Week 1: Pathology - Neoplasia, Cancer, & Chemotherapy

Neoplasia

cancer

“plasia”

formation, growth

“neo”

new

Neoplasia is defined as

new independent growth of tissue not coordinated with normal growth of surrounding tissues

Second leading cause of death in the U.S.

cancer

Studies show that about 40-50% of cancer death can be prevented by

• Not using tobacco

• Maintaining a heathy weight

• Getting plenty of PA

• Eating healthy foods

• Avoiding the midday sun and protecting skin from UV light

• Getting appropriate cancer screening tests

Screening test for breast cancer

Mammogram

Cancer risk factors

• Diet

• Cigarette smoking

• Excessive alcohol use

• Obesity

• UV radiation

• Physical inactivity

40-50% of cancers are

preventable

CAUTION acronym

C: Change in bowel or bladder habits.

A: A sore that does not heal in 6 weeks

U: Unusual bleeding or discharge.

T: Thickening or lump in the breast or elsewhere.

I: Indigestion or difficulty in swallowing.

O: Obvious change in a wart or mole.

N: Nagging cough or hoarseness.

Lung cancer can cause

indigestion and difficulty swallowing, nagging coughs and hoarseness

Skin neoplasms ABCDE

Asymmetry (uneven edges, lopsided shape, one half not like the other

Border: irregularity, irregular edges, scalloped or poorly defined edges

Color: Black, shades of brown, red, white or blue

Diameter: Larger than a pencil erase

Evolving: the mole is changing

Number 1 cancer-related death

lung cancer from smoking

Prostate cancer primarily affects

African Americans

Breast cancer mainly affects

Caucasians

Age 0-8 neoplasms

• Neuroblastoma

• Ewing's Sarcoma

• Lymphoma

• Osteogenic Sarcoma

Age 8-40 years Neoplasms

• Osteogenic sarcoma

• Chondrosarcoma

• Ewing's Sarcoma

• Lymphoma

• Secondary osteogenic or chondrosarcoma

• Metastatic carcinoma of the thyroid

• Metastatic carcinoma of the breast

Age 40-55 neoplasms

• Secondary osteogenic

• Secondary chondrosarcoma

• Multiple myeloma

• Metastatic carcinoma of the breast

• Primary osteogenic sarcoma

• Neurogenic Sarcoma

Age 55-75 malignant neoplasms

• Metastatic carcinoma of the lung

• Metastatic carcinoma of the breast

• Metastatic carcinoma of the prostate

• Secondary osteogenic or chondrosarcoma

• Multiple myeloma

• Other metastatic tumors

Metastatic breast cancer is not usually found in

Children

Leading cause of death in the US

heart disease

Characteristics of neoplasms

• Metastasis

• Encapsulation

• Growth rate

• Invasion

• Differentiation

• Anaplasia

Carcinoma in situ

a malignant tumor that has not yet disturbed or invaded the basement membrane

Malignant neoplastic cells have the capability to express

surface receptors to basement membrane component like laminin

Metastasis steps

1. Laminin receptors express

2. Collagenase breaks down basement membrane

3. Epithelial cells pass into basement membrane

Malignant eptihelial cells can enter through

blood capillary or lymphatic capillary

Metastasis

distant spread of cancerous cells through the bloodstream or lymphatic systems

Melanoma meet all criteria

for the ABDE

Melanoma

Cancer of the cells that make melanin

Melanoma can cause

pigmentation of where it was spread

Malignant melanoma can spread

anywhere in the body

Encapsulation of a neoplasm

neoplasm gets surrounded by connective tissue

What's easier to remove?

encapsulated neoplasms

Neoplasm growing within connective tissue confines means

the neoplasm is encapsulated

whats worse? encapsulated or non-encapsulated

non-encapsulate neoplasm

Invasion of neoplasm

neoplasm invading adjacent tissue

Multiple myeloma

plasma cell cancer

Multiple myeloma affects

plasma cells in the bone

Benign neoplasms chracteristics

• no metastasis

• encapsulated

• non-invasive

• slow growing

• well differentiated

• little or no aplasia

Differentiation

process in which cells become specialized in structure and function

Well-differentiated neoplasms

have cells that look and act like the normal tissue

Poorly differentiated neoplasms

don't look or act like cell of origin

Anaplasia

lack of differentiation between the cells themselves

Little - no anaplastic neoplasms

have cells that look similar

Highly anaplastic neoplasms have cells that

vary in their shape and size

malignant neoplasm charcateristics

• metastasis

• Non encapsulation

• Invasive

• Rapid growth

• Poorly differentiated

• Anaplasia to varying degrees

When a cancer shows high degree of anaplasia

the cells look very different from each other

Metastasis represents

the neoplastic cells are growing at a distant site

Histogenic classification of neoplasia

cell of origin

Epithelial or mesenchymal

Mesenchymal

connective tissue stem cells

Majority of cancer origins are

epithelial because cell are exposed to toxins in the body

Benign neoplasia are

epithelial and mesenchymal

-OMA

tumor that's benign, epithelial and mesenchymal

Lipoma

mesenchymal benign adipocyte neoplasm

Fibroma

mesenchymal tumor of fibrous tissue

Adenoma

epithelial glandular tumor

Malignant Epithelial origin

-carcinoma

Carcinoma examples

Melanoma—involves melanocytes

Adenocarcinoma—glandular cancer

Malignant Mesenchymal origin

-sarcoma

mesenchymal sarcoma examples

Fibrosarcoma

Liposarcoma

Lymphoma is actually a

malignant neoplasm

Carcinoma is a cancer that starts in the

skin or tissues that line other organs that are epithelial in origin

Sarcoma is a cancer of

the bone, muscle, cartilage and blood vessels or other connective tissue

Leukemia is a cancer of

bone marrow, which creates Blood cells

Lymphoma and myeloma are cancers of the

immune system

Lymphoma and myeloma are

malignant neoplasms

Chondrosarcoma

malignant tumor of cartilage

epithelial in origin and malignant

carcinoma

Leiomyoma (fibroids)

Benign neoplastic proliferation of smooth muscle arising from myometrium; most common tumor in females

Pre-neoplastic alterations

• hyperplasia

• metaplasia

• dysplasia

Hyperplasia

increase in number of cells

metaplasia

Mature cell type is replaced by a different mature cell type

dysplasia aka

grey zone

dysplasia can become

neoplasia

effects of smoking on goblet cells

• changes from pseudo-stratified columnar epithelium to stratified epithelium

• hyperplasia of goblet cells

• loss of cilia

effects of smoking continued

metaplasia and dysplasia cause carcinoma in situ to progress through the basement membrane

in situ

has not broken through basement membrane

neoplastic alterations

• Benign neoplasm

• malignant neoplasm

• in situ

• depth of spread

• metastasis

Environmental predisposition to cancer

environmental factors play a large role

• geographical

• cultural

• Nutritional (obesity, fat cells store and release cancer risk cells)

• Age

Genetic factors predisposition to cancer

most cancers are not genetic but could have a genetic component

º BRCA Gene mutations: Cancer risk and gentic testing for breast cancer

Exogenous Cancer Causes examples

HPV virus and other carcinogens

Obesity in women and Cancer

1/3 of cancer deaths in women are now attributable to excess body weight

Fat tissue produces estrogen which is implicated in

Breast and endometrial cancers

insulin is a growth factor for

cancer cells, and is found in excess in those that are overweight/obese

Carcinogenesis

development of cancer

Carcinogenesis: Initiation

The genetic mutations which inappropriately activate proto-oncogenes or inactivate tumor suppressor genes.

Carcinogenesis: Initiation factors

• Polycyclic aromatic hydrocarbons

• Aflotoxins

• Nitrosamines

• Oncogenes

Polycyclic Aromatic Hydrocarbons (PAHs)

A group of over 100 different chemicals that are formed during the incomplete burning of coal, oil and gas, garbage, or other organic substances like tobacco or charbroiled meat.

Aflatoxins

fungal poison that cause liver cancer found on peanuts

Nitrosamines

a type of chemical that is carcinogenic; several are found in food preservatives

Oncogenes

may initiate carcinogenesis

º can be inherited or environmental

Carcinogenesis: Promotion

mutated cells are stimulated to divide

Formation of neoplasm

Carcinogenic agent → Normal cell → DNA damage → Activation of growth promoting oncogenes, Inactivation of tumor suppressor genes, alterations of genes controllings apoptosis → Unregulated cell differentiation and growth → Malignant neoplasm

Modulators

try to keep cancer cells from forming cancer

Modulator examples

Vitamin A

Antioxidants

Immune system

Initiation and promotion

Chemical carcinogenesis requires a combination of two processes

• Induction & proliferation

• Initiation & promotion

• Replication & mutation

• Intercalation & amplification

What cells can attack cancer cells

NK cells

Cytotoxic T cells

Neutrophils

Macrophages

Problem with neoplastic cells

they hide themselves

Check-point inhibitors

prevents the neoplastic cells from cloaking themselves which allows the immune system to attack the neoplastic tissues

Problem with checkpoint inhibitors

very expensive