pathology 11 - neoplasia

Question 0

what is hypertrophy? which of these are pre-neoplastic and whcih are not?
hyperplasia?
hypoplasia?
metaplasia?
dysplasia?

Answer 0

hypertrophy - increased cell size
hyperplasia - increased cell number e.g. mammary gland
(these 2 are not pre-neoplastic.

metaplasia - transformation of one adult cell type to another e.g. vit A deficiency (cell turns from columnar to squamous.
dysplasia - abnormal pattern of tissue growth
(these 2 are pre-neoplastic.)

hypoplasia - underdevelopment of an organ or tissue.

Question 1

what is neoplasia? what else could you call it? why do you need to be careful what you call it?

Answer 1

neoplasia is when cells undergoe genetic changes which allow them to be unresponsive to their normal growth controls and to expand abnormally. growth persists after cessation of the stimulus. could also call it tumour, cancer, growth. but be careful as many clients may not know what these actually mean.

Question 2

explain the differences between benign and malignant?
anaplastic?
pleomorphic?

Answer 2

benign - cells are well differentiated, uniform size and shape of cells, normal nuclear morphology, few mitoses, encapsulated and expansive, no metastasis (but this could also mean malignant)

malignant - poorly differentiated cell (anaplastic), variable size and shape (pleomorphic) , abnormal nuclear morphology, increased mitosis, non encapsulated and infiltrative, METASTASIS!! (definately malignant!)

Question 3

what do carcinogens do? give some examples or carcinogens?

Answer 3

they cause cancer. eg. UV light, chemicals, radiation.

Question 4

epithelial neoplasms? if benign what are they called? malignant?

Answer 4

benign - papilloma (surface epithelium) adenoma (glandular ep)

malignant - carcinoma (surface) adenocarcinoma (glandular)

Question 5

mesenchymal neoplasms: benign? malignant?

Answer 5

benign - ‘oma’ (fibroma, lipoma)

malignant - sarcoma (liposarcoma)

Question 6

round cell neoplasms: eg’s?

Answer 6

1. outside bone marrow = lymphosarcoma
2. in bone marrow = leukemia
3. mast cell tumour (common in dogs)

Question 7

other types of neoplasm?

Answer 7

blastoma (embryo)
melanoma
meningioma

Question 8

3 main causes of neoplasms at a genetic level?

Answer 8

1. single inherited mutated gene - rare. eg. retinoblastoma (RB gene)
2. multiple inherited genes (familial) eg. breast cancer
3. acquired somatic mutation - majority! accumulate over time.
   a) intrinsic factors - reactive O2 species/ DNA polymerase errors.
   b) extrinsic factors - chemicals, aflatoxin (fungi), bracken fern toxicity, radiation, viruses (herpes)

BOXERS are suceptible to all!!!!

Question 9

4 molecular determinants of neoplasia:

Answer 9

1. growth promoting oncogenes
2. growth inhibiting tumour supressor genes
3. apoptosis genes
4. DNA repair genes

Question 10

how do growth promoting oncogenes cause neoplasm? eg?

Answer 10

RAS - found in cytoplasm. growth factors signal through RAS to cause growth proliferation. - if it is mutated then can become always activated and results in constant signals for transcription genes.

Question 11

growth inhibiting tumour supressor genes: eg? (2 examples)

Answer 11

P53 - located in the cycle at the g2 - M checkpoint. it is a tumour supressor gene which inhibits growth if there are problems at this stage. ‘molecular policeman’ if mutated then cells can bypass checkpoint and grow out of control.

RB (retinoblastoma) - located at g1-S part of cell cycle. inhibits replication of DNA if something is wrong. prvents excessive replication.

Question 12

apoptosis genes? eg?

Answer 12

P53 again - recognises changes/damage and leads to apoptosis (controlled cell death) if it is mutated then cells will not be killed and may just avoid this stage.

Question 13

DNA repair genes - BRCA 1/2. associated with breast cancer. role?

Answer 13

they normally repair damaged DNA which is recognised in the cell cycle. if mutated then it can carry on and replicate even though damaged.

WNT - B - catenin. pro cancer gene.attached to E-cadherin so, if wounded then e-cadherin moves to allow B-catenin to proliferate cells.

Question 14

explain the role of angiogenesis in neoplasm formation? P53 ROLE? VEGF? RAS?

Answer 14

this is the formation of new blood vessels. neoplasms couldnt grow over 1-2mm without a blood supply. the cells themselves can alter the pro-angiogenic substances to promote new vessel growth. either they create new vessels from old ones or they can recruit endothelial cells from bone marrow. vessles provide energy for growth and divison and also are a route for metastasis.
P53 - supresses VEGF (vascular endothelial growth factor) RAS promotes this.

Question 15

3 ROUTES OF METASTASIS? distant spread of a neoplasm

Answer 15

1. haematogenous - via blood vessels eg. sarcoma.
2. lymphatic - common eg. carcinoma
3. transcolomic - eg. ovary - abdomen. seeding body cavities.

Question 16

explain the metastatic signature?

Answer 16

certain cells can metastasize and some cannot. they have a certain expresion of certain genes which aid this. - can be used to predict the metastatic potential of a neoplasm.

Question 17

immunity against neoplasms? when are you predisposed? MHC molecules? other ways?

Answer 17

if you are immunocompromised then you are more likely to get them. MHC molecules are what is presented on the surface of an invading cell. CD8 T cells and lymphocytes and NK cells and macrophages can recognise and destroy them. recognise surface antigens.
cancers have ways to avoid this - get rid of MHC. downregulate surface antigens so that immune system cant recognise them. may even have abnormal antigens eg. oncofoetal.

Question 18

MHC CLASS II? what does it do?

Answer 18

major histocompatability complex 2 - expressed on APC’S (atnigen presenting cells) and put it on the cell surface. CD4 T CELL THEN ATTACH and mature. t helper cells. so they help with immunity.

Question 19

MHC CLASS I?

Answer 19

cause programmed cell death by apoptosis. to do with CD8 cells. present to killer cells.

Question 20

stem cell theory? (2)

Answer 20

1. stochastic theory - al cells can maintain tumour growth
2. stem cell theory - CSC’s cancer stem cells - only these can form new cells. - target for therapy. only certain cells.