Bikman - Neoplasms Flashcards
Benign tumor
Remains localized; easily removed. • Small • Slow growing • Non-invasive • Well-differentiated • *Local growth*
Malignant tumor
Cancer. Invasive and destructive to adjacent tissue. • Large • Usually faster growing • Invasive • Poorly differentiated • Metastasis
Examples of benign tumors
Adenoma
Leiomyoma
Chondroma
Adenoma
Benign tumor in glandular cells
Leiomyoma
Benign tumor in SM cells
Chrondroma
Benign tumor in chondrocytes
Papilloma
Nipple or finger-like fronds
Polyp
Projects outward, forming a lump
Cystadenoma
Has hollow spaces inside (may be filled with fluid)
Histiologic characteristics of malignant tumors
Anaplasia Pleomorphism Prominent nuclei Hyperchromatism High nuclear to cytoplasmic ratio May be aneuploid
Anaplasia
Complete lack of differentiation
Pleomorphism
Cells aren’t shaped the right way
Malignant Tumors
Carcinoma
Sarcoma
Carcinoma
Malignant tumor in epithelial tissue
Adenocarcinoma
Malignant tumor of glandular cells
Squamous cell carcinoma
Malignant tumor of squamous cells
Sarcoma
Malignant tumor in mesenchymal tissue
Chondrosarcoma
Malignant tumor of chondrocytes
Angiosarcoma
Malignant tumor of BVs
Rhabdomyosarcomma
Malignant tumor of skeletal tissue
Mixed tumors
Show divergent differentiation
Pleomorphic adenoma
Fibroadenoma
Pleomorphic adenoma
Mixed tumor
Glands + Fibromyxoid stoma (fibroblasts + mucous)
What are some malignancies that sound benign?
Lymphoma
Mesothelioma
Melanoma
Seminoma
What are some non-tumors that sound like tumors?
Hamartoma (mass of disorganized indigenous tissue)
Choristoma (‘normal’ cells growing elsewhere)
What are some names that seem to come out of nowhere?
Leukemia
Hydatidiform mole
What is differentiation? Are malignant or benign cells well or poorly differentiated?
The degree to which a cell resembles the cell of origin.
Benign: well differentiated
Malignant: poorly differentiated
What are some features of anaplasia?
Pleomorphism Hyperchromatic, large nuclei Bizarre nuclear shapes Lots of mitoses and atypical mitoses Architectural anarchy
What is dysplasia and what is it used to describe?
Disorderly growth
Used to describe disorderly changes in non-neoplasic epithelial cells
What is CIS and what are some of its features?
Carcinoma in situ.
A severe form of dysplasia, which isn’t yet cancer, but like a step right before cancer.
Features: Pleomorphism Hyperchromatic Lots of mitoses Architectural anarchy
What factors does the rate of growth depend on?
Blood supply
Hormonal factors
Growth fraction (portion of cells that are actively dividing)
What is metastasis and what does it depend on?
Development of secondary tumor implants in distant tissues.
Depends on:
Degree of differentiation of tumor
Type of tumor
Size of tumor
What are the three means of metastasis?
Seeding
Lymphatic spread
Hematogenous spread
What is seeding and what is an example of a cancer that spreads this way?
Tumor invades body cavity.
Bits break off and implant on peritoneal surfaces.
Ovarian cancer spreads this way.
What is lymphatic spread and what is an example of a cancer that spreads this way?
Tumor spreads to local lymph nodes.
Sentinel lymph node first.
Moves through thoracic duct.
Empties into subclavian vein.
Carcinomas tend to spread this way.
What is hematogenous spread and what is an example of a cancer that spreads this way?
Veins are easier to invade than arteries.
Liver and lungs are the most common metastatic tumors.
Some tumors like other sites better:
- Prostate –> bone
- Most lung cancers –> adrenals, brain
Sarcomas like to spread this way (but so do carcinomas).
Sarcomas metastasize to the lungs this way.
What is the most common cancer in men and women?
Men: Prostate
Women: Breast
What is the deadliest cancer in men and women?
Both: Lung
What are environmental variables in cancer and what type are they typically linked to?
Sun = skin Smoking = lung Alcohol = liver, pancreas, breast cancers
How are insulin resistance and cancer related?
The more insulin resistant an individual is, the more likely they are to develop cancer or to have a poor prognosis.
What is the “Warburg effect”?
Cancer cells use glucose.
Insulin resistance/T2 Diabetes is a ‘perfect storm’ for cancer.
Glucose and insulin provide the fuel and allow growth for cancer.
What are the three categories of heredity in cancer?
- Inherited cancer syndromes
- Familial cancers
- Syndromes of defective DNA repair
What are some examples of inherited cancer syndromes?
Tend to be Autosomal Dominant.
Retinoblastoma
Familial polyposis coli
Neurofibromatosis
What are some examples of familial cancers?
Breast
Colon
Ovary
Brain
Occur earlier with greater mortality
What are some examples of syndromes of defective DNA repair (hereditary cancer)?
Tend to be Autosomal Recessive
Xeroderma pigmentosum
What are paraneoplastic syndromes?
The indirect effects of a tumor that occur distant to the tumor.
- Likely a consequence of proteins, polypeptides, or hormones secreted by the tumor
- Usually precede dx/ID of malignancy
- Can be a sign of malignancy
(The body is experiencing consequences of the tumor)
What are the three most common neoplastic syndromes?
Endocrinopathies
Nerve and Muscle Syndrome
Dermatologic Disorders
What are mutations that can cause proto-oncogenes to transition to oncogenes?
Pathogens Toxins Radiation Aging Sexual Activity Physical Inactivity
Where are the two checkpoints in the cell cycle?
Between G2 and M
Between G1 and S
What phase of the cell cycle does p53 and Rb regulate?
G1
What is the function of p53 and Rb?
Inhibit the cell cycle
What is the function of Ras?
To inhibit p53 and Rb, thus allowing the cell cycle to start up
What do oncogenes cause that contribute to cancer?
- Autonomous growth
- Insensitivity to growth inhibitory signals
- Evasion of apoptosis
- Limitless replication
- Sustained angiogenesis
- Invasion and metastasis
What are the causes of autonomous growth? Which oncogene is compromised to allow for this?
- Increased secretion of growth factors (autocrine stimulation)
- Increased growth factor receptors
- Signal from cell-surface receptor it mutated into the on position
- Activation of cell signals that drive the cell cycle
Ras is mutated, which allows for autonomous growth.
Proto-oncogenes vs. Oncogenes
Proto-oncogenes - A normal gene whose product limits cell growth
Oncogenes - mutated proto-oncogenes that allow cells to grow unchecked. Cells lose the ability to restrict growth
Which proto-oncogene is the “Guardian of the genome”?
p53
Most common mutation
What are the four main apoptotic proteins that can undergo mutation? What happens when they mutate?
Fas
Executioner caspases
BCL2 family
p53
Cells become immortal when these proteins mutate
Autonomous Growth
Cancer cells
- Make their own growth factors
- Receptors may be overexpressed or always on
- Signal-transducing proteins may always be on
- Nuclear transcription factors may always be expressed
- Cyclins may be overactive
Insensitivity to growth inhibition
Proto-oncogenes –> Oncogenes –> Oncoprotein
Oncogenes - cells lose the ability to restrict growth
p53 and Rb allow cells to grow unchecked, when they usually would be stopped
Evasion of apoptosis
Apoptotic proteins are mutated and allow cancer cells to become immortal
Limitless replication
Telomere shortening leads to cell cycle arrest
- p53 and Rb
Stem cells and cancer cells use telomerase to maintain telomere length
Sustained angiogenesis
Tumors need blood to deliver enormous amounts of nutrition.
Tumor cells secrete VEGF (primary angiogenic hormone)
Can’t grow over 1-2cm without a blood supply
Tumor BVs are abnormal (chaotic)
Invasion and Metastasis
To invade, cells must:
- Loosen contact between cells
- Degrade ECM
- Migrate
Where do circulating cancer cells usually settle?
Nearest capillary bed
Some display tropism (preference for certain sites)
What are some necessary steps to cancer?
- Accumulation of multiple mutations (Avg # is 90)
- Mutations within cell cycle checkpoint/guardian gene
Chromosomal translocation vs. deletion
And genetic damage from them
Translocations - more commonly in hematopoietic malignancies; Philadelphia chromosome
Deletions - deletion of part or all of a chromosome; usually a tumor suppressor gene (p53); Retinoblastoma
Genetic damage:
- Subtle - invisible on a karyotype (point mutation)
- Large - visible on a karyotype (duplication)
Chemical carcinogens
Direct acting vs. Indirect acting
What do they bind/affect and what are important targets?
Direct
- Lethal as is
- Most are chemotheraphy drugs
- Cause secondary malignancy (i.e. leukemia)
Indirect
- Require a chemical conversion: hydrocarbons, aflatoxin B, nitrites
Both bind and affect DNA
Important targets: p53, Ras
How does radiation contribute to cancer development?
Emission from x-rays, radioisotopes, and other radioactive sources.
Exposure causes gene mutations and chromosome aberrations.
- Causes pyrimidine dimers formation
- Repair pathways usually fix it, but they can become overwhelmed
i.e. Squamous cell carcinoma, melanoma
What viral infections can contribute to cancer development? Which cancers?
HTLV-1: T-cell lymphoma HPV: Cervical and oropharyngeal cancers EBV: Various lymphomas HBV and HCV: Hepatocellular carcinoma H. pylori: Gastric cancer, lymphoma
Grading
Appearance
Pathological evaluation
Can reveal mitosis, pleomorphism, necrosis, etc.
LESS useful than staging
Staging
Metastasis
TNM system
MORE useful than grading
