TumorsDefinitions:

Oncology: scientific study of tumors, including their causes, effects, behavior, prognosis, diagnosis & treatment.

Tumor = Neoplasm: (neo new + plasm flesh): an abnormal mass of tissue formed by excessive uncontrolled cell proliferation.

Malignant: any tumor that invade (adjacent tissues) & spread to distant tissues.

Benign: tumor that neither invade nor spread to other tissues.

Cancer: malignant tumor

Differentiation: degree of resemblance of tumor cells to tissue of origin.

Tissue of origin: tissue from which the tumor arises.

Dysplasia: partial loss of differentiation characterized by disordered size, shape (pleomorphism) , maturation, & spatial arrangement of cells, increase nucleo-cytoplasmic ratio (N/C ratio normally 1:4-6, becomes 1:2 in dysplastic & malignant cells), nuclear hyperchromia. dysplasia may or may not progress to malignancy.

Anaplasia: complete loss of differentiation.

Carcinoma: malignant tumor of epithelial cells

Carcinoma-in-situ: severe dysplasia without invasion of basement membrane.

Sarcoma: malignant tumor of mesenchymal tissue.

Carcinogen: an agent or substance that causes cancer.

Carcinogenesis: process of development of cancer.

Grading: an attempt to assign rough numerical value (grade) to the degree of differentiation of a tumor.

S taging: a system that delineate the extent of tumor size & spread in the body.

Metastasis: deposition of malignant cells into distant non-contagious tissue.

Hamartoma: mass formed by normal tissue components of an organ (i.e., normal tissue in wrong proportion).

Choriestoma = heterotopia = heterotopic tissue = ectopic tissue: Normal tissue in wrong place (e.g., pancreatic tissue in the wall of the stomach)

EPIDEMIOLOGY OF CANCER

1

Overview: In descending order of frequency, the most frequently diagnosed neoplasms (i.e., incidence) in males are carcinomas of the prostate, lung, and colon. In females, the mostfrequently diagnosed neoplasms are carcinomas of the breast, lung, and colon. Mortality due to neoplasms varies slightly from the incidence, with carcinomas of the lung accounting for the most frequent cause of cancer deaths in males and females, followed by prostatic and colonic neoplasms in males and breast and colonic carcinomas in females.A. Sex 1. Female predominance is seen in carcinoma of the breast and thyroid cancer. 2. Male predominance is seen in esophageal cancer and pancreatic cancer. B. Age. The incidence of most tumors increases with age. Important exceptions include: 1. Retinoblastoma and Wilms tumor (peak incidence during childhood) 2. Testicular germ cell tumors (peak incidence between the ages of 25 and 45 years) 3. Hodgkin disease (peak incidence between the ages of 20 and 25 years, and then again at the age of 60 years) C. Race, ethnicity, and geography 1. Breast cancer. The incidence is lower in Japanese women, as compared with American women. 2. Gastric cancer. The incidence is higher in Japan and Iceland, as compared with the United States. 3. Hepatic cancer. The incidence is higher in sub-Saharan African countries, as compared with the United States. 4. Prostate cancer. In the United States, black men are more likely than white men to develop prostate cancer. 5. Skin cancer is more common in patients with fair skin, light hair, and blue or green eyes. D. Environmental conditions. Occupation or workplace can predispose the patient to certain cancers. For example: . Bladder cancer is seen more often in patients who work in industries involving the manufacture or use of aniline dyes, textiles, or rubber. 2. Mesothelioma is seen more often in patients whose work exposed them to asbestos (e.g., pipefitters, ship builders).

BIOLOGY OF CANCER. Malignant neoplastic cells differ from normal cells in many as- pects: A. Growth in vivo. In contrast with normal cells, tumor cells: 1. Invade the basement membranes of tissues, through the action of lytic enzymes 2. Detach from neighboring cells (i.e., they lack surface adhesion molecules, such as cadherin) 3. Have the ability to metastasize (i.e., spread via the blood, lymphatic system, or seeding of body cavities) 4. Exhibit clonal expansion (i.e., the cells originating from a single tumor cell over- grow all others) 5. Are able to induce angiogenesis

B. Growth in vitro. In contrast with normal cells, tumor cells: 1. Lack contact inhibition (i.e., they show no growth restriction in vitro) 2. Exhibit anchorage-independent growth in soft agar 3. Exhibit growth factor-independent growth (autocrine stimulation) C. Dedifferentiation (anaplasia). In contrast with normal cells, tumor cells exhibit:

2

1. A loss of specialized functions 2. Simplified cytoplasmic architecture 3. Fetal features and antigens [e.g., alpha-fetoprotein (AFP) in liver cancer, carcinoembryonic antigen (CEA) in colon cancer]

D. Pleomorphism. Tumor cells have: 1. Nuclei of varying size and shape 2. Hyperchromatic nuclei 3. Mitotic abnormalities 4. Chromosomal abnormalities, both structural and numerical.

DIAGNOSIS OF CANCER A. Clinical diagnosis encompasses the history and physical examination, radiographic studies, and laboratory studies. . B. Cytology. Cell samples are obtained for analysis via aspiration through a thin needle or via exfoliation (e.g., as in a Pap smear). C. Biopsy. Tissue samples may be obtained for analysis via a needle or by surgical excision. 1. Standard histologic slides are stained with hematoxylin (stains the nuclei blue) and eosin (stains the cytoplasm red). 2. Immunohistochemistry entails the use of specific antibodies to detect tumor markers. 3. Molecular diagnosis. Techniques include the Southern blot test (to evaluate DNA), the Northern blot test (to evaluate RNA), and the polymerase chain reaction (PCR) test. 4. Flow cytometry is used to analyze and prove the clona[ity of lymphomas and leukemias.

EFFECTS OF TUMORS3

Overview: The effects of tumors are often based upon the location of the tumor; however, neoplasms and their products can also have more systemic effects, such as cachexia and paraneoplastic syndromes.Effects of tumors based upon location Consider the location of the tumor to determine theeffects. The following list is an extensive, but not exhaustive, list of various effects neoplasms may have based upon their location.■ A 2.0-cm tumor in the brainstem may kill a patient; a 2.0-cm tumor in the leg may not even be noticed.■ A space-occupying lesion can obliterate bone marrow causing pancytopenia, impinge upon the brain leading to herniations, or it can block a cardiac valve orifice.■ Growth of a mass can impinge upon vasculature and can cause ischemia and infarction of tissue (with arterial compression) or congestion and infarction of tissue (with venous compression).■ Invasion of a blood vessel can lead to hemorrhage within a cavity (e.g., pleural or peritoneal) or hemorrhage into an organ, causing symptoms of hemoptysis or blood in the urine or feces.■ Invasion of a nerve can lead to neurologic deficits or pain.■ A mass can cause ulceration of overlying mucosa.■ A mass in the brain can serve as a focus for seizures or other neurologic deficits.■ A mass can obstruct the colon causing constipation; obstruct the bile duct causing jaundice; or obstruct the bronchus causing pneumonia or bronchiectasis.■ Bone destruction can lead to fracture (i.e., pathologic fracture).

Cachexia: : Loss of body fat and muscle; weakness and anorexia associated with a neoplasm.■ Mechanism: Caused by cytokines produced by the tumor (possibly tumor necrosis factor) and by host response to the tumor.

Paraneoplastic syndromes■ Basic description: Side effects of a neoplasm not attributable to functions normally associated with the cell type of origin or by the location of the tumor.Types of paraneoplastic syndromes, including production of hormone-like proteins and nerve and muscle syndromes, are listed below.1. Hormone production• Parathyroid hormone (PTH)-like protein: Produced by squamous cell carcinoma of the lung, breast carcinoma, and renal cell carcinomas; results in hypercalcemia.• Adrenocorticotropic hormone (ACTH)-like protein: Produced by small cell lung carcinoma and pancreatic carcinoma; results in Cushing syndrome.• Syndrome of inappropriate antidiuretic hormone (SIADH): Produced by small cell carcinoma of the lung and cerebral neoplasms; results in retention of water.• Erythropoietin: Produced by renal cell carcinoma, hepatocellular carcinoma, and cerebellar hemangioblastoma; results in polycythemia.2. Nerve and muscle syndromes, including Lambert-Eaton syndrome, which is a myasthenia gravis-like syndrome produced by small cell carcinoma of the lung and is due to antibodiesagainst presynaptic Ca2+ channels at the neuromuscular junction.

4