a common term for all malignant tumors. Greek Oncos = tumor; gives rise to Oncology
Most Common Forms of Cancer
in women:
diagnosed: breast > lung > colorectal
cause of death: lung > breast > colorectal
in men:
diagnosed: prostate > lung > colorectal
cause of death: lung > prostate > colorectal
Tumor = "mass"; now equated with Neoplasm
Neoplasia literally means "new growth"; the new growth is known as a Neoplasm
Neoplastic tissue competes with normal cell and tissues for energy supplies and nutritional substrates.
All tumors (benign and malignant) have two basic components:
(1) Parenchyma proliferating neoplastic cells
(2) Supporting Stroma connective tissue and blood vessels; called Desmoplasia when parenchymal cells stimulate the formation of an abundant collagenous stroma (as in breast cancer)
Benign vs. Malignant Tumors
Benign
Tumors: add -oma to the cell of origin (e.g. osteoma for benign tumor of the osteoblasts)
Adenoma benign epithelial neoplasm that forms a glandular patterns as well as tumors derived from glands
Polyp when a neoplasm produces a macroscopically visible projection above the mucosal surface.
Pleomorphic adenomas "mixed tumors" with different cells expressed from the same germ line
Teratoma made up of a variety of cell types that represent more than one germ layer.
features of malignancy:
invasion sends out "arms" into surrounding tissues
metastases spreads to different organs
Characteristics of Benign and Malignant Tumors
(1) Differentiation and Anaplasia
differentiation refers to the extent parenchymal cells resemble comparable normal cells, both morphologically and functionally. Benign tumors are generally well differentiated. Anaplasia, or lack of differentiation, is a sign of a malignant neoplasm.
Dysplasia
: loss of uniformity of individual cells as well as a loss in their architectural orientation. Dysplasia does not necessarily progress to cancer.
Anaplasia is marked by morphological and functional changes:
Pleomorphism of both cell and nuclei (pleomorphism = variation in size and shape)
Nuclei are hyperchromatic (due to an overabundance of DNA, therefore stain more darkly)
Nuclear : cytoplasmic ratio is off (1:1 instead of the normal 1:4 to 1:6)
Nuclear shape is variable, chromatin clumped around nuclear membrane, and large nucleoli
benign tumors grow slowly over years whereas malignant tumors grow rapidly and often erratically. In general, the growth rate of tumors correlates with their level of differentiation, and thus most malignant tumors grow more rapidly than benign lesions. More growth = more mitosis
(3) Local Invasion
nearly all benign tumors grow as cohesive expansile masses that remain localized to their site of origin and lack the capacity to infiltrate, invade, or metastasize. Usually develop a rim of compressed connective tissue (a fibrous capsule) that seperates them from the host tissue. The growth of Metastastic tumors is accompanied by progressive infiltration, invasion, and destruction of surrounding tissues.
*Carcinoma-in-situ: display features of malignancy without invasion of the basement membrane
(4) Metastases
benign neoplasms do not metastasize! With few exceptions, all cancers can metastasize.
Pathways of Spread
Hematogenus through blood, typical of sarcomas, liver and lung are frequent 20 sites
Lymphatic most common route for carcinomas, proximal lymph nodes may be enlarged due to a) spread and growth of cancer cells, or b) tumor specific immune response
Þ reactive hyperplasia
Direct Seeding of Body Cavities of Surfaces occurs when the neoplasm penetrates into a natural "open field" (peritoneum, adjacent tissues, etc)
Implantation direct transplantation on surgical instruments and transplantation from donor organs.
"Seed and Soil" theory- different cancers metastasize to certain locations, idiopathic (dont know why)
Diagnosis
done histologically
Incisional biopsy cut a portion out
Excisional biopsy- cut the whole thing out
Aspiration needle into cancer
Þ make slide
Frozen section cut sections from surgery, while the patient is on the table
Routine cytology PAP smears
Progression
measured two ways: Grading and Staging
(1) Grading
microscopic criteria
are the cells pleomorphic?
are the cells from an aggressive type of tumor?
are there lots of mitosis?
(2) Staging
using Prostate cancer as an example
I not palpable (on rectal exam), usually discovered trans-urethally
II palpable, then do a needle biopsy
III involved capsule Þ invaded the capsule of the organ
IV metastasized
How does Cancer Kill?
(1) spreads to distant vital organs and alters the function of that organ Þ organ failure Þ death
(2) "Metabolic Death" just die due to cancer, no obvious cause of death
(3) Remote Effects of Cancer syndromes commonly associated with cancer (e.g. MS-like syndromes)
Cachexia
- loss of appetite Þ wasting syndrome. Patients develop anemia and are more susceptible to disease.
Course of the Disease
is often up and down, periods of getting better interspersed with periods of getting worse
"spontaneous regression" can sometimes occur.
Epidemiology
1in 5 chance of dying of cancer in US (23% of all mortality in 1998, >½ million deaths)
Geographical/Environmental factors: rates vary due to where one lives and what one does for a living
Age: cancer is mainly later in life, some cancers strike at a particular time
Heredity:
(1) Inherited Cancer Syndromes autosomal dominant, specific cancers, specific markers
(2) Familial Cancers early onset, tumors in 2 or more close relatives, no specific markers
(3) Autosomal Recessive Syndromes of defective DNA repair
Cancer is not contagious. Sometimes patients families need to hear that.
Acquired Preneoplastic Disorders
because cell replication is involved in cancerous transformation regenerative, hyperplastic, and dysplastic proliferations are fertile soil for the origin of a malignant neoplasm. Examples: endometrial hyperplasia
Þ endometrial carcinoma
Bronchial mucosal metaplasia and dysplasia of smokers
Þ bronchiogenic carcinomas
Certain non-neoplastic disorders have such a well defined association with cancer they are termed "Pre-cancerous conditions" (e.g. solar keratosis of the skin and ulcerative colitis)
Molecular Basis of Cancer
Non-lethal genetic damage lies at the heart of carcinogenesis. Mutations due to
(1) Physical stimulus radiation
(2) Chemical stimulus carcinogens in cigarette smoke
(3) Biological stimulus- viruses (some cancers in humans are strongly linked to viruses, but not proven yet)
Three normal regulatory genes classes are the main targets of genetic damage