Neoplasia julia Flashcards
Benign Tumors
Non-cancerous and typically grow slowly without invading surrounding tissues or spreading to other parts of the body. “-oma” is used for benign tumors.
- Well-circumscribed, round
- Well-differentiated
Mesenchymal tumors = connective tissue (such as adipose tissue, fibrous tissue, bone, muscle, etc.) tumor
lipoma (benign tumor of adipose tissue) v. liposarcoma
adenoma (benign tumor of epithelial glands) v. adenocarcinoma (malignant tumor of epithelial glands)
osteoma (benign tumor of bone) v osteosarcoma (malignant tumor of bone)
malignant tumor: nomenclature
Carcinoma is used for malignancy of epithelial tissue
Sarcoma is used for malignancy of mesenchymal tissue
Misnomers include – hepatoma (hepatocellular carcinoma), melanoma, seminoma (tumor of germ cells in testes), lymphoma. These are all malignant tumors not benign, as suffix –oma would imply.
Hepatoadenoma = benign tumor @ liver
Hallmarks of Malignant tumor:
Invasion breaching BASEMENT MEMBRANE and destruction of adjacent structures and spread to distant sites (metastasize)
- oncogene activation/self-sufficient
- Warburg effect – metabolic switch to aerobic glycolysis -> allows synthesis of macromolecules needed for FAST cell growth
- p53 inactivation
- TELOMERASE -> maintain their telomeres and divide indefinitely, giving them a kind of immortality
- Sustained angiogenesis (new vessel growth)
Differentiation of tumor: what does this help categorize and describe
refers to histology and how much the tissue resembles the mature tissue of origin: well-differentiated, moderately differentiated, poorly differentiated. ==> GRADE of Tumor
well-differentiated (closely resemble normal cells)
moderately differentiated
poorly differentiated (basic primitive cells)
undiferrentiated/anaplastic - no differentiation -> once you describe something as undifferentiated its malignant
Microscopic features of cancer (malignancy)
Microscopic features of cancer (malignancy) = Grade of Tumor
pleomorphism (variation in size and shape of cells)
Abnormal nuclei
- hyperchromasia (dark blue nuclei)
- high nucleus/cytoplasmic ratio (nucleus takes up greater portion of the cell)
- Nucleus should NOT be as big as cytoplasm, should be small
prominent nucleoli
increased mitoses (especially bizarre mitoses) – indicates proliferation of tumor, loss of polarity (architectural distortion)
anaplasia (from Greek – backward formation) = lack of differentiation (well differentiation = low grade, porrly differentated = high grade)
Dysplasia and carcinoma in situ
Dysplasia – pre-cancerous but may or may not develop into malignancy
- often occurs in metaplastic epithelium: change of one type of mature cell to another
- loss of uniformity + architectural orientation
Carcinoma-in-situ = dysplastic cells involve full thickness of epithelium but do NOT invade or infiltrate the basement membrane
- Basement membrane is intact
grade vs stage
Grade is based on the histological appearance of the tumor, and is based on differentiation (see above)
- Determined microscopically
Stage is usually more important in prognosis since it takes into account the amount of local spread/infiltration/invasion, lymph node involvement, and the presence or absence of metastases.
- TNM staging system - tss/tumor, LN, mets
- Once you have metastasis = stage 4
- Determined clinically
- LN mets = important for prognosis
TNM staging system
T- Tumor size or spread; T0 = in situ; T1-T4
N - LN involved; N0-N3
- important for prognosis and risk of recurrence after initial tx
- histology: Glands don’t belong on LNs -> Abnormal metastatic LN
M - metastases
- M1: Distant metastasis is present (cancer has spread to other organs or distant tissues) -> if you have M1 = stage 4
Most common cancers:
Men: prostate (PSA), lungs, colon (CEA)
women: breast (CEA), lung, colon (CEA)
Molecular Basis of Cancer and classes of normal regulatory genes
1) Non-lethal genetic damage: damage to the DNA is significant enough to disrupt normal cell function, but it does not immediately kill the cell
2) Monoclonality: clonal expansion of a single abnormal precursor cell (one ancestor cell)
4 classes of normal regulatory genes:
- Proto-oncogenes – code for proteins that help regulate cell growth and differentiation ; Ras**, MYC
- Tumor suppressor genes: normally function to inhibit cell growth -> p53, APC, and BRCA
- DNA repair genes
- Anti-apoptosis genes: Bcl-2
oncogenes
MYC oncogene = nuclear regulator for proliferation -> deregulation of cell division
RAS oncogene = signal transducer
- present in about one-third of human cancers
- MC type of proto-oncogene abnormality
hypothesis of oncogenesis: tumor suppressor vs oncogene
“Two-hit” hypothesis of oncogenesis = 2 mutations which involve both alleles of gene is required for CA
Tumor Suppressors: Require two hits to inactivate both alleles.
- Loss of function of tumor suppressor genes leads to cancer development
- ex: p53
- li-fraumeni syndrome: genetic disorder where individuals inherit one mutant allele of p53 -> 25x more likely to get rare cancers at young age
Oncogenes: Only require a single activating mutation to drive cancer.
Gain of function (or overexpression) promotes oncogenesis
- MYC
- RAS
Gatekeeper = oncogenes, tumor suppressor genes
Caretakers = DNA repair genes
Gene mutations can lead to evasion of apoptosis
Gene mutations can lead to evasion of apoptosis
Translocations/inversion mutations in CA are commonly in
Most lymphomas/leukemias
Many non-hematologic malignancies
Telomerase
– present in greater than 90% of human cancers; change telomeres (which determine the limited number of duplications a cell will have)
==> so they will have unlimited replicative potential
