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Pathology: Neoplasia Cheat Sheet (DRAFT) by

This is a draft cheat sheet. It is a work in progress and is not finished yet.

Pathology: Neoplasia

- Neoplasia - new growth
abnormal mass of tissue
uncoor­dinated with and exceeding growth of normal tissue
persists after cessation of stimuli
-Tumor­s/n­eop­lasms/
2 basic types: benign, malign­ant­/ca­ncer/
-Basic components of tumors:
parenchyma - prolif­erating neoplastic cells, used for their nomen clature
stroma - supporting connective tissue and blood vesssels, for growth and evolution
-Neoplasm nomenc­lature:
histologic - mesenc­hym­/ep­ith­elial
mesenc­hymal - benign­/+oma/, malign­ant­/+s­arcoma
epithelial - benign­/based on type/, malign­ant­/+c­arc­inoma/
teratoma - cancer of totipotent cells mostly found in gonads
choristoma - ectopic rest of tissue
hamartoma - native tissue with uncoor­dinated growth
- Identi­fic­ation of malignant and benign tumors based on
1. differ­ent­iat­ion­/an­aplasia
2. rate of growth
3. invasi­venes
4. metastasis
1. benign are more differ­ent­iated and mature than malignant due to their slow mitosis
malignant tumors form a discrete fibrous capsule which makes them easier for surgical removal except hemangioma and neurof­ibromas
malignant tumors histol­ogi­cally present as pleomo­rphic, hyperc­hro­matic, and hyperm­itotic
carcinoma in situ - epithelial cell cancer that has not yet invaded the basement membrane
2. malignant grow more rapidly than benign
3. invasi­venes - tissue infilt­ration and destru­ction
malignant is more invasive than benign
4. metastasis - breaking of the primary tumor and wondering away
malignant are metastatic (except glioma and basal cell carcinoma) but benign aren't
metastasis is primary and invasi­venes is secondary identi­fic­ation of malignancy
- metast­ati­c/d­iss­emi­nation/ pathways
1. direct seedin­g(t­ran­sco­elemic) - mostly peritoneal cavity
2. lympatic - most common for sarcoma
3. hemato­genous - typical for carcinoma
mostly involves liver and lung (soil and seed phenom­enon)
- cancer incidence can vary based on those factors
geographic - due to specific charac­ter­stics of that area
enviro­nment - nature of work places, sanity
age - most suscep­tible are above 55 years old, below 15 are suscep­tible to specific cancers also
- Genetic predis­pos­ition to cancer
1. autosomal dominant inherited cancer syndrome
familial retino­bla­stoma
2. defective DNA repair syndrome
ataxia telang­ect­asia, xeroderma pigmen­tosa, bloom syndrome
3. familial cancers
high frequency occurence of cancer in a certain family with out a clearly defined pattern of transm­ission
charac­terized by
early age/ju­venile/ onset
tomor arise in multiple close relatives
multiple or bilateral tumors
- non hereditary predis­pos­ition to cancer
non-ne­opl­astic conditions (regen­era­tive, dyspla­stic, hyperp­lastic) give way to malignancy
- cancer genes
fall under 4 classes
1. oncogenes overex­pre­ssion from proto-­onc­ognes
2. loss or dysfun­ction of tumor supressor genes by mutation
3. over expression of gene that prevent apoptosis
4. expression of genes that hide tumors from host immune system
- driver and passenger mutations
driver mutations contribute to cancer directly by acting on the cancer genes
passenger mutations are acquired and important in 2 ways
carcinogen associated damage the genome
provide genetic variation of tumor cells making selective therapy difficult
point mutation - activate or inactivate proteins of affected genes
gene rearen­gement - transl­ocation and inversion caused cancer
e.g. philad­elephia (ph) chromo­som­e(l­euk­emia), BCL2 B cell lymphoma 2(anti/pro apoptotic gene), myc gene(i­nduce instablity in excess
deletion - may cause loss of tumor supressor gene
e.g. del13q14 gene - retino­bla­stoma, del17q13 (tp53) - multiple myeloma
gene amplif­ication - lead to oncogens by over expression in two patterns
hetero­genous staining regions, double minute
aneuploidy - chromosome number not multiple of haploid (23n)
increase oncoge­nes­(myc) and decrease tumor supres­sor­s(tp53)
- MicroRNAs: inhibit gene expression post transc­rip­tio­nally by repressing transl­ation or cleaving mRNA
in case of tumor supressor gene their over activity leads to reduced tumor supressor protein
in case of oncogenes their inactivity potent­iates occurence of cancer
- Epigenetic modifi­cation and cancer cells
epigenetic modifi­cation is reversible heritable gene expression changes without mutation
transc­ription is normally silenced by methyl­ation and histone modifi­cation
but cancer cells have global DNA hypome­thy­lation and slective promoter localized hyperm­eth­yla­tio­n(tumor supres­sors)
- Carcin­oge­nesis:
a multistep process that follows Darwinian select­ion­(ev­olu­tion)
result from accumu­lation of multiple genetic alteration leading to transf­ormed phenotype and associated hallmarks
 

- 1.Hall­marks of cancer

1. self sustai­nab­ility of growth factor
2. ignore growth inhibiting signal
3. evasion of apoptosis
4. angiog­enesis
5. unlimited replic­ative potential
6. invasion and metastasis
7. evasion of immune survei­lance
8. DNA repair defects
1. Gf sustai­nab­ility: oncopr­oteins encoded by oncogens promote cell growth
cancer cells may produce Gf or induce others to do so
they have mutated or over expressed Gf receptors
mutation of signal transd­ucing protei­n(ABL, RAS) genes gives them growth autonomy
nuclear transc­ription factors mutation of genes that regulate expression of growth promoting genes
2. insens­itivity to gowth inhibitory signals
e.g. RB - governor of cell cycle mutation leads to uncont­rolled growth
tp53 - guardian of genome eliminate neoplastic transf­orm­ations by
-quies­cence, -senes­cence, -apoptosis
tp53 is the most mutated human gene in human cancer
transf­orming growth factor beta pathway:
inhibit prolif­eration in endoth­elial, epithe­lial, hemato­poietic cell
- Contact inhibtion NF2, and APC
is inhibition of cell prolif­eration because of cell to cell contact by transm­embrane protein called Cadherin
epithelium maintained by E-Cadherin (E=epi­the­lial) by 2 ways
a. NF2 gene - produce Neurof­ibromin 2 a tumor supressor
Neurof­ibr­oma­tosis 2 - hereditary NF2 gene mutation
b. binds with beta-c­atenin
3. Altered cellular metabo­lism:
cancer cells metabolism is different from normal cell metabolism because
- increased amount of glucose consum­ption than normal
- use of glycoltic pathway and convert it to lactose regardless of presence of oxygen to meet their rapid demand
this phenomenon is called aerobic glycolysis or Warburg effect
4. evasion of apoptosis
cancer cells escape death because
- absence of tp53 gene which would normally kill them in that amount of stress and DNA defects
- over expression of anti-a­pop­totic members of BCL2 family e.g. follicular lymphoma
5. unlimited replic­ative potential
cancer cells upregulate telomerase enzyme which keeps telome­res­(pr­ote­ctive cap at the end of DNA) long enough for unlimited DNA replic­ation hence achieving immort­ality
6. angiog­enesis
cancer cells use neoang­iog­enesis for
- supply nutrient and oxygen
- stimulate neighb­oring tumor cell growth
- metast­ati­c/d­iss­emi­nation/ pathway