Cell Growth and Neoplasia Flashcards
different tissue have different homeostatic states (3)
continously dividing
quiescent
non-dividing
continuously dividing tissues?
e.g. skin, gut, epithelium, hematopoietic system
constant cell turnover
quiescent tissues?
e.g. hepatocytes
normally little to no turnover
capacity for proliferation if needed
non-dividing tissues?
e.g. CNS neurons
little to no capacity for proliferation
4 levels involved in homeostatic balance?
external environment interaction (physical environment / infectious agents / inhaled and ingested substances)
cell-extrinsic - macroenvironment (circulating factors e.g. cytokines / hormones)
cell extrinsic - microenvironment (ECM / stroma / GF and inflammatory milieu)
cell instrinsic (e.g. differentiation program / age of cell)
Physiological and pathological examples of hypertrophy?
physiological - uterus in pregnancy (actually combo of hypertrophy and hyperplasia)
pathological - heart in hypertension (high bp)
Physiological and pathological examples of hyperplasia?
physiologic - mammary gland during puberty / pregnancy
pathologic - endometrium - known risk factor for endometrial neoplasia (epithelial shifts to outnumbering stroma)
metaplasia?
change from one benign, differentiated cell type to another - usually in response to injury (e.g. inflammation)
bronchus and esophagus example of metaplasia
bronchus - columnar to squamous metaplasia - due to smoking - known risk for bronchopulmonary neoplasia
esophagus - squamous to columnar (Barrett) - due to acid reflux - risk factor for esophageal neoplasia
neoplasia =
new formation
progressive increase in cell number
clonal
irreversible
global mechanistic hallmarks of neoplasia
cell autonomous
diruption of normal homeostatic mechanisms
- altered cell autonomous mechanisms - activation of oncogenes / inactivation of tumor suppressor
-
global mechanistic hallmarks of neoplasia (cell-nonautonomous)
altered microenvironment - surrounding tissue, including stroma, blood vessels, and immune cells
altered macroenvironment -
circulating cells (immune cells) and factors (hormones / cytokines)
benign neoplasms vs malignant
gross features
sequestration and necrosis
benign - circumscribed / encapsulated - necrosis uncommon
malignant - invasive into adjacent tissue - necrosis common
benign vs malignant neoplasms
microscopic pathological features
differentiation?
turnover?
uniformity?
boundary?
benign
- well differentiated
- low rate of turnover
- cytologic uniformity (cells similar to each other)
- boundary maintained
malignant
- variable differentiation
- higher rate turnover
- cytologic pleomorphism - cells different from each other
- lose boundary
neoplasias are generally classified by?
tissue of origin
benign epithelial neoplasia?
adenoma
osteoma / chondroma / fibroma are examples of
benign mesenchymal neoplasia
malignant epithelial neoplasia
carcinoma
malignant mesenchymal neoplasia
sarcoma
malignant hematopoietic neoplasia -
lymphoma / leukemia
what is adenocarcinoma
malignant carcinoma with formation of glandular structures
clinical correlates of benign neoplasia
treatment?
recurrence?
malignancy progression?
treated by surgical resection alone may recur (especially if incompletely excised) generally do not progress to malignant - important exception - benign, but premalignant neoplasms (e.g. colonic adenoma)
what molecular pathways are involved in benign neoplasms?
don’t know - no funding
malignant neoplasia =
cancer
ratio americans get cancer
1/2
ratio american die cancer
1/5
6 hallmarks of cancer pathobiology
- sustained angiogenesis
- limitless replicative potential
- tissue invasion / metastasis
- insensitivity to anti-growth signaling
- self sufficiency in growth signaling
- evading apoptosis
what are the most common cancers?
carcinomas (cancer of epithelia)
what is dysplasia?
disordered growth
dyplasia in epithelia is hallmark of?
early premalignant neoplasia
characteristic histological features of dysplasia? (3)
loss of cytologic uniformity
loss of normal histologic maturation
loss of architectural orientation
marked / extensive dysplasia =
carcinoma in-situ
non-genetic factors influencing cancer etiology (6)
age lifestyle (etoh / tobacco) occupation (carcinogens) radiation infection (oncogenic) inflammation (IBD / UC)
Type of heritable cancers (3)
dominant tend to be oncogene
recessive tend to be tumor suppressor
there are also familial clustering familial cancers
Histological grade
degree of tumor histologic differentiation (i.e. resemblance of normal tissue counterpart)
grade vs stage?
grade is less reliable than stage
Tumor Stage TNM
T =
N =
M =
Tumor - invasion extent
N - lymph node involvement
M - distance of metastasis
T1 or T2 N0 M0
Stage 1 (93)
T3 N0 M0
Stage 2A (85)
T4 N0 M0
Stage 2B (72)
T1 or T2 N1 M0
Stage 3A (83)
T3 or T4 N1 M0
Stage 3B (64)
Any T N2 M0
Stage 3C (44)
Any T Any N M1
Stage 4 (8)
Tis
tumor in situ
T1
tumor invades submucosa
T2
Tumor invades into, but not through, muscularis propria
T3
Tumor invades through muscularis propria
T4
Tumor invades adjancent organs
NX
Lymph nodes cannot be assessed
N0
No lymph node
N1
Metastasis to 1-3 regional lymphnodes
N2
Metastasis to >3 regional lymph nodes
M0
No distant metastasis
M1
Distant metastasis / seeding or abdominal organs
what makes sarcoma unique from carcinoma in initial presentation?
no pre-malignant lesion and no in-situ state
what makes CNS neoplasms unique from carcinoma in initial presentation?
no pre-malignant nor in-situ phase
does the carcinoma cancer progression paradigm apply to other cancer? (sarcoma / heme / cns?)
no
what makes cns neoplasms metastasis unique?
rare outside neuraxis
where do pediatric neoplasms tend to originate?
developmental precursors
what behavior do pediatric neoplasms tend to recapitulate?
aspects of developmental program of tissue of origin
latency and metastasis in pediatric cancer
short latency
early metastasis
mutations in pediatric neopalsms?
fewer mutations
prominent role for oncogenic fusions and epigenetic dysregulation
