Module 2 - Neoplasia

Question 1

What is neoplasia

Answer 1

Neoplasia (cancer) is the unregulated growth of abnormal cells, with patterns of altered cell differentiation.

Question 2

What is a neoplasm?

Answer 2

A neoplasm is the new growth itself. It lacks normal regulatory controls over cell growth and division.

Question 3

Elements of normal tissue renewal and repair

Answer 3

proliferation, differentiation, and apoptosis.

Question 4

What is proliferation?

Answer 4

Proliferation is a process of cell division, is an adaptive process for new cell growth to replace old cells or when additional cells are needed. Neoplasms tend to have genetic abnormalities that cause excessive and uncontrolled proliferation that is regulated by normal growth regulating stimuli.

Question 5

What is differentiation

Answer 5

Differentiation is the process by which cells become more specialized with each mitotic division.

Question 6

What is apoptosis?

Answer 6

Apoptosis eliminates old (senescent), damaged, or unwanted cells through a process of controlled cell death.

Question 7

What is the role of proto-oncogenes?

Answer 7

Proto-oncogenes encode proteins that signal for the cell to proliferate through a tightly regulated process.

Question 8

What is the role of tumor suppressor genes?

Answer 8

Tumor suppressor genes encode proteins that inhibit cell growth and signal (when necessary) for apoptosis. For example, should a particular cell growth become unregulated, which if left unregulated could lead to tumor formation, the tumor suppressor genes will initiate apoptotic events to eliminate the potential tumor cells.

Question 9

Describe the cell cycle

Answer 9

The cell cycle is a process by which a cell duplicates its genetic information and divides between two genetically identical daughter cells. The G1 (gap 1) phase: DNA synthesis stops while the cell enlarges and both RNA and protein synthesis begins. The S phase: DNA synthesis occurs, producing two separate sets of chromosomes, one for each daughter cell. The G2 (gap 2) phase: DNA synthesis again stops while RNA/protein synthesis continues. These first three phases are called the interphase. At the end of each phase are cell cycle checkpoints which ensure the cell is ready to proceed to the next phase. If not, the cycle is halted and allowed to complete its replication or repair DNA damage (when detected), thereby ensuring all genetic information is passed on correctly. The M phase: consists of mitosis (dividing up the DNA) and cytoplasmic division. Some cells go from one mitotic division to another (epithelial cells) and others go into a resting phase called G0 when nutrients or growth factors are unavailable or when highly specialized cells first leave the cell cycle. Some highly specialized and terminally differentiated cells (neurons) may permanently stay in G0.

Question 10

What is the process of cell proliferation?

Answer 10

Cell proliferation is the process of increasing cell numbers by mitotic cell division. In normal tissues, the number of new cells being produced is equivalent to the number of cells dying or being shed.

Question 11

What are the two categories of human cells?

Answer 11

Gametes (ovum and sperm) and somatic (non-reproductive)

Question 12

What are the three groups of cells that proliferate?

Answer 12

1. Well differentiated neurons and cells of skeletal and cardiac muscles that rarely divide and reproduce.
2. Progenitor or parent cells that continue to divide and reproduce (blood, skin, and liver cells)
3. Undifferentiated stem cells that can enter the cell cycle and produce large numbers of progenitor cells if needed.

Question 13

What is cell differentiation?

Answer 13

Cell differentiation refers to the process by which cells become more specialized in their structure and function. As differentiation progresses, the process within each developing cell type must become more tightly regulated. We would not want cardiac cells to start differentiating into renal cells.

Question 14

What are progenitor cells?

Answer 14

Progenitor or parent cells are not yet fully differentiated to the same extent as mature specialized cells and yet are differentiated enough to give rise to daughter cells of the same lineage.

Question 15

What are stem cells?

Answer 15

Stem cells remain incompletely differentiated and dormant until they are needed. When needed, they begin to divide, producing not only other stem cells, but also cells capable of of carrying out the functions of the needed differentiated cells: Stem cell - (stem cell) + (progenitor cells…..differentiated cells)

Question 16

What are the two notable properties that stem cells possess?

Answer 16

1. Self-renewal, meaning the stem cell can undergo numerous mitotic divisions while maintaining an undifferentiated state.
2. Potency, which describes the differentiation potential of stem cells.
   Pluripotent stem cells, “master cells,” can potentially differentiate into any cell type.
   Multipotent stem cells can differentiate into only a few select types.
   Unipotent stem cells are restricted to a single cell type but can maintain self-renewal.

Question 17

What are the two types of stem cells?

Answer 17

1. Embryonic stem cells - play a major role in the developing embryo, giving rise to the three main germ layers (endoderm, mesoderm, and ectoderm) which in turn develop into all the organ systems of the body.
2. Adult stem cells have significant roles in homeostasis, contributing to tissue regeneration and replacement of cells lost to apoptosis.

Question 18

What is the difference between a tumor and a neoplasm?

Answer 18

A tumor is a cancerous mass of cells, but it can be caused by several conditions. A neoplasm refers to the new cell growths.

Question 19

What is the difference between a benign and a malignant neoplasm?

Answer 19

A benign neoplasm has well-differentiated cells, resemble the cells of tissues of origin, and have a slow progressive rate of growth. The grow by expansion and remain localized to their site of origin, not capable of metastasizing. They develop a fibrous capsule which aids in surgical removal. And benign tumors are less of a threat unless they interfere with vital functions (e.g. brain tumor compressing brain structures)

A malignant neoplasm invades and destroys tissue; grow rapidly, spread to other parts of the body via the circulatory or lymphatic systems, they lack well-defined margins, they can compress blood vessels, outgrow their blood supply which causes ischemia and tissue injury. Some secrete hormones, liberate toxins, or elicit an inflammatory response. Many secrete vascular endothelial cell growth factor which increases blood supply to the tumor and facilitates more rapid growth.

Question 20

What is anaplasia?

Answer 20

Anaplasia describes the loss of cell differentiation in cancerous tissue. These undifferentiated cancer cells display many morphological changes. The cells and nuclei have variations in size and shape (pleomorphism). Highly anaplastic cells resemble undifferentiated or embryonic cells, rather than the tissue of origin.

Question 21

What is seeding?

Answer 21

Seeding of cancer cells describes the process of how shed tumor cells enter circulation and move into similar or different body cavities. Most often, seeding occurs into the peritoneal cavity (e.g. ovarian cancer). This will cause fluid accumulation. Seeding into other areas of the body can also be a complication following the removal of cancerous cells - as the cells are disturbed during removal, the cancerous cells may migrate into new body cavities.

Question 22

What is metastasis?

Answer 22

Metastasis is when a secondary tumor develops in a location distant from the primary tumor. The secondary tumor usually retains many of the characteristics of the primary tumor, and this makes it possible to determine the site of the primary tumor.

Question 23

What is the sentinel node?

Answer 23

The sentinel node is the first lymph node to which the primary tumor drains. The extent of disease may be determined through lymphatic mapping and sentinel lymph node biopsy.

Question 24

What is angiogenesis?

Answer 24

Angiogenesis is the development of new blood vessels within the tumor.

Question 25

Describe the spread of hematologic cancers.

Answer 25

The cancerous cells enter the venous system that drains the site of the primary neoplasm. It then invades the surrounding extracellular matrix where it gains access to a blood vessel. If the cancerous cells survive its passage in the bloodstream, it must emerge in a favorable location, invade the surrounding tissue, begin to grow, establish a blood supply and growth factors.

Question 26

What are the genetic events that lead to oncogene formation?

Answer 26

Point mutation - a single nucleotide base change due to an insertion, deletion, or substitution.
Chromosomal translocation - the unusual movement or rearrangement of a segment of chromosomal DNA.
Gene amplification - unusual increase in the number of copies of a certain gene. This amplification leads to an unwanted over-expression of the gene. As the amount of proteins encoded by the gene drastically increases, the result is often an increase in cell proliferation.

Question 27

Describe role of tumor suppressor genes.

Answer 27

Tumor suppressor genes slow down cell division, repair DNA mistakes, or tell cells when to die. They inhibit the proliferation of cells in a tumor. If this functioned is removed, unregulated growth can occur.

Question 28

What are the genes that increase susceptibility to cancer?

Answer 28

Defects in DNA repair mechanisms, defects in growth factor signaling pathways, evasion of apoptosis, avoidance of cellular senescence, development of sustained angiogenesis, and metastasis and invasion.

Question 29

Describe the three stages that cause normal cells to become cancerous.

Answer 29

Initiation - exposure of cells to a carcinogenic agent that makes them vulnerable to cancer transformation. These agents can be physical, chemical, or biologic and cause irreversible alteration to the cellular genome.

Promotion - allows for the abundant growth of cells, usually triggered by multiple growth factors or chemicals. The result is reversible if the promoter substance is removed. Promotion can occur at any time, as initiated cells may be promoted even after long latency periods.

Progression - final step when tumor cells become malignant.

Question 30

Name the risk factors linked to cancer.

Answer 30

Heredity - BRCA 1 and 2 for breast cancer
Obesity
Hormones - breast, ovary, endometrium, and prostate
Immune mechanisms - a decline or impairment of the surveillance capacity of the immune system. AIDS associated with Kaposi sarcoma
Carcinogens - either direct reacting agents which are carcinogenic and active as soon as it enters the body or indirect reacting agents which must be metabolized before becoming active.
Smoking, dietary factors, alcohol
Ionizing radiation
UV radiation

Question 31

What are four DNA viruses that have been linked to cancer?

Answer 31

HPV - cervical cancer
EBV - Burkitt lymphoma
HHV-8 - Kaposi Sarcoma
HBV - liver cancer

Question 32

What are the potential clinical manifestations of cancer?

Answer 32

Tissue integrity compromised; bleeding is common.
Fluid in the pleural, pericardia, or peritoneal spaces.
Wasting - weight loss, wasting of body fat and muscle tissue, extreme weakness, anorexia, and anemia.
Fatigue and sleep disturbances.
Anemia - possibly due to the effects of treatment or because of blood loss, hemolysis, or impaired red blood cell production.

Question 33

How is cancer screening done?

Answer 33

Observation - skin, mouth, external genitalia
Palpation - breast, thyroid, rectum and anus prostate, lymph nodes
Lab tests and procedures - pap smear, colonoscopy, mammography

Question 34

How do tumor markers present?

Answer 34

1. Antigens expressed on the surface of tumor cells.
2. Substances released from normal cells in response to the presence of a tumor.
   Additional markers include hormones and enzymes that become overexpressed because of cancer or oncofetal proteins that are produced during fetal development and reappear later in life from benign or malignant neoplasms.

Question 35

What are the methods used to diagnose and stage cancer?

Answer 35

Blood tests for tumor markers, cytologic studies and tissue biopsy, endoscopic examinations, ultrasonography, xray studies, MRI, computed tomography (CT), and positron emission tomography (PET) scans.

Question 36

What are histologic and cytologic studies?

Answer 36

Laboratory methodologies used to examine the structural, compositional, and functional characteristics of tissues and cells.
Pap test - used to detect cancer cells examined on a prepared slide. Most often for cervical cancer, but also pleural or peritoneal fluid, nipple drainage, gastric and anal washings.
Tissue biopsy - removal of tissue for microscopic study and is essential in diagnosing the correct cancer and histology.
Immunohistochemistry - uses antibodies which recognize and bind to specific cell products or surface markers to correctly identify the desired antigen. Can be helpful to determine the site of origin of metastatic tumors by determining which tissues in the surrounding area have the same antigens.
Microarray technology - uses gene chips that can perform hundreds of miniature assays to detect and quantify the expression levels of a large number of genes.

Question 37

Describe the two main strategies for classifying cancer:

Answer 37

Grading - based on the cellular characteristics of the tumor and degree of abnormalities present; level of differentiation. Grades I-IV.
Staging - the assessment of the clinical spread of the disease, stages I-IV.

A more sophisticated staging system is the TNM system - tumor, nodes, metastasis.

Question 38

What are the three goals of cancer treatment?

Answer 38

Curative, control, palliative

Question 39

What are the five common cancer treatments?

Answer 39

Surgery
Radiation - uses high energy particles or waves to destroy or damage cancer cells, leads to creation of free radicals which damage cell structures. Radiation injures all proliferating cells but normal tissues is usually able to recovery from the damage more readily than cancerous tissue.
Chemotherapy - Prevent cell growth and replication by halting protein, DNA, and RNA synthesis while simultaneously inhibiting enzyme production and cell mitosis.
Hormonal therapy - consists of drugs designed to disrupt the hormonal environment of cancer cells and deprive cancer cells of the hormonal signals that otherwise would stimulate the cells to divide.
Biotherapy - uses immunotherapy and biologic response modifiers to change the person’s own immune response to cancer.

Question 40

What is a polyp?

Answer 40

A polyp is a growth that projects from a mucosal surface.

Question 41

What is carcinoma in situ?

Answer 41

It is the localized preinvasive lesion. They can typically be removed surgically or treated and recurrence is less likely.

Question 42

What are two broad etiologic causes of cancer?

Answer 42

1. The genetic and molecular mechanisms that transform normal cells to cancer cells.
2. The external factors such as age, heredity, and environmental agents.

Question 43

What are the 6 molecular and cellular mechanisms that are known to facilitate the development of cancer?

Answer 43

Defects in DNA repair mechanisms, defects in growth factor signaling pathways, evasion of apoptosis, avoidance of cellular senescence, development of sustained angiogenesis, and metastasis and invasion.

Question 44

What are paraneoplastic syndromes?

Answer 44

Paraneoplastic syndroms are symptoms not directly affected by the disease. Examples: inappropriate ADH secretion, Cushing syndrome due to ectopic ACTH production, and hypercalcemia.