Neoplasia Study Guide, General Pathology

Any abnormal growth or mass

Tumor

New growth, a genetic disorder of cell growth triggered by acquired or inherited mutations affecting a single cell and its progeny

Neoplasm

A benign neoplasm is:

1. Localized

2. Generally amendable to surgical resection

A malignant neoplasm:

1. Invade and destroy adjacent structures

2. Has potential to metastasize to distant sites

3. Pursue a deadly course without treatment

4. Generally referred to as ‘cancer’

tumors of uncertain malignant potential means:

there are tumors which do not fit neatly into the ‘benign or malignant’ dichotomy

Tumors of squamous epitheliium:

1. Squamous cell papilloma (benign)

2. Squamous cell carcinoma (malignant)

tumors of glandular epithelium:

1. Adenoma (benign)

2. Adenocarcinoma (malignant)

Tumors of smooth muscle (soft tissue tumors):

1. Leiomyoma (benign)

2. Leiomyosarcoma (malignant)

Tumors of bone (soft tissue tumors):

1. Osteoma (benign)

2. Osteosarcoma

Tumors of cartilage (soft tissue tumors):

1. Chondroma

2. Osteochondroma

Tumors of fat (soft tissue tumors)

1. Lipoma

2. Liposarcoma

Tumors of blood vessels (soft tissue tumors)

1. Hemangioma (benign)

2. Angiosarcoma (malignant)

Hematopoietic (blood) neoplasms

1. Tumors of the lymph nodes

2. tumor of the blood/bone marrow

Tumors of lymph nodes:

Lymphoma (malignant, no benign counterpart)

Neoplasms of the blood/bone marrow:

Leukemia (malignant, no benign counterpart)

tumors of mesothelial cells:

1. Adenomatoid tumor

2. Benign multi-cystic peritoneal mesothelioma

3. well-differentated papillary mesothelial tumor

4. Solid papillary mesothelial tumor (benign)

5. Mesothelioma (malignant)

Tumors of the melanocytes:

1. Nevus (benign)

2. Melanoma (malignant)

Mixed tumors (composed of both epithelium and soft tissues)

1. Pleomorphic adenoma (benign)

2. Leiomyfibroma (benign)

3. Adenosarcoma (malignant)

Benign disorganized masses of cells indigenous to the involved tissue

Hamartomas

How closely a tumor resembles its tissue of origin

Differentiation

Well-differentated tumors are more likely to be (not guaranteed):

to be benign

Poorly-differentiated tumors are more likely (but not guaranteed):

to be malignant

A lack of clear differentation:

anaplasia

Reserved for tumors that show no clear lineage even after careful work up

Undifferentiated

Variation in size and shape of tumor cells

Pleomorphism

Generally ‘malignant tumors show at least some of the following morphology:

1. Large nuclei

2. Basophilic nuclei

3. Irregular nuclear contours

4. Nuclear crowding/overlapping

5. Prominent nucleoi

Mitoses are dividing cells, and increased mitotic activity is an indication of:

malignancy

Malignant tumors may also show ‘atypical’ mitoses, in which a disordered cell attempts to:

divide into more than two progeny

Loss of normal cell polarity/organization generally goes along with dedifferentiation, and is an indicator of:

malignancy or progression toward malignancy

The presence of malignant tumor can induce changes in the surrounding stroma, such as:

1. Desmoplasia (scar)

2. Inflammation

3. Vascular proliferation

This is the destructive invasion of surrounding tissue

local invasion

By contrast, benign tumors tend to expand slowly and:

push surrounding tissue aside

A helpful indicator of malignancy in certain tissues, specifically the nucleoli is:

areas of condensed chromatin within the nucleus

Rapid growth of tumors may expand past their blood supply and begin to die

necrosis

the spread of tumor cells to distant sites through the:

blood and lymphatic vessels

Direct invasion into an adjacent organ does not:

count as metastasis

Tests or exams designed to detect cancers at an early or premalignant stage to allow early preventative treatment or intervention.

Screening

Screening tests are performed on:

healthy individuals

Requirements for effective screening tests:

1. Disease must have an early stage or pre-cancerous stage, amendable to treatment

2. Treatable stage must last long enough to allow a reasonable chance of detection

3. There must be a mechanism to detect early or precancerous stage (endoscopy, imaging, biopsy)

4. Proposed screening test must be safe and cost effective

As opposed to screening, this refers to imaging or other techniques to monitor the extend of the disease in someone who is known to be sick.

Surveillance

Environmental risk factors for cancer:

1. Viruses and bacterial infections

2. HPV

3. EBV

4. Merkel Cell Polyoma virus

5. Hepatitis B and C

6. Human T-cell lymphotrophic virus

7. Human Herpes virus 8

8. H. pylori

9. HIV

How can viruses and bacterial infections cause cancer?

1. Production of specific oncogenic viral proteins

2. Accumulation of random mutations due to integration of viral DNA into the host genome

3. General mitogenic effects of chronic inflammation

4. Physiological responses to chronic infection (CIRRHOSIS)

Low risk subtypes of HPV cause:

benign squamous papillomas

High risk subtypes of HPV can cause:

cervical, anal and head and neck squamous cell carcinoma

In healthy people, the immune system will usually do what to the HPV?

Clear the virus before it leads to malignancy

Oncogenic proteins (found in high risk variants), HPV:

E6, binds to the P53 tumor suppressor gene

E7, various affects that increase cellular replication by lifting checkpoints in the cell cycle

this is the first virus to be linked to a human tumor:

EBV

We know that EBV is linked to:

1. Burkitt lymphoma

2. Nasopharyngeal carcinoma

3. Hodgkin lymphoma

EBV infected cells produce this protein:

latent membrane protein 1

LMP1 does the following:

1. Acts a surface receptor for helper T-cells, which then give B-cell mitogenic signals

2. Directly stimulates B-cell proliferation

3. Blocks apoptosis by activating BCL2

The triad or pro-proliferative effects and the loss of apoptosis (EBV), eventually lead to:

more mutations and development of cancers

Merkel Cell Polyoma virus leads to:

Merkel cell carcinoma, through an unknown mechanism

What is the possible cause of merkel cell carcinoma?

a combination of UV exposure and mutations, caused by viral integrations into the cell genome

Chronic hepatitis infection (B and C), lead to:

cirrhosis, which is high risk factor for hepatocellular carcinoma

HTLV-1 (Human T-cell lymphotropic virus), leads to:

Adult T-cell leukemia/lymphoma in 3-5% of those infected

what is the probable cause of HTLV-1?

Accumulation of random mutations as viral NDA is integrated randomly in the host genome

HTLV-1 has a long:

latent period (4-6 decades)

This infection occurs during childhood and is usually asymptomatic and harmless and a small percentage of patients will develop Kaposi’s sarcoma.

Human Herpes Virus (HHV-8)

HHV-8 is what kind of virus? Affecting 2-10% of the global population

Endemic virus

In HIV positive individuals, Kaposi sarcoma can develop:

quickly

In healthy individuals, Kaposi sarcoma develops:

late in life

H. Pylori is linked to:

Malt associated lymphoma (MALToma/extranodal marginal zone lymphoma of mucosa associated lymphoid tissue)

gastric adenocarcinoma

Helicobacter Pylori infects the:

bacteria that infects the stomach lining

Reactive T-cells seem to induce B-cell proliferation through:

various inflammatory pathways leading to cancer

Compared to healthy individuals, HIV positive individuals:

1. 500x more likely to be diagnosed with Kaposi sarcoma

2. 12x more likely to be diagnosed with Non-hodgkin lymphoma

3. 3x more likely to be diagnosed with cervical cancer

Kaposi sarcoma, non-hodkins lymphoma, and cervical cancer are considered (in HIV positive individuals):

AIDS defining illnesses

How does HIV facilitate the development of numerous cancers?

1. Immunodeficiency directly harms the body’s ability to detect and destroy early tumors

2. Immunodeficiency also allows various infectious agents to persist and eventually cause cancer

What are the 3 types of carcinogens?

1. Direct carcinogens

2. Indirect carcinogens

3. Ultimate carcinogens

Direct carcinogens are carcinogenic in their current form and:

1. require no metabolic activation

2. tend to be weaker carcinogens

Indirect carcinogens require:

metabolic activation to be carcinogenic and tend to be stronger carcinogens

Ultimate carcinogens are the:

active carcinogenic final form of indirect carcinogens

The main cancer risk of tobacco:

Lung cancer (smoking), among many others

Cigarettes contain what kind of carcinogens?

Direct carcinogens

Tobacco smoke also acts as a direct irritant with carcinogenic properties due to:

increased inflammation

the main cancer risk of alcohol is:

Hepatocellular carcinoma (among others)

Alcohol is another example of what kind of carcinogen?

indirect carcinogen

Alcohol is metabolized to what by alcohol dehydrogenase in the liver?

acetaldehyde

At high blood levels, cytochrome molecules (CYP2E1) also help metabolize alcohol, increases carcinogenicity in two ways:

1. CYPs can produce oxygen radicals

2. Alcohol competes with other toxins for CYP metabolism

Obesity triggers elevated:

insulin levels

Obesity also increases production of steroid hormones because:

Estrogen and androgen progenitors aer stored by fat cells

Obesity also inhibits sex hormone binding globulin, leading to:

increased estrogen/androgen availability

Obesity is associated with pro-inflammatory state:

1. Increased C-reactive protein (CRP) and increased tumor necrosis factor (TNF)

2. Increased inflammation generally causes high cell turnover and general stimulation resulting in increased risk for cancer

Adiponectin is reduced in people who are:

insulin resistance

In normal circumstances, adiponectin works to reduce:

cell proliferation and increase the activity of p53

Examples of exogenous carcinogens:

Aflatoxin

Aflatoxin is produced by:

Aspergillus Flavus

Aflatoxin is a risk factor for what cancer?

Hepatocellular carcinoma

The cancer risk with aflatoxin has an additive effect with:

HBV infection

Nitrates and nitrites are not intrinsically carcinogenic, but they are converted to:

carcinogenic nitrosamines when used as meat preservatives

Low fiber intake is an example of lacking a:

protective factor

High fiber can increase:

stool bulk, decreased stool transmit time, bind some toxins in stool

Ultraviolet radiation increases the risk of:

Squamous cell carcinoma

Basal cell carcinoma

melanoma

Merkle cell carcinoma

In chronic exposure of UV radiation, you can get:

BCC and SCC

Sporadic intense UV radiation exposure, you can get:

melanoma

What is the mechanism of UV radiation and causing cancer?

1. Absorption of UVB photons by DNA molecules

2. These dimers are repaired by nucleotide excision pathway

3. Nucleotide excision pathway is overwhelmed, error-prone DNA repair pathways take over resulting in the accumulation of mutations

X-rays, Gamma rays, alpha particles, beta particles, protons, and neutrons can all be:

carcinogenic

Sources of ionizing radiation:

1. Medical radiation

2. Mining of radioactive elements

3. Radon

Carcinogenic effects of neoplastic therapy, like alkalyting agents will kill rapidly dividing cancer cells through direct DNA damage but can:

damage normal cells and confer a significant risk of solid and hematologic malignancies

CT scans (for diagnosis and surveillance), constitute significant:

radiation exposure

These are mutations that drive cancer formation.

Driver mutations