Neoplasia

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					Introduction




               1
        Glossary of cancer
Oncology: the study of tumors
Neoplasia: new growth (autonomy with
a loss of response to growth controls)
Benign tumor: localized and amenable
to surgical removal; good prognosis
Malignant tumor: invasive and capable of
destroying structures and spreading to distant
sites (metastasis); may result in patient death.
All cancers are malignant by definition.

                                                   2
   Glossary of cancer (cont.)

Carcinogen: A cancer-producing agent or
substance.
Co-carcinogen: An agent that increases the
effect of carcinogens.
Mutagen: A factor that can transform a normal
cell into a malignant cell
Metastases: the spread of cancer from one part
of the body to another; cells in the new lesion
are like those in the original tumor

                                                  3
 Examples of benign tumors


fibroma: benign tumor of fibrous tissue
lipoma: benign tumor of fat
adenoma: benign glandular tumor
chondroma: benign cartilaginous tumor


                                          4
Leiomyomas




             5
Adenoma




          6
Examples of malignant tumors


Sarcoma (mesenchymal derivation:
fibrosarcoma, chondrosarcoma)
Carcinoma (epithelial derivation:
adenocarcinoma, squamous cell
carcinoma)
Lymphoma/leukemia

                                    7
Adenocarcinoma




                 8
Lung carcinoma




                 9
       Clinical behavior


The terms “benign” and “malignant”
describe the biologic behavior of a tumor
The biologic behavior of malignant tumor
is characterized by:
    - degree of differentiation
    - the rate of growth
    - the rate of cell death
                                            10
           Differentiation

Well-differentiated tumors contain cells
that resemble the normal cells of origin
Poorly-differentiated or undifferentiated
tumors contain cells that do not resemble
their normal counterparts (ancillary studies
may be needed to determine the cell of
origin)

                                           11
Well-differentiated




                      12
Poorly-differentiated




                        13
       Morphologic features

Benign tumors: composed of
well-differentiated cells
Malignant tumors: a wide range of cellular
differentiation.
Anaplasia (a feature of malignant tumors:
- cellular pleomorphism
- hyperchromatic nuclei
- high nucleus: cytoplasm ratio
- giant cells
- bizarre nuclei
                                             14
Anaplasia




            15
              Dysplasia

Denotes a loss of architectural organization
and a loss of cell uniformity in epithelium
Pleomorphism and mitoses are more
prominent than in the normal cells
Usually graded: mild, moderate, severe, and
carcinoma-in-situ
Mild to moderate dysplasia is potentially
reversible

                                               16
              Dysplasia


Dysplasia is a non-neoplastic proliferation
Dysplasia may or may not progress
to cancer


                                              17
Dysplasia   Normal epithelium




                          18
            Growth rate
In general, benign and well-differentiated
malignant tumors have a slower growth
rate than moderately-differentiated and
poorly-differentiated malignant tumors
There are exceptions. Blood supply, site,
and hormonal stimulation can affect the
growth rate of tumors

                                             19
              Invasion

Benign tumors usually grow by slow
expansion
Malignant tumors usually infiltrate and may
destroy surrounding tissues (cell surface
and the extracellular matrix play
an important role)

                                          20
             Metastasis

A discontinuous spread of the tumor
Always indicates malignancy
Ways of metastasis:
   - seeding of body cavities
   - lymphatic spread
   - hematogenous spread
                                      21
Metastatic ovarian carcinoma




                               22
MRI: metastatic adenocarcinoma




                                 23
Metastatic adenocarcinoma




                            24
       Grading and staging

Grading (G)
- based on the microscopic features
  of the tumor cells
- specific for the tumor type
Staging (TNM)
- based on clinical, radiological, and surgical
  criteria: tumor size (T), involvement of regional
  lymph nodes (N) and presence of metastases (M)

                                                25
Morbidity and mortality

 Metastases
 Rupture into major vessels
 Compression of vital organs
 Organ failure
 Infection

                               26
Can we prevent cancer?



                         27
Carcinogenic agents


Chemical
Physical
Oncogenic microorganisms
Cancer risk factors


Age
Heredity
Impaired immunity
Life style and environment

                             29
                  Age

Most carcinomas: >55 years old
Childhood cancers:
– acute leukemia,
– neuroblastoma
– retinoblastoma
– Wilms tumor (kidney),
– rhabdomyosarcoma (skeletal muscle)
                                       30
          Heredity

Autosomal dominant inherited cancer
syndromes
Autosomal recessive syndromes
of defective DNA repair
Familial cancers

                                      31
                Heredity

Autosomal dominant inherited cancer
syndromes
– Familial retinoblastoma
– Familial adenomatous polys of the colon
– Multiple endocrine neoplasms
– Neurofibromatosis
– Von Hippel-Lindau syndrome
                                            32
              Heredity

Autosomal recessive syndromes
of defective DNA repair
– xeroderma pigmentosum
– ataxia-telangiestasia
– Bloom syndrome
– Fanconi anemia


                                33
                 Heredity

Familial cancers
– familial clustering of certain cancers
– role of inheritance not clearly defined
  in individual cases
     breast cancer
     ovarian cancer
     colon cancer other than familial
     adenomatous polyps

                                            34
         Impaired immunity

Primary (inherited)
Secondary (eg. AIDS, immunosuppresive
agents)

Immunosuppresive agents (transplant
recipients):
  8% annual risk of cancer (100 x higher
  compared to normal population);
  partcularly high incidence of lymphomas
  and leukemias
                                            35
Impact of environmental carcinogens


80-90% of all cancers may be related to
environmental agents including diet, life style,
and viruses
Several environmental agents often act together
(co-carcinogenesis)
Life style factors

Cigarette smoke
Diet, obesity
Alcohol abuse
Occupational factors
Sexually transmitted viruses
Sun exposure
European Code Against Cancer

Do not smoke; if you smoke, stop doing
so. If you fail to stop, do not smoke
in the presence of non-smokers
Avoid obesity
Undertake some brisk, physical activity
every day
Increase your daily intake of vegetables
and fruits
Moderate your alcohol consumption
Avoid excessive sun exposure
                                           38
European Code Against Cancer (cont.)
  Avoid exposure to known cancer-causing
  substances
  Women from 25 years of age should
  participate in cervical screening
  Women from 50 years of age should
  participate in breast screening
  Men and women from 50 years of age
  should participate in colorectal screening
  Participate in vaccination programs
  against hepatitis B virus infection

                                               39
        Do not smoke.
 If you smoke, stop doing so.
   If you fail to stop, do not
smoke in the presence of non-
            smokers


                                 40
 Annual risk of death from various causes

Cause                               Personal risk/year

Smoking 10 cigarettes per day       1:200
All natural causes (age 40 years)   1:850
Influenza                           1:5,000
Traffic accident                    1:8,000
Leukemia                            1:12,500
Futball                             1:25,000
Accident at home                    1:26,000
Accident at work place              1:43,500
Suicide                             1:100,000
Railway accident                    1:500,000
Thunder hit                         1:10,000,000
                                                    41
   The role of cigarette smoking
Attributable to 30% of all malignacies
(40% in men and 20% in women)

Most important tobacco-related tumors: lung,
larynx, oral cavity, esophagus, bladder, pancreas,
cervix cancer

The risk of developing lung cancer only in heavy
smoker (40 cigarettes a day): 1:8, or 20x higher
compared to non-smoker

The wives of smokers: doubled risk of lung cancer
                                                     42
      Hazards for the individual
           cigarette user
Big risk, especially among those who start smoking cigarettes
regularly in their teenage years
If keeping smoking steadily, about half will eventually
be killed by tobacco (approximately one-quarter in old age
plus one-quarter in middle age)
Those killed by tobacco in middle age (35-69 years) lose
an average of 20-25 years of non-smoker life expectancy
Throughout the European Union, tobacco is much the
greatest single cause of death
In non-smokers, cancer mortality is decreasing slowly and
total mortality is decreasing rapidly
Most of those killed by tobacco were not particular "heavy"
smokers
                                                                43
10 most important causes
     of lung cancer
       Smoking
       Smoking
       Smoking
       Smoking
       Smoking
       Smoking
       Smoking
       Smoking
       Smoking
       Other causes
                           44
Stopping smoking works!


  Even in middle age, stopping before
 having cancer or some other serious
disease avoids most of the later excess
 risk from tobacco, and the benefits of
    stopping at earlier ages are even
                 greater

                                      45
    Thank you
 for not smoking.
  We’d rather die
of natural causes!
     Anonymus
            Avoid obesity

Undertake some brisk, physical activity
             every day

    Increase your daily intake of
vegetables and fruits: eat at least five
            servings daily

 Limit your intake of foods containing
       fats from animal sources
                                           47
Cancers related to overweight

    colon,
    breast (post-menopausal)
    endometrium
    kidney
    oesophagus (adenocarcinoma)
    gallbladder


                                  48
How to lose weight?

Increase physical activity
Eat less fat and fatty foods
Eat less sugar and sweets
Avoid too much alcohol



                               49
      Role of dietary factors

Negative           Positive
 Fats                Vitamins (A, E, C)
 Animal proteins     Fiber
 Aflatoxins          Microelements
 Nitrosoamines
 Acroleins

                                          50
Limit high-protein and fatty foods

Choose more:      Choose less:
  - vegetables      - eggs
  - fruits          - meats
  - cereals         - fats


                                     51
      Beware of aflatoxins!

Choose:           Never eat:
  - dry nuts      - moldy nuts,
  - grains          especially peanuts
  - seeds         - moldy bread,
  - corns           crackers, cereals,
                    beans


                                     52
   Beware of nitrosoamines!
Choose more of:       Choose less:
- fresh foods         - cured bacon
- fresh meats         - sausages
- poultry             - hams
- seafood             - hot dogs
- fresh vegetables    - frankfurters
  and fruits          - luncheon meats
- foods containing    - some beers
  vitamines A and C


                                         53
          High-protein foods

Chose more of:            Choose less:
- steamed, braised        - high-fat smoked
  or baked,                 meats
  low-temperature         - smoked meat,
  roasted meats             ham and fish
- fresh, lower fat fish   - smoked cheese
- low-fat cheeses



                                              54
Recommended vitamin A foods

Dark-green vegetables (broccoli, spinach,
green peppers, collards)
Turnip greens
Yellow-orange vegetables (carrots, sweet
potatoes, pumpkin, red peppers)
Yellow-orange fruits (peaches, apricots)

                                            55
A wise man always eats well

       Chinese proverb



                          56
Moderate your alcohol
   consumption




                        57
       The role of alcohol

Alcohol abuse attributable to 3-7%
of all malignancies
Most common alcohol-related tumors:
cancer of the mouth, pharynx, esophagus,
larynx and breast
Acts as a co-carcinogen in cigarette
smokers

                                           58
colon, breast (post-menopausal), endometrium, kidney and oesophagus (adenocarcinoma




                                                                                      59
figure_04i.gif




                 60
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        Alcohol consumption:
         recommendations

Restrict intake of alcohol to two drinks
per day if you are a man and one drink
per day if you are a woman
Do not drink alcohol during pregnancy
Abstain from smoking when drinking
Maintain excellent oral hygiene, which is
particularly important if you drink
and smoke
                                            63
Avoid excessive sun exposure




                               64
65
             Ultraviolet rays

Ultraviolet light
– UVA (320 – 400 nm)
     probably non muatgenic
– UVB (280 – 320 nm)
     mutagenic
     associated with increased incidence skin
     carcinomas, malignant melanoma
– UVC (200 -280 nm)
     mutagenic but filtered by oozone

                                                66
 Avoid exposure to known
cancer-causing substances




                            67
             Occupational risk factors

Agent                 Cancer site
Arsenic compounds     Lung, skin, hemangiosarcoma
Asbestos              Lung, mesothelioma
Benzene               Leukemia, Hodgkin disease
Beryllium compounds   Lung
Cadmium compounds     Prostate
Chromium compounds    Lung
Ethylene oxide        Leukemia
Nickel compounds      Lung
Radon                 Lung
Vinyl chloride        Angiosarcoma, liver
                                                    68
           Ionizing radiation

Ionizing particles (e.g. alpha and beta particles),
gamma rays and x-rays
Hydrolyze water into free radicals, which are
mutagenic to DNA  activating protooncogenes
to c-oncs



                                                  69
           Ionizing radiation

Radiation induced cancers
– leukemias (except chronic lymphocytic)
– most common overall radiation induced
  cancer
– most frequently observed in the atomic bomb
  victims
Papillary carcinoma of the thyroid
– children irradiated to the head and neck area
Angiosarcoma of the liver
– patients exposed in the past to thorotrast dye

                                               70
            Examples
  of radiation induced cancers

Cancers of lung, breast, salivary gland
– intermediate frequency
GI, skin, bone
– relatively resistant to radiation-induced
  neoplasia
Lung cancer
– in uranium miners


                                              71
  Participate in vaccination
programs against hepatitis B
        virus infection



                               72
Viral and microbial carcinogenesis

About 18% of human cancers worldwide
are currently attributable to persistent
infections with viruses, bacteria or
parasites (in the European Union about
10%)
Most common infection-related
malignancies: cervix, liver and stomach
cancers, some hemo-lymphopoietic
tumors
Antibacterial and antiviral treatments,
as well as vaccination programs,           73
74
Human papilloma virus (HPV)
DNA virus
HPV 16 & 18 (most common)
31, 33, 35, 51 (less common)
– associated with squamous carcinoma
  of the cervix, vagina, and vulva
  (anus in homosexuals)
HPV 6 & 11
– associated with genital warts
HPV 1,2, 4 & 7
– squamous papillomas
                                       75
   Epstein-Barr Virus (EBV)

DNA virus
Burkitt lymphoma (Africa)
Nasophayrngeal carcinoma
 – Southern China, Artic Eskimos, parts of Africa
Hodgkins lymphoma
B-cell lymphomas in immunosuppressed
individuals (HIV, organ transplant recipients)
CNS lymphomas in HIV patients

                                                76
   Hepatitis B and C viruses

Virus type
   DNA (B)
   RNA (C)
Associated with hepatocellular carcinoma
Repeated cell death and regeneration
– expands actively proliferating cell pool  increased
  chance for spontaneous mutations and mutations
  induced by environmental agents

                                                         77
        Helicobacter pylori
Associated with gastric B-cell lymphoma
and gastric carcinoma
Chronic infection  H. pylori T-cells 
polyclonal B-cell proliferation 
accumulation of mutations  malignant
transformation
Antibiotic treatment of H. pylori may result
in lymphoma regression

                                               78
”Prevention is so much better
than healing because it saves
   the labor of being sick”
           Thomas Adams
        17th-century physician




                                 79
 e-mail addresses:

Department of Oncology
  and Radiotherapy
  onkol@amg.gda.pl

     Jacek Jassem:
 jjassem@amg.gda.pl

                         80

				
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posted:10/11/2011
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