Good Cells Gone Bad Flashcards
What is neoplasia?
•Neoplasia
–Literally, new growth
•Tumor
–Literally, swelling
–Non-specific term that is now near-synonymous with neoplasm
•Not all new growth is neoplastic: wound healing and repair
Examples of growth that are not neoplastic: scabs, a form of secondary intention. It occurs under very certain physiological conditions.
Not all new growth is neoplastic:
- wound healing and repair
- Hyperplasia: increase in number of cells in an organ/tissue
–Occurs in response to stimulus
–Ends when stimulus removed
•Hypertrophy: increase in cell size
–Result of increased production of proteins inside the cell
–No cell division
- Hypertrophy and hyperplasia both result in increase in size of organ
- Hypertrophy and hyperplasia frequently occur together
- Metaplasia: reversible change in which one differentiated cell type is replaced by another
–Nearly always found in association with tissue damage/repair/regeneration
–Typically replacing cell type better suited to alterations in local environment
- Underlying stem cells reprogrammed to differentiate along new pathway
- Pregnancy
Examples of growth that are not neoplastic: scabs, a form of secondary intention. It occurs under very certain physiological conditions.
Physiologic hyperplasia of breast tissue under influence of estrogen/progesterone during menstrual cycle
What organ undergoes pathologic hyperplasia? Maternal breast tissue, endometrium, BPH (benign prostatic hyperplasia)
Metaplasia: Normal columnar cells of trachea/bronchi (w/ cilia) replaced by stratified squamous epithelium (more rugged) in smokers
Cancer has stem cells that populate new cells in a tissue
Cross section; “Four-chamber cut”
These are examples of hypertrophy. Hypertension increases resistance on heart and causes it to work harder. It’s just like working out any other muscle in the body.
Not all new growth is neoplastic: metaplasia (Example)
Normally we have columnar epithelium (why? Cilia brushes things away). Upon smoking damage, however, they are replaced with squamous cells. This is why they cough, there is no cilia brushing away debris. It’s the stem cells that grow and replace the normal columnar epithelium.
Not all new growth is neoplastic: metaplasia (Ciliated cell metaplasia in salivary duct cysts)
Not normally surrounded with cilia. Under a metaplastic change, cells adapt to have cilia to brush away the irritant/mucous plug blocking the duct.
Stem cells
•In adults, present (small percent) in all tissues that continuously divide (bone marrow, skin, GI tract lining…)
–Responsible for generating differentiated cells of a tissue
–Characterized by self-renewal properties
So, what is neoplasia?
•Sir Rupert Willis (1930s)
–A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change
- Pretty good for the pre-molecular era!
- Disorder of cell growth triggered by series of genomic alterations
–Excessive proliferation is independent of and uncontrolled by physiologic growth signals, such as in wound healing
–Alterations give neoplastic cells survival and growth advantage
–Alterations affect a single cell and its clonal progeny
•Neoplasms are clonal
Chemotherapy targets cell proliferation
Neoplasms: benign and malignant
•Patients with benign neoplasms generally survive
–Remains localized/does not spread to other sites (does not metastisize)
–Well-circumscribed growth that is non-infiltrative
–Usually amenable to surgical removal
•Malignant neoplasm: cancer
–Invasive growth that can destroy adjacent tissues
–Can spread to distant sites (metastasize)
–Treatment algorithm complicated, especially in advanced stage disease
–Can cause death
•However:
–May occasionally be quite small and treated conservatively
When explaining metastasis, you refer to the originating location of the cancer as the “primary site”
- meaning of non-infiltrative: cancer comes from the word crab, meanng going all over.
“Malignant neoplasm” is synonymous with “cancer”
Cancer also means “crab”; thinking of all the arms of a crab, cancer finds a way to infiltrate itself into the body.
Ameloblastoma
Ameloblastoma, characterized by locally accelerated growth…but it’s not cancer
38 YOF with history of polyostotic fibrous dysplasia
Lower left portion of the jaw shows a large radiolucency
- polyostotic; multiple bones involved.
Secondary osteosarcoma arising in fibrous dysplasia
Squamous cell carcinoma in 34 YOM with no symptoms
Can be mistaken as simply friction, callous from rubbing up against the teeth; a biopsy is needed.
Rapidly growing, painful nodule in 67 YOF: metastatic lung adenocarcinoma
metastasized from lung cancer!
- lung adenocarcinoma is primary that metastasized and spread to the gingiva.
Basal cell carcinoma has low metastatic potential and is treated by conservative removal in vast majority of cases
Typically exhibit very indolent growth patterns.
Benign vs. malignant: clinical features
•Painting in broad brush strokes…..
–Small (b) vs. large (m)
–Expansile (b) vs invasive (m)
–Slow growth (b) vs. rapid growth (m)
–Not metastasizing (b) vs. metastasizing (m)
Expansile referring to a very uniform, or concentric growth pattern
Lipoma
Liposarcoma
Why might the inside of a tumor or cancer source be necrotic: there is a lack of blood supply because it is growing so fast it outgrows its ability to grow blood system.
All malagniies in salivary galnds are……….
Adenocarcinoma
Benign vs. malignant: microscopic features
- Encapsulated vs. infiltrative
- Well-differentiated (resembling normal tissue) vs. poorly-differentiated (not resembling normal tissue)
–Typical organization vs. Atypical tissue structure
–Rare, normal mitoses vs. Frequent, abnormal mitoses
•Histologic features of malignancy
–Pleomorphism: variable size and shape of cells/nuclei
–High nuclear/cytoplasmic ratio
–Loss of identifiable differentiation
Benign vs. malignant
- Look at it yourself. Just review of what we just went over.
Benign neoplasms: basic vocabulary
•Attach suffix –oma to name of originating cell type
–Lipoma, osteoma, hemangioma…
•Unfortunately, historical exceptions exist (Let Me be Malignant)
–►Lymphoma: malignancy of lymphocytes
–►Melanoma: malignancy of melanocytes
–►Mesothelioma: malignancy of mesothelium
Hemangioma: neoplasms of blood vessels, typically occurs is congenital or infantile
Malignant neoplasms:
basic vocabulary
•Suffix varies based on tissue origin
–Carcinoma: epithelial origin
•Adenocarcinoma: epithelial malignancy growing in a glandular pattern (breast, pancreas, endometrium, lung, etc.)
–-sarcoma: mesenchymal origin (ex. osteosarcoma)
–►Leukemia/lymphoma: blood-forming cells origin
–►Melanoma: melanocytic origin
——————–
You can have different regions of cancerous tissue being both squamous carcinoma and adenocarcinoma (due to hyperplasia)
Adenocarcinoma
►Adenocarcinoma: epithelial malignancy growing in a glandular pattern (breast, pancreas, endometrium, lung, etc.)
►All the malagnincies in the salivary glands are adenocarcinomas. Salivary glands have epithelial cells and the serve a separatory function.
If he doesn’t take the time to talk about it, then you don’t need to take the time to study it, but it’s here becasue knowledge is good.
Vocabulary: examples
- Fibroma, fibrosarcoma: fibroblasts
- Lipoma, liposarcoma: adipose tissue
- Chondroma, chondrosarcoma: cartilage
- Osteoma, osteosarcoma: bone
•Hemangioma, angiosarcoma: blood vessels. (Exception, becomes angio for malignant)
- Leiomyoma, leiomyosarcoma: smooth muscle
- Rhabdomyoma, rhabdomyosarcoma: skeletal muscle
- Adenoma, adenocarcinoma: glandular epithelium (of any origin)
- he didn’t spend much time on this.
Dysplasia: intraepithelial neoplasia
•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
Dysplasia to Carcinoma
Notice the areas of infiltrated growth (circled)
Dysplasia becoming carcinoma is like the fence getting broken through!
Carcinoma in situ:
Very commonly used term in surgery
Other words you should be
aware of…Teratoma
•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)
Other words you should be
aware of…Hamartoma
•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.
Other words you should be
aware of…Choristoma
•Choristoma: benign proliferation of cells in non-native site
–For example, small nodule of pancreatic tissue in submucosa of stomach
Epidemiology of cancer
•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
Lifetime risk of developing or dying from cancer
•Males
–Risk of developing: 42%
–Risk of death: 22%
•Females
–Risk of developing: 38%
–Risk of death: 19%
Prostate, lung, colon, breast cancer: ~50% of cancer diagnoses/deaths in USA
Memorize these four cancers; together they are about half of all cancer diagnoses and deaths related to cancer
Some cancers are more aggressive than others
Basal cell carcinoma and
squamous cell carcinoma of skin
•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
Cancer survival
•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
Cancer and age
•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
Rate of Cell Division vs. Cancer Risk
•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
Stem cells and cancer
•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
Environmental factors
•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
Cancer incidence in males
Environmental factors:
infectious agents
•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
Environmental factors: tobacco
•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.
Environmental factors: alcohol
•Increased risk of cancers of
–Oral cavity
–Pharynx
–Larynx
–Esophagus
–Liver
•Alcohol and tobacco synergistically increase risk of cancers in upper aerodigestive tract
Environmental factors: obesity
•Weight strongly associated with cancer risk
–15-20% of cancer deaths attributed to obesity
Environmental factors:
reproductive history
•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
Worldwide incidence of breast cancer
Environmental factors:
environmental carcinogens
•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)
Acquired predisposing conditions: chronic inflammation
•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
Gastric reflux: increased risk of esophageal carcinoma
Mucosal lining is changed (Barrett’s esophagus) to bare the acidity of the reflux
Acquired predisposing conditions: immunodeficiency states
•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
Acquired predisposing conditions: precursor lesions
- Benign neoplasia
- Hyperplasia
- Metaplasia
- Dysplasia
Some benign neoplasia will never turn malignant, some can
Acquired predisposing conditions: benign neoplasia
Colonic adenoma (colon polyp): 5-50% progress to carcinoma (depending on subtype) if untreated
Acquired predisposing conditions: metaplasia
Barrett esophagus: 30x greater risk of developing esophageal cancer (and it looks like gastric adenocarcinoma)
Acquired predisposing conditions: dysplasia
