1. 2. Lymphatic spread
- The pattern of lymph node involvement depends principally on the site of the primary neoplasm and the natural pathways of local lymphatic drainage.
- For example Carcinoma of the breast usually arises in the upper outer quadrant and first spreads to the axillary nodes

2. Of note,
- Although enlargement of nodes near a primary neoplasm should arouse concern for metastatic spread, it does not always imply cancerous involvement.
- The necrotic products of the neoplasm and tumor antigens often evoke immunologic responses in the nodes, such as hyperplasia of the follicles (lymphadenitis) and proliferation of macrophages in the subcapsular sinuses (sinus histiocytosis).

3. - Is the favored pathway for sarcomas, but carcinomas use it as well.
- Thus, histopathologic verification of tumor within an enlarged lymph node is required.
3. Hematogenous spread
- Is the favored pathway for sarcomas, but carcinomas use it as well.
- Arteries are penetrated less readily than are veins.
- With venous invasion, the malignant cells follow the venous flow draining the site of the neoplasm,

4. - Since all portal area drainage flows to the liver, and all caval blood flows to the lungs, the liver and lungs are the most frequently involved secondary sites in hematogenous dissemination
- Cancers arising near the vertebral column often embolize through the paravertebral plexus; this pathway probably is involved in the frequent vertebral metastases of carcinomas of the prostate

5. .
- Certain carcinomas have a propensity to grow within veins.
- For example, renal cell carcinoma often invades the renal vein to grow in a snakelike fashion up the inferior vena cava, sometimes reaching the right side of the heart.
- Remarkably, such intravenous growth may not be accompanied by widespread dissemination.

6. - Many observations suggest that the anatomic localization of a neoplasm and its venous drainage cannot wholly explain the systemic distributions of metastases ;For example, bronchogenic carcinomas tend to involve the adrenals and the brain
- Conversely, skeletal muscles, although rich in capillaries, are rarely the site of secondary deposits.

7. Epidemiology: causes of cancer
1. Geographic and Environmental Variables
- Environmental factors that give rise to somatic mutations are the predominant cause of the most common sporadic cancers.
- This is supported by the geographic differences in death rates from specific forms of cancer.
- For example, death rates from breast cancer are about fourfold to fivefold higher in the United States and Europe compared with Japan.

8. - Conversely, the death rate for stomach carcinoma in men and women is about seven times higher in Japan than in the United States.
- Liver cell carcinoma is relatively infrequent in the United States but is the most lethal cancer among many African populations.
- There is no paucity of environmental carcinogen, they can be subtle like sunlight

9. 2. Age
- In general, the frequency of cancer increases with age.
- Most cancer mortality occurs between ages 55 and 75
- The rising incidence with age may be explained:
a- By the accumulation of somatic mutations associated with the emergence of malignant neoplasms
b- The decline in immune competence that accompanies aging also may be a factor. .

10. - Cancer causes slightly more than 10% of all deaths among children younger than 15 years
- The major lethal cancers in children are leukemia, tumors of the central nervous system, lymphomas, soft tissue sarcomas, and bone sarcomas

11. 3.Heredity
- The evidence now indicates that for many types of cancer, including the most common forms, there exist not only environmental influences but also hereditary predispositions.
- Hereditary forms of cancer can be divided into three categories

12. A. Inherited cancer syndromes
B. Familial cancers
C. Autosomal recessive syndromes of defective DNA repair

13. A. Inherited cancer syndromes
- Inherited cancer syndromes include several well-defined cancers in which inheritance of a single mutant gene greatly increases the risk of developing a tumor.
- The predisposition to these tumors shows an autosomal dominant pattern of inheritance.

14. 1. Childhood retinoblastoma is the most striking example of this category.
- A tumor suppressor gene has been implicated in the pathogenesis of this tumor.
- Carriers of this mutant gene have a 10,000-fold increased risk of developing retinoblastoma, usually bilaterally and there is a risk to develop another cancer like osteosarcoma.

15. 3. 3. Li-Fraumeni syndrome, due to mutations in P53 gene
2. Familial adenomatous polyposis is another hereditary disorder marked by an extraordinarily high risk of cancer
- Individuals who inherit the autosomal dominant mutation have, at birth or soon thereafter, innumerable polypoid adenomas of the colon, and virtually 100% of patients develop a carcinoma of the colon by age 50
3. 3. Li-Fraumeni syndrome, due to mutations in P53 gene

16. Note:
- Tumors within this group are :
1. often associated with specific marker phenotype,
2. there may be multiple benign tumors in the affected tissue, as occurs in familial polyposis of colon who have many adenomas of colon
3. Malignant tumors can be multiple or bilateral

17. Polyposis of the colon

18. B. Familial Cancers:
- Virtually all the common types of cancers that occur sporadically have been reported to occur in familial forms.
- Examples include carcinomas of colon, breast, ovary, and brain
- Features that characterize familial cancers include:

19. a. Early age at onset,
b. Tumors arising in two or more close relatives of the index case,
c. and sometimes multiple or bilateral tumors
d. Cancers are not associated with specific marker phenotype
e. The transmission pattern is not clear ,in general siblings have a relative risk between 2 and 3 time risk to develop carcinoma