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34 Cards in this Set

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What is dysplasia?

Dysplasia is the disordered growth with abnormal cytological appearance and tissue architecture.

What is a carcinoma in-situ?

A carcinoma in-situ is a dysplasia involving full thickness of epithelium with no penetration of basement membrane.

What is the definition of a tumour or neoplasm?

A tumour or neoplasm is an abnormal mass of tissue, with the following:



  1. Its growth exceeds the growth of normal tissues.
  2. Its growth is uncoordinated with the growth of normal tissues.
  3. Its growth continues after the stimulus that caused the tumour has disappeared.

A tumour or neoplasm is an abnormal mass of tissue, with the following three characteristics.

What is differentiation?

Differentiation refers to the degree of similarity in appearance and function, between tumour tissue and the tissue of origin.




Benign tumours are generally well differentiated; malignant tumours may be well differentiated or poorly differentiated.

Differentiation refers to the degree of s_________ in a___________ and f_______, between tumour tissue and the tissue of origin.




What is the difference between benign and malignant tumours?

What is anaplasia?

Anaplasia refers to poor differentiation; poorly differentiated tumours are described as analastic.




Benign tumours are never anaplastic, whereas malignant tumours are sometimes anaplastic.

What are some features seen in anaplastic tumour cells?


  1. Pleomorphism (variable size and shape of cells and cell nuclei)
  2. Abnormal nuclear morphology (increased size, hyperchromasia, prominent nucleoli)
  3. Mitoses (increased number; atypical)
  1. Pleomorphism
  2. Abnormal nuclear morphology
  3. Mitoses

Benign tumours grow as expansile masses. What are the characteristics of such tumours?


  • They do not infiltrate surrounding tissues
  • They do not invade
  • They are clearly demarcated from surrounding tissue
  • They often have a capsule

Four characteristics.

What is metastasis?

Metastasis is the distant spread of cancer via lymphatics or blood vessels.

What are the clinical features of benign tumours?

Slow growth


Ulceration is unusual


Hemorrhage is unusual


No evidence of metastasis

Growth


Ulceration


Hemorrhage


Metastasis

What are the clinical features of malignant tumours?

Rapid growth


Frequent ulceration


Frequent hemorrhage


Much evidence of metastasis

Growth


Ulceration


Hemorrhage


Metastasis

What is the gross appearance of a benign tumour?

Tumour edge is smooth due to expansile growth, and may be encapsulated


Bland, homogenous cut surface


No evidence of secondary spread

Tumour edge


Cut surface


Evidence of secondary spread

What is the gross appearance of a malignant tumour?

Irregular tumour edge, due to infiltrative growth


Variegated cut surface, due to hemorrhage and necrosis within tumour


Draining lymph nodes or adjacent structures may obviously be infiltrated (secondary spread)

Tumour edge


Cut surface


Evidence of secondary spread

What are the microscopical features of a benign tumour?

Good resemblance to tissue origin


Fairly uniform cell size and shape


Very few and all normal mitotic figures


No invasion of blood vessels, lymphatics or periueural space


No dysplasia in adjacent tissues

Resemblance to tissue origin


Cell size and shape


Mitotic figures


Invasion of blood vessels, lymphatics and perineural space


Dysplasia in adjacent tissues

What are the microscopical features of a malignant tumour?

Poor resemblance to tissue origin


Highly variable cell size and shape


Numerous and frequently abnormal mitotic figures, e.g. tripolar mitoses


Invasion of blood vessels, lymphatics and perineural space often present


Dysplasia in adjacent tissues sometimes present



Resemblance to tissue origin


Cell size and shape


Mitotic figures


Invasion of blood vessels, lymphatics and perineural space


Dysplasia in adjacent tissues

What are some causes of cancer?

Genetics


Age


Environment

What is the effect of age upon the cancer?

Incidence of cancer increases with age


Cancers seen in infancy and childhood are different from those seen in later life

What is a carcinogen?

A carcinogen is a substance capable of causing cancer in living tissue. Chemicals, microbes and radiation are all carcinogens.

What is the molecular basis of cancer?


  1. DNA damage
  2. Cells divide and mutations accumulate
  3. Mutations accumulate in correct combinations

What are the four classes of normal regulatory genes that are the principal targets of cancer-causing mutations?


  1. Growth-promoting proto-oncogenes
  2. Growth-inhibiting tumour suppressor genes
  3. Genes regulating programmed cell death (apoptosis)
  4. Genes involved in DNA repair

What are the hallmarks of cancer?


  1. Self-sufficiency in growth signals
  2. Insensitivity to growth-inhibitory signals
  3. Altered cellular metabolism
  4. Evasion of apoptosis
  5. Limitless replicative potential (immortality)
  6. Sustained angiogenesis
  7. Ability to invade and metastasize
  8. Ability to evade the host immune response

What are oncogenes?

Oncogenes are created by mutations in proto-oncogenes, and encode proteins called oncoproteins that have the ability to promote cell growth in the absence of normal growth-promoting signals.

Oncogenes are created by mutations in ________________, and encode proteins called _____________ that have the ability to ...?

What are the common mutations that activate oncogenes?

Point mutation


Translocation


Amplification

TAP

What are some functions of the protein products of tumour suppressor genes?


  • Transcription factors
  • Cell cycle inhibitors
  • Signal transduction molecules
  • Cell surface receptors
  • Regulators of cellular responses to DNA damage

What are the factors involved in the limitless replication potential of


  1. Evasion of senescence
  2. Evasion of mitotic crisis (usually due to upregulatin of telomerase)
  3. The capacity for self-renewal ("cancer stem cells")

What are the four steps of tissue invasion?


  1. Loosening of cell: cell contacts (inactivation of E-cadherin)
  2. Degradation of ECM (proteolytic enzymes secreted by tumour cells and stromal cells, e.g. MMPs and cathepsins)
  3. Attachment to novel ECM components
  4. Migration of tumour cells

What are the various routes of metastasis?

  1. Hematogenous
  2. Lymphatic
  3. Trans-coelomic

What are the various classes of tumour antigens?


  • Products of mutated proto-oncogenes, TSG
  • Overexpressed or aberrantly expressed proteins
  • Tumour antigens produced by oncogenic viruses
  • Oncofetal antigens
  • Altered glycolipids and glycoproteins
  • Cell type specific differentation antigens

What are the factors leading to the failure of immunosurveillance?

  1. Selective outgrowth of antigen-negative variants
  2. Loss or reduced expression of histocompatibility antigens
  3. Downregulation of co-stimulatory molecules
  4. Immunosuppression
  5. Antigen masking
  6. Apoptosis of cytotoxic T cells

What are the factors that lead to tumour evolution?


  1. Tumour environmental selection pressure (e.g. hypoxia, pH changes)
  2. Immune surveillance
  3. Treatment
  4. Genetic instability with high rate of random mutations

What are the differences between direct and indirect acting carcinogens?

Direct acting



  • Do not require chemical activation
  • Highly reactive electrophiles



Indirect acting (procarcinogen)



  • Requires metabolic conversion into active carcinogens
  • Potency: balance between activation and inactivation

What are the risk factors associated with lung cancer?

Tobacco smoking


Radiation


Asbestos exposure

What is the main cause of radiation carcinogenesis?

UV light causes especially melanoma and basal cell carcinoma. It induces the formation of pyramidine dimers. Patients with Xeroderma pigmentosa have increased risk of skin cancers due to congenital deficiency of DNA repair enzymes

UV light causes especially m________ and b____ cell c__________. It induces the formation of p___________ d______. Patients with X__________ p___________ have increased risk of skin cancers due to congenital deficiency of DNA repair enzymes.

What are some causes of radiation carcinogenesis?

UV light


Ionising radiation


X-ray, gamma-rays


α, β particles, protons, neutrons


Susceptible tissue/organs


Leukemia in radiology workers


Lung cancers in uranium miners


Pediatric thyroid cancer


Atomic bombs?

What are some microbial carcinogens?

Viruses, e.g. DNA oncogenic viruses (HPV, HBV, EBV, etc.), RNA oncogenic viruses (Human T-cell leukemia virus type 1, HCV, etc).