Topics A53-57. Neoplasm 1: General characteristics, Histology Classification, Growth Rate, Invasion, Metastasis

Question 1

Neoplasm definition

Answer 1

Simple definition: Abnormal mass or tissue, “new growth”

Other descriptions:

• Uncontrolled cell growth which exceeds normal tissue
• Genetic abnormality of cell which is passed to daughter cells
• Autonomous growth, independent from factors like hormones

Question 2

What 2 things are neoplastic tissue composed of?

Answer 2

1. Parenchyma: neoplastic cells
2. Stroma: connective tissue that is non-neoplastic but provides support, blood supply
   (basically the same as any other tissue)

Question 3

The big one: What are the 10 biological features of neoplastic tissue?

Answer 3

1. Autocrine growth
2. Resistance to apoptosis
3. Limitless capacity for growing/division
4. Loss of cell differentiation
5. Inducing angiogenesis
6. Invasion into tissues
7. Metastases
8. Remodeling of Metabolic Pathways
9. Insensitivity to Growth Signal Inhibitors
10. Evades the immune system

Question 4

What is a benign tumor?

Answer 4

A tumor with “favorable clinical behavior” - localized, doesn’t invade surrounding tissue, does not metastasize.

After surgery, there is no recurrence of benign tumors. They are usually encapsulated.

Benign tumor cells are usually more differentiated than malignant cells

Question 5

What is a malignant tumor?

Answer 5

A tumor with aggressive behavior. Grows rapidly, invades the surrounding tissue, provides metastases. The cells are poorly differentiated - do not resemble normal parenchymal cells.

Likely to reappear after surgery.

Question 6

What is an example of a tumor that cannot metastasize yet is still very dangerous? (blurs the definitions of benign and malignant)

Answer 6

Glial cell tumors: primary brain tumors that cannot get outside of skull, but can still be aggressive and dangerous

Question 7

What are the 2 “semi-malignant” tumors? Why do they fit this definition?

Answer 7

1. Basal cell carcinoma / basolioma: invades tissue locally, but after surgery there is no recurrence (really know this one because Hungarian from this dept first identified it, also this is the most common cancer)
2. Pleomorphic adenoma: a salivary gland tumor that is benign and encapsulated, yet recurs after surgery because it has protrusions along the nerves that are not easily removed

Question 8

What is the most-used example of a “borderline” tumor?

What is a borderline tumor?

Answer 8

Ovarian cystadenoma: epithelial tumor over the ovary. Epithelial cells do not invade the deep ovarian tissue, so it’s similar to malignant but with no invasion. May be the early phase of neoplasm.

Borderline tumors are ones whose behavior cannot be predicted by morphological presentation - mostly they don’t metastasize, but sometimes they do.

Question 9

What suffix do benign tumors usually get?

What suffix do malignant tumors usually get? (3 kinds)

Answer 9

Benign: -oma

Malignant:

• carcinoma (epithelial)
• sarcoma (mesenchymal)
• teratocarcinoma (germ cell)

Question 10

How do you call benign tumors of:

• Epithelium
• Mesenchyme
• Germ cell

Answer 10

• Epithelial: adenoma
• Mesenchymal: depends on origin (e.g. hemangioma, osteoma, fibroma)
• Germ cells: teratoma

Question 11

What are 3 exceptions to the -oma suffix where it’s used for malignant tumors instead of benign? (and it’s not part of longer suffix like carcinoma, sarcoma)

Answer 11

1. Lymphoma: only malignant, never benign
2. Melanoma: also always malignant (benign = nevus)
3. Astrocytoma, Glioblastoma: glial tumors named by their anatomical location more than histo appearance. Gliobastoma is high grade form.

Question 12

What are the 4 different classifications of lymphoma?

Answer 12

1. Low-grade lymphoma
2. High-grade lymphoma
3. Hodgkin lymphoma
4. Non-Hodgkin lymphoma

Question 13

What is a polyp?

Answer 13

A mass that projects from a mucosal surface. Can be benign or malignant

Question 14

What is a hamartoma?

Answer 14

Non-neoplastic, disorganized, tumorlike overgrowth of cell types regularly found within an affected organ

Example: Hemangioma - an irregular accumulation of blood vessels

Question 15

What is anaplasia?

Answer 15

Loss of differentiation. The neoplastic cells are pleomorphic: their size and shape are variable.

Maturation is blocked, they have abnormal nuclear morphology. Atypical mitosis occurs. May look vacuolar.

Cells lose their function and also polarity: e.g. epithelial layers are completely disoriented

Question 16

How differentiated are the cells in these neoplasms:

• Benign
• Malignant
• Semimalignant
• Borderline

Answer 16

• Benign: look mostly differentiated
• Malignant: Variable: often lose their differentiation
• Semimalignant: Mostly differentiated
• Borderline: Mostly undifferentiated

Question 17

What are the histo features of anaplasia?

Answer 17

1. Pleomorphism: variable shape and size
2. Hyperchromatism: dark staining nuclei
3. Increased nuclear-cytoplasmic ratio
4. Prominent nucleoli (commonly)

Question 18

Which type of neoplasm cells are anaplastic?

• Benign
• Malignant
• Semimalignant
• Borderline

Answer 18

• Malignant cells can be, with some exceptions

- Borderline tumors are too

Question 19

Can you give an example of a malignant neoplasm that is still well-differentiated?

Answer 19

Adenocarcinoma of the thyroid: normal glandular structure is visible in histology, just like its benign counterpart. However, there is a distinct invasive pattern too.

Question 20

What is the “monoclonal theory” of oncology?

How is it proven?

Answer 20

A single cell first becomes neoplastic, then all the other tumor cells are daughter cells of the original one.

This is proven by the homogeneity of isoenzymes like glucose-6-phosphate dehydrogenase (G6PD) and other X chromosome-linked markers. Also the HUMARA (human androgen receptor gene) is commonly used to determine clonality.
(Atherosclerotic plaques also have monoclonal G6PD isoforms)

Question 21

How many divisions does a tumor cell have to have made in order to be microscopically detectable?

What if it divides another 10 times after this point?

Answer 21

At least 30 divisions. Should make a tumor mass of ~ 1mg.

If it divides 10 more times, it can weigh up to 1kg theoretically. This could be lethal.

Question 22

What is the “proliferative phase” of tumor growth?
What is the “non-proliferative phase?”

What are some examples of cancers that stick in proliferative phase more, and which are more likely to be non-proliferative?

Answer 22

Proliferative: ~first 30 divisions or so, after which many cells go into non-proliferative phase: G0 phase, apoptosis, or maybe differentiate

Lymphomas, acute leukemias, small cell lung cancer are more proliferative

Breast and colon cancer are less proliferative

Question 23

Which type of cancers does chemotherapy work better on, proliferative or non-proliferative? Why?
How does this determine treatment?

Answer 23

Proliferative: paradoxically the most aggressively proliferating tumors also respond better to chemotherapy because of their fast division rate

Unfortunately many tumors have grown to where they are in non-proliferative, and so it’s better to surgically remove as much as possible and then the other cells will re-enter proliferative phase, and this is an ideal time for chemotherapy.

Question 24

How do benign tumors undergo local invasions?

Answer 24

“Expansive” invasion
Dividing cells push on the surrounding tissue, degenerating it, making the surrounding cells into a “pseudocapsule”

Or benign tumor is truly encapsulated with a fibrous CT layer

Question 25

How do malignant tumors undergo local invasions?

Answer 25

They infiltrate the surrounding tissue, without forming a capsule or pseudocapsule. It's difficult to define the border.

Question 26

What is desmoplasia?

Answer 26

Fibrous growth caused by malignant neoplasia: neoplastic cells produce cytokines that initiate fibroblasts and scar tissue proliferation. It will be sclerotic ("scirrhous") Invasive ductal breast carcinomas often have scirrhous, stellate appearance - "orange peel" phenomenon as the scar tissue contracts and pulls on the skin

Question 27

How does a semimalignant invasion appear histologically?

Answer 27

Appears benign, encapsulated with normal cells around it However, it is difficult to remove the protrusions. Some tissue fragments may regrow after removal

Question 28

What is carcinoma in situ?

Answer 28

Despite the epithelial neoplasm, the basement membrane is not disrupted and so the tumor has not become truly invasive. If you can remove the tumor before invasion, then the cancer can be cured. (Characteristic in epitheloid cancers like breast or prostate)

Question 29

What is most common molecule to bind neoplastic cells to one another? How does this relate to the first step of metastasis?

Answer 29

E-Cadherin: keeps epithelial cells together and produces anti-growth signals First step of metastasis: E-Cadherin level is decreased, and so the neoplastic cells can easily separate before they migrate. (EMT = Epithelial to Mesenchymal Transformation - E-cadherin function is lost)

Question 30

What substance do metastatic cancers produce to help them digest surrounding connective tissue?

Answer 30

Matrix metalloproteases They also mobilize monocytes/macrophages that also use metalloproteases to help them move

Question 31

How do metastases "hide" from the immune system in the circulation?

Answer 31

They get coated in platelets

Question 32

The first phase of metastasis (invasion of the extracellular matrix) has 3 steps:

Answer 32

1. Detachment of tumor cells from one another (E-Cadherin expression decreased) 2. Degradation of ECM: via matrix metalloproteinases 3. Migration of tumor cells: after they degrade the basement membrane of vessels or other tissues, they migrate

Question 33

The second phase of metastasis (spreading) has 3 different ways in which neoplastic cells spread

Answer 33

1. Spread via lymphatics: most common way. The lymphatic openings are more accessible than the blood system 2. Hematological spread: always starts on venous side, either through capillaries or A-V shunts. 3. Spread via body cavities: e.g. lung cancer that infiltrates the pleural space ("carcinosis pleurae")

Question 34

What is a sentinel lymph node? | What is a "skip metastases?"

Answer 34

Sentinel lymph node: the first lymph node that could be reached from a cancer. Dyes are injected into the tumor to visualize it. Normally, if the sentinel lymph node is intact, then the other lymph nodes are also non-cancerous. However, "skip metastases" can occur where the sentinel lymph node was skipped and alternative pathways were taken.

Question 35

Where is Virchow's lymph node? What is the significance?

Answer 35

It's the left supraclavicular lymph node. Stomach cancer may spread there, and this would be the most easily accessible/palpable.

Question 36

How can hematogenous spreading enter the systemic circulation?

Answer 36

It can cross arterio-venous shunts and go directly into the arterial circulation (But this is rare)

Question 37

What are the 3 courses of hematogenous spreading of metastases?

Answer 37

1. Cava metastasisl: Neoplasm travels through the vena cava, then the right side of the heart, and then spread first to the lung 2. Portal metastasis: any of the organs that drain through the portal vein will go through the liver before it drains into the IVC, so liver metastases are common. 3. Vertebral metastasis: prostate has drainage to perivertebral plexuses, so prostate cancer may cause spinal metastases

Question 38

Which 2 organs can produce tumors that have "snake-like" growing through the vascular structures?

Answer 38

1. Kidney: snake-like growing along vascular wall can even reach the heart 2. Liver tumor: may grow into the portal system or hepatic veins

Question 39

Which of these neoplasms can produce metastases? - Benign - Malignant - Semimalignant - Borderline

Answer 39

- Benign: No - Malignant: Yes - Semimalignant: No - Borderline: No

Question 40

Which of these neoplasms can invade locally? - Benign - Malignant - Semimalignant - Borderline

Answer 40

- Benign: Not really, won't cross BM - Malignant: Yes - Semimalignant: Maybe - Borderline: No

Question 41

What is the rate of growth of these neoplasms? - Benign - Malignant - Semimalignant - Borderline

Answer 41

- Benign: Low - Malignant: High - Semimalignant: Low - Borderline: Low