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Programmed cell death; ATP required. Intrinsic or extrinsic pathway; both pathways lead to activation of cytosolic caspases that mediate cellular breakdown. No significant inflammation (unlike necrosis). Characterized by deeply eosinophilic cytoplasm, cell shrinkage, nuclear shrinkage (pyknosis) and basophilia, membrane blebbing, nuclear fragmentation (Karyorrhexis), and formation of apoptotic bodies, which are than phagocytosed. DNA laddering is a sensitive indicator of apoptosis; during karyorrhexis, endonucleases cleave at internucleosomal regions, yielding fragments in multiples in 180 bp. Radiation therapy causes apoptosis of tumors and surrounding tissue via free radical formation and dsDNA breakage. Rapidly dividing cells (eg skin, GI mucosa) are very susceptible to radiation therapy-induced apoptosis.


Intrinsic apoptotic pathway

Involved in tissue remodeling in embryogenesis. Occurs when a regulating factor is withdrawn from a proliferating cell population (eg a decrease in IL-2 after a completed immunologic reaction leading to apoptosis of proliferating effector cells). Also occurs after exposure to injurious stimuli (eg radiation, toxins, hypoxia). Changes in proportions of anti- and pro-apoptotic factors leading to an increase in mitochondrial permeability and cytochrome c release. BAX and BAK are proapoptotic proteins; Bcl-2 is antiapoptotic. Bcl-2 prevents cytochrome c release by binding to and inhibiting Apaf-1. Apaf-1 normally induces the activation of caspases. If Bcl-2 is overexpressed (eg follicular lymphoma), then Apaf-1 is overly inhibited, leading to a decrease caspase activation and tumorigenesis.


Extrinsic pathway

There are two pathways: ligand receptor interactions (FasL binding to Fas [CD95]) and immune cell (cytotoxic T-cell release of perforin and granzyme B). Fas-FasL interaction is necessary in thymic medullary negative selection. Mutations in Fas increases the number of circulating self- reacting lymphocytes due to failure of clonal deletion. After Fas crosslinks with FasL, multiple Fas molecules coalesce, forming a binding site for a death domain-containing adapter protein, FADD. FADD binds inactive caspases, activating them. Devective Fas-FasL interactions contribute to autoimmune disorders.



Enzymatic degradation and protein denaturation of cell due to exogenous injury, leading to leak of intracellular components. Inflammatory process (unlike apoptosis).


Coagulative necrosis

Seen in ischemia/infarcts in most tissue (except brain). It is due to ischemia or infarction; proteins denature, then enzymatic degradation. On histology, cell outlines are preserved; there is also an increase in cytoplasmic binding of acidophilic dyes.


Liquefactive necrosis

Seen in bacterial abscesses, brain infarcts (due to an increase in fat content). It is due to neutrophils releasing lysosomal enzymes that digest the tissue; enzymatic degradation first, then proteins denature.


Caseous necrosis

Seen in TB, systemic fungi (eg Histoplasma capsulatum), Nocardia. It is due to macrophages walling off the infecting microorganism, leading to granular debris. On histology, there are fragmented cells and debris surrounded by lymphocytes and macrophages.


Fat necrosis

Seen in enzymatic acute pancreatitis (saponification) and nonezymatic breast trauma. It is due to damaged cells release lipase, which breaks down fatty acids in cell membranes. On histology, there is an outlines of dead fat cells without peripheral nuclei; saponification of fat (combined with Ca) appears dark blue of H&E stain.


Fibrinoid necrosis

Seen in immune reactions in vessels. It is due to immune complexes combined with fibrin, leading to vessel wall damage. On histology, there are vessel walls that are thick and pink.


Gangrenous necrosis

Seen in distal extremity, after chronic ischemia. In dry gangrenous necrosis, it is due to ischemia (on histology, coagulation is seen). In wet gangrenous necrosis, it is due to superinfection (on histology, liquefaction is seen).


Cell injury reversible with O2

There is ATP depletion, cellular/mitochondrial swelling (a decrease in ATP leads to a decrease activity of Na/K pumps), nuclear chromatin clumping, a decrease in glycogen, fatty change, ribosomal/ polychromal clumping detachment (a decrease in protein synthesis), and membrane blebbing.


Cell injury irreversible with O2

There is nuclear pyknosis, karyorrhexis (destructive fragmentation of the nucleus of a dying cell), karylolysis (the complete dissolution of the chromatin of a dying cell), plasma membrane damage (degradation of membrane phospholipid), lysosomal rupture, mitochondrial permeability/ vacuolization; phospholipid- containing amorphous densities within mitochondria (swelling alone is reversible).


Ischemia susceptible areas of the brain

They are located between the cortical territories of the anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) boundary areas. Watershed areas (border zones) receive dual blood supply from most distal branches of 2 arteries, which protects these areas from single-vessel focal blockage. However, these areas are susceptible to ischemia from systemic hypoperfusion. Hypoxic ischemic encephalopathy (HIE) affects pyramidal cells of hippocampus and Purkinje cells of the cerebellum.


Ischemia susceptible areas of the heart

Subendocardium (left ventricle)


Ischemia susceptible areas of the kidney

Straight segment of the proximal tubule (medulla) and the thick ascending limb (medulla)


Ischemia susceptible areas of the liver

Area around central vein (zone III)


Ischemia susceptible areas of the colon

Splenic flexure and rectum. Watershed areas (border zones) receive dual blood supply from most distal branches of 2 arteries, which protects these areas from single-vessel focal blockage. However, these areas are susceptible to ischemia from systemic hypoperfusion.


Red infarcts

Red (hemorrhagic) infarcts occur in venous occlusion and tissue with multiple blood supplies, such as liver, lung, and intestine; reperfusion (eg after angioplasty). Reperfusion injury is due to damage by free radicals. Red=Reperfusion.


Pale infarcts

Pale (anemic) infarcts occur in solid organs with a single (end-arterial) blood supply, such as heart, kidney, and spleen.



There is a reduction in the size and/or number of cells. Causes include: a decrease in endogenous hormones (eg post menopausal ovaries); an increase in exogenous hormones (eg factitious thyrotoxicosis, steroid use); a decrease in innervation (eg motor neuron damage); a decrease in blood flow/nutrients; a decrease in metabolic demand (eg prolonged hospitalization, paralysis); an increase in pressure (eg nephrolithiasis); occlusion of secretory ducts (eg cystic fibrosis, calculus/stone).



Characterized by rubor (redness), dolor (pain), calor (heat), tumor (swelling), and fanctio laesa (loss of function).


Vascular components of inflammation

an increase in vascular permeability, vasodilation, and endothelial injury.


Cellular components of inflammation

Neutrophils extravasate from circulation to injured tissue to participate in inflammation through phagocytosis, degranulation and inflammatory mediated release.


Acute inflammation

It is neutrophil, eosinophil, and antibody mediated. Acute inflammation has a rapid onset (seconds to minutes) and of short duration (minutes to days). Outcomes include complete resolution, abscess formation, or progression to chronic inflammation.


Chronic inflammation

It is mononuclear cell and fibroblast mediated. Characterized by persistent destruction and repair. It is associated with blood vessel proliferation, and fibrosis. There are granulomas, which are nodular collections of epithelioid macrophages and giant cells. Outcomes include scarring and amyloidosis.



A process involving the neuronal cell body following axonal injury. Changes reflect an increase in protein synthesis in effort to repair the damaged axon. It is characterized by round cellular swelling, displacement of the nucleus to the periphery, dispersion of Nissl substance (is a large granular body, found in neurons, of rough endoplasmic reticulum (RER) with rosettes of free ribosomes, and are the site of protein synthesis) throughout cytoplasm.


Dystrophic calcification

Ca deposition in abnormal tissue secondary to injury or necrosis. It tends to be localized (eg calcific aortic stenosis). It is seen in TB (lungs and pericardium), liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis (a disease caused by infection with freshwater parasitic worms in certain tropical and subtropical countries), Monckeberg arteriolosclerosis ( calcium deposits are found in the muscular middle layer of the walls of arteries (the tunica media)), congenital CMV and toxoplasmosis, psammoma bodies. It is not directly associated with serum Ca levels (patients are usually normocalcemic). On histology, there can also be small bony tissue and thick fibrotic walls.


Metastatic calcification

Widespread (ie diffuse, metastatic) deposition of Ca in normal tissue secondary to hypercalcemia (eg primary hyperparathyroidism, sarcoidosis, hypervitaminosis D) or high calcium- phosphate product levels (eg chronic renal failure with secondary hyperparathyroidism, long-term dialysis, calciphylaxis ( a syndrome of vascular calcification, thrombosis and skin necrosis), and warfarin). Ca deposits predominantly in interstitial tissues of kidney, lung, and gastric mucosa (these tissues lose acid quickly; an increase in pH favors deposition). Patients are usually not normocalcemic. Metastatic calcification can be seen in alveolar walls in acute pneumonitis.


Leukocyte extravasation

Extravasation predominantly occurs at postcapillary venules. WBCs exit from blood vessels at sites of tissue injury and inflammation in 4 steps: 1. Margination and rolling. 2. Tight-binding. 3. Diapedesis. 4. Migration.


Migration and rolling of leukocytes along vessels

This is defective in leukocyte adhesion deficiency type 2, which is due to a decrease of Sialyl-LewisX (a tetrasaccharide carbohydrate that is usually attached to O-glycans on the surface of cells and plays a vital role in cell-to-cell recognition processes). Components of the vasculature/ stroma responsible for binding PMNs in this step includes E-selectin (which binds Sialyl-LewisX), P-selectin (which binds Sialyl-LewisX), GlyCAM-1 (which binds L-selectin), CD34 (which binds L-selectin).


Tight-binding of leukocytes to vessels

This is defective in leukocyte adhesion deficiency type 1, which is due to a decrease in CD18 integrin subunit. Components of the vasculature/ stroma responsible for binding PMNs in this step includes ICAM-1 (CD54), which binds CD11/18 integrins (LFA-1 and MAC-1) of PMNs, and VCAM-1 (CD106), which binds VLA-4 integrin.


Diapedesis of leukocytes

The movement or passage of white blood cells, especially white blood cells, through intact capillary walls into surrounding body tissue. Components of the vasculature/ stroma responsible for binding PMNs in this step includes PECAM-1 (CD31), which binds PECAM-1 (CD31) of leukocytes.


Migration of leukocytes through interstitium

WBCs travel to site of injury or infection guided by chemotactic signals. Chemotactic products released in response to bacteria includes C5a, IL-8, LTB4, kallikrein, and platelet-activating factor.


Free radical injury

Free radicals damage cells via membrane lipid peroxidation, protein modification, and DNA breakage. Initiated via radiation exposure (eg cancer therapy), metabolism of drugs (phase I), redox reactions, nitric oxide, transition metals, WBC (eg neutrophils, macrophages) oxidative burst. Free radicals can be eliminated by scavenging enzymes (eg catalase, superoxide dismutase, glutathione peroxidase), spontaneous decay, antioxidants (eg vitamins A, C, E) and certain metal carrier proteins (eg transferrin and ceruloplasmin).


Pathologies of free radical injury

Retinopathy of prematurity is a disease of the eye affecting prematurely-born babies generally having received intensive neonatal care, in which oxygen therapy is used on them due to the premature development of their lungs. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that affects newborns (mostly premature) and infants. It results from damage to the lungs caused by mechanical ventilation (respirator) and long-term use of oxygen. Carbon tetrachloridewas formerly widely used in fire extinguishers, as a precursor to refrigerants, and as a cleaning agent and leads to liver necrosis (fatty change); acetaminophen overdose. Acetaminophen overdose leads to fulminant and renal papillary necrosis. Iron overload due to hemochromatosis. Reperfusion injury, especially after thrombolytic therapy, results in inflammation and oxidative damage (eg superoxide) through the induction of oxidative stress rather than restoration of normal function.


Inhalation injury and sequelae

Pulmonary complication associated with smoke and fire. It is caused by heat, particulates (less than 1 micrometer diameter), or irritants (eg NH3) leads to chemical tracheobronchitis, edema, and pneumonia, and ARDS. Many patients present secondary to burns, CO inhalation, or arsenic poisoning. Bronchoscopy can show severe edema, congestion of bronchus, and carbon soot deposition 18 hours after inhalation injury and can largely resolve within weeks of the injury.


Scar formation

70-80% of tensile strength regained at 3 months, little additional tensile strength will be regained afterword.


Hypertrophic scars

There is an increase in collagen synthesis. Collagen is arranged in parallel. The scar's borders are confined to the original wound. It infrequently recur following resection.


Keloid scars

There is a significant increase in collagen synthesis. The collagen arrangement is disorganized. The scar's borders extend beyond the borders of the original wound. It will frequently recur following resection. There is a higher incidence in African Americans. The scar often has a characteristic "claw-like" projections.


Platelet-derived growth factor (PDGF)

A wound healing tissue mediator. It is secreted by activated platelets and macrophages. It induces vascular remodeling and smooth muscle cell migration. It also stimulates fibroblast growth for collagen synthesis.


Fibroblastic growth factor (FGF)

A wound healing tissue mediator. It stimulates angiogenesis.


Epithelial growth factor (EGF)

A wound healing tissue mediator. It stimulates cell growth via tyrosine kinases (eg EGFR as expressed by ERBB2).


Transforming growth factor beta (TGF-β)

A wound healing tissue mediator. It induces angiogenesis, fibrosis, cell cycle arrest.



A wound healing tissue mediator. It induces tissue remodeling.


Vascular endothelial growth factor (VEGF)

A wound healing tissue mediator. It stimulates angiogenesis.


Phases of wound healing

Inflammatory (up to 3 days after a wound), proliferative (from day 3 to weeks after a wound), and remodeling (from 1 week to over 6 months after a wound).


Inflammatory phase of wound healing

Occurs up to three days after an injury. Mediators include platelets, neutrophils, and macrophages. Characteristics include clot formation, increase vessel permeability and neutrophil migration into tissue. Macrophages clear debris two days later.


Proliferative phase of wound healing

Occurs from three days to weeks after a wound. Mediators include fibroblasts, myofibroblasts, endothelial cells, keratinocytes, and macrophages. Characteristics include deposition of granulation tissue and collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, and wound contraction (mediated by myofibroblasts).


Remodeling phase of wound healing

Occurs from 1 week to over 6 months. Mediators include fibroblasts. Characteristics include type III collagen replaced by type I collagen and an increase in the strength of tissue.


Granulomatous diseases

Includes Baronella henselae (cat scratch disease), Berylliosis, eiosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), Crohn disease (noncaseating granuloma), foreign bodies, Francisella tularensis (causes tularemia), fungal infections (caseous necrosis), granulomatosis with polyangiitis (wegener), Listeria monocytogenes (granulomatosis infantiseptica-pyogenic granulomas distributed over the whole body), M. leprae (leprosy; Hansen disease), M. tuberculosis (caseous necrosis), Treponema pallidum (tertiary syphilis), sarcoidosis (noncaseating granuloma), Schistosomiasis.


Formation of a granuloma

Th1 cells secrete IFN-gamma, activating macrophages. TNF-alpha from macrophages induces and maintains granuloma formation. Anti-TNF drugs can, as a side effect, cause sequestering granulomas to break down, leading to disseminated disease. Always test for latent TB before starting anti-TNF therapy.



Think thick. It is composed of cells, it is protein rich with a specific gravity greater than 1.020. It occurs due to lymphatic obstruction, inflammation/infection, and malignancy.



Think thin. It is hypocellular, protein-poor with a specific gravity less than 1.012. It occurs due to an increase in hydrostatic pressure (eg HF), a decrease in oncotic pressure (eg cirrhosis, nephrotic syndrome), and Na retention.


Erythrocyte sedimentation rate

Products of inflammation (eg fibrinogen) coat RBCs and cause aggregation. The denser RBC aggregates fall at a faster rate within a pipette tube. Often co-tested with CRP.


An increase in ESR

Can be due to most anemias, infections, inflammation, cancer, pregnancy, and autoimmune disorders.


An decrease in ESR

Can be due to sickle cell anemia (altered shape), polycythemia (an increase in RBCs dilute aggregation factors), heart failure, microcytosis, hypofibrinogenemia.



Abnormal aggregation of proteins (or their fragments) into beta pleated sheets, which causes damage and apoptosis. Congo red stain shows amyloid deposits, which appear apple green birefringence under polarized light.


AL amyloidosis

It is considered primary and is due to deposition of proteins from Ig Light chains. It can occur as a plasma cell disorder or associated with multiple myeloma. It often affects multiple organ systems, including renal (nephrotic syndrome), cardiac (restrictive cardiomyopathy and arrhythmia), hematologic (easy bruising and splenomegaly), GI (hepatomegaly), and neurologic (neuropathy).


AA amyloidosis

It is considered secondary and is seen with chronic inflammatory conditions such as rheumatoid arthritis, IMD spondyloarthropathy, protracted infection. Fibrils are composed of serum Amyloid A. It often involves multiple systems like AL amyloidosis.


Dialysis related amyloidosis

Fibrils composed of beta-2-microglobulin (a component of MHC class I molecules) occur in patients with end-stage renal disease (ESRD) and/or on long term dialysis. It may present as carpal tunnel syndrome.


Heritable amyloidosis

This is a heterogeneous group of disorders, including familial amyloid polyneuropathies due to transthretin gene mutation.


Age related (senile) systemic amyloidosis

This occurs due to deposition of normal (wild-type) transthyretin in myocardium and other sites. There is slower progression of cardiac dysfunction relative to AL amyloidosis.


Organ specific amyloidosis

Amyloid deposition localized to a single organ. The most important form is amyloidosis in Alzheimer disease due to deposition of beta-amyloid protein cleaved from amyloid precursor protein (APP). Islet amyloid polypeptide (IAP) is commonly seen in diabetes mellitus type 2 and is caused by deposition of amylin in pancreatic islets.



A yellow brown wear and tear pigment associated with normal aging. Formed by oxidation and polymerization of autophagocytosed organellar membranes. Autopsy of elderly person will reveal deposits in heart, colon, liver, kidney, eye, and other organs.


Hallmarks of cancer

Evasion of apoptosis, growth signal self-sufficiency, anti-growth signal insensitivity, sustained angiogenesis, limitless replicative potential, tissue invasion, and metastasis.



cells increase in number. Distinct from hypertrophy (an increase in size of cells). Reversible



Abnormal proliferation of cells with loss of size, shape, and orientation in comparison to normal tissue maturation; commonly preneoplastic. Reversible


Carcinoma in situ

It is preinvasive. Neoplastic cells have not invaded intact basement membrane. There is an increase in nuclear/cytoplasmic (N/C) ratio and clumped chromatin. Neoplastic cells encompass entire thickness.


Invasive carcinoma

Cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases). Cell-cell contacts lost by inactivation of E-cadherin.



Spread to distant organ (eg metastatic cells in liver parenchyma). Seed and soil theory of metastasis: seed= tumor embolus, soil=target organ, which is often the first-encountered capillary bed (eg liver, lungs, bone, brain).



Also known as multidrug resistance protein 1 (MDR1). Classically seen in adrenal cell carcinoma but also expressed by other cancer cells (eg colon and liver). Used to pump out toxins, including chemotherapeutic agents (one mechanism of a decrease responsiveness or resistance to chemotherapy over time).



One adult cell type is replaced by another. Often secondary to irritation (eg Barrett esophagus) and/or environmental exposure (eg smoking induced tracheal/bronchial squamous metaplasia). Also occurs where two different epithelia meet (eg squamocolumnar junction of the uterine cervix). Reversible



Loss of structural differentiation and function of cells, resembling primitive cells of same tissue; often equated with undifferentiated malignant neoplasms. May see giant cells with single large nucleus or several nuclei. Irreversible.



An uncontrolled and excessive clonal proliferation of cells. Neoplasia may be benign or malignant. Irreversible.



Fibrous tissue formation in response to neoplasm (eg linitis plastica in diffuse stomach cancer). Irreversible.


Grade of tumor

Degree of cellular differentiation and mitotic activity on histology. Usually graded 1-4; 1=low grade, well differentiated; 4=high grade, poorly differentiated, anaplastic. State almost always has more prognostic value than grade.


Stage of tumor

Degree of localization/spread based on site and size of primary lesion, spread to regional lymph nodes, presence of metastases. Based on clinical (c) or pathology (p) findings. Example: cT3N1M0. TNM staging system (Stage=Spread): T=Tumor size, N=Node involvement, M=Metastases. Each TNM factor has independent prognostic value.


Tumor nomenclature

Carcinoma implies epithelial origin, whereas sarcoma denotes mesenchymal origin. Both terms imply malignancy. Most carcinomas spread via lymphatics; most sarcomas spread hematogenously. Terms for non-neoplastic malformations include hamartoma (disorganized overgrowth of tissues in their native location, eg Peutz-Jaghers polyps) choristoma (normal tissue in a foreign location, eg gastric tissue located in small bowel in Meckel diverticulum).



Benign tumor of the epithelium



Benign tumor of the epithelium



Benign tumor of blood vessels



Benign tumor of smooth muscle



Benign tumor of striated muscle



Benign tumor of connective tissue



Benign tumor of bone



Benign tumor of fat



Malignant tumor of the epithelium


Papillary carcinoma

Malignant tumor of the epithelium



Malignant tumor of white blood cells



Malignant tumor of blood cells



Malignant tumor of blood vessels



Malignant tumor of smooth muscle



Malignant tumor of striated muscle



Malignant tumor of connective tissue



Malignant tumor of bone



Malignant tumor of fat


Benign tumor

Usually well differentiated, well demarcated, low mitotic activity, no metastasis, and no necrosis.


Malignant tumor

May show poor differentiation, erratic growth, local invasion, metastasis, and a decrease in apoptosis. Upregulation of telomerase prevents chromosome shortening and cell death.



Weight loss, muscle atrophy, and fatigue that occur in chronic disease (eg cancer, AIDS, heart failure, TB). Mediated by TNF-alpha (nicknamed cachectin), IFN-gamma, IL-1, and IL-6.


Acanthosis nigricans association with neoplasm

Associated with gastrointestinal neoplasms. Rare paraneoplastic indicator of visceral malignancy, but is more commonly associated with insulin resistance.


Barrett esophagus association with neoplasm

Precursor to esophageal adenocarcinoma.


Chronic atrophic gastritis, postsurgical gastric remnants association with neoplasm

Predisposes to gastric adenocarcinoma


Cirrhosis association with neoplasm

Predisposes to hepatocellular carcinoma


Ulcerative colitis association with neoplasm

Predisposes to colon adenocarcinoma


Actinic keratosis association with neoplasm

Precursor to squamous cell carcinoma of the skin. Lesions are usually dry and pale in color, but can also present as hyperpigmented lesions.


Dermato- and polymyositis association with neoplasm

Predispose to visceral malignancies, particularly genitourinary


Dysplastic nevus association with neoplasm

Precursor to malignant melanoma


Multiple seborrheic keratoses association with neoplasm

They are associated with GI, breast, lung, and lymphoid malignancies


Paget disease of the bone association with neoplasm

Predisposes to secondary osteosarcoma and fibrosarcoma


Pulmmer-Vinson syndrome association with neoplasm

Predisposes to squamous cell carcinoma of the esophagus


Tuberous sclerosis association with neoplasm

Often manifests with multiple hamartomatous (benign) tumors including giant cell astrocytomas, renal angiomyolipomas, cardiac rhabdomyomas; tumors may become melanoma


Xeroderma pigmentosum, albinism association with neoplasm

Predispose to squamous cell carcinoma, basal cell carcinoma, and melanoma


AIDS association with neoplasm

Predisposes to aggressive lymphoma (non-hodgkin) and Kaposi sarcoma


Autoimmune diseases (eg Hashimoto thyroiditis and SLE) association with neoplasm

Predispose to lymphoma


Down syndrome association with neoplasm

Predisposes to acute lymphocytic leukemia


Immunodeficiency association with neoplasm

Predisposes to lymphoma, melanoma, renal cell carcinoma


Li-Fraumeni syndrom association with neoplasm

p53 mutation predisposes to various cancer types at a young age (eg sarcoma, breast, leukemia, adrenal gland).


Radiation exposure association with neoplasm

High risk of developing leukemia, sarcoma, papillary thyroid cancer, and breast cancer



Gain of function leads to an increase cancer risk. Need damage to only 1 allele



An oncogene. Gene product is tyrosine kinase. Associated with CML and ALL



An oncogene. Gene product is an anti-apoptotic molecule (inhibits apoptosis). It is associated with follicular and undifferentiated lymphomas



An oncogene. Gene product is a serine/threonine kinase. Associated with melanoma, non-hodgkin lymphoma



An oncogene. Gene product is a cytokine receptor. Associated with gastrointestinal stromal tumor (GIST)



An oncogene. Gene product is a transcription factor. It is associated with Burkitt lymphoma. (burCitt)


HER2/neu (c-erbB2)

An oncogene. Gene product is a tyrosine kinase. It is associated with breast, ovarian, and gastric carcinoma.



An oncogene. Gene product is a transcription factor. It is associated with Lung cancer.



An oncogene. Gene product is a transcription factor, It is associated with Neuroblastoma.



An oncogene. Gene product is a GTPase. It is associated with colon cancer, lung cancer, and pancreatic cancer.



An oncogene. Gene product is a tyrosine kinase. It is associated with MEN 2A and 2B, medullary thyroid cancer.


Tumor suppressor genes

Loss of function leads to an increase cancer risk; both alleles must be lost for expression of disease



A tumor suppressor gene, on chromosome 5. It is associated with colorectal cancer (associate with FAP)



A tumor suppressor gene. BRCA 1 is on chromosome 17, BRCA 2 is on chromosome 13. It is associated with BReast and ovarian cancer. Its gene product is a DNA repair protein.



A tumor suppressor gene, on chromosome 18. It is associated with colon cancer. DCC=Deleted in Colon Cancer.



A tumor suppressor gene, on chromosome 18. It is associated with pancreatic cancer. DPC=Deleted in Pancreatic Cancer



The multiple endocrine neoplasia 1, or MEN1 gene, is located on chromosome 11 and encodes the tumor suppressor protein known as menin. It is associated with MEN type 1 syndrome which is characterized by abnormalities in the parathyroid, pancreas and pituitary glands.



The neurofibromin 1, or NF1 gene, located on chromosome 17, is associated with RAS GTPase activation and is mutated in neurofibromatosis type 1.



The neurofibromin 2, or NF2, located on chromosome 22, codes for a cytoskeletal protein, merlin, and is associated in neurofibromatosis type 2.



The P16 gene, which is located on chromosome 9, is a cyclin-dependent kinase inhibitor and is associated with melanoma.



The P53 gene, located on chromosome 17, regulates cell cycle progression from the G1 to S phase and is involved in most human cancers. Li-Fraumeni syndrome is autosomal dominant cancer syndrome caused by germline mutation of the p53 gene, characterized by an increased risk for developing sarcomas, leukemias, and cancers of the breast, brain, and adrenal glands at young age.



The PTEN gene, located on chromosome 10, is associated with ​breast cancer, prostate cancer, endometrial cancer, and Cowden Syndrome (autosomal dominant disorder in which a hereditary PTEN mutation predisposes patients to breast cancer, follicular thyroid carcinoma, endometrial carcinoma, as well as benign skin tumors and GI hamartomas).



Retinoblastoma, or Rb gene, located on chromosome 13, blocks the G1 to S phase progression and is associated with retinoblastoma and osteosarcoma.



The TSC1 gene, located on chromosome 9, codes for the tumor suppressor protein hamartin and is associated with tuberous sclerosis. This disease is associated with numerous benign, hamartomatous neoplasms, including angiofibromas of the skin, angiomyolipomas of the kidney, rhabdomyomas of the heart, and subependymal giant cell astrocytoma of the brain



The TSC2 gene, located on chromosome 16, codes for the tuberin protein and is associated with tuberous sclerosis. This disease is associated with numerous benign, hamartomatous neoplasms, including angiofibromas of the skin, angiomyolipomas of the kidney, rhabdomyomas of the heart, and subependymal giant cell astrocytoma of the brain.



The von Hippel-Lindau (VHL) gene, located on chromosome 3, normally acts to inhibit hypoxia inducible factor (HIF) 1a. Loss of VHL results in constitutive expression of HIF and excess activation of angiogenic growth factors, resulting in von Hippel-Lindau disease. Neoplasms common to this disease include​ renal cell carcinoma (often bilateral), hemangioblastoma (of the retina, cerebellum, and brain stem), pheochromocytoma, and cavernous hemangiomas of the skin, mucosa, or organs



Wilms tumor proteins, WT1 and WT2, located on chromosome 11, are associated with Wilms tumor (nephroblastoma) in children.


Tumor markers

Tumor markers should not be used as the primary tool for cancer diagnosis or screening. They may be used to monitor tumor recurrence and response to therapy, but definitive diagnosis is usually made via biopsy.


Alkaline phosphatase

A tumor marker of metastases to bone or liver, Paget disease of the bone, seminoma (placental ALP).


alpha- Fetoprotein

A tumor marker of hepatocellular carcinoma, hepatoblastoma, yolk sac (endodermal sinus) tumor, and mixed germ cell tumor. It is normally made by the fetus. Transiently elevated in pregnancy; high levels are associated with neural tube and abdominal wall defects, while low levels are associated with Down syndrome.



A tumor marker of Hydatidiform moles (molar pregnancy) and Choriocarcinomas (Gestational trophoblastic disease), testicular cancer, and mixed germ cell tumor. It is normally produced by syncytiotrophoblasts of the placenta.


CA 15/CA 27-29

A tumor marker of breast cancer.


CA 19-9

A tumor marker of pancreatic adenocarcinoma


CA 125

A tumor marker of ovarian cancer



A tumor marker of medullary thyroid carcinoma.



CarcinoEmbryonic Antigen. It is very nonspecific but is produced by about 70% of colorectal and pancreatic cancers; it is also produced by gastric, breast, and medullary thyroid carcinomas.



A tumor marker of neuroendocrine tumors/carcinoid.



Prostate specific antigen. A tumor marker of prostate cancer. It can also be elevated in BPH and prostatitis. There is questionable risk/benefit for screening.


EBV association with cancer

It is associated with Burkett lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, primary CNS lymphoma (in immunocompromised patients).


HBV and HCV association with cancer

They are associated with hepatocellular carcinoma


HHV-8 association with cancer

It is associated with Kaposi sarcoma


HPV association with cancer

It is associated with cervical and penile/anal carcinoma (types 16 and 18) and head and neck cancer


H. pylori association with cancer

It is associated with gastric adenocarcinoma and MALT lymphoma


HTLV-1 association with cancer

It is associated with adult T-cell leukemia/ lymphoma


Liver fluke (Clonorchis sinensis) association with cancer

It is associated with cholangiocarcinoma


Schistosoma haematobium association with cancer

It is associated with bladder cancer (squamous cell)



Aflatoxins derived from Aspergillus are associated with hepatocellular carcinoma.


Alkylating agents

Alkylating agents used in chemotherapy is associated with leukemia/lymphoma.


Aromatic amines (eg benzidine and 2-naphthylamine)

Aromatic amines, such as benzidine and 2-Naphthylamine, which are used in dyes, are associated with transitional cell carcinoma of the bladder.



Arsenic, which is present in cigarette smoke is associated with angiosarcoma of the liver, lung cancer, and squamous cell carcinoma of skin (In the Victorian era, a form of arsenic was mixed with vinegar and chalk and eaten by women as it was thought to improve complexion.)



Asbestos was widely used in construction and is associated with bronchogenic carcinoma and mesothelioma. Asbestos exposure is more likely to cause bronchogenic carcinoma than mesothelioma.


Azo dyes

Azo dyes are indirect-acting carcinogens that are associated with bladder cancer.


Carbon tetrachloride

Carbon tetrachloride, or CCl4, is associated with centriolobular necrosis and fatty change of the liver. It is a colorless liquid that was used in cleaning agents and fire extinguishers.


Cigarette smoke

Cigarette smoke is the most common carcinogen in the world and can lead to cancer of the following organs: lung (squamous cell carcinoma, adenocarcinoma, small cell carcinoma); larynx/esophagus (squamous cell carcinoma); pancreas (adenocarcinoma); kidney (renal cell carcinoma); bladder (transitional and squamous cell carcinoma); and cervix (cervical carcinoma)



Ethanol is associated with hepatocellular carcinoma and squamous cell carcinoma of the esophagus (especially in conjunction with cigarette smoke).


Ionizing radiation

Exposure to ionizing radiation, especially in childhood, is highly associated with papillary thyroid carcinoma.



Nitrosamines, which are found in processed or smoked foods (especially meats and beer), are associated with gastric cancer.



Radon, a noble gas, is the second leading cause of lung cancer after cigarette smoke.


Vinyl chloride

Vinyl chlorides, which are used to produce PVC pipes, are associated with angiosarcoma of the liver.


Paraneoplastic syndromes associated with Hodgkin lymphoma

Hypercalcemia due to production 1, 25-(OH)2 D3 (calcitriol)


Paraneoplastic syndromes associated with non-Hodgkin lymphoma

Hypercalcemia due to production 1, 25-(OH)2 D3 (calcitriol)


Paraneoplastic syndromes associated with small cell lung carcinoma

Cushing syndrome due to ACTH production, SIADH due to ADH production, Lambert- Eaton myasthenic syndrome (muscle weakness) due to production of antibodies directed against presynaptic Ca channels at NMJ.


Paraneoplastic syndromes associated with renal cell carcinoma

Cushing syndrome due to ACTH production, polycythemia due to erythroprotein production, hypercalcemia due PTHrP


Paraneoplastic syndromes associated with intracranial neoplasms

SIADH due to ADH production


Paraneoplastic syndromes associated with hemangioblastoma

polycythemia due to erythroprotein production


Paraneoplastic syndromes associated with hepatocellular carcinoma

polycythemia due to erythroprotein production


Paraneoplastic syndromes associated with leiomyoma

polycythemia due to erythroprotein production


Paraneoplastic syndromes associated with pheochromocytoma

polycythemia due to erythroprotein production


Paraneoplastic syndromes associated with squamous cell lung carcinoma

hypercalcemia due PTHrP


Paraneoplastic syndromes associated with breast cancer

hypercalcemia due PTHrP


Psammoma bodies

Laminated, concentric spherules with dystrophic calcifications. Seen in (PSaMMoma): Papillary carcinoma of the thyroid, Serous papillary cystadenocarcinoma of ovary, Meningioma, Malignant mesothelioma.


Most common cancers in men

1. Prostate, 2. Lung, 3. Colon/ rectum. Lung cancer incidence has dropped in men but has not changed significantly in women.


Most common cancers in women

1. Breast, 2. Lung, 3. Colon/rectum


Mortality of cancers in men

1. Lung, 2. Prostate, 3. Colon/ rectum


Mortality of cancers in women

1. Lung, 2. Breast, 3. Colon/ rectum


Common metastases of the brain

In order of most common at least: Lung, breast, prostate, melanoma, and GI. 50% of brain tumors are from metastases. Commonly seen as multiple well-circumscribed tumors at gray/white matter junction.


Common metastases of the lung

In order of most common at least: Colon (most common by far), stomach, pancreas. Liver and lung are the most common sites of metastasis after the regional lymph nodes.


Common metastases of bone

In order of most common at least: prostate and breast, lung, thyroid, and kidney. Bone metastasis is much more common than primary bone tumors (eg multiple myeloma, lytic). Common mets to bone: breast (mixed), lung (mixed), thyroid (lytic), kidney (lytic), prostate (blastic). Predilection for axial skeleton.