"new growth"; lack of responsiveness to normal growth controls
define benign neoplasm
remains localized, amenable to surgical removal and patient survival
define malignant neoplasm
"cancer"; potential to invade and destroy adjacent normal tissue and spread to distant anatomic sites (metastisis). may cause death.
transformed or neoplastic cells; determines biologic behavior of the particular neoplasm
supporting tissue of the tumor: non-neoplastic blood vessels and CT
what suffix is used for benign tumors?
"-oma", ex. Chondroma: benign tumor of cartilaginous origin.
what suffix is used for malignant mesenchymal neoplasms?
"-sarcoma"; ex. Osteosarcoma: malignancy of osseous tissue.
what suffix is used for malignancies of epithelial origin?
"carcinoma"; ex. Squamous cell carcinoma or adenocarcinoma (malignancy of glandular epithelial origin)
What are two exceptions to the malignancy suffix rule?
Lymphoma and Melanoma (both are malignant instead of benign)
degree parenchmyal tissue of a neoplasm resembles the parent tissue, functionally and morphologically
malignancies composed of poorly differentiated cells are described as being this.
What is anaplastic---correct for $200!!
altered growth pattern that may become cancerous eventually
what is the most severe form of dysplasia?
carcinoma-in-situ. contains microscopic features of cancer but the atypical cells have not invaded the host yet
describe the growth rates for benign and malignant neoplasms
- benign: grow slowly
- malignant: most grow rapidly
most benign tumors have this band of fibrous connective tissue on the periphery
what is a "capsule"
what are 2 common exceptions to benign tumors with capsules?
hemangioma and neurofibroma
process of portions of a malignancy breaking free and traveling to distant sites to form new tumor masses
what two malignancies readily metastasize?
osteosarcoma and melanoma
what malignancy rarely metastasizes?
basal cell carcinoma
what percent of newly diagnosed patients with solid tumors will present with metastases?
how are anaplasia and metastasis related?
greater anaplasia = greater tendency to metastasize
what are 3 ways in which malignancies spread?
- 1. seeding within body cavities
- 2. lymphatic spread
- 3. hematogenous spread (by blood)
which method of metastasis is favored by sarcomas?
what are the two most frequent sites for metastatic deposits via hematogenous spread and why?
lung and liver. the lungs act to filter the blood above the diaphram while the liver filters blood below the diaphram
what are the 3 categories for genetically influenced cancers?
- 1. inherited cancer syndromes (autosomal dominant like retinoblastoma)
- 2. familial cancers (breast, ovarian, colon)
- 3. defective DNA repair syndromes (xeroderma pigmentosum)
define Aquired Preneoplastic Disorder
cancer arising from disorder within the life of the patient (not inherited or environmental necessarily)
list 4 acquired preneoplastic disorders
- 1. persistent regenerative cell replication
- 2. hyperplastic and dysplastic proliferations
- 3. leukoplakia of oral mucosa/vulva/penis
- 4. villous adenomas of the colon
what is the predominant reason of carcinogenesis?
nonlethal genetic damage. most cancers are clonal proliferations that arise from one genetically altered cell.
list the 3 classes of normal regulatory genes that are principle targets of genetic damage
- 1. protooncogenes (growth promoting)
- 2. cancer suppressor genes (growth inhibiting)
- 3. apoptosis regulatory genes
how do DNA repair genes affect carcinogenesis?
if DNA repair genes are disabled, increased frequency of mutations and increased rate of neoplastic transformation
oncoproteins are products of oncogenes. list 5 examples of oncoproteins.
- 1. growth factors
- 2. growth factor receptors
- 3. signal-transducing proteins
- 4. nuclear transcription factors
- 5. CDKs (cyclin-dependent kinases)
give 2 examples of growth factors involved with carcinogenesis
- 1. platelet-derived growth factor (glioblastoma)
- 2. TGF-a (sarcomas)
give 2 examples of growth factor receptors involved with carcinogenesis
- 1. ERBB-1: overexpressed in 80% of squamous cell carcinomas of the lungs
- 2. ERBB-2: amplified in some breast cancers leading to poorer prognosis
give an example of a signal-transducing protein involved with carcinogenesis
RAS. Mutated RAS binds to GAPs but GTPase activity is not accentuated. cell continues to receive signals to divide as a result.
give an example of a nuclear transcription factor involved in carcinogenesis
MYC: overexpression causes continuous cell proliferation
give an example of CDKs involved with carcinogenesis
CDKs are responsible for determining if a cell will start the cell cycle or not. Dysregulation/overexpression favors cell proliferation.
give an example of a tumor suppressor gene
explain the "two-hit" hypothesis
in order for retinoblastoma to develop, both Rb alleles must be disabled or mutated ("hit"). Children inherit one defective Rb gene and the second "hit" is very likely to occur as a somatic mutation resulting in tumor formation
which tumor suppressor gene is the single most common target for genetic alteration in human tumors?
describe the normal function of TP53
- 1. slows down DNA replication when mutations have affected the DNA
- 2. activates the transcription of DNA repair enzymes. if DNA cannot be repaired TP53 activates apoptosis
What is the prototypical anti-apoptosis gene?
define Xeroderma pigmentosum
defective nucleotide excision repair system. risk for skin cancer from UV light
define Bloom Syndrome
hypersensitivity to DNA damage
What 2 genes are involved with familial breast cancer?
BRCA1 and 2
List 3 karyotypic changes in tumors
- 1. balanced translocations
- 2. deletions
- 3. gene amplifications
Philadelphia chromosome is an example of balanced translocation. define what a philadelphia chromosome is.
occurs in chronic myelogenous leukemia: it is a translocation between chromosome 22 and 9. as a result 22 is shortened.
what deletions are common to colon cancer?
17p, 5q, 18q
what deletions are common in oral cancers?
3p, 9p, 17p
are all carcinogens electrophiles or nucleophiles?
radiation has a latent period for the development of cancer. how long is it?
8-12 years from exposure
what two types of viruses can cause cancer?
RNA and DNA oncogenic viruses
give an example of an RNA oncogenic virus
Human T-cell leukemia virus Type 1 (HTLV-I)
give 3 examples of DNA oncogenic viruses
HPV, EBV, HBV
give an example of a tumor-specific antigen
MAGE-1 (melanoma-associated antigen)
give an example of a tumor-associated antigen
prostate-specific antigen. expressed in a normal state but levels are elevated in a neoplastic state
list 4 antitumor effector mechanisms
- 1. CD8 T cells
- 2. NK cells
- 3. Macrophages
- 4. Humoral mechanisms
list 4 ways in which cancer can initiate from immune competent patients
- 1. selective outgrowth of antigen-negative subclones (antigenic subclones are attacked and killed by immune system leaving tumor cells that are essential invisible to the immune system)
- 2. lost or reduced expression of MHC antigens
- 3. lack of co-stimulation for t-cell response
- 4. immunosuppression from a carcinogenic agent
list 5 ways in which benign tumors can cause complications in a patient
- 1. location: a benign tumor next to the pituitary can compress it and cause damage
- 2. hormone production: common in well-differentiated benign tumors. adenomas and carcinomas from beta cells in the pancreas can produce hyperinsulinism
- 3. ulceration (breaking through epithelial surface)
- 4. cachexia (progressive loss of body fat and lean body mass)
- 5. paraneoplastic syndrome (A set of symptoms that is associated with cancer but is not directly caused by the cancer)
attempt to assess the aggressiveness of a malignancy based on degree of differentiation of the tumor cells and number of mitoses
assessment of the size of the primary lesion, presence or absence of lymph node involvement and presence or absence of metastatic lesions involving other distant tissues. Stage I: most localized, Stage IV: most disseminated. Staging is more valuble than grading for determining prognosis
explain the TNM method to classify squamous cell carcinomas
- T: primary tumor diameter
- N: lymph node involvement
- M: metastases