Download slide#5 - DENTISTRY 2012

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
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).
- 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,
- 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
.
- 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.
- 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.
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.
- 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
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.
.
- 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
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
A. Inherited cancer syndromes
B. Familial cancers
C. Autosomal recessive syndromes of defective DNA
repair
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.
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.
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
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
Polyposis of the colon
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:
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