Neoplasia Flashcards
(119 cards)
1
Q
Define neoplasia
A
abnormal growth of cells that persists after the initial stimulus is removed, irreversible
2
Q
Define dysplasia
A
pre-neoplastic alteration in which cells show disordered tissue organisation.
It is not neoplastic = reversible - also represents altered differentiation.
Mild, moderate and severe dysplasia indicates worsening differentiation
3
Q
Define tumour
A
clinically detectable lump/swelling
4
Q
Define cancer
A
any malignant neoplasm
5
Q
Define metastasis
A
malignant neoplasm that has spread from its original site to a new non-contiguous site
original location is the primary site and the place to which it has spread is a secondary site
6
Q
Define anaplasia
A
Cells with no resemblance to any tissue
7
Q
When a benign/malignant tissue is described as well differentiated, what does that mean?
A
Tissue that closely resembles the parent tissue
8
Q
Define pleomorphism
A
increasing variation in size and shape of cells and nuclei
9
Q
Define progression
A
The process of a neoplasm emerging from a monoclonal population, characterised by the accumulation of yet more mutations
10
Q
Describe and compare benign and malignant tumours
A
Benign = confined to origin, pushing outer margin, rarely dangerous, do not metastasise.
Malignant = potential to metastasise, irregular outer margin/shape, may show areas of necrosis and ulceration (if on a surface)
11
Q
What are the microscopic characteristics of neoplasms showing varying degrees of differentiation?
A
With worsening diff individual cells = increasing nuclear size and nuclear to cytoplasmic ratio,
increased nuclear staining (hyperchromasia),
more mitotic figures and increasing variation in size and shape of cells and nuclei
12
Q
Define grade
A
Clinicians use the term grade to indicate differentiation, high grade being poorly differentiated
13
Q
Distinguish between in-situ and invasive malignancy
A
In-situ = no invasion through epithelial basement membrane
Invasive = penetrated through basement membrane
14
Q
What 3 factors enable a neoplasms to come about?
A
Initiators, mutations, promotors
15
Q
Describe clonality of neoplasms
A
combination of initiators/promoters = expanded, monoclonal population of mutant cells.
Chemicals, infections, radiation = initiators but can also act as promoters.
Mutations can be inherited
16
Q
What is lyonisation?
A
In early female embryogenesis one allele is randomly inactivated in each cell
17
Q
What are proto-oncogenes?
A
Play normal role in cell signally for cell growth – when they change/mutate they remain always switched on
18
Q
What are tumour suppressor genes?
A
Recessive (have to inactivate both alleles)
normally oppose/suppress neoplasm formation,
inhibiting cell cycle,
become inactive in cancer
19
Q
What does the suffix –oma mean?
A
Benign neoplasm
20
Q
Define carcinoma
A
Epithelial malignant neoplasm
21
Q
Define sarcoma
A
Stromal malignant neoplasm
22
Q
Define blastomas?
A
Formed from immature precursor cells
23
Q
Where is squamous carcinoma found?
A
Squamous epithelial = skin larynx, oesophagus
24
Q
What is adenocarcinoma?
A
Epithelial neoplasm of the glands
25
What is malignant melanoma?
Neoplasm of melanocytes or cells that devel from melanocytes
26
What is a teratoma?
Tumour composed of tissues not normally present – germ cell origin forms cell representing all 3 germ cell layer
27
What is Hodgkin’s lymphoma?
Type of lymphoma – with the presence of multinucleated Reed–Sternberg cells (RS cells) in lymph nodes
28
What does adenoma refer to?
Glandular
29
What is a papilloma?
Benign epithelial tumour growing exophytically (outwardly projecting)
30
Where is transitional cell carcinoma found?
transitional epithelial = bladder, ureters
31
What is a benign mesenchymal tumour?
Connective tissue neoplasm
32
What is a glioma?
Benign connective tissue neoplasm – in the brain/spine
33
Lymphomas
malignant neoplasms of lymphocytes, mainly affecting lymph nodes
34
What is a germ cell neoplasm?
arise from pluripotent cells, mainly in the testis or ovary
35
What is leukaemia?
neoplasm of blood-forming cells arising in the bone marrow
36
What is a myeloma?
Malignant neoplasm of plasma cells
37
What is a neuroendocrine tumours?
Arise from hormone secreting cells distributed throughout the body
38
Define invasion
Property of malignant neoplastic cells enabling them to infiltrate normal tissues and enter blood vessels/lymphatics
39
Outline the process that leads to metastasis
Grow/invade at primary site,
Enter a transport system and lodge at a secondary site,
Grow at the secondary site to form a new tumour (colonisation)
40
Invasion involves what 3 important alterations?
Altered adhesion, stromal proteolysis and motility
41
Explain epithelial-to-mesenchymal transition
Altered adhesion, stromal proteolysis and motility
= create a carcinoma cell phenotype that sometimes appears more like a mesenchymal cell than an epithelial cell
42
How is adhesion altered in carcinoma cells?
reduction in E-cadherin expression, changes in Integrin expression
43
How is stromal proteolysis altered in neoplasia?
cells must degrade basement membrane and stroma to invade
= altered expression of proteases, notably matrix metalloproteinases (MMPs)
44
How is motility altered in carcinoma cells?
changes in the actin cytoskeleton.
Signalling through integrins is important and occurs via small G proteins such as members of Rho family.
45
Describe the routes of metastases
Lymphatic,
blood: via capillaries and venules,
transcoelomic: fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles)
46
What is a micrometastases?
Surviving microscopic deposits that fail to grow - apparently disease-free person may harbour many micrometastases, a phenomenon known as tumour dormancy
47
Outline what determines the site of metastases
1) where the regional drainage of blood (first capillary bed)/lymph (lymph node)/coelomic (elsewhere in coelomic space) fluid drain to.
2) seed and soil = interactions between malignant cells and local tumour environment (niche)
48
How do carcinoma spread vs sarcomas?
C = lymph. S = blood
49
List the common sites of blood-borne metastases
Lung, bone, liver, brain
50
List the neoplasms that most frequently spread to bone
Breast, bronchus, kidney, thyroid, prostate
51
How can the effects of a neoplasm be broken down?
Local = Primary neo, secondary neo.
Systemic = burden, hormones, miscellaneous
52
What is a paraneoplastic syndrome?
The systemic effects a neoplasm has on the body
53
Which neoplasms commonly cause osteolytic lesions?
Osteosarcoma of the knee, breast/kidney/lung cancer metastasis
54
which neoplasms commonly cause sclerotic lesions?
Prostate adenocarcinoma
55
Describe the local effects of benign/malignant neoplasms
1) Direct invasion/destruction of normal tissue.
2) Ulceration at surface = bleeding.
3) Compression of adjacent structures.
4) Blocking tubes/orifices
56
Describe the systemic effects of neoplasms
1) Endocrine: hormone prod by endocrine tumour, ectopic hormone prod.
2) Haematological: anaemia, thrombosis, DIC.
3) Neurological.
4) Dermatological.
5) General: cachexia, malaise, immunosuppression, fever, finger clubbing, hypercalcaemia, pruritis, myositis
57
Discuss colorectal carinoma
predisposing = diet, obesity, smoking, lack of physical activity
pres = blood in the stool, a change in bowel movements, weight loss, lethargy
macroscopic = tumor growing outward
microscopic = irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma
staging = TNM
marker = over express cyclooxygenase-2 (COX-2) enzyme
screening = fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy
58
What is the presentation and appearance of osteosarcoma?
pres = bones pain
macroscopic = tumour on the bone
microscopic = neoplastic osteoblast
59
What is the presentation and appearance of ovarian teratoma?
pres = pain/pressure in pelvis, irregular periods
macroscopic = contain hair, sebum, teeth
microscopic =tissue of all three germ layers
60
What is the presentation of chronic lymphocytic leukaemia?
pres = enlarged lymph nodes , lethargy, breathless, hepatosplenomegaly
61
What is the presentation and appearance of uterine leiomyoma?
Benign tumours from overgrowth of SM and CT in the uterus
pres = excessive menstrual bleeding (menorrhagia), anemia, infertility
macroscopic = multiple tumours
microscopic = spindle cells
62
What is the most frequent cancer in men/women?
prostate/breast
63
What are the 2 most common oesophagal tumours?
squamous cell carcinoma
adenocarcinoma
64
What is an exophytic tumour?
grows out from the surface
common in benign neoplasms, indicated non-invasive
65
What is a papillary tumour?
finger like projections
66
What is a polypoid tumour?
exophytic mass often on a stalk
67
What is a sessile tumour?
raised by flat
68
What is an annular tumour?
encircling like a ring
69
What is an endophytic tumour
invasion into surrounding tissue, irregular tumour margin
70
When is tumour necrosis seen?
when the tumour grows rapidly and out-strips its blood supply
usually a feature of malignant tumours
71
What is a lipoma?
benign neoplasm of adipose tissue
72
What is kaposi's sarcoma?
vascular neoplasm caused by human herpes virus 8 (HHV8)
usually in HIV +ve
73
What does carcinogenesis mean?
causes of cancer
74
Explain the multifactorial nature of neoplasia pathogenesis
Intrinsic = hereditary, age, gender, hormonal
extrinsic = environment, behaviour, lifestyle
75
Explain how migration studies illustrate the relative contribution of intrinsic and extrinsic factors
Japanese-USA migration studies show 85% cancer risk extrinsic
76
Outline extrinsic carcinogenic agents and their mechanisms of action
Chemicals = polycyclic hydrocarbons, aromatic amines, e.g., 2-naphylamine, nitrosamines
Radiation = UV and ionising
Infections = HPV, Epstein Barr virus, hep B/C, HIV, Helicobacter pylori, parasites
77
What are pro-carcinogens?
Chems converted to carcinogens by CP450
78
How is HIV carcinogenic?
acts indirectly by lowering immunity and allowing other potentially carcinogenic infections to occur
79
How is HPV carcinogenic?
direct carcinogen because it expresses the E6 and E7 proteins that inhibit p53 and RB protein function respectively, both of which are important in cell proliferation.
80
How is hepatitis carcinogenic?
indirect carcinogens that cause chronic liver cell injury and regeneration
81
The functions of proto-oncogenes
Abnormally activated versions of normal genes that enhance neoplastic growth
82
What is a tumour suppressor gene?
Inhibit neoplastic growth
Both alleles inactivated in neoplasia
83
What is the role of RAS?
Proto-oncogene
Encodes G protein that pushes cell past cell restriction point
84
What is the role of c-myc?
Transcription factors
85
What is the role of c-erbB-2 (HER-2)?
Growth factor receptor
86
What is the role of RB protein?
Major cell-cycle checkpoint = inhibit free entry in
Inactivation in both alleles in neoplasia
87
What is the role of p53?
Role in inducing apoptosis
88
What are caretaker genes?
Genes that maintain genetic stability
89
What is the inheritance of Hereditary non-polyposis colon cancer syndrome?
Autosomal dominant
germline mutation affects one of several DNA mismatch repair genes
90
What is the inheritance of Familial breast cancer?
Associated with BRCA1 BRCA2 genes that are important for repairing dsDNA breaks
Mutations can be found in sporadic malignant neoplasms
91
What is the inheritance Retinoblastoma and the two hit hypothesis?
Dominant
2 hit hypo = first hit was delivered through the germline and affected all cells in the body. The second hit was a somatic mutation
In contrast, sporadic retinoblastoma has no germline mutation and so requires both hits to be somatic mutations and to occur in the same cell
92
What is the inheritance of Xeroderma pigmentosum?
Autosomal recessive
Mutation in one of the 7 genes that affect DNA nucleotide excision repair
= very sensitive to UV damage = skin cancer at young age
93
What are the 3 stages in carcinogensis?
Initiation
Promotion
Progression
94
Outline initiation
= mutagens
95
Outline promotion
Cause prolonged proliferation
96
Outline progression including the adenoma-carcinoma sequence
= accum of multiple mutations
illustrated by colon carcinoma, which usually starts as a colonic adenoma, from which arises a carcinoma
97
What are the 6 hallmarks of cancer?
1) self-sufficiency in growth signals;
2) resistance to growth stop signals;
3) no limit on the number of times a cell can divide (cell immortalisation);
4) sustained ability to induce new blood vessels (angiogenesis);
5) resistance to apoptosis;
6) the ability to invade and produce metastases
98
What is genetic instability?
When chromosome segregation during mitosis is abnormal in malignant cells
99
How is asbestos exposure related to the devel of tumours?
Rock can be ground down to for fibers
Used for buildings
Fibers can crumble = carcinogenic = lodge in lung = mesothelioma
100
Why does the dye industry have linked to the devel of malignancies?
Exposure to 2-napthylamine = carcinogen
Show long delay between exposure and malignant neoplasm onset
Showed risk depends on carcinogen dosage
101
What are the conditions associated with an increased risk of malignancy?
UC
Cirrhosis
Hashimotos thyroiditis
Chronic atrophic gastritis
102
What is the leading cause of cancer-related death?
Lung 22%
103
What is the commonest type of cancer in adults?
Breast, prostate, lung, colon/rectum = carcinomas = 53%
104
What is the commonest type of cancer in children?
<14 = leukaemia, CNS, lymphomas
105
Describe what is meant by tumour stage and understand its significance
TNM staging translated into I, II, III, IV
Standardised across the world
106
Understand the principals of TNM staging
```
T = size of primary tumour (T1-4)
N = nodes mets (N0-3)
M = metastatic spread (M0-1)
```
107
Outline the Ann Arbor
Staging for lymphoma
I = single node
II = 2 separate regions on one side of diaphragm
III = spread both ides of diaphragm
IV = diffuse involvement of one or more extra-lymphatic organs such as bone marrow/lung
108
What is the Dukes’ staging systems
```
Staging for colorectal carcinoma
A = not through bowel
B = invasion through bowel wall
C = involve lymph nodes
D = distant mets
```
109
Describe what is meant by tumour grade and understand its significance
Used for squamous cell carcinoma and colorectal carcinoma
```
G1 = well-diff
G2 = moderately diff
G3 = poorly diff
G4 = undiff/anaplastic
```
110
Briefly outline the Bloom Richardson grading system for breast carcinoma
Assesses tubule formation, nuclear variation, number of mitoses
111
Describe the principles behind surgery as a treatments for cancer
Surgery = aim to de-bulk tumour
112
Describe the principle of radiotherapy as a treatment for cancer
x-rays or other types of ionising radiation to kill rapidly dividing cells.
Ds-DNA breaks cause damaged chromosomes preventing M phase from completing. Given in fractionated doses
113
Describe Chemo as a treatment for cancer
antimetabolites = mimics normal substrates in DNA replication
alkylating = cross link DNA, lead to apoptosis
Abx = inhib DNA topoisomerase needed for DNA synthesis
plant-derived = blocks microtubules assembly and mitotic spindle formation
114
Describe hormone therapy as a treatment for cancer
preventing oestrogen binding in breast cancer, blocking androgens binding in prostate cancer
115
Describe targeted molecular therapies as a treatment for cancer
drugs that block immune checkpoints, targeting chromosomal translocations
116
What is adjuvant treatment?
Why used: given after surgical removal of primary tumour to eliminate subclinical disease
Clinical disease free but on the premise they have micro-mets
117
What is neoadjuvant treatment?
why used: given to reduce size of primary tumour prior to surgical excision
In-operable to operable
118
Describe the use of tumour markers in diagnosis and monitoring of disease
Useful for monitoring tumour burden
Hormones = human chorionic gonadotropin (HCG)
Oncofetal antigens = carcinoembryonic antigen (CEA), alpha fetoprotein (AFP)
Specific proteins = prostate specific antigen (PSA)
Mucins and glycoproteins = cancer antigen 125 (CA 125)
119
Describe UK cancer screening programs
Aim = detect as early as possible when the chance of cure is highest
Problems = lead time bias, length bias (how long it takes for a growth to present), over diagnosis picking up benign but believing they are malignant)
E.g. Cervix, breast, colorectal
