Good Cells Gone Bad Flashcards

Question

**Dysplasia: intraepithelial neoplasia**

Answer 1

**•Precursor lesion to carcinoma** * Genetically altered cells are **confined to epithelium by basement membrane** * **Barrier function of basement membrane** in dysplasia of utmost clinical significance –**Dysplasia cannot grow aggressively or metastasize (yet)** –The patient can be cured by surgical excision ------------------------- Image is a white spot clinically referred to as leukoplakia

Answer 2

------------------------ Notice the areas of infiltrated growth (circled) Dysplasia becoming carcinoma is like the fence getting broken through!

Answer 3

--------------- Very commonly used term in surgery

Answer 4

•**Teratoma**: benign tumor containing cells/tissues from more than one germ layer –(Germ layers: endoderm/mesoderm/ectoderm ) –Unique because nearly all neoplasms consist of cells from single germ layer –Originates from germ cells •**Totipotential** stem cells normally present in testes and ovaries ---------------- Teratomas are rare because **neoplasia is clonal,** it’s produced by one cell line. Pluripotency is when teratomas can arise Examples of teratomas (cells have differentiated into hair follicles, teeth, etc)

Answer 5

**•Hamartoma:** benign proliferation of cells indigenous to involved site –Typically considered type of neoplasm as most are clonal ---------------- Most common is odontoma, benign toothlets (image)…..redundant word.

Answer 6

**•Choristoma**: benign proliferation of cells in non-native site –For example, small nodule of pancreatic tissue in submucosa of stomach

Answer 7

**•Cardiovascular disease leading cause of death in US** **•Cancer is the second leading cause of death in US** –$88.7 billion in health care costs –Leading cause of death worldwide

Answer 8

•Males –Risk of developing: 42% –Risk of death: 22% •Females –Risk of developing: 38% –Risk of death: 19%

Answer 9

Memorize these four cancers; together they are about half of all cancer diagnoses and deaths related to cancer

Answer 10

•By far, the most common human cancers –BCC: up to 4.3 million cases per year in US –SCC: up to 1.1 million cases per year in US •Never included in cancer registries or epidemiology statistics –Typically very indolent –Far more common than all other cancers -------------------- BCC: Basal carcinoma of the skin SCC: Squamous carcinoma of the skin These are so common that epidemiologists do not include it is cancer registries/statistics

Answer 11

**•In the last 20-25 years, overall cancer death rate has decreased** **–Decreased use of tobacco products** •Reduction in lung cancer deaths **–Papanicolaou (Pap) smear test** **•Sharp decline in cervical cancer deaths** –Improved detection/treatment •Reduction in prostate, colorectal, breast cancer deaths

Answer 12

•Most cancers occur over 55 years of age –Men aged 60-79: main cause of death –Women aged 40-79: main cause of death •Explained by: **–Accumulation of genomic alterations in (stem) cells over lifetime** **–Decline in immune system competence** **•Sadly, cancer accounts for 10% of all deaths in children as well**

Answer 13

**•Number of cell divisions normally occurring by stem cells present in adult tissues varies according to tissue type** **•There exists a strong correlation (0.8) between average number of stem cell divisions per tissue and rate/risk of cancer in that tissue**

Answer 14

•Carcinogenesis results from accumulation of complementary genomic alterations –These alternations must be accumulated in a stem cell (or a non-stem cell that acquires stem-like properties) •Broadly speaking, genomic (genetic and epigenetic) alterations come from three sources –Inherited/hereditary genetic mutations **•5-10% of cancer have hereditary component** –Induced by environmental factors (Ex: UV light) –Result from **DNA replication errors** during (stem) cell division * Approximately 65-70% of mutations in human cancers * **Approximately 3 mutations** and an unknown number of epigenetic alterations occur every time a normal human stem cell divides

Answer 15

**•Remarkable geographic variation in cancer incidence** –Evidence of role of environmental carcinogens **•Environmental influences appear to be dominant risk factors for many cancers** **–Approximately 20-40% of cancers may be preventable**

Answer 16

•15% of cancers worldwide caused by infectious agents –30-45% of cancers in the developing world •Many individuals infected with hepatitis C virus (HCV) may develop hepatocellular (liver) carcinoma **•Human papillomavirus (HPV)** **–Cause of cervical carcinoma** –Cause of increasing fraction of head and neck cancers •Oropharynx, in particular (alternative sexual practices) –Incidence of HPV-positive **oropharyngeal cancer has now surpassed incidence of cervical carcinoma** (because of pap smears) -------------------- - HPV uniformly causes cervical cancers

Answer 17

**•Single most important factor contributing to premature death in US** **•Implicated in 90% of lung cancer deaths** •Also implicated in cancers of –Oral cavity –Pharynx –Larynx –Esophagus –Pancreas –Bladder ---------------------- Why might smoking cause bladder cancer? Toxic metabolites excreted through urine.

Answer 18

•Increased risk of cancers of –Oral cavity –Pharynx –Larynx –Esophagus –Liver •Alcohol and tobacco synergistically increase risk of cancers in upper aerodigestive tract

Answer 19

•Weight strongly associated with cancer risk –15-20% of cancer deaths attributed to obesity

Answer 20

**•Cumulative exposure to estrogen stimulation increases risk of breast and endometrial cancer** –½ the risk of breast cancer if age at first full-term pregnancy \< 20 years compared to \> 35 years •Postmenopausal hormone replacement therapy: increases risk of breast cancer ------------------- Earlier pregnancies and more frequent pregnancies disrupt the estrogen levels associated with a regular menstrual cycle, thus decreasing the risk of developing breast cancer

Answer 21

•Already discussed several –Tobacco, alcohol, dietary fat •Many other carcinogens well-characterized –In environment: UV rays, smog –In workplace: asbestos –Diet: grilled meat, fat, alcohol ------------- Picture is of a truck driver, left side of his face is much more worn than the other; emphasizes the impact the environment has. (not a picture of cancaer though)

Answer 22

•Chronic inflammation (infectious or non-infectious) **–Increased cell proliferation to repair damage** •Increased opportunity for genetic mutations –Activated immune cells **•Produce reactive oxygen species that are directly genotoxic** Alcoholism -\> pancreatitis: increased risk of pancreatic carcinoma

Answer 23

------------- ## Footnote Mucosal lining is changed (Barrett's esophagus) to bare the acidity of the reflux

Answer 24

•Intact immune system, in particular **intact T-cell immunity**, critical for normal cell surveillance **•Deficits in immune function associated with increased cancer risk** –HIV/AIDS –Chronic pharmacologic immunosuppression

Answer 25

* Benign neoplasia * Hyperplasia * Metaplasia * Dysplasia ------------- Some benign neoplasia will never turn malignant, some can

Answer 26

Colonic adenoma (colon polyp): 5-50% progress to carcinoma (depending on subtype) if untreated

Answer 27

Barrett esophagus: 30x greater risk of developing esophageal cancer (and it looks like gastric adenocarcinoma)