2.%20Lymphatic%20spread

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• 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

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• 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).

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• - 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,

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• - 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

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• .
• - 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.

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• - 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.

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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.

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• - 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

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• 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.
• .

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• - 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

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• 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

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

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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.

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• 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.

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• 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

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• 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

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Polyposis of the colon
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• 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

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• 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