Pathology - Q3 - Neoplasia

Front 1

Mechanisms of carcinogenesis in terms of gene involvement; ie, what can go wrong? (5)

Back 1

Mutations, rearrangement, amplification, deletion, altered expression

Front 2

Oncogenes (3)

Back 2

Growth, survival, differentiation

Front 3

Oncogenic agents/events (4)

Back 3

Chemicals, viruses, radiation, stochastic events

Front 4

Types of DNA damage (4)

Back 4

-Alkylation
-Depurination/depyrimidation
-Bulky adducts
-Double-strand breaks

Front 5

Indirect vs. direct acting mutagens

Back 5

Direct acting do not require metabolic activation to be reactive with DNA. Indirect acting are metabolized to electrophilic species that are able to react with DNA

Front 6

What determines targeting of carcinogens (what cell type will be affected)?

Back 6

-Route of contact
-Direct vs. indirect acting
-Distribution of carcinogen in body
-Ability of cell/tissue to activate or detoxify the carcinogen

Front 7

Mechanisms of radiation damage (3)

Back 7

DNA damage, chromosomal breakage, cytogenic abnormalities (aneuploidy, polyploidy, etc.)

Front 8

Stochastic events

Back 8

Mutations resulting from aberrant intracellular events that do not require an external agent (eg, oxidative damage)

Front 9

DNA repair mechanisms

Back 9

Prereplicative (high fidelity), postreplicative (high and low fidelity)

Front 10

Xeroderma pigmentosum

Back 10

Recessive. PREreplicative repair deficiency leads to predisposition to develop skin cancer following exposure to sunlight

Front 11

HNPCC

Back 11

"Hereditary nonpolyposis colon cancer". DNA MISMATCH REPAIR linked to hMSH2 and related genes

Front 12

Bloom's syndrome

Back 12

Recessive. CHROMOSOMAL INSTABILITY leads to predisposition to leukemia, lymphoma, carcinoma.

Front 13

Modifiers of carcinogenesis

Back 13

*Enzyme induction (CYP)
*Detoxification (protective enzymes and molecules, eg antioxidant GSH)
*Genetic poymorphisms (activating enzymes, protective enzymes)
*Diet (antioxidants, vitamin A, caloric intake)
*Cell cycle (dividing cells are at greater risk of mutation)

Front 14

Steps in chemical carcinogenesis

Back 14

Initiation (exposure to mutagen, first genetic event) --> Promotion (epigenetic events that increase rate of cell division, eg) --> Progression (genetic events confer malignant phenotype)

Front 15

Latent period

Back 15

Time between "initiation" and clinical detection of tumor (often in "progression" phase)

Front 16

Benign

Back 16

Neoplasm that grows locally without invasion or metastastis

Front 17

This type of neoplasm is highly differentiated

Back 17

Benign

Front 18

Malignant

Back 18

Neoplasm that can invade and/or metastasize [Metastasis usually occurs after invasion, but not always; pieces can break off from the surface and "float" within body cavities to new sites, without ever having invaded past the BM of the epithelium]

Front 19

Secondary neoplasm

Back 19

Metastatic neoplasm. Metastatic spread usually occurs through lymphatics or blood vessels (neoplasm has invaded past BM to penetrate into vessels), but can also occur when cells of non-invasive neoplasms within body cavities (eg, peritoneum) break off from the primary neoplasm and "float" to a new site where they metastasize.

Front 20

Frequent sites of metastatic cancer

Back 20

Lymph nodes, liver, lungs

Front 21

Carcinoma

Back 21

Maligant neoplasm of epithelial origin. Described by (1) cell type and/or (2) degree of differentiation

Front 22

Adenocarcinoma

Back 22

A maligant neoplasm of epithelial origin (carcinoma) arising from glandular tissue

Front 23

Carcinoma in situ

Back 23

Histologically malignant, but has not yet invaded. Recognized by severe dysplasia. "Premalignant" or "precancerous".

Front 24

Sarcoma

Back 24

Malignant neoplasm of mesenchymal origin (CT, bone, fat, muscle). Desribed by cell type (eg, fibrosarcoma).

Front 25

Anaplasia

Back 25

Failure of cells to differentiate. Characteristic of malignant transformation.

Front 26

Hamartoma

Back 26

Mass-forming malformation; NOT a neoplasm, growing at the same rate as the normal tissue. Consists of cells normally present in that organ, but in an abnormal arrangement, often with one cell type predominating.

Front 27

Pleomorphism

Back 27

Variation of cellular appearance, size and shape WITHIN a tumor

Front 28

Atypia

Back 28

Nuclei may be larger, darker and have irregular contours

Front 29

Acinar

Back 29

Secretory unit of a gland (ie, not ductal).

Front 30

Teratoma

Back 30

Benign neoplasm with components representing all three germ layers (ectoderm, mesoderm, endoderm)

Front 31

Desmoplastic stroma

Back 31

Stroma dominated by dense fibrous tissue

Front 32

Leiomyoma, leiomyosarcoma

Back 32

Neoplasm of smooth muscle cells

Front 33

Rhabdomyosarcoma

Back 33

Malignant neoplasm of striated muscle cells

Front 34

Non-neoplastic tumors

Back 34

Metaplasia. Hyperplasia. Hypertrophy. Hamartoma.

Front 35

Examples of benign neoplastic tumors

Back 35

Adenoma, squamous papilloma, osteoma, leiomyoma

Front 36

Examples of malignant neoplastic tumors

Back 36

Adenocarcinoma, squamous cell carcinoma; osteosarcoma, leiomyosarcoma

Front 37

Mixed tumor

Back 37

Both epithelial and stromal components are neoplastic (eg, mixed tumor of the salivary gland in which both components probably arise from the same initiated cell). Contrast to teratoma.

Front 38

These kind of neoplasms retain specialized function (eg, bile secretion), and are usually associated with better prognosis/less aggressive behavior

Back 38

Well differentiated

Front 39

These kind of neoplasms have lost specialized function, and may even exhibit unexpected function (eg, expression of fetal proteins), and are often aggressive/have a poor prognosis

Back 39

Poorly differentiated

Front 40

Benign lesions can cause these problems (4)

Back 40

-Location
-Deformation
-Function
-Transformation

Unfortunate location (eg, acoustic nerve, heart). Deformation of tissue in cosmetically sensitive area. Exhibit function (eg, hormone production). Malignant transformation.

Front 41

Three steps (usually) necessary for metastastis to occur

Back 41

1. Access lymph/blood. 2. Localize to target tissue. 3. Proliferate

Front 42

Pathways of metastasis

Back 42

Seeding, Lymphatic spread, Hematogenous spread

Front 43

Metastasis by seeding

Back 43

Peritoneal--eg, ovarian carcinoma. Pleural--eg, lung, breast, lymphoma. Pericardial--eg, lung, breast, lymphoma.

Front 44

This type of metastasis is typical of sarcomas

Back 44

Hematogenous

Front 45

Hematogenous spread

Back 45

Mostly via VEINS. Circulating malignant cells are often filtered by liver and lungs. Arterial spread is unusual--arteries are more resistant to invasion. Capillaries and post-capillary venules are most vulnerable.

Front 46

Arterial spread

Back 46

Lung cancers that access alveolar capillaries can be disseminated arterially. Otherwise, arterial spread is extremely uncommon; venous spread is more typical. Technically, the lung cancer is following the behavior of other cancers by spreading through the small (capillary or post-capillary) vessels--it's just that once it penetrates the capillary or post-capillary venule, it is entering arterial circulation rather than venous.

Front 47

Cancer grade

Back 47

Mitotic rate and degree of differentiation

Front 48

Cancer stage

Back 48

Extent of spread

Front 49

Which is more helpful for determining the aggressiveness of a tumor?

Back 49

Stage

Front 50

Grading is helpful for this kind of tumor

Back 50

Prostate

Front 51

Grading is NOT helpful for this kind of tumor

Back 51

Melanoma

Front 52

How do you characterize cancer stage (extent of spread)?

Back 52

Size of primary neoplasm, lymphatic/nodal involvement, extranodal dissemination. [T,N,M]

Front 53

What are the two staging systems currenty in use?

Back 53

TNM (Tumor, Node, Metastasis). AJCC (American Joint Committee on Cancer Staging).

Front 54

AJCC

Back 54

Staging system: stages I-IV

Front 55

TNM

Back 55

Staging system: T0-T4, N1-N3, M0-M2

Front 56

These are examples of hereditary DNA repair mechanism disorders that predispose the person to cancer

Back 56

Bloom's syndrome, HNPCC, Xeroderma pigmentosa