M1 | Neoplasia (LEC)

tinamad nako what the fuck

NEOPLASIA

new growth; a tumor (neoplasm)

ONCOLOGY

study of tumors or neoplasms

“ONCOS”

Greek word for cancer

TRUE

[TRUE or FALSE] tumors can be benign (not cancer) or malignant (cancer)

epithelial, mesenchymal, lymphoid or neural

these can be the origin of neoplasm

TRUE

[TRUE or FALSE] tumors can be with or without differentiation

• Parenchyma

• Reactive Stroma

2 components of all neoplasms (similar to normal cells)

Parenchyma

neoplastic cells that compose or make the neoplasm

Reactive Stroma

connective tissue, blood vessels, cells from the immune system (ex. Lymphocytes) in the neoplasm

FALSE | fleshy tumors have less stroma

[TRUE or FALSE]
fleshy tumors have more stroma

Schirrous Tumors

tumors with plenty of reactive stroma (desmoplastic reaction or desmoplasia) can be stone hard

some breast tumors

example of Schirrous Tumors

parenchyma

a tumor whether benign or malignant are named according to their [BLANK]

BENIGN TUMORS

have the suffix “oma”; appear “innocent” (gross and microscopic), remains localized, does not spread to other sites, amenable to surgical excision

“oma“

suffix for benign tumor

• fibroma

• chondroma

• lipoma

• fibroadenoma

4 benign mesenchymal tumors

• glandular tumor → adenoma

• cystic and glandular tumor → cystadenoma

• made up of fingerlike structures → papilloma

3 benign epithelial tumors

polyp

if adenoma has stalk, it can be called:

• angioma

• osteoma

• leiomyoma

give 3 other examples of benign tumors | A O L

MALIGNANT TUMORS

adding either sarcoma or carcinoma; can spread, can invade, can metastasize, can cause death

• Lymphoma

• Melanoma

• Mesothelioma

tumors that end with suffix “oma” but are NOT benign:

lymphoma

for malignant tumors arising from lymphoid cells/tissues

leukemias

for malignant tumors arising from blood forming cells

mixed tumors

tumors that have epithelial components within a mesenchymal component

Chondroid Syringoma

example of mixed tumor

teratomas

tumors that have all three components arising from the 3 germ layers (ecto, meso and endoderm)

• differentiation and anaplasia

• metaplasia and dysplasia

• local invasion

• metastasis

Characteristics of benign and malignant tumors:

differentiation

refers to the extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells, both morphologically and functionally; benign tumors are generally well differentiated

anaplasia

lack of differentiation; considered a hallmark of malignancy; high N:C ratio, nuclei are hyperchromatic and may have bizarre shapes and sizes

• Pleomorphism – variation of shapes and sizes of cells

• Abnormal nuclear morphology – bizarre-looking nuclei

• Mitoses – very high in malignant tumors

• Loss of polarity - the orientation of anaplastic cells is markedly disturbed; sheets or large masses of tumor cells grow in an anarchic, disorganized fashion

Anaplastic Features

Pleomorphism

Anaplastic Features | variation of shapes and sizes of cells

Abnormal nuclear morphology

Anaplastic Features | bizarre-looking nuclei

Mitoses

Anaplastic Features | very high in malignant tumors

Loss of polarity

Anaplastic Features | the orientation of anaplastic cells is markedly disturbed; sheets or large masses of tumor cells grow in an anarchic, disorganized fashion

• Rapid growth

  • due to high mitotic rate

  • most benign tumors have slower growth rate

  • will require more nutrients and oxygen through blood supply

• Require more blood supply

  • lack of blood supply will lead to necrosis, usually found in the middle

• Necrosis

  • blood supply cannot cope with the fast rate of growth

Other changes of anaplastic cells:

metaplasia

nearly always seen in areas where there is tissue damage, repair and regeneration; could lead to certain cancers in the future

dysplasia

“disordered growth”; cells will exhibit pleomorphism and hyperchromatic nuclei; not commonly seen in benign tumors

hyperchromasia

characteristics of dysplasia | nuclei appear to be dark, smudged, or opaque when stained

pleomorphism

characteristics of dysplasia | variation of shapes and sizes of cells

carcinoma-in-situ

dysplastic cells occupy the entire thickness of the epithelium, but has NOT penetrated the basement membrane

local invasion

1. Progressive growth of cancer cells

2. Destruction of surrounding structures

capsule

benign tumors are generally surrounded by a [BLANK]; some benign tumors can grow very big and can be very destructive

metastasis

• spread to distant sites; invasion is no longer localized

• seen in malignant neoplasms

metastatic site

where the tumors spread

hematogenous (blood vessels) and lymphatic routes

metastasis spread via:

• degree of differentiation

• rate of growth

• local invasiveness

• distant spread

Benign and malignant tumors can be distinguished from one another based on these 4:

Benign tumors

tumors that resemble the tissue of origin and are well differentiated

malignant tumors

are poorly or completely undifferentiated (anaplastic)

Benign tumors

tumors that are tend to be slow growing

malignant tumors

tumors that generally grow faster

Benign tumors

tumors that are well circumscribed and have a capsule

malignant tumors

tumors that are poorly circumscribed and invade the surrounding normal tissues

Benign tumors

tumors that remain localized to the site of origin

malignant tumors

tumors that are locally invasive and metastasize to distant sites

Benign tumors resemble the tissue of origin and are well differentiated; malignant tumors are poorly or completely undifferentiated (anaplastic).

compare degree of differentiation in benign tumors and malignant tumors

Benign tumors tend to be slow growing, whereas malignant tumors generally grow faster.

compare rate of growth in benign tumors and malignant tumors

Benign tumors are well circumscribed and have a capsule; malignant tumors are poorly circumscribed and invade the surrounding normal tissues.

compare local invasiveness in benign tumors and malignant tumors

Benign tumors remain localized to the site of origin, whereas malignant tumors are locally invasive and metastasize to distant sites.

compare distant spread in benign tumors and malignant tumors

• diet

• smoking

• alcohol consumption

• reproductive history

• infectious agents

give 5 most important environmental exposures linked to cancer

asbestos

environmental carcinogen that can cause lung cancer

vinyl chloride

environmental carcinogen that can cause hepatocellular carcinoma

benzene

environmental carcinogen that can cause leukemia

later years of life (>55 years)

most carcinomas occur in what age

• 40 to 79

• 60 to 79

cancer is the main cause of death among women aged [BLANK] and among men aged [BLANK]

80

decline in deaths after age [BLANK] is due to the lower number of individuals who reach this age

• Chronic inflammations

• Precursor lesions

• Immunodeficiency states

3 examples of acquired predisposing conditions

Chronic inflammations

for example chronic cystitis can lead to urinary bladder carcinoma

Precursor lesions

ex. An adenoma of the colon (colonic polyp) can lead to adenocarcinoma

lung carcinoma

Squamous metaplasia and dysplasia of bronchial mucosa, seen in in habitual smokers—a risk factor for:

endometrial carcinoma

Endometrial hyperplasia and dysplasia, seen in women with unopposed estrogenic stimulation—a risk factor for

squamous cell carcinoma

Leukoplakia of the oral cavity, vulva, and penis, which may progress to

colorectal carcinoma

Villous adenoma of the colon, associated with a high risk for progression to

familial cancers (if one inherits mutated copies of BRCA-1 and 2 genes, increase risk of breast carcinoma)

an example of Genetic Predisposition and Interactions Between Environmental and Inherited Factors

• driver (pathogenic) mutations

• passenger (neutral) mutations

Mutations in cancer cells fall into two major classes:

Passenger mutations

may become driver mutations if selective pressure on the tumor changes, for example, in the setting of treatment with an effective therapeutic drug

Tumor cells

may acquire driver mutations through several means, including point mutations and nonrandom chromosomal abnormalities that contribute to malignancy; these include gene rearrangements, deletions, and amplifications

Gene rearrangements

(usually caused by translocations, but sometimes by inversions of other more complex events) contribute to carcinogenesis by overexpression of oncogenes or generation of novel fusion proteins with altered signaling capacity

Deletions

frequently affect tumor suppressor genes, whereas gene amplification increases the expression of oncogenes

Overexpression of miRNAs

can contribute to carcinogenesis by reducing the expression of tumor suppressors, while deletion or loss of expression of miRNAs can lead to overexpression of proto-oncogenes

Tumor suppressor genes and DNA repair genes

also may be silenced by epigenetic changes, which involve reversible, heritable changes in gene expression that occur not by mutation but by methylation of the promoter

cellular and molecular hallmarks of cancer:

self-sufficiency in growth

The [BLANK] that characterizes cancer cells generally stems from gain-of-function mutations that convert proto-oncogenes to oncogenes.

Oncogenes

genes that promote autonomous cell growth in cancer cells

Proto-oncogenes

unmutated counterparts of oncogenes

Oncogenes

are created by mutations in proto-oncogenes and encode proteins called oncoproteins that have the ability to promote cell growth in the absence of normal growth promoting signals

Oncoproteins

resemble the normal products of proto-oncogenes but bear mutations that are often inactivate internal regulatory elements; consequently, their activity in cells does not depend on external signals

Proto-oncogenes

normal cellular genes whose products promote cell proliferation

Oncogenes

mutant or overexpressed versions of protooncogenes that function autonomously without a requirement for normal growth-promoting signals

products of tumor suppressor genes

Whereas oncogenes encode proteins that promote cell growth, the [BLANK] apply brakes to cell proliferation.

• Rb (retinoblastoma) gene

• p53 gene (the guardian of the genome)

2 tumor suppressor genes

p53

responsible for DNA repair and helps regulate cellular division (cell cycle)

Rb

regulator of the cell cycle

p21

prevents Cdk and cyclin from interacting

Cdk and cyclin

promotes cellular division

• Rb

• p53

In DNA replication, proofreading is done to check for any damages and repairs are done. Proofreading is accomplished through regulatory protooncogenes:

Rb

Governor of the Cell Cycle

Rb

a key negative regulator of the cell cycle, is directly or indirectly inactivated in most human cancers

TP53

Guardian of the Genome

TGF-β

inhibits proliferation of many cell types by activation of growth-inhibiting genes such as CDKIs and suppression of growth-promoting genes such as MYC and those encoding cyclins

TGF-β

function is compromised in many tumors by mutations in its receptors (colon, stomach, endometrium) or by mutational inactivation of SMAD genes that transduce TGF-β signaling (pancreas)