Hallmarks Of Malignant Diseases

Malignant neoplasms or cancers have several distinguishing features that enable the pathologist or experimental cancer biologist to characterize them as abnormal. The most common

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Figure 1-3. Annual age-adjusted cancer death rates* among males for selected cancer types, United States, 1930 to 2001. *Rates are age adjusted to the 2000 U.S. standard population. Because of changes in ICD coding, numerator information has changed over time rates for cancers of the lung and bronchus, colon and rectum, and liver are affected by these changes. (From U.S. Mortality Public Use Data Tapes, 1960 to 2001, U.S. Mortality Volumes, 1930 to 1959, National Center for Health Statistics, Centers for Disease Control and Prevention, with permission.)

Year of Death

Figure 1-3. Annual age-adjusted cancer death rates* among males for selected cancer types, United States, 1930 to 2001. *Rates are age adjusted to the 2000 U.S. standard population. Because of changes in ICD coding, numerator information has changed over time rates for cancers of the lung and bronchus, colon and rectum, and liver are affected by these changes. (From U.S. Mortality Public Use Data Tapes, 1960 to 2001, U.S. Mortality Volumes, 1930 to 1959, National Center for Health Statistics, Centers for Disease Control and Prevention, with permission.)

types of human neoplasms derive from epithelium, that is, the cells covering internal or external surfaces of the body. These cells have a supportive stroma of blood vessels and connective tissue. Malignant neoplasms may resemble normal tissues, at least in the early phases of their growth and development. Neoplastic cells can develop in any tissue of the body that contains cells capable of cell division. Though they may grow fast or slowly, their growth rate frequently exceeds that of the surrounding normal tissue. This is not an invariant property, however, because the rate of cell renewal in a number of normal tissues (e.g., gastrointestinal tract epithelium, bone marrow, and hair follicles) is as rapid as that of a rapidly growing tumor.

The term neoplasm, meaning new growth, is often used interchangeably with the term tumor to signify a cancerous growth. It is important to keep in mind, however, that tumors are of two basic types: benign and malignant. The ability to distinguish between benign and malignant tumors is crucial in determining the appropriate treatment and prognosis of a patient who has a tumor. The following are features that differentiate a malignant tumor from a benign tumor:

1. Malignant tumors invade and destroy adjacent normal tissue; benign tumors grow by expansion, are usually encapsulated, and do not invade surrounding tissue. Benign tumors may, however, push aside

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Figure 1-4. Annual age-adjusted cancer death rates* among females for selected cancer types, United States, 1930 to 2001. *Rates are age adjusted to the 2000 U.S. standard population. Because of ICD coding, numerator information has changed over time, rates for cancers of the uterus, ovary, lung and bronchus, and colon and rectum are affected by these changes. Uterus cancers are for uterine cervix and uterine corpus combined. (From U.S. Mortality Public Use Data Tapes, 1960 to 2001, U.S. Mortality Volumes, 1930 to 1959, National Center for Health Statistics, Centers for Disease Control and Prevention, with permission.)

normal tissue and may become life threatening if they press on nerves or blood vessels or if they secrete biologically active substances, such as hormones, that alter normal homeostatic mechanisms.

2. Malignant tumors metastasize through lymphatic channels or blood vessels to lymph nodes and other tissues in the body. Benign tumors remain localized and do not metastasize.

3. Malignant tumor cells tend to be "anaplastic," or less well differentiated than normal cells of the tissue in which they arise. Benign tumors usually resemble normal tissue more closely than malignant tumors do.

Some malignant neoplastic cells at first structurally and functionally resemble the normal tissue in which they arise. Later, as the malignant neoplasm progresses, invades surrounding tissues, and metastasizes, the malignant cells may bear less resemblance to the normal cell of origin. The development of a less well-differentiated malignant cell in a population of differentiated normal cells is sometimes called dedifferentiation. This term is probably a misnomer for the process, because it implies that a differentiated cell goes backwards in its developmental process after carcinogenic insult. It is more likely that the anaplastic malignant cell type arises from the progeny of a tissue ''stem cell'' (one that still has a capacity for renewal and is not yet fully differentiated), which has been blocked or diverted in its pathway to form a fully differentiated cell.

Examples of neoplasms that maintain a modicum ofdifferentiation include islet cell tumors of the pancreas that still make insulin, colonic adenocarcinoma cells that form glandlike epithelial structures and secrete mucin, and breast carcinomas that make abortive attempts to form structures resembling mammary gland ducts. Hormone-producing tumors, however, do not respond to feedback controls regulating normal tissue growth or to negative physiologic feedback regulating hormonal secretion. For example, an islet cell tumor may continue to secrete insulin in the face of extreme hypoglycemia, and an ectopic adrenocortio-cotropic hormone (ACTH)-producing lung carcinoma may continue to produce ACTH even though circulating levels of adreno-cortical steroids are sufficient to cause Cushing's syndrome (see Chapter 6). Many malignant neoplasms, particularly the more rapidly growing and invasive ones, only vaguely resemble their normal counterpart tissue structurally and functionally. They are thus said to be ''undifferentiated'' or ''poorly differentiated.'' 4. Malignant tumors usually, though not invariably, grow more rapidly than benign tumors. Once they reach a clinically detectable stage, malignant tumors generally show evidence of significant growth, with involvement of surrounding tissue, over weeks or months, whereas benign tumors often grow slowly over several years.

Malignant neoplasms continue to grow even in the face of starvation of the host. They press on and invade surrounding tissues, often interrupting vital functions; they metastasize to vital organs, for example, brain, spine, and bone marrow, compromising their functions; and they invade blood vessels, causing bleeding. The most common effects on the patient are cachexia (extreme body wasting), hemorrhage, and infection. About 50% of terminal patients die from infection (see Chapter 8).

Differential diagnosis of cancer from a benign tumor or a nonneoplastic disease usually involves obtaining a tissue specimen by biopsy, surgical excision, or exfoliative cytology. The latter is an examination of cells obtained from swabbings, washings, or secretions of a tissue suspected to harbor cancer: the ''Pap test'' involves such an examination.

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