less flexible, more tensile strength)

• Infection
• -S. aureus

• 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

• 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:
• -increased hydrostatic pressure
• -decreased oncotic pressure
• -Na+ retention

• Exudate:
• -lymphatic obstruction
• -inflammation

• -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)

-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

• 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

• 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

• 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

• 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

• -heterogenous group of disorders
• -eg: "Familial Amyloid Cardiomyopathy"

• Pathophysiology:
• -mutated serum transthyretin (TTR)
• -deposits in heart → restrictive cardiomyopathy

• Pathophysiology:
• -deposition of wild-type transthyretin (TTR)
• -in myocardium and other sites

• Presentation:
• -slower progression of cardiac dysfunction vs AL amyloidosis
• -usually asymptomatic

• Alzheimer's
• -deposition of amyloid-β protein cleaved from amyloid precursor protein (c 21)

• -evasion of apoptosis
• -self-sufficiency in growth signals
• -insensitivity to anti-growth signals
• -sustained angiogenesis
• -limitless replicative potential
• -tissue invasion
• -metastasis

• 1. Normal
• 2. Hyperplasia/Dysplasia
• 3. Carcinoma in situ/preinvasive
• 4. Invasive Carcinoma
• 5. Metastasis

• -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

• -loss of size, shape and orientation
• -often arises from long-standing hyperplasia or metaplasia
• -reversible!

• -neoplastic cells have not invaded basement membrane
• -high nuclear/cytoplasmic ratio and clumped chromatin
• -neoplastic cells encompass entire thickness

• -cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases)
• -can metastasize if they reach a blood or lymphatic vessel

• -spread to distant organ
• -must survive immune attack

• "Seed and Soil" theory of metastasis:
• -seed = tumor embolus
• -soil = target organ

• 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

• 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

• 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

• 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)

• -well differentiated
• -slow growing
• -well demarcated
• -mobile
• -no potential for metastasis

• -may be poorly differentiated (does not have to be)
• -erratic growth/fast growing
• -locally invasive/diffuse
• -may metastasize

• Presentation:
• -weight loss
• -muscle atrophy
• -fatigue

• Occurs in chronic disease
• -cancer
• -AIDS-heart failure
• -TB

• Mediated by:
• -TNFa (cachectin)
• -IFNg
• -IL6

• ALL ("we ALL fall Down")
• AML

• Melanoma
• Basal cell carcinoma
• Squamous cell carcinoma (especially)

• Melanoma
• Basal cell carcinoma
• Squamous cell carcinoma (especially)

Gastric adenocarcinoma

Gastric adenocarcinoma

Gastric adenocarcinoma

• Giant cell astrocytoma
• Renal angiomyolipoma
• Cardiac rhabdomyoma

Squamous cell carcinoma of skin

Esophageal adenocarcinoma

Squamous cell carcinoma of esophagus

Hepatocellular carcinoma

Colonic adenocarcinoma

• Secondary Osteosarcoma
• Secondary Fibrosarcoma

Malignant Lymphoma

• Aggressive malignant lymphomas (Non-Hodgkins)
• Kaposi's Sarcoma

Lymphoma

• Visceral malignancy (stomach, lung, uterus)
• -associated with gastric carcinoma

Malignant melanoma

• Leukemia
• Sarcoma
• Papillary thyroid cancer
• Breast cancer

• -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

• Associated tumor:
• -CML

• Gene Product:
• -tyrosine kinase

• Associated Tumor:
• -Burkitt's lymphoma

• Gene Product:
• -transcription factor

• Associated Tumor:
• -Follicular and undifferentiated lymphoma

• Gene Product:
• -anti-apoptotic molecule

• Associated Tumor:
• -breast carcinoma
• -ovarian carcinoma
• -gastric carcinoma

• Gene Product:
• -tyrosine kinase
• -epidermal growth factor receptor

• Associated tumor:
• -colon cancer
• -mutated in 70-80% of human tumors

• Gene Product:
• -GTPase (signal transduction of growth signal)

• Associated tumor:
• -Lung tumor

• Gene Product:
• -transcription factor

• Associated tumor:
• -neuroblastoma

• Gene Product:
• -transcription factor

• Associated Tumor:
• -MEN2A, MEN2B

• Gene Product:
• -tyrosine kinase

• Associated tumor:
• -gastrointestinal stromal tumor (GIST)

• Gene Product:
• -cytokine receptor

-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

• Associated tumor:
• -Retinoblastoma
• -Osteosarcoma
• **non-familial: unilateral retinoblastoma

• Gene Product:
• -inhibits E2F
• -blocks G1 to S phase transition

• Associated Tumor:
• -most human cancers
• -Li Fraumeni syndrome

• Gene Product:
• -transcription factor for p21
• -blocks G1 to S phase transition

• Associated tumor:
• -breast cancer
• -ovarian cancer

• Gene Product:
• -DNA repair protein

• Associated tumor:
• -Melanoma

• Associated Tumor:
• -Melanoma

• Gene Product:
• -Braf

• Associated Tumor:
• -Colorectal cancer
• -associated with FAP

• Associated Tumor:
• -Wilm's Tumor (nephroblastoma)

• Associated Tumor:
• -NF type 1

• Gene Product:
• -RAS GTPase activating protein (RAS-GAP)

• Associated tumor:
• -Pancreatic cancer

• Gene Product:
• -DPC: Deleted in Pancreatic Cancer

• Associated tumor:
• -colon cancer

• Gene Product:
• -DCC: Deleted in Colon Cancer

• 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

• -used to follow prostate carcinoma
• -can also be elevated in BPH and prostatis
• -questionable risk/benefit for screening

-prostate carcinoma

CarcinoEmbryonic Antigen

• -very non-specific
• -produced by 70% of colorectal and pancreatic cancers
• -also produced by gastric, breast and medullary thyroid carcinomas

-normally made by fetus

• -Hepatocellular carcinoma
• -non-seminomatous germ cell tumors (testis, ovary)

• Hydatidiform moles
• Choriocarcinoma
• (Gestational trophoblastic disease)

*commonly associated with pregnancy

Ovarian cancer

• Melanoma
• Neural tumors
• Schwannomas

• -metastases to bone
• -Paget's disease of bone

• Neuroblastoma
• Lung cancer
• Gastric cancer

Tartrate-Resistant Acid Phosphatase (TRAP)

-Hairy cell leukemia (B cell neoplasm)

"TRAP the Hairy animal!"

Pancreatic adenocarcinom

Medullary Thyroid Carcinoma

• HTLV1
• HBV, HCV
• EBV
• HPV
• HHV-8
• H pylori
• Schistosoma haematobium
• Liver fluke (clonorchis sinesis)

Adult T cell leukemia/lymphoma

Hepatocellular carcinoma

• Burkitt's lymphoma
• Hodgkin's lympohoma
• Nasopharyngeal carcinoma (asian men)
• CNS lymphoma (in immunocompromised)

• Cervical Carcinoma
• Penile/Anal Carcinoma
• Upper respiratory SCC

• Kaposi's sarcoma
• Body cavity fluid B cell lymphoma

Gastric adenocarcinoma and lymphoma

Bladder cancer (squamous cell)

Cholangiocarcinoma

• Aflatoxin
• Vinyl chloride
• Carbon tetrachloride
• Nitrosamines
• Cigarette smoke
• Asbestos
• Arsenic
• Napthalene (aniline) dyes
• Alkylating agents

-from aspergillus (can get into improperly stored grains)

• Associated Tumor:
• -hepatocellular carcinoma

• Associated Tumor:
• -hepatic angiosarcoma

• Centrilobular necrosis
• Fatty change

(decrease protein synthesis of apolipoproteins)

-from smoked foods

• Associated Tumor:
• -gastric cancer

• 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

• Associated Tumors:
• Bronchogenic carcinoma > Mesothelioma

• Associated Tumors:
• -Squamous cell carcinoma (keep skin fair)
• -Liver angiosarcoma

-found in cigarette smoke

• Associated Tumors:
• -Transitional cell carcinoma

-chemotherapeutics

• Associated tumors:
• -leukemia

• Ectopic Hormones:
• -ACTH
• -ADH
• -PTHrP
• -Calcitriol
• -Epo
• -Lambert-Eaton Syndrome

• Effect:
• -Cushing's syndrome

• Neoplasms:
• -Small cell lung carcinoma

• Effect:
• -SIADH

• Neoplasms:
• -Small cell lung carcinoma
• -intracranial neoplasms

• Effect:
• -hypercalcemia

• Neoplasms:
• -Squamous cell lung carcinoma
• -renal cell carcinoma
• -breast cancer

1,25 (OH)2 Vitamin D

• Effect:
• -Hypercalcemia

• Neoplasm:
• -Hodgkin's lymphoma
• -some non-Hodgkin's lymphomas

• Effect:
• -Polycythemia

• Neoplasms:
• -Renal cell carcinoma
• -Hemangioblastoma
• -Heptatocellular carcinoma
• -pheochromocytoma

Antibodies against presynaptic Ca channels at NMJ

• Neoplasms:
• -Small cell lung carcinoma

• Description:
• -laminated, concentric, calcific spherules

• Seen in:
• -Papillary adenocarcinoma of thyroid
• -Serous papillary cystadenocarcinoma of ovary
• -Meningioma
• -Malignant Mesothelioma

PSaMMoma

• 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

• 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

• Brain
• Liver
• Bone

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

Lung > Breast > GU > Osteosarcoma > Melanoma > GI

• 50% of brain tumors are from mets
• Typically multiple well-circumscribed tumors at gray/white matter junction

Colon >> stomach > pancreas

Liver and lung are the most common sites of metastasis after regional LNs

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