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  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 reflectsthe growth potential of the lesions). Lesions are called well differentiated or low grade if they closelyresemble their parent tissue and predictably have slow growth potential. They are called poorlydifferentiated or undifferentiated or high grade if they have little resemblance to their parent tissue orpredictably will be very aggressive.

Teratoma is the name given to neoplasms of more than one embryologic tissue of origin. Choristomais the name given to the presence of normal tissue in an abnormal location such as a tooth in the pituitarygland.

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. Knowthis box and its components well.

Features of Malignancy:

Differentiation/anaplasia:

Spread of Neoplasms:

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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). Somemay be due to our ability to diagnose cancer better. Figure 6-13 depicts the frequency of various cancersand changes in occurrence over the years.

Geographic and Environmental Factors - There are big differences in cancer rates in somecountries. The USA, for instance, has a higher breast cancer rate than Japan where it is uncommon. Livercancer is rare in the USA but a leading cancer in Africa. People in the southwest USA have a highincidence of melanoma; but the rate in New England is a tenth of that in Texas. Table 6-2 outlines someknown 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. Notablehereditary cancers is a special form of colon disease known as adenomatous polyposis coli. 100% ofpersons 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 havemalignant neoplasms arise in them. Some of these are chronic fistulae, cirrhosis of the liver, endometrialhyperplasia, 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 controlDNA repair).

3.Carcinogensis is a multistep process. Cancers exhibit a variety of mutations and differing growthpatterns over time. These changes result in various characteristics of cancer cells:

Oncogenes and Cancer - Genes that promote autonomous cell growth in cancer cells are calledoncogenes. They are derived by mutations in normal regulatory genes and are characterized by the abilityto promote cell growth in the absence of normal growth promoting signals. Their products, calledoncoproteins, resemble the normal products of normal genes except they are devoid of importantregulatory elements.

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  CLINICAL FEATURES OF NEOPLASIAEffects 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. Thereis reduced appetite, high caloric expenditure of neoplasms, cytokines (TNF and IL-1 reduceappetite and lipase activity).

PARANEOPLASTIC SYNDROMES – wide ranging symptoms that occur in about 15% of cancerpatients. 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. TNMsystem 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 aneoplasm using light and/or electron microscopy.

Immunohistochemistry - looking for specific markers a tissue line may express and/or looking forgenetic 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).