ePathoPlusPage

Cancer

Outline

A.Definitions

    1. Anaplasia: transformation of cells to a less differentiated state (or more primitive embryonic type) with greater capacity for multiplication         but less ability to specialize

    2. neoplasm: a new growth that can be accompanied by a loss as well
       as a gain cells.May be benign or malignant

    3. tumor: frequently use interchangeably with term neoplasm but strictly
        speaking a tumor is a swelling that can be caused either by an increase
        in the number of cells or by inflammation or accumulation of blood or fluid in a localized area of tissue

    4. carcinoma:  malignant neoplasm of epithelial tissue    

    5. sarcoma:  a malignant neolasm of connective tissue

    6. adenoma: a benign epithelial neoplasm with a glandlike structure
        (compare to adenocarcinoma which is a malignant neoplasm of
        the same tissue)

B. Benign vs Malignant cells

    1. benign cells have the following characterisitics:

        a. limited growth potential

        b. localized

        c. fibrous capsule

        d. rarely recur after removal

        e. cells similar to parent cells

    2. malignant cells are characterized as follows:

        a. proliferate rapidly

        b. metastasize

        c. no enclosing capsule

        d. irregular shape with poorly defined borders

        e. cells are much different than parent cells (degrees of anaplasia)

        f. morphological changes include

            1. pleomorphism of nuclei and cells

            2. coarsely distributed DNA

            3. increased number of nucleoli

             4. disorderly cell growth (abnormal mitosis)

C. Role of Oncogenes and Tumor Suppressor Genes

   1. Cell Cycle

    2. oncogenes = accelerators of cell growth, a mutated proto-oncogene
        that is inappropriatrely activated and thus leads to cancer

    3. tumor suppressor genes -  ordinarily act as brakes to cell growth, if mutated cannot suppress cell growth and will lead to cancer

        a. p53, a tumor supressor gene thought to be responsible for
        nearly 50 % of all cancers

D. Theory of Immune Surveillance

    1. Transformation of Cells

    2. Formation of a tumor in situ

        a. blocking factor - produced by tumor cells to prevent their
        destruction by sensitized lymphocytes and by antibodies

        b. recognition factor- produced by immune system to enhance
        destruction of tumor cells

    3. Tumor growth

        a. lack of vascularization limiting factor to tumor growth

        b. role of angiogenesis factor

        c. tumor cell burden (TCB)

    4. Metastases

        a. mechanisms of spread (lymphatic permeation, embolization,
        diffusion)

    5. Re-establishment of tumor at new site

    a. escaping blood vessel into surrounding tissue

E. Etiology of Carcinogenesis

    1.  Host suceptibility    

        a. genetic factors

        b. hormonal factors

        c. precancerous lesions

        d. chronic irritation

        e. immunologic factors

    2. Environmental factors

        a. ionizing radiation

        b. chemical pollutants

    3. Health practices

        a. smoking (obviously increases risk of lung cancer, but also
            increases risk of bladder and esophageal cancer)

        b. nutrition - excess of some foods thought to cause cancer,
            some foods thought to protect against cancer, e.g  foods
            high with naturally occuring anti-oxidants)

        c. alcohol

        d. sexual practices

    4. Viruses (oncoviruses)

    5. Psychosocial factors (stress, certain personality types)

F. Problems resulting from malignancies

    1. obstruction

    2. pain - occurs in 60- 80% of all terminally ill pts

    3.cachexia

        1. role of cachectin (a tumor necrosis factor)

    4. bleeding

    5. infection

    6. electrolyte imbalances

    7. endocrine disorders

    8. fatique  

Discussion  

    Cancer arises when, at the cellular level, there is an inappropriate activation of a proto- oncogene (turning it into an oncogene) or an inappropriate supression of a tumor suppressor gene. What causes this to happen? It may happen just by chance. After all there are 30 million cells in a normal body and each cell contains all the genes that every other cell has, including the full complement of upwards of 30 proto- oncogenes and an untold number of tumor suppressor genes. Just by chance alone some of these genes in some of these cells might become mutated, leading to the beginning of the transformation of that cell and all of its progeny into a cancer cell. Of course, the odds of this happening can greatly be increased by a variety of well documented behaviors and or health practices or exposure to certain environmental factors. For example, smoking. Smoking,  perhaps because of it chronic irritant effect, introduction of carcinogens etc,  increases the chances that cells will have to divide more (increasing odds that the genes that control cell growth will be activated more and, therefore, increasing the chances they may become permanently and inappropriately activated) or by the introduction of carcinogens directly into the cell which can then permanently alter these genes. There may be a genetic predisposition- some people may have inherited a more unstable allele of these genes then other people, making them more lkely to beome inappropriately activated. For example BRCA-1 and BRCA-2 have been recently discovered. These genes, which are tumor supreesor genes, carry an increased risk for breast cancer.
    One cannot control the risks asscociated with cancer that are genetically derived or occur just by chance. However, behaviors, health practices and exposure to certain environmental stiumuli which are known to increase the risk of cancer can, in many instances, be controlled. This is the area where patient education is most important.  
    One of the postulates of the immune surveillance theory is that   transformation of a cell to a cancerous state is not a once in a lifetime phenomenon. It probably occurs with regular frequency. The reason most people do not devlop cancer is because the immune sytem is somehow able to recognize these cells in an early stage of their transformation and then, through a variety of immune mechanisms, kill them before they become clinically apparent. It seems that cancer cells "give themselves away" in many instances. They exhibit on their surface what are called tumopr specific antigens (TSA) that then serve as a recognition signal to immune cells to kill them. These antigens (proteins not normally displayed by similar cells) may be oncofetal antigens (e.g. alpha fetoprotein), viral antigens, carbohydrate tumor antigens, protein tumor antigens (e.g. PSA or prostate specific antigen) or oncogene coded antigens such as ras, myc, neu. They may even be Class II MHC proteins not normally displayed by those cells.
    Most chemotherapy works because the chemotherapeutic agent, targeting rapidly dividing cells, penetrates the cell and binds to the DNA. Many of the side effects of chemotherapy is related to the fact that chemotherapeutic agents cannot distinguish adequately enough between rapidly dividing cells that are cancer cells and normal rapidly dividing but non cancerous cells. In the latter category, would be cells that line the GI tract and the cells at the base of hair follicles. Hence these cells are also killed and the client suffers nausea, vomiting, dry mouth, alopecia. After a few doses of chemotherapy, cancer cells can become resistant to further chemotherapy. Some cancer cells may have had a  mutation that enables them to make a p-glycoprotein that can pump out toxic metabolites from the cell (hence they can pump out chemotherapeutic agents before they penetrate to the nucleus)  . These cells were "left standing" aftre the initial treatment with chemotherapy. All the other cells were killed. Enough of the other cells were killed so there is a significant decrease in TCB and a remission of symptoms. But the resistant cells rapidly multiply so that soon the entire new tumor is made up of resistant cells.

Clinically  

    Staging and grading is clinically useful to document the extent of the cancer, offer a prognosis and determine appropriate therapy. Grading is detrmined by examining the cancer cell microscopically and assessing it's degree of anaplasia. Cells are assigned a grade of I - IV (the higher the grade, the higher the degree of anaplasia). Staging is a clinical determination based on health history, physical exam and lab data. It employs a TNM classification system.:
T (tumor)
    To        no evidence of primary tumor
    Tis        carcinoma in situ
    T( 1-4) progressive increase in tumor size

N (nodes)
    No        no evidence of lymph node involvement
    N (1-3) increasing involvement of regional lymph nodes

M (metastases)
    Mo        no distant metastases
    M1        distant metastases present

A subscript "X" might be assigned for either T, N or M if it cannot be adequately assessed The value for each system (T, N, M) is then documented and a corresponding satage assignes according to the combination of values..