What are the characteristics, anatomical structure and types of tumor? Information about the causes and diagnosis of tumor.
Information About Tumor
TUMOR, a neoplasm, or new growth of tissue. The term was once used to designate any kind of swelling, even one resulting from inflammation. But by the mid-19th century, improved microscopic techniques made it easier to identify cases of new tissue growth, and gradually the certain recognition of most tumors became routine.
Tumors can occur any place in the body. Some mysterious change occurs in the manner of growth of a single or a small group of cells that makes them independent of influences which restrict the growth of normal tissues. Neoplastic cells tend to grow progressively and continuously without respect for their surroundings or for orderly patterns of tissue structure.
All tumors contain at least two different kinds of cells: (1) tumor cells and (2) stroma. It is the tumor cells that are of basic importance. The future of the tumor and the survival of the host depend upon the growth characteristic of these cells. When it is their nature to grow slowly and locally, a benign tumor will result. When they grow rapidly and break free of local restraint, a malignant tumor results. The stroma, consisting of connective tissue and blood vessels, is composed of normal cells of the part that provides a skeletal framework and blood supply.
Benign and Malignant Tumors.—A tumor that grows as a slowly expanding mass and never shows any tendency to spread to other parts of the body is designated as benign. Examples are the leiomyoma, in lay terms called “fibroid,” of the uterus, or the fibroadenoma of the breast. A benign tumor affects the individual by causing pressure on the tissue in which it grows. When the growth becomes large, it may cause extensive distortion, obstruction of secretions, or actual destruction of the tissue and may even affect structures in nearby organs. If such a tumor occurs in a vital location, for example in the brain, even a “benign” tumor may cause serious disability and death. It does this purely as a result of its expansion and local pressure.
Malignant tumors show an aggressive behavior not seen in benign tumors. The cells have the capacity to separate themselves from those of the main mass. As isolated tumor cells or in small groups, they creep into normal tissue spaces. Presumably, they do this by means of ameboid motion, a phenomenon that can be demonstrated in tissue culture. They squirm their way between the normal cells and may spread to great distances. This tendency to filter into or invade tissues is spoken of as infiltration. Of even greater danger to life is the capacity of malignant cells to enter the blood or lymphatic vessels. Once they pass through the thin wall of a capillary or lymphatic channel, they can grow more easily. They fill the vessel and are often swept away in the stream of blood or lymph. Carried to distant organs, such as the lymph node, lung, -or liver, they may lodge and grow. This process of spreading via the blood or lymphatic streams to distant sites is called metastasis and is seen only in the malignant tumor.
The surgeon who attempts to treat a cancer will be successful only when he is able to remove or destroy all of the tumor cells. As these may have spread much farther’into apparently normal tissues than can be seen with the naked eye, he must excise cancers widely. Once lymph node metastases have occurred, the chance of complete removal is less and, when distant organs are affected, the situation becomes practically hopeless.
Terminology.—Tumors have a multitude of complicated and frightening names. These can usually be deciphered by the novice if he recognizes that the suffix, -oma, designates a tumor. When used in the form carcinoma (cancer of epithelial cells) or sarcoma (cancer of connective tissue cells), it signifies a malignant tumor. Thus, the benign tumor of fibrous connective tissue is a fibroma; the benign tumor of glandular tissue an adenoma; and the benign tumor of bone an osteoma. The malignant tumors that correspond are called fibrosarcoma, adenocarcinoma, and osteogenic sarcoma. There are, however, so many variations and inconsistencies that a specialist’s help may be necessary.
Cancer is the general term applied to all malignant tumors, no matter what their type. Leukemia means a malignant growth of white blood cells, the leukocytes. As the mature leukocyte is normally invasive, it is not surprising that, in leukemia, infiltration of tissues is extensive and the number of cells circulating in the blood is often enormously increased.
Anatomical and Histological Characteristics.—The attention of a patient or physician is first attracted to a tumor growth by some irregularity in the usual uniform appearance of an organ. There may be an irregular lump or nodule that is different in its shape, color, or consistency from the surrounding normal tissue. Such a change may be noticed when still quite small if it is located upon a surface that can be observed directly, as the skin or mucous membrane. In softer tissues, the presence of a firm tumor will produce an irregularity that can be palpated.
The consistency of any tumor will depend upon the kind of cells and cell products that make up the bulk of the mass. It may vary from the hardness of dense bone to the softness of fat or a fluid-filled sac. For example, those that contain supporting or tendonlike connective tissue fibers known as fibromas, are quite firm, while those containing fat, lipomas, are quite -soft. Many epithelial tumors stimulate a heavy growth of stroma and will be quite hard. This is characteristic of many cancers of the breast. Other breast cancers which do not have a heavy stroma can be soft.
The form assumed by a neoplasm depends in some measure upon its anatomical position. Tumors growing within a loose or a uniform tissue usually form well-defined, spherical masses. When growing on or near a surface, they project as a hemispherical mass. Neoplasms arising from skin or intestinal surfaces may throw it into folded, fingerlike or cauliflowerlike elevations described as a papilloma or polyp. These project above the surface and may actually develop a mobile stalk. When a tumor grows where the tissue consistency is not uniform, the shape of its growth may be restricted by the firmer tissues that surround it. A tumor in which the cells retain their capacity to form a secretion may assume the form of cysts with a thin fibrous wall lined by tumor cells and a central sac filled with great quantities of watery or mucinous secretion. Certain tumors of the ovary have been recorded in which the cyst and its fluid weighed more than 150 pounds, or considerably more than the patient herself.
As a tumor grows larger, there is a tendency for parts of it to die; it undergoes necrosis. Probably this results from the cutting off of nutrition due to pressure on blood vessels or perhaps, at times, to the accumulation of noxious metabolites or secretions. When a tumor occurs on or near a surface, there is a tendency for both the tumor and the compressed normal “tissues to become necrotic. This results in ulceration of the surface, in consequence of which there is danger of severe hemorrhage or bacterial invasion.
When a tumor is examined by microscopic techniques, it is seen that neoplastic cells commonly bear a resemblance to normal cells. The degree of resemblance, called differentiation, is extremely variable. Some are so like the normal that they can be distinguished with great difficulty; others are so different that only faint clues as to their origin are to be found. Tumor cells that have lost many or all of the characteristics or functions that distinguish the specialized cell are said to be poorly differentiated, undifferentiated, or anaplastic. They resemble primitive embryonic cells. Well-differentiated cells tend to retain specialized functions, such as the ability to produce exocrine and endocrine secretions. Benign tumors are sometimes composed of cells so well differentiated that they can be distinguished from normal only by irregularities of arrangement, as in a lipoma where the individual cells may appear quite normal. Nearly all malignant tumors display some loss of differentiation. At times this may be extreme but this is uncommon. More frequently, the cell of origin is clear but the form of the cells is bizarre and their arrangement distorted.
The degree of differentiation may give some idea of the rapidity with which a tumor may be expected to grow. The better-differentiated tumors grow slowly; the more anaplastic tumors grow rapidly and metastasize early. However, individual tumors show wide variations and dogmatic predictions of the course any given tumor may take are unwise.
Tumor nuclei are larger and contain more desoxyribonucleic acid (DNA) than their normal counterparts. Mitoses are seen much more frequently in malignant cells than in normal tissu^ or benign tumors. Often these are bizarre in character, and there is evidence that they often have an abnormal complement of chromosomes.
It has been demonstrated (by Dale Coman, 1944) that certain cancer cells have a greatly diminished adhesiveness, that is, they do not adhere as firmly to neighboring cells as do their normal counterparts. It is believed that this is related to physiochemical alteration of the ccll surface associated with lowered calcium at the surface membrane. A similar loss of adhesiveness can be produced in the cells of young dividing sand-dollar or sea-urchin embryos by lowering the concentration of calcium in the seawater. Decreased adhesiveness may play a vital role in determining invasive behavior of tumor cells and in favoring their desquamation in surface secretions.
Endocrine Function.—An interesting and important property of tumors arising in endocrine organs is their ability to produce hormones similar to those normally produced by the tissue of origin. Thus, the pituitary, thyroid, parathyroid, ovary, testis, adrenal cortex and medulla, and placenta can be the sites of secreting tumors. As a tumor contains many more cells than the normal organ, the amounts of hormone produced may be enormously increased. The usual physiologic balance is upset and bizarre symptoms due to hyperfunction may occur. Examples are giantism or acromegaly due to pituitary tumors and precocious sexual development due to adrenal or ovarian tumors. Nonfunctioning tumors occur in the same organs and produce effects by causing pressure atrophy and reduced endocrine function. Also, on rare occasions, certain tumors have been shown to produce chemical substances which are given off into the blood and excreted in the urine. Examples are the black pigment melanin produced by the malignant melanoma, abnormal proteins (described by Henry Bence-Jones 1814?-1873) produced by certain myelomas of bone, and 5-hydroxytryptamine produced in carcinoid tumors (usually arising from the bowel) which have metastasized to the liver. This latter substance, also known as serotonin, produces peculiar vasomotor reactions in affected individuals.
Causes of Tumors.—The cause of tumors is unknown. An enormous amount of effort and money has gone into studying this puzzling disease and many interesting things have been discovered, but none of these yet provides a satisfactory explanation for the origin of tumors. Rather naturally, most study has been directed toward the cause of malignancy. Through experimental study, it has been shown that cancers can be caused by viruses, chemical carcinogens, radiant energy, and heredity.
Viruses.—The Rous’ sarcoma in chickens was long ago demonstrated to be transmissible from one animal to another by a cell-free filtrate. The Shope rabbit papilloma, normally present in wild rabbits, can be transmitted to domestic rabbits by means of a cell-free extract. The Bittner mammary cancer of mice is transmitted via some unknown factor to the infant female in the mother’s milk during nursing. Certain mouse leukemias are caused by a filter-passing virus which can infect young mice.
No human tumor, except possibly the common skin papilloma, has ever been proved to be due to a virus.
Chemical Carcinogens.—Many hundreds of chemical substances are capable of producing cancer in experimental animals. Coal tar and many specific hydrocarbons (such as 3,4-benz-pyrene; 1,2,5,6-dibenzanthracene; and 20-methyl-cholanthrene) are active when painted on a skin surface or when implanted in tissues. Others, such as the azo dye, butter yellow (ρ-dimethyl-amino-azobenzene), are active when fed by mouth, causing tumors in the liver.
Certain human tumors are believed to be due to externally applied carcinogens. Cancer of the scrotum was recognized as being unusually common in chimney sweeps as long ago as the 18th century. Unprotected workers in the azo dye industry have an unusually high incidence of cancers of the bladder and urinary tract.” There is, however, as yet no direct evidence for or against known carcinogens playing an important role in the genesis of most human cancers. Many are disputed, the best example being the argument over the importance of cigarette smoking as a cause of lung cancer.
Radiant Energy.—Many forms of radiant energy are carcinogenic. The early workers with unprotected X-ray apparatus received heavy doses that injured the skin and,- after many years, skin cancers developed in the affected regions. There is also evidence to suggest that radiologists have an increased incidence of leukemia (cancer of blood cells), and it is postulated that this is related to their exposure to small cumulative doses of radiation. Japanese survivors of the 1945 atomic bomb also seem to have a high incidence of leukemia.
The story of the women who painted luminous watch dials with radium paint is well known. They moistened and pointed brushes with their lips and so ingested radium salts. These lodged in the skeleton and the radiation eventually caused bone damage, blood changes, and a star-tlingly high incidence of the malignant bone tumor, osteogenic sarcoma. Skin cancers occur frequently in white persons heavily exposed to sunlight (ultraviolet radiation). In experimental animals, cancers have been produced by exposure to these and other forms of radiant energy.
Heredity.—Strains of experimental animals can be bred that have a high or low incidence of spontaneous tumors of certain kinds. There are many marked differences in incidence of specific tumors among the races of man. On the other hand, there seems to be little evidence of a tumor tendency in families. Though much discussion is heard on this point, reliable data are hard to find.
Diagnosis.—The treatment of a patient with a neoplasm will be determined by the character of the tumor, principally whether it is benign or malignant, and the site or sites affected. A definitive diagnosis is essential for proper treatment and must depend upon microscopic examination of tumor tissue.
Whenever feasible, tissue for diagnosis is obtained before a major operation is attempted. A small piece is cut out with a knife or a large-bore needle. This procedure is known as biopsy. Frequently, the pathologist can assist the surgeon in the operating room by making rapid sections (called frozen sections because the tissue is hardened by freezing). A diagnosis can frequently be available in less than five minutes, and the operation can then proceed.
A simpler procedure can be used for screening large numbers of patients who, because of age or symptoms, are suspected of having tumors on surfaces that provide suitable secretions. These are smeared on a slide, stained, and examined with a microscope (Papanicolaou technique). Tumor cells that have been discharged from an ulcerated surface may be identified. Suspicious cases can then be biopsied to confirm the diagnosis before radical treatment is initiated. This smear procedure has been shown to be most effective for cancers of the female genital tract and of the lung. It is used, but with less confidence, in the urinary tract and bowel.