CHAPTER 6

Neoplasia

DEFINITIONS There are six definitions you need to know. Neoplasia - uncontrolled new growth, the emphasis being on uncontrolled. Tumor - a generic term for a growth. Technically it only means "swelling." Oncology - the study of neoplasia; however, more recent usage implies the treatment of cancers. Cancer - "crab" - probably used in antiquity to describe the persistent nature of cancer growth. Benign - "friendly" - or at least not overtly harmful (however a benign tumor can kill, depending on the location). Malignant - "malicious, harmful" - describes the lethal behavior of some cancers. NOMENCLATURE - the convention by which things are named. Neoplasms have a compound name, one part being the tissue from which it arose and another part designating benign or malignant. Other conventions include the morphologic pattern of the neoplasm, e.g. papilloma - a warty looking lesion, polyp - a projecting mass, adenoma - a neoplasm of gland origin. Malignant neoplasm of epithelial origin are called carcinoma while those of non-epithelial origin are referred to as sarcoma. Table 6-1 list a variety of benign and malignant neoplasms. In addition, malignant neoplasms are "classified" by their histologic pattern (which to one degree or another reflects the growth potential of the lesions). Lesions are called well differentiated or low grade if they closely resemble their parent tissue and predictably have slow growth potential. They are called poorly differentiated or undifferentiated or high grade if they have little resemblance to their parent tissue or predictably will be very aggressive. Teratoma is the name given to neoplasms of more than one embryologic tissue of origin. Choristoma is the name given to the presence of normal tissue in an abnormal location such as a tooth in the pituitary gland. CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS The box on page 181 provides a summary of the features that distinguish benign from malignant neoplasms. However, there is only one feature that a benign neoplasm can never exhibit, metastasis. Benign tumors may have any or all of the features of malignant neoplasms, EXCEPT metastasis. Know this box and its components well. Features of Malignancy:

Differentiation/anaplasia:

Spread of Neoplasms:

EPIDEMIOLOGY Cancer Incidence - in general, there is a rise in the incidence of some cancers and a lowering of others. Some of this rise may be due to our living longer (cancers occur more commonly in older persons). Some may be due to our ability to diagnose cancer better. Figure 6-13 depicts the frequency of various cancers and changes in occurrence over the years. Geographic and Environmental Factors - There are big differences in cancer rates in some countries. The USA, for instance, has a higher breast cancer rate than Japan where it is uncommon. Liver cancer is rare in the USA but a leading cancer in Africa. People in the southwest USA have a high incidence of melanoma; but the rate in New England is a tenth of that in Texas. Table 6-2 outlines some known occupational exposures which increases one risk for developing cancer. Age - except for some childhood cancers, most cancers occur with increasing age, generally over 50. Childhood cancers account for 10% of pediatric deaths. Hereditary - Actually, few cancers are hereditary, although the predisposition to cancer may be. Notable hereditary cancers is a special form of colon disease known as adenomatous polyposis coli. 100% of persons with this disease develop colon cancer over time. Retinoblastoma is another example. Acquired Preneoplastic Disorders - It is well known that certain conditions in and of themselves are not malignant; however, under certain adverse conditions, these diseases have been known to have malignant neoplasms arise in them. Some of these are chronic fistulae, cirrhosis of the liver, endometrial hyperplasia, bronchial metaplasia, chronic gastritis and esophagitis, ulcerative colitis, oral leukoplakia, and colon polyps (especially villous polyps). MOLECULAR BASIS OF CANCER There are several steps normal cells have to go through to become malignant. 1. The most significant one is that a cell must undergo a permanent, non-lethal mutation in its DNA before it can transform into a malignant cell. 2.There must be mutation in one or more growth regulatory genes (growth promoting protooncogenes, growth inhibitor genes, genes controlling apoptosis, and/or in the genes that control DNA repair). 3.Carcinogensis is a multistep process. Cancers exhibit a variety of mutations and differing growth patterns over time. These changes result in various characteristics of cancer cells:

Oncogenes and Cancer - Genes that promote autonomous cell growth in cancer cells are called oncogenes. They are derived by mutations in normal regulatory genes and are characterized by the ability to promote cell growth in the absence of normal growth promoting signals. Their products, called oncoproteins, resemble the normal products of normal genes except they are devoid of important regulatory elements.

CLINICAL FEATURES OF NEOPLASIA Effects of Tumors on Host LOCATION - small benign tumors in the wrong location can kill. CANCER CACHEXIA - the weight loss form cancers is more than tumor drain on the host. There is reduced appetite, high caloric expenditure of neoplasms, cytokines (TNF and IL-1 reduce appetite and lipase activity).

PARANEOPLASTIC SYNDROMES wide ranging symptoms that occur in about 15% of cancer patients. May be very diverse. Hypercalcemia (from lung cancer), Cushing syndrome, pemphigus, hypercoagulation (from pancreatic cancer). See Table 6-5.

Grading and Staging Cancers - A scheme for deciding on prognosis and therapy. Grading - characterizing the aggressiveness of a neoplasm based on its morphology (differentiation). They may be graded by some scale (I - IV) or low, intermediate and high grade. Staging - An attempt to determine the extensiveness of a neoplasm throughout the body. TNM system a common one.

Laboratory Diagnosis of Cancer MORPHOLOGIC AND MOLECULAR METHODS Biopsy, FNA (fine needle aspiration) and cytology. All these look at the histomorphology of a neoplasm using light and/or electron microscopy.

Immunohistochemistry - looking for specific markers a tissue line may express and/or looking for genetic mutations that might indicate a neoplastic event.

BIOCHEMICAL ASSAYS - Looking for tumor associated or specific antigens such as: PSA: prostate specific antigen CEA: corioembryonic antigen (useful for bowel cancers). Alfa-fetoprotein (useful for liver cancers).