Neoplasia Flashcards
Neoplasia definition
Uncontrolled growth of cells
Normal regulation of proliferation fails
Cell growth is autonomous, excessive, and disorganized
Tumor definition
Proliferation of neoplastic cells that forms a mass
Cancer definition
Malignant neoplasms
Benign versus malignant neoplasm
Benign: limited growth potential, typically good outcome, no metastases
Malignant: uncontrolled growth and spread, potential to kill host, can metastases
Metastasis definition
Spread of a neoplasm from one site in the body to another
Only malignant neoplasms are capable of doing this
Gross appearance of benign versus malignant tumors
Benign: smooth borders, looks the same throughout
Malignant: infiltrative border, spreads into other tissues, hemorrhage and necrosis, can get into blood and lymph vessels
Epithelial tumors
Benign ones are often called adenomas
Benign ones in the skin, urinary bladder, and larynx that protrude above the surface are often called papillomas
Malignant ones are called carcinomas
Epithelial tumor classification:
- Glands/ducts
- Squamous epithelium
- Transitional cells
- Neuroendocrine cells
- Liver cells
- Kidney cells
- B: adenoma, M: Adenocarcinoma
- B: Squamous papilloma, M: squamous cell carcinoma
- B: Transitional cell papilloma, M: transitional cell carcinoma
- B: neuroendocrine tumor, M: small or large cell neuroendocrine carcinoma
- B: Hepatocellular adenoma, M: hepatocellular carcinoma
- B: Renal adenoma, M: renal cell carcinoma
Mesenchymal tumors
Neoplasms originating from connective tissues such as adipose, bone, muscle
Ending in -oma
Mesenchymal tumor classification:
- Fibroblast
- Fat cell
- Blood vessel
- Smooth muscle
- Striated muscle
- Cartilage
- Bone
- B: fibroma, M: fibrosarcoma
- B: lipoma, M: liposarcoma
- Hemangioma, angiosarcoma
- Leiomyoma, leimyosarcoma
- Rhabdomyoma, Rhabdomyosarcoma
- Chondroma, chondrosarcoma
- Osteoma, osteosarcoma
Benign versus Malignant tumors in:
- Neural cells
- Glial and neural support cells
- Germ cells
- Melanocytes
- Mesothelium (only M)
- Ganglioneuroma, neurblastoma
- Glioma, glioblastoma multiforme
- Teratoma, seminoma or embryonal carcinoma
- Melanocytic nevus, melanoma
- M = mesothelioma
Teratoma
Benign tumor derived from germ cells
Contains tissue formed from all 3 germ layers (ecto, meso, endoderm)
Ovary most common
Contain teeth, hair, skin, etc
Blastoma
Tumors composed of embryonic cells originating from embryonic primordia
Mostly in children
Eponymic tumors (3 examples)
Carry name of physicians who described them first
Hodgkin’s disease: a type of lymphoma
Ewing’s sarcoma: type of bone sarcoma
Kaposi’s sarcoma: type pf vascular malignancy
What is grading versus staging based on?
Grading: based on histologic examination
Staging: based on clinical assessment during gross examination, surgery, x-rays, etc
What does TMN stand for?
T = size and local invasiveness of tumor N = presence of lymph node metastases M = distant metastases
Grading
Degree of differentiation (well to poor)
Based on tissue architecture, mitoses, degree of cell atypia
Low grade looks like normal tissue
Less important than staging with a few exceptions
Staging
TNM
T1-4 based on size of tumor or depth of invasion
N0-N3 based on number and location of involved lymph nodes
M0-M2 based on presence, location, and number of metastases
More prognostic significance than grade (usually)
Metastasis definition
The process of malignant cells moving from one site in the body to another site
3 pathways of metastasis
- Lymphatics
- Blood (hematogenous spread)
- Seeding of the surface of the body cavities
To metastasize, a tumor (clone) must be able to…
Escape the immune system
Be capable of entering the bloodstream/lymph/body cavity
Arrive at the new site, invade and be capable of forming a new blood supply (angiogenesis)
3 general classes of exogenous causes
Chemical agents
Physical agents
Biologic agents
2 classes of endogenous causes
Oncogenes
Tumor suppressor genes
Examples of chemical carcinogens (4)
- Polycyclic aromatic hydrocarbons (3,4-benzopyrene from tobacco tar, aflatoxin from fungus)
- Aromatic amines (Beta napthylamine from rubber and dye industry)
- Nitrosamines (nitrates from food additives)
- Steroid hormones (estrogens from hormone replacement therapy)
Carcinogen
Absorbed either preformed or in the form of procarcinogen (transformed into active carcinogen)
Carcinogen action
- Initiation (genetic change induced in cell)
- Promotion (initiated cell promoted to grow)
- Coversion (change into new cell type)
- Progression (cells proliferate following removal of initiating carcinogen and promoters)
- Clonal expansion
4 physical carcinogens
- UV light
- X-rays
- Radioactive isotopes
- Atomic bomb
3 Natural biologic carcinogens
- Aflatoxin (derived from fungus Aspergillus flavus; contaminated peanut a source, acts as liver carcinogen)
- Schistosoma haematobium (parasite; acts as urinary bladder carcinogen)
- Opisthorchis sinensis (chinese liver fluke; acts as carcinogen for bile duct or liver)
Human carcinogenic DNA (3) and RNA (1) viruses
- HPV (warts, cervical cancer, oropharynx cancer)
- Epstein-Barr virus (lymphomas, nasopharyngeal carcinoma)
- Hep B (liver cancer)
- Human T-cell leukemia/lymphoma virus
Clinical manifestations of neoplasia
Local (effects due to invasion or compression of adjacent normal tissues)
Systemic (cachexia and paraneoplastic syndromes)
Cachexia
Wasting caused by cancer
Weight loss, weakness, fatigue
Paraneoplastic syndromes
Caused by substances secreted by cancer (often hormones)
Incidence
Number of new registered cases over specific time in a defined population
Prevalence
Number of all cases, new and old, within defined population at defined time
Oncogenes
Genes that promote autonomous cell growth in cancer cells
Abnormally activated forms of proto-oncogenes
Proto-oncogenes
Normal genes
Have roles in normal cells that are related to growth and proliferation
Proteins encoded by them may be growth factors, their receptors, signal transducers, transcription factors, or cell cycle components
Oncoproteins
Protein products of oncogenes
Similar to normal products of proto-oncogenes, but lack important internal regulatory elements
Act independently of growth factors and other external signals
Can make cell growth autonomous
4 mechanisms of the transformation of proto-oncogenes into oncogenes
- Point mutation
- Gene amplification
- Chromosomal rearrangment
- Insertion of viral oncogene
Point mutation
A single base substitution in the DNA
Results in a miscoded protein, typically with an amino acid substituted with another
Common mutations in RAS and RAF gene families
Gene amplification
The cell acquires an increased number of copies of the proto-oncogene
The more copies of the oncogene, the more malignant the cell becomes
Chromosomal rearrangements
A translocation can occur where one chromosome fragment attaches to another, juxtaposing two genes
A deletion can also result in a juxtaposition
The resulting gene complexes can cause overexpression of proto-oncogenes, due to stimulation by the adjacent promoter gene
Insertion of viral genome
Insertion of portions of the viral genome disrupts normal chromosomal architecture
Changes can accumulate gradually in slow transforming viruses such as hep B
Tumor suppressor genes
Normal cells have regulatory mechanisms that protect cells against activated or newly acquired oncogenes
Their products apply brakes to cell proliferation
Retinoblastoma gene (RB-1)
Found in patients with pediatric eye tumor retinoblastoma
Its a tumor suppressor gene
Hereditary version - already only have 1 copy of the gene
Often die of other tumors - osteosarcoma
Product regulates the checkpoint between G1 and S
When it is not functioning, the cell will proliferate without regulation
TP53
p53 is the protein product
Probably the most important TSG
3 actions p53 does after sensing DNA damage
- Activates temporary cell cycle arrest (quiescence)
- Induces permanent cell cycle arrest (senescence)
- Triggers apoptosis
Neurofibromatosis 1
Numerous subcutaneous neural sheath tumors (neurofibromas) and cafe-au-lait macules
Patients can develop other tumors
NF1 is a TSG inactivating signal transduction by the RAS proto-oncogene
NF1 gene which is defective or lost results in tumor formation
Familial Adenomatous Polyposis Coli
Defects in the tumor suppressor gene APC
Innumberable colonic polps by age 20
Most patients will die of colon cancer without colectomy at an early age
Wilms’ tumor
Malignant kidney tumor of childhood
Caused by defects in the tumor suppressor gene WT1
Hereditary breast cancer
Most common cause is defects in TSG Braca 1 and 2
Much higher chance of getting breast cancer
Many elect to have a prophylactic bilateral mastectomy
What are CEA and AFP markers for?
CEA (carcinoembryonic antigen): marker for adenocarcinoma of colon
AFP (Alpha-fetoprotein): marker for heptaocellular carcinoma and certain germ cell tumors that contain yolk sac components
Keytruda (pemrolizumab)
Inhibit PD-1 receptor, cannot interact with ligand on tumor cells, immune cells can kill!
Just induces remission for a couple of months
Can get hypersensitivity reactions to it
Cushing’s syndrome
Small cell carcinoma of the lung
Hypercalcemia
Squamous cell carcinoma of the lung
Polycythemia
Renal cell carcinoma
Venous thrombosis
Pancreatic carcinoma
Myasthenia gravia
Thyoma
BCG
Attenuated tuberculosis bacillus of Calmette-Guerin used for treatment of bladder cancer
