Cancer Cytology

Front 1

1. What is cell differentiation?

Back 1

This refers to the orderly process of cellular maturation in order to achieve a specific function. This process is under the control of genes, growth factors, nutrients and environmental stimulation.

Front 2

2. What is a differentiated and a non differentiated cell? Give examples.

Back 2

Differentiated cells with a specific function such as red blood cells, and undifferentiated cells such as stem cells and progenitor cells are 2 examples.

Front 3

3. What are Stem cells?

Back 3

These are highly undifferentiated units that possess the potential to divide into progenitor cells, then daughter cells, which then are able to mature into more differentiated units with a specific task or function.

Front 4

4. Define an undifferentiated cell.

Back 4

These cell units are valued for their adaptability and flexibility. With each step towards differentiation, the cell loses its ability to to respond and adapt, but gains the ability to carry out an important physiological function.

With blood loss for example, daughter cells are directed differentiate into RBCs to replace the lost blood.

Front 5

5. When a cell loses its ability to differentiate, the cell rendered incapable of carrying out a designated function. True/False

Back 5

True.

Front 6

6. Give a brief definition of what cancer is at the cellular level.

Back 6

At the cellular lrvrl, cancer arises because of unrepaired gene malfunction. It is caused by changing or altering those genes that control cell reproduction, growth, differentiation and/or death. The cell grows uncontrollably, and loses any specific physiological function.

Front 7

7. Neoplasms can emerge from either parenchymal or stromal tissue. True/False

Back 7

True. Parenchymal is functional tissue and stromal is supportive tissue.

rapidly dividing cells such as epithelial cells and blood cells are highly prone to the development of neoplasms. Permanent undividing cells such as cardiac myocytes, ( primary cardiac neoplasms are rare) mature neurons and the lens of the eye are not.

Front 8

8. How is cancer manifested after birth?

Back 8

It is manifested through genetic mutations after birth. This is related likely to harmful environmental exposures, which damage the cell DNA and alter the proliferation and differentiation of cells.

Front 9

9. App. 1% of heritable cancer syndromes are passed along germ line cells and many follow a Mendelian pattern of inheritance. True/False

Back 9

True.

Front 10

10. What is meant by monoclonal origin?

Back 10

Cancer is often thought to originate from a single mutated cell. Most of these are spontaneous alterations in DNA replication or repair without an obvious cause. Fortunately the majority of mutations have little influence on genes that regulate cell growth and stability.

Front 11

11. What are the three major categories of genes that exist, that when altered could result in a cancerous condition?

Back 11

1. Mutator genes- genes that repair mutated DNA and protect the genome.

2. Oncogenes- genes that code for proteins involved in cell growth or regulation

3. Tumor suppressor genes- genes that prohibit overproliferation of cells and regulate apoptosis.

Front 12

12. What are mutator genes more specificly?

Back 12

DNA is always being damaged by the environment. These genes repair DNA and along with tumor suppressor genes, protect the genome. Mutator genes are highly effective and a rather large number of mutations in mutator genes are needed to produce cancerous neoplasms.

Front 13

13. What are Oncogenes?

Back 13

Oncogene means " cancer gene". Oncogenes promote unregulated cell growth and development and can also inhibit cell death.

The conversion from a normal gene to one that induces neoplasia depends on the mutation of protooncogenes.

Front 14

14. Protooncogenes are important normal genes in the body with a vital role in regulating cell function. True/False

Back 14

True. These are precursor genes, that once stimulated become oncogenes through one of three ways:

1. Point mutation

2. Translocation

3. Gene amplification

Front 15

15. What is a point mutatioin?

Back 15

This damages a single nucleotide base pair in the DNA that leads to the development of altered unregulated proteins in somatic cells. These can arise from chemicals to U/V rays.

Front 16

16. What is chromasomal translocation?

Back 16

The chromosome breaks, relocates and unites with another chromosome. Encoded proteins become excessive and the cell deviates from expected growth, differentiation and death cycles.

Leukemias, Lymphomas and solid tumors usually arise from these aberrations.

Front 17

17. What is gene amplification?

Back 17

This is a process of altering the chromosome by accelerating the replication of genes. This is a problem of overproducing gene products.

It is implicated in many types of solid tumors, including breast cancer and neuroblastoma. The greater the gene amplification, the poorer the prognosis.

Front 18

18. With each type of oncogene transformation, what are the three basic mechasnisms of action?

Back 18

1. Encoding growth factors- to stimulate cell over proliferation

2. Disturbing cell surface receptors, and restricting cell to cell communicztion

3. Encoding proteins in the cell, nucleus to alter the cell cycle, restrict apoptosis and impact differentiation of the cell.

Front 19

19. What happens with viral oncogenes?

Back 19

The virus inserts itself into the genetic material of thehost cell, replicates and then moves on to infect other cells.

the virus may capture a portion of the host's celll genetic material along with its own.

Front 20

20. What are the notations for oncogenes regarding identification?

Back 20

These are usually three letter abbreviations such as , "ras, neu or myc". The origin or location of the gene is indicated by the prefix of "v" for virus, or "c" for cell or chromosome.

breast cancer has been linked to the c-neu oncogene and lung cancer to the c-L--myc gene. More than 60 human oncogenes have been identified.

Front 21

21. What are tumor suppressor genes?

Back 21

TSG are the genes that regulate the rate at which cells divide and die. A major mechanism for regulating proliferation is to control apoptosis, so that the optimal number of cells is maintained for homeostasis.

Front 22

22. What happens when tumor suppressor genes are mutated?

Back 22

The cell becomes immortal through alteration of the mitochondria. There is effectively unrestricted proliferation.

Front 23

23. How many tumor suppressor genes exist?

Back 23

Several are known to exist. The p53 gene, retinoblastoma (Rb) gene and BCL-2 gene. The p53 gene is the most noted gene to cause cancer. It is located on chromosome 17. It is deleted or mutated in four types of colorectal cancer.

Front 24

24. The p53 gene is responsible for opposing cell division in response to cell DNA damage by delaying cell development. True/False

Back 24

True. This delay allows time for DNA to be repaired. Without p53, cells are unresponsive to the need for repair.

Front 25

25. What is the Rb gene?

Back 25

This is a tumor suppressor gene, that when mutated can result in a rare childhood cancer of the retina (retinoblastoma). About 40% are germline mutations and the rest are spontaneous.

The Rb has a major role in suppressing tumor proliferation.

Front 26

26. What other cancers have been associated with the Rb gene?

Back 26

Osteosarcoma, breast cancer, pancreatic cancer and lung cancer.

Front 27

27. What is the BCL-2 gene?

Back 27

It has been shown to inhibit apoptosis. When this gene is mutated, the cell with the altered gene ignores all of the normal triggers to die and becomes immortal. Cell division is mitotic.

Leukemia has been associated with the BCL-2 gene.

Front 28

28. What is a carcinogen?

Back 28

It is a known cancer causing agent. They interfere with molecular pathways and can initiate or promote tumors to form in the body.

Front 29

29. What is a direct carcinogen?

Back 29

These can cause modification of cell DNA and interfere with cell function.

Indirect carcinogens induce immunosuppression or chronic inflammation or act in conjunction with other carcinogens to induce DNA damage.

Front 30

30. What are some known carcinogens?

Back 30

Radiation

Exposure to reactive o2species (free radicals)

Hormones

Tobacco

Infectious microorganisms

Chemicals

Some asbestos species

Because cancer exhibits a prolonged latent period between the initiation and onset of clinical ,manifestations, identification of a precise carcinogen can be challenging.

Front 31

31. What are some forms of high energizing radiation?

Back 31

Gamma rays

X rays

Ultraviolet rays

These rays can cause genetic damage in a cell, and even kill the cells themselves.

Front 32

32. How does radiation induce injury?

Back 32

It produces reactive O2 species. These molecules damage the cell membrane, permitting the radiation energy to interrupt cell DNA and invoke mutations.

Front 33

33. Labile cells are most affected by radiation. True/False

Back 33

True. Radiation takes advantage of this with the treatment aimed directly at killing highly proliferative cells, most notably, cancer cells.

Front 34

34. what is ultraviolet radiation?

Back 34

U/V is short wavelength electeromagnetic energy , that within a certain range is also capable of inducing carcinogenesis. Sun exposure is a primary source. Length of exposure increases the risk factor. The U/V exposure (290-320) nm directly kills cells and can induce cellular mutation.

Front 35

35. TRumors of the breast often contain have receptors that are responsive to hormone levels in these tissues. True/False

Back 35

True. This is also true for the uterus, the prostate and adrenal glands.

Front 36

36. Can hormones also be considered a treat ment for cancer?

Back 36

Yes. The adrenal corticosteroid hormones (prednisone) can directly kill tumor cells, especially lymph cells and can inhibit mitosis. These drugs also have anti inflammatory effects.

Estrogen and testosterone can be used to starve the tumor and prohibit further growth.

Front 37

37. How does Tamoxifen work?

Back 37

It blocke the action of estrogen and inhibits tumor growth in the estrogen sensitive breast tissues.

Front 38

38. How might chemicals indirectly lead to cancer?

Back 38

Metabolic conversion is required to initiate or promote cancer development. Enzymes in the body are responsible for metabolizing and activating or inactivating potentially carcinogenic chemicals. These enzymes cause the chemicals to react with DNA to start a carcinogenic response. Genetic and environmental factors influence these enzyme levels.

Front 39

39. Viruses are estimated to be responsible for app. 15% of all cancers. True/False

Back 39

True. The most prevalent of these is caused by human papilloma virus (HPV) and the hepatitis viruses. HPV has been largely implicated to cause cervical cancers (strains 16 and 18) Other cancers such as esophageal cancer has also been implicated ac possibly caused by HPV. Hepatitis N and C is highly linked to liver cancers.

HIV is implicated in Kaposi's sarcoma.

Front 40

40. Are there any bacterial species thought to provoke cancer growth?

Back 40

Yes. H. pylori is highly suspected in some forms of gastric cancers.

Front 41

41. What is the Initiation Promotion Progression Theory?

Back 41

One such theory proposes that an initiating event must be combined with a promoting event for cancer to develop and then progress.

The initiating event causes a mutation in the cell. it is often not identified.

The promoting event is an expansion of the mutated cell's growth and reproduction.

Ex, chronic gastritis has been implicated in the development of gastric cancers.

Front 42

42. What is the progression phase in the Initiating-Promoting pathway of cancer origin?

Back 42

Progression is an extension of the promotion phase; now the cancerous growth is no longer dependent on continued exposure to the promotor. The growth and expansion is now autonomous.

Front 43

43. Regarding neoplasms, differentiate between autonomy and anaplasia.

Back 43

Autonomy refers to the unregulated proliferation of the neoplasm. Anaplasia refers to the loss of cell differentiation and therefore the loss of cell function. The greater the degree of anaplasia,, the more aggressive or malignant the neoplasm.

Front 44

44. List several characteristics of neoplasms.

Back 44

1. Loss of cell to cell communication, more unrestricted growth

2. Increased energy expenditure

3. Increased motility and loss of cohesion/adhesion, promotes movement to other bodily regions

4. Rapid sngiogenesis, increased blood flow to tumor cells

5. Substance secretion, alters metabolism

6. Present foreign antigens on cancer cell surface, which triggers an immune response

Front 45

45. Neoplastic cells are not sensitive to cell to cell messages. True/False

Back 45

True. Neoplastic cells do not recognize that other cells are nearby and do not respond accordingly by decreasing the rate of reproduction.

The blood flow demands of neoplastic cells deprive neighboring tissues of adequate O2 and other nutrients, which result in ischemia and necrosis.

Front 46

46. Why does immunodeficiency result in a higher risk of cancer?

Back 46

Tumor cells express antigens seen as foreign to the host. Many cellular transformations are removed from the body by these active defense mechanisms and never progress to form tumors in the body.

Front 47

47. What are paraneoplastic syndromes?

Back 47

These are hormonal, neurologic, hematologic and chemical disturbances in the body, which are not directly related to invasion by the primary tumor or metastasis.

Front 48

48. In paraneoplastic syndromes, what is the significance of ectopic changes?

Back 48

An important characteristic of many neoplasms is the ability to produce and secrete ectopic hormones. This refers to hormone secretion from a site outside of an endocrine gland. These hormones are not under control of the endocrine system and do not respond to feedback mechanisms. They may be secreted at the whim of the neoplasm.

Front 49

49. Give an example of an ectopic secretion by a tumor.

Back 49

Some tumors secrete excess antidiuretic hormone (ADH). The body by nature of the hormone will retain water and sodium. severe edema and death can result.

Front 50

50. How might tumors cause generalized numbness, weakness and loss of neurologic function?

Back 50

They can promote brain hemorrhage, promoting infection in the CNS or denying the vascular supply and O2 to neuronal tissues.

Front 51

51. Are all benign tumors harmless?

Back 51

No. Benign tumors can over proliferate but do not show a significant loss of differentiation. Large benign tumors can impinge on nearby structures obstructing vital functions. Such tumors, also noted as severe space occupying lesions, have caused death, though this is a rare occurrence.

Front 52

52. Malignant tumors are usually invasive and destructive. True/False

Back 52

True. They tend to metastasize, though malignant tumors may metastasize differently based on the nature of tissue.

They promote ischemia and tissue necrosis because the tumor uses energy and nutrients are needed by unaffected tissues.

Front 53

53. What is suggested by a " local spread" of cancer?

Back 53

This is the proliferstion of the neoplasm within the tissue of origin.

Front 54

54. What is Direct extension regarding tumor extension?

Back 54

This is a process of tumor cells moving into adjacent tissues and organs. The process of spread beyond local tissues is a defing characteristic of malignancy.

Penetration of the basement membrane incur less resistance to invade distally. The neoplastic cells adhere to the extracellular matrix by expressing surface adhesion molecules. The tumor cells can release enzymes that can dissolve the extracellular matrix.

Front 55

55. What is cancer seeding?

Back 55

This is another form of direct extension in which neoplastic proliferation occurs within peritoneal and pleural cavities surrounding the affected tissue or organ.

Front 56

56. What is cancer in situ?

Back 56

Carcinoma in situ: Cancer that has stayed in the place where it began and has not spread to neighboring tissues (for example, squamous cell carcinoma in situ). In epithelial tissues, cancers that have not broken through the basement membrane are in situ.

Front 57

57. How do neoplasms gain access to other bodily regions?

Back 57

1. Breaking through the basement membrane and extracellular matrix

2. Gaining access to and circulating within the blood vessels or lymph ystem

3. Leaving the blood vessels or lymph system and adhering to distant tissues

4. establishing a new nutrient network at the distant tissues through a process of angiogenesis

Front 58

58. Regarding cancer spread, what is organ tropism?

Back 58

This is aterm used to describe the affinity of a primary tumor to a specific distant site. Factors that may promote a preferential location include:

A favorable environment offered by the new tissue or organ.

Adherence molecule compatibility between the neoplasm and the new tissue or organ.

The location of the organ in relation to the path of blood flow.

Front 59

59. In reference to question 58, give an example of organ tropism.

Back 59

Tumors that originate in the colon are prone to metastasizing in the liver. There is an easy access of colon tumor cells throught he veins of the portal circulation, which travels directly to the liver.

Another common site for metastatic growth is the lung where tumor cells adhere after being transported through the vena cava.

Front 60

60. Define the following:

epithelioma

papilloma

adenoma

teratoma

osteoma

chondroma

Back 60

Epithelioma=A benign tumor of squamous epithelium

Papilloma- when the same cell origin presents as fingerlike projections

Adenoma- benign tumors of glandular epithelium

Teratomas- benign tumors of germ cells

Osteomas- benign tumor of bone cells

Chondroma- benign tumor of chondrocytes (cartilage)

The suffix of oma denotes benign tumors.

(Lymphoma is an exception, though the name lymphosarcoma is the more correct term).

Hepatoma is a malignant tumor of the liver. (Hepato-carcinoma is a more correct term).

Front 61

61. How are malignant tumors named?

Back 61

Tumors of epithelial tissue are termed carcinomas, and those of connective tissue are called sarcomas.

A malignant tumor of epithelial cells is called an adenocarcinoma.

A malignant tumor of chondrocytes is called chondrosarcoma.

Bone- osteosarcoma

Front 62

62. Define cancer staging.

Back 62

This is a process of classifying the extent or spread of neoplasms and refers to the tumor size, location, lymph node involvement and spread.

The higher the number, the more extensive the tumor size and expansion.

The TNM classification system is often used.

Front 63

63. Briefly describe the TNM system.

Back 63

T= tumor size, and presence of neoplasm

N= node (lymph) involvement, involvement of regional L/Ns

M= metastases, indicates extent of metastases.

Tumor grading is a process of differentiating the level of anaplasia depicted by the tumor.

Front 64

64. Tumors are graded from 1-1V. True/False

Back 64

True. 1 indictaes that it is well differentiated, and 1V indicates high undifferentiation.

As the grade increases, the cells become more deviant from the tissue of origin.

Those graded lower, such as 1 and 11 resemble the tissue of origin, in terms of size, shape and structure and mitotic activity.

Those of 111 and 1V show little resemblance to the tissue of origin.

Front 65

65. The immunoreactivity that accompanies neoplasias is often a low grade chronic hyperplasia that is nontender. True/False

Back 65

True. The supraclavicular nodes are often described as sentinel L/Ns, as these are often the first L/Ns to receive lymphatic drainage from a malignant tumor.

Front 66

66. Why are fevers sometimes evident in neoplastic conditions?

Back 66

Unexplained fever are occasionally a characteristic of neoplasia. Fever results from the release of pyrogens directly from cancer cells and other cells active in the inflammatory response. Chemical mediators often cause a loss of appetite.

Front 67

67. What is cancer cachexia?

Back 67

cachexia is belived to be a result of early feelings of fullness with eating coupled with the release of chemical mediators, such as tumor necrosis factor, that induces a lack of appetite.

TNF also suppresses the enzymes that are needed to release fatty acids from lipoproteins for use by tissues. Lipid energy becomes unavailable to tissues.

Front 68

68. What effects can tumors exert on the blood?

Back 68

High levels of circulating calcium (hypercalcemia) can result from breakdown of bone by tumor cells or as a paraneoplastic syndrome of excess parathyroid like hormone secretion.

Crowding of blood cells in the marrow can result in suppression of RBCs and platelet production.

Anemia, bruising and poor clotting are also common characteristics.

Front 69

69. What are tumor markers?

Back 69

These are substances that may be detected in cells or body fluids, and can provide clues to the presence, extent and treatment response of certain neoplasms.

These markers may be produced by cancer cells or by unaffected cells in the body.

Front 70

70. What comprises tumor markers?

Back 70

They may be comprised of hormones, enzymes and immunoglobulins. many of these markers are expressed as protein antigens.

Prostate specific antigen (PSA) is produced by cells in the prostate, and is present in low concentrations in adult males.

Front 71

71. What may cause a rise in PSA levels?

Back 71

This may be found in the blood of men with inflammation (prostatitis), benign enlargement (benign prostate hypertrophy) and malignant neoplasms of the prostate.

Front 72

72. What is CA 125?

Back 72

This is an antigen expressed tumor marker for ovarian cancer, but it can also be increased in uterine, cervical, pancreatic, lung, colon, breast and gastro-intestinal cancers.

Curiously, it can also be raised in pregnancy, pelvic inflammatory disease, pancreatitis, liver disease and in pulmonary inflammatory conditions.

Front 73

73. What is CEA marker?

Back 73

This is carcinoembryonic antigen (CEA). It is primarily used to monitor colorectal cancer disease and treatment. It can also be raised in some lung cancers, breast, pancreas, stomach, cervix, b;adder, kidney, thyroid, liver and ovary . It may be raised in other inflammatory conditions such as inflammatory bowel disease.

Diagnoses are rarely made solely on tumor marker analyses.

Front 74

74. Where do lung carcinomas originate?

Back 74

They originate most frequently in the epithelial lining of the bronchi, bronchioles and alveoli.

The neoplasms can penetrate epithelial layers and move into lung tissue , pleural cavity, chest wall and beyond. Large lung tumors allow compression on lower cervical and upper thoracic nerves. Metastatic spread is via lymph and vascular routes.

Front 75

75. Lung carcinoma is organotropic to which tissues?

Back 75

Bone, liver and brain.

Front 76

76. Lung carcinoma is divided into which 4 categories?

Back 76

1. Adenocarcinoma

2.Squamous cell carcinoma

3. Small cell carcinoma

4. Large cell carcinoma

Front 77

77. Briefly describe adenocarcinoma.

Back 77

This covers about 35% of cases. Neoplasms develop in the peripheral bronchiolar and alveolar lung tissue leading to pleural fibrosis and adhesions. There is an acinar, papillary and bronchoalveolar form.

This form is more common in women and nonsmokers.

Front 78

78. Briefly describe the pulmonary squamous cell carcinoma form.

Back 78

This is seen in about 30% of cases. It usually begins with injury to the bronchial columnar epithelium, usually from smoking. It leads to squamous metaplasia, dysplasia, carcinoma in situ and an invasive tumor. Tumor cells can be observed in expectorated sputum. More commonly found in men, and is strongly linked to smoking.

Front 79

79. Briefly describe small cell carcinoma.

Back 79

This is seen in about 20% of lung cancer cases, This is considered a highly malignant epithelial tumor that grows and metastasizes rapidly. There is hemorrhage and necrosis.

Small cell carcinoma historically has demonstrated a 10:1 male to female ratio, but currently, the ratio is about 2:1.

Front 80

80. Briefly describe Large cell carcinoma.

Back 80

This form is responsible for app. 15% of lung cancers. These tumor cells are large, and show high levels of anaplasia, and metastasize readily. The exclusion of other types usually confirms this form.

Front 81

81. The presence, extent and prognosis of lung carcinomas are often based on CEA levels. True/False

Back 81

True. Because patients with small cell carcinoma tend to develop distant metastases, surgical resection and radiation rarely contribute to long term survival.

Front 82

82. Treatment of small cell carcinoma is often based on what?

Back 82

It is based on the ability or inability to resect all or part of the tumor. If adenocarcinoma, squamous cell carnioma and large cell carcinoma can be resected, the cancer may be cured by surgery alone or by surgery and chemotherapy.

Small and Large cell carcinomas carry the least favorable prognosis.,

Front 83

83. About 75% of patients with colorectal cancer are unable to identify a clear cause and do not have evidence of inheriting the disease. True/False

Back 83

True. Apparently, the major risk factor is age. More than 90% of cases are diagnosed in adults over the age of 50 years.

Front 84

84. What are some other risk factors for colorectal cancer?

Back 84

Family history, smoking, alcohol consumption, chronic inflammatory bowel disease, obesity and physical inactivity, and a diet high in fat and low in fruits and vegetables.

Front 85

85. Why is a diet higher in fiber believed to be a possible preventive measure of colorectal cancer?

Back 85

Higher amounts of fiber in the diet have been shown to bind to potential mutagens and move contents more quickly through the colon preventing

A reduced fat diet may reduce the secretion of bile into the intestine and limit the exposure of the bowel to the tumor promoting effects of bile acids.

Front 86

86. Are there any nutrients that masy have a protective effect against colorectal cancer?

Back 86

Selenium, vitamin E, C, and A, as well as vegetables like broccoli, cauliflower, cabbage and brussel sprout.

Front 87

87. Colorectal cancers are classified into three groups: What are they?

Back 87

1. Nonneoplastic polyps ( not considered a precursor of cancer)

2. Neoplastic polyps (adenomatous polyps, adenomas, increased risk of developing carcinomas of the colon

3. Cancers, most often adenocarcinoma.

Front 88

88. An average of nine major deleterious mutations are harbored within cancerous tumors of the colon and rectum. True/False

Back 88

True. About 5-7 mutations are needed to promote the development of malignant tumors.

At least 2 pathways have been identified that can lead from healthy epithelium to carcinoma:

1. A series of events triggering chromosomal instability (85%)

2. Replication errors (15%)

Front 89

89. In colorectal cancer, what is chromosomal instability based on?

Back 89

It is based on alterations in chromosome number (aneuploidy), and chromosome deletions, particularly od chromosomes 5q, 18q, 17p and the mutation of the KRAS oncogene. This instability leads to a loss of tumor suppression function, and impaired DNA repair is heavily implicated in the transformation to adenocaercinomas.

Front 90

90. What is the APC gene?

Back 90

Early activation of neoplasia is often related to a mutated loss of a tumor suppressor gene called APC (Adenomatous polyposis coli ) gene. This leads to adenomatous polyps which are a major precursor to malignant tumor development.

Front 91

91. In colorectsal cancer, where does the cellular transformation begin?

Back 91

In both of the above scenarios, cellular transformation forms in the mucosal epithelium of the bowel begins at the base of the crypts or mucosal epithelial depressions. This is where mitosis occurs. As the cell matures it moves up the crypt and reaches the surface of the bowel where the cell then dies and is sloughed off and removed through the colon.

Front 92

92. What happens with APC gene mutation?

Back 92

Tumor cells in the bowel resist apoptosis and accumulate on the bowel surface. The cells continue to proliferate to form benign adenomatous polyps. The removal of these usually reduces the risk of the development of adenocarcinomas. Other mutations further promote the transformation to a malignant tumor, such as the deletion of other tumor suppression genes, the DCC (deleted in colon cancer) gene, and the p53 gene.

Front 93

93. What are some clinical manifestations of colorectal cancers?

Back 93

early stages are usually asymptomatic. As the tumor enlarges, ulceration and hemorrhage result in occult blood in the stool if the tumor is along the ascending colon.

Frank or visible blood in the stool, abdominal pain and bowel obstruction are more likely if the tumor is located along the descending colon or in the rectum.

Anemia is often seen as well as a result of blood loss.

Front 94

94. What are some diagnostic features for colorectal cancer?

Back 94

Based on digital rectal exams

Colonoscopy

CEA levels are not a valuble screening test for these casncers. There are many false negative and positive results which make its employment insignificant.

Front 95

95. What is the treatment protocol for colorectal cancer?

Back 95

Early detection is always best.

Surgery and chemotherapy when applicable

The prognosis is directly related to the location and degree of penetration of the tumor through the bowel, obstruction and perforation. L/N involvement is valuable in evaluating the outcome. Distant metastases can alter a long term successful outcome.

Front 96

96. Brain metastases outnumber primary tumors at a ratio of about 10:1. True/False

Back 96

True. These metastases have primary tumors that originate most often in the lungs, breast, skin or colon. These primary tumors then relocate to the cerebral hemispheres 80% of the time, while cerebellar sites account for about 15% of targets, and the brainstem is affected about 5% of the time.

Front 97

97. Primary CNS and peripheral nervous system tumors originate from which 4 structures?

Back 97

1. Glial cells- these are non-neurons in the CNS and PNS and include eprndymal cells, astrocytes, oligodendrocytes and microglia.

2. Meninges- membranous coverings in the brain (dura mater, arachnoid and pia matera) Meningiomas emerge in middle to late adulthood, are slow growing and can erode the cranium.

3. Schwann cells - These cells produce myelin and collagen. Schwannomas arise within the brain, spinal nerves and peripheral nerves and are rarely malignant.

4. Ectopic tissues- Somer tumors in the CNS arise in embryonic cells that have migrsated to the brain and spinal cord and have proliferated. An example would be a lipoma. These begin as embryonic adipose cells that have migrated to the CNS during embryogenesis. This tumor rows slowly, and can go unnoticed for a lifetime.

Front 98

98. What is the most common tumor type originating in the brain?

Back 98

Gliomas. The genetic variation is variable depending on the subtype.

Grade two diffuse astrocytomas most often occur in patients with inherited p53 germline mutations or with a deletion of chromosome band 17p13.1.

Front 99

99. Astrocytomas most often present in the brainstem or cerebellum of the child, spinal cord of young adults, and cerebral hemispheres of the adult. True/False

Back 99

True. About 20% are well differentiated, 40% are highly undifferentiated, and the remaining are somewhat in between.

Gliomas can be benign or malignant. Tumors that impinge on brain structures will affect activity in that region, and may even be fatal.

Gliomas rarely metastasize outside the CNS.

Prognosis is based on level of anaplasia. The more undifferentiated, the poorer the prognosis.

Front 100

100. Is the TNM system employed in the CNS.

Back 100

It is not used for the following reasons.

1. Tumor size is less relevant than the location and histology

2. The brain and spinal cord have no lymphatics

3. Most patients with CNS tumors do not live long enough to develop metastatic disease.

Front 101

101. What are some clinical manifestations of brain tumors?

Back 101

This will depend on the size and location.There are motor or sensory losses, such as vision changes, numbness, weakness or paralysis.

Cognitive or behavioral and personality changes are also common and may manifest as irritability, forgetfulness and depression. Speech may be affected.

Headaches are noted due to build up of fluids from inflammatory reactions around the tumor.

Seizures are not uncommon

Tumor compression on the respiratory or cardiac centers can result in death.

In endstage cases, patients tend to become comatose before dying.

Front 102

102. What diagnostic approaches are used for CNS tumors?

Back 102

Neurologic exams ( based on symptoms and signs)

MRI

PET scans

MRIs

Angiographies

Front 103

103. What are some treatment options for Brain tumors?

Back 103

This will depend on the location and physical impact of the growth. The goal of surgery is to remove the growth (space occupying lesion) while attempting to restore and maintain as much neurologic function as possible.

Radiation is a common treatment approach.

Chemotherapy for chemosensitive tumor types such as gliomas, medulloblastomas and some germ cell tumors. Some drugs are placed directly in the brain.

For brain metastases, whole brain radiation therapy may be required.

Palliative care is essential and may include anticonvulsants to treat tumors.

Front 104

104. What is Leukemia?

Back 104

These are malignant neoplasms of the blood and blood forming organs. It is associated with overproliferation and lack of differentiation in WBCs, but can also affect other cell types. Bone marrow cells are replaced with immature proliferating neoplasms. These immature cells are called blast cells. These cells are for the most part, nonfunctional.

Front 105

105. What is the etiology of leukemia?

Back 105

It is not fully understood, however, radiation and certain chemical exposures have been implicated.

Certain drugs that treat lymphoma, appear to place recipient patients at higher risk.

Those with Down syndrome are more prone to leukemia and lymphoma due to chromosomal translocations.

Front 106

106. How are the Leukemias classified?

Back 106

They are classified as acute or chronic, and according to cell type. Acute cases appear rather suddenly and result in a noticeable loss of function.

Chronic leukemias are more gradual in onset, and early symptoms are vague.

Cells affected are either lymphoid or myeloid types.

Front 107

107. Lymphocytic leukemias involve immature lymphocytes that originate in the bone marrow. True/False

Back 107

True.

Myelogenous leukemias involve myeloid stem cells in the marrow. These leukemias interfere with the maturation of all blood cells, including erythrocytes and platelets.

Front 108

108. Acute lymphocytic leukemia (ALL) is the most common cancer in children, but can occur throughout adulthood. True/False

Back 108

True. Immature B lymphocytes and occasionally T lymphocytes are the malignant cells in this form of leukemia.

Front 109

109. What is the genetic etiology of ALL?

Back 109

Over 80% of childhood ALL originates as a B cell precursor and is expressed on CD79a, CD19, HLA-DR, CD10 and other B cell associated antigens.

Front 110

110. Acute Myelogenous leukemia (AML) is the most common acute leukemia and most commonly occurs in adults. True/False

Back 110

True. IN AML, immature myeloid cells proliferate in the bone marrow and lack the ability to differentiate into specific functional blood cells, resulting in anemia, leukopenia and therombocytopenia.

Front 111

111. What are some risk factors for AML?

Back 111

1. Male gender

Smoking

Previous chemotherapy or radiation treatment

History of ALL

Exposure to atomic bomb radiation or benzene

History of myelodysplastic syndrome.

Front 112

112. Can certain chromosomal aberrations predict the outcome of the disease?

Back 112

Sometimes. Similar to ALL, certain chromosomal aberrations in AML are associated with prognostic significance. Translocations of chromosomes 8 and 21 or 15 and 17 or an inversion of chromosome 16 are associated with a more favorable outcome.

Front 113

113. The clinical manifestations are similar in ALL and AML. True/False

Back 113

True. There is immaturity of WBCs and other cells originating in the bone marrow. This will lead to an increase in infections.

There is crowding of leukemic cells in the bone marrow. This will suppress RBC and platellet production. Spontaneous epistaxis and bruising are often observed. Infiltration of leukemic cells in the CNS, lymph nodes, liver and spleen. Headaches, visual disturbances, fatigue and seizures are seen.

Front 114

114. How is diagnosis achieved with Leukemia?

Back 114

It is based on patient history The blood cell count demonstrates blast cells greater than 20% and micro examination of blood cells is often diagnostic.

Front 115

115. What is the most common treatment protocol for ALL?

Back 115

Thisd includes a systemic combination of chemotherapy and specific prophylactic CNS intrathecal chemotherapy with or without cranial radiation. The treatment protcol is divided into : Induction, Intensification and maintenance. Myelosuppression and immunosuppression is common during this protocol. App. 95% of children will achieve remission , with an 85% 5 year survival rate.

Front 116

116. What is the treatment for AML?

Back 116

This also includes systemic combination chemotherapy in 2 phases: Induction ( to achieve remission) and postremission. CNS intrathecal chemotherapy is rarely used because only 5% of those with AML develop CNS disease.

Front 117

117. How are B lymphocytes affected in Chronic lymphocytic leukemia? (CLL)

Back 117

The result is an overproliferation of B lymphocytes that relatively mature but are not fully functional. The cells do not readily form antibodies. It impacts myelogenous cell types.

Front 118

118. What is the pathophysiology of the chronic leukemias?

Back 118

These are differentiated by presenting certain B cell antigens and other genetic and chromosomal aberrations.

The Phikadelphia chromosome is observed in approximately 95% of those with Chronic myelogenous leukemia. (CML) There is a chromosome 9 and 22 translocation, which activates oncogenes

The BCR-ABL gene then becomes fused allowing production of abnormal tyrosine kinase protein, leading to disordered myelopoiesis (formation of bone marrow).

Front 119

119. What are the clinical manifestations for the chronic leukemias?

Back 119

They are subtle and hardly noticed until the disease is well advanced. They are similar to acute leukemias.

There may be spleen enlargement.

The Philadelphia chromosome is seen in CML.

Front 120

120. What is the trewtment protocol for the chronic leukemias?

Back 120

More than half of patients may be cured with bone marrow or stem cell transplantation. A suitable donor who is good health and preferably young is considered an ideal choice.

Patients with blood cell counts >100,000 require immediate chemotherapeutic treatment to avoid deasth from obstructed blood perfusion to vital organs. Spleen removal may be necessary.

Front 121

121. What is the median survival times for both CML and CLL?

Back 121

CML- 4-6 years

CLL- 8-12 years

Front 122

122. What is Hodgkin lymphoma?

Back 122

This is a malignant disorder of the lymphoid tissue often characterized by the painless, progressive enlargement of cervical L/Ns. Its exact cause has not been established.

Front 123

123. What are some risk factors for for Hodgkin lymphoma? (HL)

Back 123

Virus exposure, such as Epstein-Barr, genetic factors and immunosuppression. Incidence is highest in those between 10 and 30 years, and those older than 50.

Front 124

124. What is the pathophysiology of HL?

Back 124

It is characterized by the presence of multinucleated giant cells (macrophages) called Reed-Sternberg cells, or Hodgkin cells. This cell has been identified as the neoplastic origin, capable of clonal expansion. It originates in the cell components of L/Ns following a B lymphocyte lineage.

It arises in B cells that are unable to synthesize immunoglobulin and are resistaent to apoptosis.

Front 125

125. Why is there a potential relationship between HL and EB virus?

Back 125

EBV genetic material which can often be detected in these affected cells. The risk of developing EBV positive HL is increased in those affected with this virus. HL is believed to be inherited, though this is a very rare event.

Front 126

126. HL is organ tropic to which tissues?

Back 126

Lungs, liver, bone and bone marrow

Front 127

127. What is the WHO classification of HL?

Back 127

This is based on the revised European and American Lymphomas classification (REAL) The two major categories differ based on B cell immunophenotype.

1. Classic HL, with subcategories of nodular sclerosis, HL, Mixed cellularity HL, Lymphocyte depletion HL and Lymphocyte rich HL

2. Nodular lymphocyte predominant HL

Front 128

128. What is the staging of HL?

Back 128

It ranges from 1 (involvement of a single L/N region) to 1V (disseminated involvement of one or more organs outside the lymphatic system) (multicentric)

These stages are further distinguished as "A" (absence of specific systemic manifestations, and B (the presence of systemic manifestations). There are unexplained fevers and severe night sweats.

Front 129

129. What are some clinical manifestations of HL?

Back 129

App. 80% of individuals with HL present with a nontender enlarged L/N or group of nodes often in the neck.

Low grade fever, fatigue, weight loss, pruritus, and night sweats, are associated with the release of cytokines (inflammatory mediators) by Reed-Sternberg or Hodgkin cells.

About 20% of patients will have a mediastianl mass that is greater than one third of the chest diameter. Splenomegaly and hepatomegaly may also be detected.

Front 130

130. What are some diagnostic criteria?

Back 130

This is based on patient history, physical exam, lab studies, and thoracic and abdominal CT scans.

Reed -Sternberg cells

Front 131

131. What is the treatment for HL?

Back 131

This is based on clinical staging. Chemotherapy and radiation are the primary treatment modalities leading to a relapse free survival of 77% in all patients newly diagnosed with HL.

More severe cases will require a more complex combination of treatment protocols.

Front 132

132. What is Non Hodgkin lymphoma? (NHL)

Back 132

This is a generic classification made up of a broads range of B cell and T cell malignancies within the immune system.

NHL occurs more frequntly than HL, and does not exhibit Reed-Sternberg cells or Hodgkin cell and is more likely to affect noncontiguous L/Ns.

Front 133

133. What is the etiology of NHL?

Back 133

It is often unknown, yet, viruses immunodeficiency and genetic factors are implicated.

Front 134

134. Is there a genetic susceptibility for NHL?

Back 134

It is highly variable, depending on the specific cell affected by neoplasia.

Mutation of the BCL-2 gene is present in more than 90% of patients with follicular lymphoma (type of indolent NHL). There is an over expression of the BCL-2 protein and is associated with the inability to limit apoptosis and overproliferation of lymph tissue.

Front 135

135. NHL is organ tropic to which tissues?

Back 135

The liver, spleen and bone marrow.

Front 136

136. What is the staging system for NHL?

Back 136

It is similar to that of HL. It recognizes three major categories of lymphoid malignancies based on morphology and cell linkage: B cell neoplasms, T cell/Natural killer neoplasms and HL. Both the lymphomas (solid tumors in lymph) and leukemias (circulating neoplasms with immune cell lineage) are included in this classification.

Front 137

137. How is NHL assessed by prognosis?

Back 137

It is based on the stage, cell characteristics, age, treatment response, tumor size, lactate dehydrogenase values and the number of targeted L/Ns.

Front 138

138. How is NHL diagnosed?

Back 138

Patient history and physical examination.

Lymph node biopsy

CT scans

Blood assessment

Front 139

139. How is NHL treated.

Back 139

Genetic profiling

Morphologic and biologic characteristics.

Currently, treatment is based on two prognostic groups:

Indolent (painless and passive) lymphomas and the aggressive lymphomas.

Early stage, 1 and 11, indolent NHL can be treated effectively with radiation therapy alone with a good prognosis.

Later stage, 333 and 1V require a combination of chemotherapy with or without radiation. For aggressive forms, the remission rate are between 60-80%. Though in general overall long term disease free survival is about 30-50%.