17th lecture (oncology)

Question 1

Oncology definiton? monoclonal theory? Independent growth?

Answer 1

Neoplasm: abnormal cell or tissue growth (neoplastic cells overgrow the normal tissue)
The neoplasm is caused by a genetic alteration that causes it to divide, and all the neoplastic cells are from one neoplastic cell. This is called monoclonal theory of neoplastic cells.

Independent growth: the growth of normal cells is controlled by different factors such as cytokines, but tumors have no such control.

Question 2

what are the 2 different tissues that make up the neoplasm?

Answer 2

• The neoplastic cells itself (parenchyma)

- tissue that supplied by blood and vascular structure that helps the neoplastic cells (part of normal cell population)

Question 3

what are the biological characterisics of neoplasms?

Answer 3

• Autonome regulation of growth (normal cell growth is regulated by substances, but neoplastic cells have no regulation)
• Resistance to apoptosis
• limitless of cell division (telomerase shortening which limits cell division number is gone)
• loss of differentiation (blasts (immature cells) accumulate with no further differentiation)
• initiating angiogenesis (vessel formation)
• invasion into the tissues
• metastasis (can be seperated from original tumor and go to another organ)
• remodeling of cell metabolic pathways
• resistant to growth protecting signals
• ways to avoid the immune system

Question 4

Define neoplasm?

Answer 4

new and abnormal growth

Question 5

Define tumor?

Answer 5

enlargement (also characteristic for inflammation)

Question 6

Define cancer/carcinoma?

Answer 6

most of the cancers are related to epithelial tumors. The term came from a crab that would grab things with its claws and whatever it would grab would be difficult to get away from it.

Question 7

define benign? (in the terms of a tumor)

Answer 7

Tumor that has “good behaviour” such as;
- localized growth
- expansive growth (do not invade surrounding tissue) Easy to remove via surgery
- No metastasis (does not end up in another tissue)
Benign tumors also have a capsule around them.

Question 8

Define Malignant: (in the context of tumors)

Answer 8

This type of tumor will invade the surrounding tissues. They also have a chance to reacure after surgery. Metastatic.

Question 9

define semi-malignant (in the context of tumors)

Answer 9

• pleomorphic adenoma of salivatory glands; A benign neoplasm (capsulated) and seperated from the normal tissue. But in the parotid gland they are close to nerves and vessels, and they like to grow along the vascular structure. This makes it difficult to remove the tissue in one piece. Thus it can re-grow.
• Basal cell carcinoma; tumor of the basal cells that grows locally in the skin for a long time. Later they will form small nests in the surrounding tissues. The metastasis is very rare.
  it is a malignant tumor since it invades tissues, but is very easy to remove, rarely metastasis, rare reaccurance.

Question 10

Define borderline

Answer 10

ovarian cancer; cystadenocarcinoma; the neoplastic cells are localized to the epithelium and do not invade into the deeper tissue.
It is malignant and will later on invade.

Question 11

Describe the nomenclature of a A/ benign neoplasm

Answer 11

the suffice -oma is placed after a benign tumor;

• epithelial tumor: adenoma
• papillary: papillaryadenoma
• follicular: follicularadenoma
• cyst: cystadenoma
• mesenchymal: osteoma (new piece of bone growing on another piece of bone)
• mixed cell: epithelial and mesenchymal components (pleomorphic adenoma)
• germ cell tumor: teratoma

Question 12

Describe the nomenclature of B/ Malignant tumor

Answer 12

• epithelial = carcinoma (basal cell carcinoma) (squamous cell carcinoma)
• mesenchymal = sarcoma (angio sarcoma)
• Germ = malignant teratoma

Question 13

what are some of the exceptions to tumor cell nomenclature?

Answer 13

• lymph tumor = lymphoma (benign tumor the lymph does not exist to we assume its malignant)
• Lymphoma maligna is sometimes used as a term
• High and low grade lymphoma is used
• hodgkin lymphoma (when the cancer originates from a specific type of white blood cells called lymphocytes)
• Melanoma malignum: pigmented cell tumor
• glioma (tumor that occurs in the brain and spinal cord) from the glial cells
• astrocytoma: brain cancer coming from a particular kind of glial cells

Question 14

what are the morphological characteristics of different tumors?

Answer 14

Be = benign
M = malignant
B = borderline
                          Be, M, B
Differentiation: +   -    -
anaplasia:          -   +   +
Local growth:    -   +    -
Metastasis:       -    +    -

benign looks very similar to the normal tissue (differentiated)
if there is a vascular invasion or capsule invasion then its malignant
Anaplasia: loss of the mature or specialized feature of a cell or tissue (lack of differentiation).

Question 15

what are the characteristics of Anaplasia?

Answer 15

1. lack of differentiation/maturation (in basal cell carcinoma, all the epithelial cells will become basal cells)
2. Pleomorphism: different size, shape and morphology of the cell. For example muscle cells are quite uniform but if they are invaded by cancer then they will contain different shaped cells (rhabdomyocyte = rod-shaped muscle cell)
3. Loss of polarity
4. Nuclear abnormalities: they have larger nuclei but do to the aggressive DNA transcription, translation the DNA is more open; loose chromatin structure instead of the normal nucleoli.
5. mitotic activity is high, mitosis could be atypical = Triangular or disbalanced mitosis (chromosomes are not properly divided).
6. Functional alteration; epithelial cells that secrete chemicals could loose this function if they become neoplastic, others gain other types of expression; they could also start secreting hormones.

Question 16

describe how a local benign neoplasm that is a local growth can cause harm?

Answer 16

The local benign neoplasm; there is usually a cohesive cell group is capsulated making it easy to remove with surgery. They can cause pressure on the surrounding tissue, causing pressure atrophy. They can also grow along vessels making them hard to remove.

In malignant growth there are no cohesive sheets, and satellites of the tumor that invade the surrounding normal tissue and no capsule is present.

In situ growth: epithelial cells neoplastic cells growth respects the basement membrane. (this is before they disrupt the basement membrane) borderline?

Question 17

Describe the growth rate of neoplastic cell?

Answer 17

one neoplastic cell is about 10 micro-meter

• 30 divisions need to take place to form 1mg neoplasm (the 1mg is the limit at which we can detect the tumor)
• an aditional 10 divisions are needed to form 1kg (1kg is the largest tolerated cancer size in the human body)

Question 18

what is proliferative and non-proliferative fraction of the neoplastic cells?

Answer 18

one cell that suffers genetic damages and all the other daughter cell will become neoplastic cells.
when they reach the 1mg phase they may go down one of the following routes:
- G0 phase (getting out of the cell cycle)
- apoptosis
- necrosis
- differentiation

The routes above are called NON-proliferative phase (this phase happend AFTER the 1mg is reached)

Most cytostatic drugs affect only the proliferative phase since they affect cell division, mitosis. Since the cancer tissue is too close to the normal tissue its hard for the chemotherapy to select the cancer tissue from the normal one. Thus by the time we detect the tumor its already in the non-proliferative phase. This is why we use surgery to do the “de-bulking” of tumor to push the cell into proliferative phase to make chemotherapy more affective.

Question 19

Describe metastasis?

Answer 19

This is the strongest feature of malignancy. 3 way to metastasis:

1. to get on the surface of the sheets of the body cavities and grow along the organs (such as the peritoneum); tumors in the abdominal cavities (gastric colon, ovarian cancer) they may distrupt the organ, and get into the surface of the peritoneum. This is called carcinosis peritonei, lung cancer can disrupt the pleura causing carcinosis pleurae.
2. get into the lymphatics. Breat cancer can get into axillary lymph nodes as the cancer follow the lymphatic drainage. The 1st lymph nodes are called SENITNEL lymph nodes that is a tell-tale sign of metastasis.
3. get into the blood stream (hematogeneous) via venous structure since the arteries are more resistant to neoplasm.
   - portal: GI cancer it could metastasize in the liver
   - vena cava: metastasize in the lung (vena cava type spreading)
   - paravertebral: Prostate cancer drains into vertebral plexus causing metastasis in the vertebra.

Question 20

Describe the steps of metastasis? (metastatic cascade)

Answer 20

In a normal cell there are gap-junction connecting cells to seperate the cell from the tissue structure (E-cadherin is most important for linking cell) there need to be a mutated or decreased E-cadherin expression to liberate cells from the connective tissue. To allow the migration of the cells they need to dissolve the basement membrane and ECM.

1. decrease in E-cadherin expression
2. dissolve ECM and basement membrane (neoplastic cells secrete MMP (matrix metalloproteinases) to allow cell migration. They stimulate monocytes and fibroblasts to make the MMP or they could secret it themselves
3. migration of the cell once they are free of the ECM. (they stimulate themselves to migratie, autocrine)
4. vascular dissemination (they ingrow into the vascular system and they cover themselves via platelets and lymphocytes to mask themselves.
5. extravasation, when they reach a certain area they leave the vascular system and they start to grow and proliferate.