Cell Death and Neoplasia

Question 1

Discuss key concepts of normal cell growth and differentiation control

Answer 1

Normal cell growth: growing like

• active cell growth during developments (morphogenesis)
• proliferation
• migration
• differentiation
• change relationship to neighboring cells
• apoptosis

Differentiation Control:

• Non-dividing tissues (little/no proliferation, i.e. brain)
• Quiescent tissues (normally do no proliferate, but can do so in response to stimuli, i.e. liver)
• Continuously dividing tissues (i.e. gut)

Question 2

Define and give examples of types of abnormal cell growth/differentiation: Hypertrophy:

Answer 2

increase in cell size, usually in response to a stimulus.

-ex. Pregnant uterus (physiologic) or hypertensive cardiac hypertrophy (pathologic)

Question 3

Define and give examples of types of abnormal cell growth/differentiation: Hyperplasia:

Answer 3

Increase in cell number, often in response to some stimulus

-ex. Breast during puberty/pregnancy (physiologic) or endometrium (pathologic)

Question 4

Define and give examples of types of abnormal cell growth/differentiation: Metaplasia:

Answer 4

change from one BENIGN, DIFFERENTIATED cell to another, usually in response to injury
-ex. Bronchus (columnar to squamous metaplasia, cause: smoking; known risk factor for bronchopulmonary neoplasia)
&
Esophagus (squamous to columnar metaplasia (“Barrett esophagus”), cause: acid reflux; known risk factor for esophageal neoplasia)

Question 5

Define and give examples of types of abnormal cell growth/differentiation: Neoplasia:

Answer 5

autonomous, progressive cell growth, involving clonal cell population

Question 6

Define and give examples of types of abnormal cell growth/differentiation: Tumor:

Answer 6

Latin “swelling,” generally synonymous with neoplasm

Question 7

Define and give examples of types of abnormal cell growth/differentiation: Dysplasia:

Answer 7

“Disordered growth.” In epithelia, hallmark of early premalignant neoplasia.

• Characteristic histologic features
• –Loss of cytologic uniformity
• –Loss of normal histologic maturation
• –Loss of architectural orientation
• Usually assigned histologic “grade” (low versus high; marked/extensive dysplasia = “carcinoma in-situ”)

Question 8

Gross features of benign neoplasms:

Answer 8

• –Circumscribed/ encapsulated

- –Necrosis uncommon

Question 9

Gross features of malignant neoplasms

Answer 9

• –Invasive into adjacent tissue

- –Necrosis common

Question 10

Microscopic features of benign neoplasms

Answer 10

• –Generally relatively well differentiated
• –Generally low rate of cell turnover (proliferation and apoptosis)
• –Cytologic uniformity (cells similar to each other)
• –Boundary between tumor and adjacent tissue generally maintained (ie: tumor not invasive)

Question 11

Microscopic features of malignant neoplasms

Answer 11

• –Variable differentiation; generally less than benign tumors
• –Generally high rate of cell turnover (proliferation and apoptosis)
• –Cytologic pleomorphism (cells different from each other, often markedly so)
• –Generally loss of boundary between tumor and adjacent tissue (tumor invasive)

Question 12

Discuss key general concepts related to malignant neoplasia (cancer): Etiology:

Answer 12

Causes:

• Age
• Lifestyle/
• Environment
• Occupational hazards
• Radiation
• Chronic Inflammation
• Infectious agents
• Genetics

Question 13

Discuss key general concepts related to malignant neoplasia (cancer): Epidemiology:

Answer 13

Almost 1 in 2 Americans will get cancer, and 1 in 5 Americans will die from it

Question 14

Discuss key general concepts related to malignant neoplasia (cancer): Pathology (including tumor grade) and Biology:

Answer 14

(injury/infection/other homeostatic disturbance) –> (metaplasia/hyperplasia) –> dysplasia/carcinoma-in-situ –> invasive carcinoma –> metastatic carcinoma… these changes roughly parallel clonal evolution of the tumor cells (below), including acquisition of additional mutations and selection of phenotypic traits favorable to proliferation and survival
Degree of tumor histologic differentiation (ie: resemblance of normal tissue counterpart)
—Low grade: more differentiation/ greater resemblance to normal
—High grade: less differentiation/ resemblance to normal

Question 15

TMN Classification:

Answer 15

T= Tumor (T1-4)

1. invades submucosa
2. invades into, but not through, muscularis propria
3. invades through muscularis propria
4. invades adjacent organs or visceral peritoneum

N = Regional Lymph Nodes (NX,0-2)
X. LNs cannot be assessed
0. no regional LN metastasis 
1. Metastasis in 1-3 regional LNs
2. Metastasis in 4+ regional LNs

M = Distant Metastasis (MX,0,1)
X. distant metastasis cannot be assessed
0. No distant metastasis
1. Distant metastasis or seeding of abdominal organs

Question 16

Stage and relationship to clinical outcome (5-year survival %)

Answer 16

I = T1, T2, N0, M0 = 93%
II = T3, T4, N0, M0 = 72-85%
III = any T, N1-2, M0 = 44-83% 
IV = Any T, Any N, M1 = 8%