cancer basics Flashcards
normal cell type replaced by another
metaplasia
barrett’s esophagus
metaplasia:
squamous epithelium → columnar epithelium (intestinal)
abnormal growth
loss of normal size, shape, orientation
dysplasia
REVERISBLE changes in histoogy
hyperplasia
metaplasia
dysplasia
cells regressing
less differentiated
less like mature cells, more like primitive cells
anaplasia
high nucleus to cytoplasmic ratio
prominent nucleoli
clumping of nuclear chromatin
mitotic figures
anaplastic characteristics
cells growing in uncontrolled fashion
benign OR malignant
neoplasia
IRREVERISBLE changes in histology
anaplasia
neoplasia
adenoma: glandular architecture (colon polyp)
papilloma: finger-like architecture
benign tumor arising from epithelium
carcinoma:
adenocarcinoma
papillary carcinoma
use cytokeratin stain
malignant tumor arising from epithelium
tumors that spread via lymphatics
epithelial tumors
tumors that spread hematogenously
mesenchymal tumors
malignant blood cell tumors
leukemia
lymphoma
multiple myeloma
hemangioma (cherry)
benign blood vessel tumor
angiosarcoma (usually liver)
malignant blood vessel tumor
osteoma
benign bone tumor
osteosarcoma
malignant bone tumor
lipoma
benign fat tumor
liposarcoma
malignant fat tumor
benign mesynchymal tumors rarely progress to
sarcoma (vs epithelial tumors: adenoma → carcinoma)
sarcomas (mesenchymal) are more aggressive than
carcinomas
rhabdomyoma
benign skeletal muscle tumor
rhabdomyosarcoma
malignant skeletal muscle tumor
leiomyoma
benign smooth muscle tumor
leiomyosarcoma
malignant smooth muscle tumor
tumor with more than 1 cell type
mature: mature tissues, no anaplastic cells (ovarian tumor)
immature: MALIGNANT
teratoma
how much cellular differentiation and mitotic activity the tumor cells show
grade
low grade: well-differentiated, cells resemble normal cells
high grade: less differentiated
size of tumor
how much it has spread
stage
TNM staging system
Tumor size
Nodal involvement
Metastasis
prognostic value + treatment options depends on
stage
neoplastic progressoin
normal → hyperplasia → dysplasia (lose normal size, shape, orientation) → carcinoma in situ (malignant cells haven’t invaded BM yet) → invasive carcinoma (malignant cells break thru BM: locally invasive)→ metastasis (invade lymphatic or blood vessel)
liver metastasis (more common than 1° liver cancer)
Cancer Sometimes Penetrates Benign Liver: Colon (drains to liver) Stomach (drains to liver) Pancreas Breast Lung
↑ LFTs: ↑ alk phos liver tenderness ab pain hepatomegaly hepatic dysfunction: ascites, jaundice
liver mets S/S
brain metastasis (50% brain tumors are mets = most common brain tumor is mets)
Lots of Bad Stuff Kills Glia: Lung Breast Skin (melanoma) Kidney (renal cell carcinoma) GI tract (colon cancer)
headache - 50% cases
focal neuro dysfunction: hemiparesis
cognitive dysfunction: memory loss, personality changes
seizures
brain mets S/S
bone metastasis (more common than 1° bone tumors)
Permanently Relocated Tumors Like Bone Prostate Renal cell cancer Thyroid Lung Breast
lytic: break down bone (lung, multiple myeloma, breast)
blastic: build new bone - but disordered and weak (prostate, breast)
bone mets S/S
profound weight loss
fat + lean muscle loss
cause: tumor produces cytokines (TNF α) that raise BMR
main cause of cancer death + disability
cachexia
histological finding in: papillary thyroid cancer Serous papillary cystadenocarcinoma of ovary Meningioma Malignant mesothelioma
psammoma body
laminated, concentric, calcified spherules
psammoma body
malignant tumors arise from clonal expansion of
single precursor cell
daughter cells pass on mutated DNA
4 main targets of genetic damage:
proto-oncogenes
tumor suppressor gene
genes that regulate apoptosis
DNA repair genes (susceptible to ionizing radiation, chemical carcinogens)
malignant transformation is due to
nonlethal genetic damage (no trigger for apoptosis)
multistep: multiple mutations (protooncogene + dna repair gene, etc)
normal genes that regulate cell proliferation and differentiation (code for GF, GF R, tyrosine kinase) but when mutated become called
proto-oncogenes: normal
oncogenes: mutated
regulate cell cycle
tumor suppressor genes:
G1→ S: DNA repair, if can’t repair: p53, Rb (stays bound to E2F TF)
G2 →M: p53
cyclin D activates CDK4
cyclin D-CDK 4 phosphorylates Rb → Rb unbinds from E2F TF → allow G1 to S
how many mutations in tumor suppressor alleles to get cancer
two:
TWOmor suppressor alleles
p53
acts through p21 to cause cell cycle arrest
works at G1/S and G2/M checkpoints
causes apoptosis by inducing TF of pro-apoptotic genes (BAX)
p53 binds to damaged DNA → stop cell cycle → either repair DNA or trigger apoptosis
mutation in Rb
not bound to E2F: G1→S
mutation in p53
progress through cell cycle despite presence of DNA damage/mutations
cell growth in absence of normal mitotic signals
oncogenes: oncoproteins are missing important regulatory elements
GOF mutation
how many mutations in proto-oncogene alleles to get cancer
ONE mutation
most common oncogene abnormality in human tumors:
15% all human tumors have mutated RAS proteins
ras oncogene
most common mutations that cause cancer
p53 (50% human cancers) ras oncogene (20% human cancers)
RAS proto-oncogene protein product
part of G protein in GF receptor → when GF + RAS protein bind to GF R → activate MAP kinase → stimulate cell proliferation
