Oncology: Pathology - Neoplasia Flashcards

1
Q

Define neoplasia

A

An abnormal mass of tissue, the growth of which exceeds (and is uncoordinated with) that of normal tissue and persists in the same excess manner after cessation of the stimuli which evoked the change

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2
Q

Define differentiation

A

The extent to which neoplastic cells resemble comparable normal cells, both morphologically and functionally

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3
Q

Define anaplasia. What are the five characteristics of anaplasia?

A

A lack of differentiation, characterised by:
1. Pleiomorphism
2. Abnormal nuclear morphology
3. Mitoses
4. Loss of polarity (disturbed orientation of cells)
5. Other changes (e.g. formation of tumour giant cells, necrosis)

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4
Q

Define pleiomorphism

A

Variation in size and shape of cells and nuclei

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5
Q

Define dysplasia

A

A loss in the uniformity of individual cells (pleiomorphism) as well as a loss in their architectural organisation (morphologic change, encountered principally in epithelia)
Mitotic figures more abundant than usual, but almost always conform to normal patterns

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6
Q

Is dysplasia reversible or irreversible?

A

Mild-to-moderate dysplasia is reversible if the stimulus is removed, and does not necessarily progress to cancer

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7
Q

Define grading

A

An estimate of the clinical gravity of a tumour, based on the degree of differentiation and the number of mitoses within the tumour
Generally ranges from two (low- vs high-grade) to four categories within a grading system

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8
Q

What are some of the pitfalls of grading?

A

Imperfect because different parts of tumour may display different degrees of differentiation, and grade may change with growth

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9
Q

Define staging

A

An estimate of the clinical gravity of a tumour, based on the anatomic extent of the tumour

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10
Q

What are the two main staging systems in use?

A
  1. TNM:
    - T = tumour
    - N = lymph nodes
    - M = metastases
    - Assigned a number based on extent and specific regions of involvement (varies between different cancers)
  2. American Joint Committee (AJC)
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11
Q

Define cancer

A

A term for all malignant tumours

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12
Q

Define carcinoma in situ

A

Marked dysplastic changes involving the entire thickness of the epithelium, but the lesion is confined to the normal tissue
Considered to be a preinvasive neoplasm

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13
Q

What are the two main structural components of a neoplasm? Which of these informs the nomenclature of the tumour?

A
  1. Parenchyma*: clonal (proliferating) neoplastic cells
  2. Reactive stroma: non-neoplastic supportive tissue (connective tissue, blood vessels, variable numbers of macrophages and lymphocytes)
  • nomenclature of tumours based on parenchymal component
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14
Q

How are benign tumours named?

A

Add -oma to cell type for all benign mesenchymal tumours (e.g. fibroma, chondroma, osteoma)
Benign epithelial tumours are variably classified based on cells of origin (e.g. adenoma), microscopic pattern (e.g. papilloma), or macroscopic architecture (e.g. cystadenoma)

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15
Q

How are malignant tumours named?

A

Tumours mesenchymal in origin are called sarcomas (e.g. fibrosarcoma, chrondrosarcoma, leiomyosarcoma, rhabdomyosarcoma)
Tumours epithelial in origin are called carcinomas (e.g. adenocarcinoma if glandular growth pattern, squamous cell carcinoma if produces recognisable squamous cells)

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16
Q

Compare and contrast benign vs malignant tumours in terms of their degree of cellular differentiation, rate of growth, patterns of local invasion, and propensity to metastasise

A
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17
Q

What % of newly diagnosed patients with solid tumours (excluding skin cancers other than melanoma) present with metastases?

A

30%

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18
Q

What is an unequivocal sign of malignancy? What is the next-most reliable feature?

A

Metastasis (benign tumours do not metastasise)
Next-most reliable feature is local invasion

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19
Q

Describe the four steps involved in local invasion of malignant tumours

A
  1. Detachment of tumour cells from each other via downregulation of epithelial cadherins
  2. Attachment to matrix proteins laminin and fibronectin via cell surface receptors
  3. Degradation of extracellular matrix via secretion of proteolytic enzymes by tumour cells
  4. Migration of tumour cells (poorly understood)
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20
Q

What are three possible routes of metastasis of cancers and which types of cancers are most commonly utilise each?

A
  1. Seeding of body cavities and surfaces (e.g. peritoneal, pleural, pericardial, subarachnoid): particularly characteristic of ovarian carcinoma
  2. Lymphatic spread: most common initial pathway for carcinomas but also used by sarcomas
  3. Haematogenous spread: typical of sarcomas but also seen with some carcinomas
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21
Q

Describe the typical lymphatic spread of breast carcinoma

A

Most carcinomas of the breast arise in the upper outer quadrant which drains to the axillary lymph nodes
If develops in inner quadrants, drains via nodes along internal mammary artery to infra- and supra-clavicular nodes

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22
Q

Describe the typical lymphatic spread of lung carcinomas which arise in the major respiratory passageways

A

Drain to perihilar and mediastinal nodes

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23
Q

Which types of blood vessels are more frequently invaded by metastasising tumour: arteries or veins?

A

Veins as they are more thin-walled

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24
Q

Is nodal enlargement in proximity to a cancer always indicative of metastatic spread?

A

No: may be purely reactive

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25
Q

What are the most common sites of haematogenous spread and why?

A

Lung: receives caval venous outflow
Liver: receives portal venous outflow

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26
Q

Why do cancers located in close proximity to the vertebral column (e.g. thyroid, prostate) tend to metastasise there?

A

Because they embolise via the paravertebral plexus

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27
Q

Describe the pattern of haematogenous spread that can be seen with renal cell carcinoma. Which other cancer displays a similar pattern of metastasis?

A

May grow into and within renal vein before extending into IVC (may even reach right side of heart)

HCC may similarly grow into portal venous channels

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28
Q

What are the three cellular mechanisms dictating the distribution of metastases?

A
  1. Tumour cell adhesion molecules: ligands that are normally preferentially expressed on target organ cells
  2. Chemokines: for target organs present in tumour cells
  3. Chemoattractants: from target cells
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29
Q

What are four most commonly diagnosed cancers in men vs women (and their relative proportions)?

A

Men:
1. Prostate (33%)
2. Lung (13%)
3. Colorectal (10%)
4. Others (18%)

Women:
1. Breast (31%)
2. Lung (12%)
3. Colorectal (11%)
4. Others (22%)

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30
Q

What cancers cause the most deaths in men vs women (and their relative proportions)?

A

Men:
1. Lung (31%)
2. Colorectal (10%)
3. Prostate (10%)
4. Others (23%)

Women:
1. Lung (26%)
2. Breast (15%)
3. Colorectal (10%)
4. Others (23%)

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31
Q

What is the relative proportion of cancer risk attributable to environmental vs heredity factors?

A

Environmental ~65%
Hereditary 26-42%

32
Q

What is the causative gene, pattern of inheritance, and cancer predisposition in retinoblastoma?

A

Causative gene: RB1 (tumour suppressor)
Pattern of inheritance: AD
Cancer predisposition: retinoblastoma, others especially osteosarcoma

33
Q

What is the causative gene, pattern of inheritance, and cancer predisposition in familial adenomatous polyposis?

A

Causative gene: APC (tumour suppressor)
Pattern of inheritance: AD
Cancer predisposition: colon cancer

34
Q

What is the causative gene, pattern of inheritance, and cancer predisposition in Li-Fraumeni syndrome?

A

Causative gene: p53 (tumour suppressor)
Pattern of inheritance: AD
Cancer predisposition: various

35
Q

What is the causative gene, pattern of inheritance, and cancer predisposition in multiple endocrine neoplasia 1/2?

A

Causative gene: MEN1, RET (transcription factor, tyrosine kinase)
Pattern of inheritance: AD
Cancer predisposition: adrenal, thyroid, parathyroid

36
Q

What is the causative gene, pattern of inheritance, and cancer predisposition in hereditary nonpolyposis colon carcinoma?

A

Causative gene: MSH2, MSH6, MLH1 (DNA mismatch repair)
Pattern of inheritance: AD
Cancer predisposition: colon, small intestine, endometrial, ovarian

37
Q

Seven important physiological changes seen in tumour cells

A
  1. Self-sufficiency in growth signals
  2. Insensitivity to growth inhibitory signals
  3. Evasion of apoptosis
  4. Limitless replicative potential
  5. Sustained angiogenesis
  6. Ability to invade and metastasise
  7. Defects in DNA repair
38
Q

What four classes of genes are involved in the molecular basis of carcinogenesis?

A
  1. Proto-oncogenes (growth promoting)
  2. Tumour suppressor genes (growth inhibiting)
  3. Genes regulating apoptosis
  4. Genes involved in DNA repair
39
Q

What is the Warburg effect? What is the clinical relevance of this?

A

Even in presence of ample oxygen, cancer cells will preferentially shift glucose metabolism from oxygen-dependent mitochondrial mechanisms to glycolysis (“aerobic glycolysis)
Responsible for PET avidity of cancers (cells are “glucose hungry”)

40
Q

Four examples of proto-oncogenes

A
  1. RAS
  2. RET
  3. ABL
  4. C-MYC
41
Q

Four examples of tumour suppressor genes

A
  1. APC
  2. p53
  3. BRCA 1/2
  4. RB1
42
Q

11 examples of chronic inflammatory states associated with increased risk of cancer

A
  1. Asbestosis/silicosis
  2. Bronchitis
  3. Cystitis
  4. Gingivitis
  5. IBD
  6. Lichen sclerosis
  7. Chronic pancreatitis
  8. Reflux oesophagitis
  9. Sialadenitis
  10. Sjogren syndrome
  11. Hashimoto thyroiditis
43
Q

9 examples of chronic or recurrent infectious states associated with increased risk of cancer

A
  1. Cholangitis
  2. Chronic cholecystitis
  3. Gastritis/ulcers due to H. pylori
  4. Hepatitis
  5. EBV
  6. AIDS
  7. Osteomyelitis
  8. PID
  9. Chronic cystitis
44
Q

List six classes of carcinogenic chemical agents, giving examples. Which of these are direct-acting carcinogens and which are procarcinogens requiring metabolic activation?

A

Direct-acting carcinogens:
1. Alkylating agents: cyclophosphamide, busulfan (use in cancer treatment and for immunosuppression)

Procarcinogens requiring metabolic activation:
2. Aromatic hydrocarbons: found in cigarette smoke, increase risk of lung cancer
3. Aromatic amine/amides, azo dyes: B-naphthylamine (previously used in rubber industry) increases risk of bladder cancer
4. Natural plant/microbial products: aflatoxin B from Aspergillus increases risk of HCC
5. Nitrosamines and amides: synthesised in GIT from ingested nitrites or proteins and increase risk of gastric cancer
6. Miscellaneous: asbestos, vinyl chloride, nickel, oestrogens

45
Q

Describe two types of carcinogenic radiation and the cancers associated with them

A
  1. Natural UV radiation (especially UVB): induces DNA damage (+/- immunosuppression) and increases risk of skin cancers
  2. Ionising radiation: increases risk of myeloid leukaemias and thyroid cancer (rarely breast and lung cancer)
46
Q

Give three examples of DNA viruses associated with increased cancer risk

A
  1. HPV: cervical cancer
  2. EBV: Burkitt lymphoma, nasopharyngeal carcinoma, B cell lymphomas and some types of Hodgkins lymphoma
  3. HBV: HCC
47
Q

Give an example of a RNA oncogenic virus associated with increased cancer risk

A

HTLV-1: leukaemia, lymphoma

48
Q

H. pylori infection is associated with an increased risk of which cancers?

A

Gastric lymphoma and carcinoma
MALToma (B cell tumour)

49
Q

What are six mechanisms of immune evasion displayed by malignant neoplasms?

A
  1. Selective outgrowth of antigen-negative variants
  2. Loss or decreased expression of MHC molecules
  3. Lack of costimulation
  4. Immunosuppression
  5. Antigen masking
  6. Apoptosis of cytotoxic T cells
50
Q

What are three possible sequelae of the local (physical) effects of tumour growth?

A
  1. Impingement/compression of adjacent structures
  2. Bleeding and infection due to ulceration through adjacent tissues
  3. Symptoms resulting from tumour rupture or infarction
51
Q

Is hormone production more commonly seen in benign or malignant neoplasms?

A

Benign (malignant may lack cellular machinery due to loss of differentiation)

52
Q

What is the pathogenesis of cancer cachexia?

A

Unclear but not related to metabolic demands of tumour or anorexia of patient
Thought to be due to TNF release in response to tumour cells

53
Q

Define cancer cachexia

A

Progressive loss of fat and lean body mass, with lethargy, weakness, and loss of appetite

54
Q

Define paraneoplastic syndrome

A

Symptom complexes that occur in patients with cancer that cannot be readily explained by local or distant spread of the tumour, or by release of hormones normally produced by the tissue of origin

55
Q

What are six types of paraneoplastic syndromes? Give examples of each

A
  1. Endocrinopathies:
    - Cushing syndrome
    - SIADH
    - Hypercalcaemia
    - Hypoglycaemia
    - Carcinoid
    - Polycythaemia
  2. Nerve and muscle syndromes:
    - Myaesthenia
  3. Dermatologic disorders:
    - Acanthosis nigricans
    - Dermatomyositis
  4. Osseous, articular and soft-tissue changes:
    - Hypertrophic osteoarthropathy and clubbing of fingers
  5. Vascular and haematologic changes:
    - Venous thrombosis (Trousseau phenomenon)
  6. Others:
    - Nephrotic syndrome
56
Q

Give three examples of cancers that can cause Cushing syndrome via a paraneoplastic syndrome. What is the mechanism?

A
  1. Small cell lung Ca
  2. Pancreatic Ca
  3. Neural tumours

Via release of ACTH or ACTH-like substance

57
Q

Give two examples of cancers that can cause SIADH via a paraneoplastic syndrome. What is the mechanism?

A
  1. Small cell lung Ca
  2. Intracranial neoplasms

Via release of ADH or ANP

58
Q

Give two examples of cancers that can cause SIADH via a paraneoplastic syndrome. What is the mechanism? How does this manifest clinically?

A
  1. Squamous cell Ca
  2. Breast Ca
  3. Renal Ca
  4. Adult T-cell leukaemia/lymphoma
  5. Ovarian Ca

Via release of PTH-related peptide, TGF-a, TNF, IL-1
Manifests clinically with symptoms of hypercalcaemia and bone resorption (NOT due to metastases)

59
Q

Give two examples of cancers that can cause hypoglycaemia via a paraneoplastic syndrome. What is the mechanism?

A
  1. HCC
  2. Fibrosarcoma

Via release of insulin or insulin-like substance

60
Q

Give four examples of cancers that can cause carcinoid syndrome via a paraneoplastic syndrome. What is the mechanism?

A
  1. Bronchial adenoma (carcinoid)
  2. Pancreatic Ca
  3. Gastric Ca
  4. Appendiceal Ca

Via release of 5HT and bradykinin

61
Q

Give an example of a cancer that can cause polycythaemia via a paraneoplastic syndrome. What is the mechanism?

A
  1. Renal Ca

Via release of EPO

62
Q

Give three examples of cancers that can cause acanthosis nigricans via a paraneoplastic syndrome. What is the mechanism?

A
  1. Gastric Ca
  2. Lung Ca
  3. Uterine Ca

Mechanism is immunological and related to secretion of epidermal growth factor

63
Q

Give an example of a cancer that can cause hypertrophic osteoarthropathy and finger clubbing via a paraneoplastic syndrome. What is the mechanism?

A
  1. Bronchogenic Ca

Unknown mechanism

64
Q

Give two examples of cancers that can cause venous thrombosis via a paraneoplastic syndrome. What is the mechanism?

A
  1. Pancreatic Ca
  2. Bronchogenic Ca

Via tumour products (e.g. mucins that promote clotting)

65
Q

Which cancer(s) are associated with HCG?

A

Trophoblastic tumours
Nonseminomatous testicular tumours

66
Q

Which cancer(s) are associated with calcitonin?

A

Medullary carcinoma of thyroid

67
Q

Which cancer(s) are associated with catecholamine and its metabolites?

A

Phaeochromocytoma

68
Q

Which cancer(s) are associated with AFP?

A

HCC
Germ cell tumours of testis

69
Q

Which cancer(s) are associated with CEA?

A

Colon Ca
Pancreatic Ca
Lung Ca
Gastric Ca
Cardiac Ca

70
Q

Which cancer(s) are associated with PSA?

A

Prostate Ca

71
Q

Which cancer(s) are associated with neuron-specific endolase?

A

Small cell lung Ca
Neuroblastoma

72
Q

Which cancer(s) are associated with immunoglobulin?

A

MM
Other gammopathies

73
Q

Which cancer(s) are associated with CA-125?

A

Ovarian Ca

74
Q

Which cancer(s) are associated with CA-19-9?

A

Colon Ca
Pancreatic Ca

75
Q

Which cancer(s) are associated with CA-15-3

A

Breast Ca