PREINVASIVE MALIGNANCY:
Recently, cancer screening programs have emphasized the prevalence of lesions, which appear to be early stages in the development of cancers. They share some cytological features of infiltrative (invasive) tumors, but have not yet become infiltrative themselves.The implication is strong that they might become infiltrative if left long enough, although we cannot say how long would that be. Nor it is possible to tell how far they have evolved from normality in terms of time or biological events, or if any of these events are reversible.
HYPERLINK "photo%20neoplasia/dysplasia%20to%20neoplasia.ppt" []
These changes are referred to as dysplasia (disorganization of tissue structure).
Dysplasia have been described in the epithelia of the
cervix
vulva
urinary bladder
bronchial mucosa
larynx
oral cavity
skin
prostate etc,.
In the cervix, vulva and the prostate they are called intraepithelial neoplasia.
The cells show many of the cytological changes of malignant tumors, like cellular overcrowding, pleomorphism, hyperchromatic nuclei, loss of normal orientation (loss of polarity) and disorderly maturation (e.g. dyskeratosis), mitotic activity above the basal layers.Despite these manifestations of abnormal cell behavior, the changes are all within the normal confines of the epithelium; the basement membrane is not breached.
When the entire thickness of the epithelium is involved by the above cellular changes, this has been referred to as carcinoma in situ and presently as grade 3 or high-grade intraepithelial neoplasia. HYPERLINK "photo%20neoplasia/severe%20dysplasia.ppt" []
Carcinoma in situ is the forerunner, in many cases, of invasive malignancy.
However mild degrees of dysplasia (grade 1 or low-grade intraepithelial neoplasia), common in the uterine cervix, dont always lead to cancer and are often reversible.GRADING AND STAGING OF TUMORS
Grading is the attempt to assign a rough numerical value to the extent of histological deviation from the normal. Thus, grade 1 neoplasms are well differentiated and show less cytological abnormality than grade 3 tumors which are poorly differentiated. Grade 2 lies inbetween grade 1 and 2. HYPERLINK "photo%20neoplasia/Grading.ppt" []Staging is an exercise in which clinical and histopathological informations are combined to describe the extent of tumor spread.
The commonest staging system presently in use is the TNM (tumor, node, metastsis) staging system, which incorporates the extent of local infiltration by the tumor (T), status of lymph node involvement (N), and the presence of distant metastasis (M). The precise meaning of the T numerical stages vary with the tumor site. e.g., in the breast they refer to tumor size, while in the gastrointestinal tract they refer to the depth of infiltration of the wall. HYPERLINK "photo%20neoplasia/TNM%20staging.ppt" []
Another staging system is that used by the American Joint Committee (AJC System).
Both grading and staging are valuable for thedetermination of prognosis and
planning of therapy,
although staging has proved to be of greater clinical value.
Grading is imperfect because, different parts in the same tumor may display different grade of differentiation, and the grade of a tumor may change as the tumor grows (cancer progression).
CANCER EPIDEMIOLOGY
Geographic and environmental factorsCancer is responsible for about 23% of annual death rate in USA. There, cancers of the prostate, lung and colon and are the leading cancers in males.
In females cancers of the breast, lung, and colon are the commonest.
In Iraqi males the commonest cancers are those of the lung, bladder, larynx as well as nonHodgkins lymphomas (NHL) and leukemias. In Iraqi females breast, NHL, Leukemia, CNS tumors and lung cancers are the commonest.
Environmental factors significantly affect the occurrence of specific forms of cancer in different parts of the world.
In Japan carcinoma of the stomach is commoner than in USA while carcinoma of the colon is uncommon. In Japanese immigrants to the USA, the incidence of both cancers is intermediate between Japanese and USA natives.
Hepatocellular carcinoma is particularly common in South East Asia.
Esophageal carcinoma is common in north of Iraq, north of Iran as well as in central Asia.Other examples of environmental factors:
Occupational exposure to asbestos is associated with lung carcinoma, pleural and peritoneal mesotheliomas.Occupational exposure to aniline dyes is associated with bladder carcinoma.
Occupational exposure to polyvinyl chloride monomers is associated with liver angiosarcoma.
Cigarette smoking is associated with carcinomas of the oropharynx, larynx and lung.
Air pollution is associated with lung cancer.
AGE
Cancer is most common in those over 55 years of age, a fact pointing that cancer evolution requires multiple independent events, apparently taking place over a long priods of time.
However certain tumors are particularly common in children (under 15 years of age), these include
tumors of hemopoetic system (Leukemias and lymphomas),
neuroblastomas
Wilmstumor
Ewings sarcoma
osteosarcoma
rhabdomyosarcomas
retinoblastomas.
HEREDITY
Heredity plays a role in the development of cancer even in the presence of clearly defined environmental factors.Hereditary forms of cancer can be divided into three categories
Inherited cancer syndromes. These are characterized by inheritance of a single mutant gene that greatly increases the risk of developing a tumor. The predisposition to tumor is an autosomal dominant trait, as exemplified by familial retinoblastoma and familial adenomatous polyposis coli (FAPC). These syndromes are associated with the inheritance of a single mutant allele of the cancer suppressor genes. In each of these syndromes only specific tissues are affected, and usually there is an associated marker phenotype e.g., the presence of many colonic adenomatous polypi in FAPC HYPERLINK "photo%20neoplasia/Familial%20polyposis%20G.ppt"[] and multiple endocrine neoplasia (MEN) .
Familial cancers. These are characterized by familial clustering of specific forms of cancer, but the transmission pattern is not clear in an individual case. Familial forms of breast, colon, brain and ovarian cancer are recorded. Unlike inherited cancer syndromes, there is no marker phenotype, i.e. cancer of the colon doesnt arise in pre-existing polyps.
Autosomal recessive syndromes of defective DNA repair. These are characterized by chromosomal or DNA instability that greatly increases the predisposition to environmental carcinogens e.g., Xeroderma pigmentosa HYPERLINK "photo%20neoplasia/Xeroderma%20pigmentosum.ppt" [] .
AQUIRED PRENEOPLASTIC DISORDERS
Certain clinical conditions are associated with an increased risk of developing cancer:Cirrhosis of the liver predisposis to hepatocellular carcinoma.
Atrophic gastritis type A (of pernicious anemia) predisposis to gastric carcinoma.
Chronic idiopathic ulcerative colitis predisposis to colonic carcinoma.
Leukoplakia of oral and genital mucosa predisposis to squamous cell carcinoma.
The subsequent development of malignancy in a benign tumor is quite uncommon, most malignant tumors arise de novo. However, there
are few exceptions, e.g., villous adenoma of the colon often develops into carcinoma.