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56 Cards in this Set

  • Front
  • Back

Dysplasia

Abnormal cytological appearance and abnormal tissue architecture (precancerous associations)

Clinical features of malignancy

• Definition of mass
• Characteristic of mass (hard, irregular)
• Involvement of nearby tissues


• Change in character / size


• Involvement of distant tissues / organs


• Presence / absence of pain

Triple approach to examining a mass

1. clinical examination


2. radiological examination


3. pathological examination

Malignant features on histology

• loss of architecture


• necrosis


• mitosis


• nuclear pleomorphism

What information is acquired from pathological examination?

• Tumour type
• Tumour grade (how closely a tumor resembles tissue of origin)
• Tumours stage
• Excision margins
• Other features of prognostic value (i.e. vascular invasion, staining -ER, HER-2)

primary vs. secondary tumor

primary - arose from the tissue that the tumor is located in


secondary - arose from other tissue (metastasized to new location)

Tumor Staging Classification

TNM classification:


* size and/or extent (reach) of the primary tumor (T),
* whether cancer cells have spread to nearby (regional) lymph nodes (N),
* and whether metastasis (M), or the spread of the cancer to other parts of the body, has occurred.

carcinoma

cancer arising from epithelia

sarcoma

cancer arising from mesenchymal tissues

Leiomyosarcoma

Cancer of smooth muscle (i.e. fibroid)

Cancer of the CNS (e.g. glial cells)

Glioma

Cancer of germ cells

Teratoma


Seminoma/dysgerminoma

Cancer of plasma cells

Plastocytoma

Cancer of placenta

Choriocarcinoma

Peak age for testicular cancer

30s

Common age for leukemia

Children and old people (60+)

Common age for bone cancer

20s and old age (60+)

Which cancers are most commonly associated with old age?

Breast (40+), colon (50+), lung (50+)

What are some examples of cancers strongly associated with genetics?

- Retinoblastoma (autosomal dominant - loss of tumor suppressor genes)


- Familial Adenomatous Polyposis Coli - FAP

What causes mesothelioma?

Asbestos

How do causes of hepatocellular carcinoma differ across the globe?

Africa- due to Hep B


Western countries - due to alcohol

What kinds of cancers are associated with radiation?

• Leukemia


• Thyroid Cancer


• Lung, Breast, etc

What virus is associated with Burkitt's lymphoma?

EBV

What kind of cancer can be described on histological appearance as having a "starry sky"?

Burkitt's lymphoma (8-14 translocation)

Theories of metastatic spread

1. Seed and soil: tumor will spread to tissue that is most conducive to its growth


2. Blood supply: tumor will spread to areas that it can access through nearby blood vessels

The Metastatic Cascade

Clonal expansion, growth, diversification, angiogenesis


→ Metastatic subclone


→ Adhesion to and invasion of basement membrane


→ Passage through ECM


→ Intravasation


→ Interaction with host lymphoid cells


→ Tumor cell embolus


→ Adhesion to BM


→ Extravasation


→ Metastatic deposit


→ Angiogenesis


→ Growth


How do cancer cells invade the ECM?

down regulation of cell adhesion (e.g. epithelial cadherins)


attachment of tumour cells to matrix through expression of matrix binding receptors (e.g. receptors for laminin, fibronectin)


degradation of extracellular matrix through secretion of proteases (e.g. collagenase 4 which degrades basement membrane)

Are renal cell carcinomas likely to metastasize?

Yes

Routes of tumor spread

• Direct Extension


• Lymphatic Spread


• Vascular Spread
• Transcoelomic
• CNS Spread


• Field Effect

Transcoelomic spread

The dissemination of malignant tumors throughout the surfaces and organs of the abdominal and pelvic cavity covered by peritoneum. For example, ovarian tumors can spread transperitoneally to the surface of the liver.

Common type of spread for:


-Ovarian/gastric cancer


- Rhabdosarcoma


- Breast


- Lung

- Ovarian/gastric cancer: transcoelomic


- Rhabdosarcoma: hematologic


- Breast: lymphatic


- Lung: direct extension

CNS spread

usually doesn't spread outside of CNS; travels within CSF

Field effect

Several sites experience cancerous growth due to exposure to the same carcinogen

General cancer symptoms

Weight loss, malaise, lethargy



Arise due to a combination of



• metabolic and hormonal influences


• Malnutrition
• Infection
• Anaemia

Local effects

» Compression


» Obstruction
» Ulceration (eg GI tract)
» Haemorrhage (eg intracerebral tumor)


» Perforation (eg GI tumors)


» Infarction

Examples of tumors that cause compression

- Pituitary adenoma compresses optic nerve resulting in bitemporal hemianopia


- Meningioma, astrocytoma, oligodendroglioma cause rise in intracranial pressure

Paraneoplastic Effects

Symptoms not readily explained by local or metastatic disease:



- Clubbing


- Hypercalcaemia


- Peripheral neuropathy


- Cerebellar degeneration

Driver mutation

A mutation that confers selectional advantage to that cell over its neighbors, initiating early stages of neoplastic development

Passenger mutation

A mutation that confers little to no growth advantage to a cell

3 types of cancer genes

1. Oncogenes


2. Tumor suppressor genes


3. Genome stability/DNA repair genes

Products of tumor suppressor genes are involved in controlling

- Growth factor signalling


- Cell cycle


- Cell division


- DNA replication, repair and genome surveillance

Cyclins and CDKs

oncogenes

Guardian of the genome

TP53

ABL

dominant oncogene; CML

BRAF

dominant oncogene; melanoma/thyroid cancer

APC

Tumor suppressor gene; colon cancer

BRCA1/2

Tumor suppressor gene; breast/ovarian cancer

RAS

dominant oncogene; thyroid/colon cancer

ERBB-2

dominant oncogene; breast/ovarian carcinoma

NF1

Tumor suppressor gene; neurofibromatosis

WT1

Tumor suppressor gene; Wilm's tumor

RET

dominant oncogene; thyroid carcinoma

c-MYC

dominant oncogene; Burkitt's lymphoma

BCL2

dominant oncogene; follicular lymphoma

What kind of genetic defect is associated with Burkitt's lymphoma?

translocation of c-myc gene from 8 to 14

What are some of the hallmarks of cancer?

- Sustaining proliferative signaling


- Evading growth suppressors


- Avoiding immune destruction


- Enabling replicative immortality


- Tumor-promoting inflammation


- Activating invasion and metastasis


- Inducing angiogenesis


- Genome instability and mutation


- Resisting cell death


-Deregulating cellular energetics