Neoplasia

Neoplasia

Cancer is the second leading cause of death in the United States; only cardiovascular diseases exact a higher toll. Even more agonizing than the mortality rate is the emotional and physical suffering inflicted by cancer. Patients and the public often ask, "When will there be a cure for this scourge?" The answer to this simple question is difficult because cancer is not one disease but many disorders with widely different pathogeneses, natural histories, and responses to treatments. Some cancers, such as Hodgkin lymphoma, are highly curable, whereas others, such as pancreatic adenocarcinoma, are virtually always fatal. The only hope for controlling cancer lies in learning more about its causes and pathogenesis. Fortunately, great strides have been made in understanding its molecular basis, and some good news has emerged: cancer mortality for both males and females in highly resourced countries such as the United States and Europe began to decline during the last decade of the twentieth century, a trend that has continued to the present day.

In this chapter, we describe the vocabulary of tumor biology and pathology and then review the morphologic characteristics that define neoplasia and allow benign and malignant tumors to be identified and distinguished. Also reviewed is the epidemiology of cancer, which provides a measure of the impact of cancer on human populations and clues to its environmental causes-insights that have led to effective prevention campaigns against certain cancers. Building on this foundation, we then discuss the biologic properties of tumors and the molecular basis of carcinogenesis, emphasizing the critical role that genetic alterations play in the development of neoplasia. Finally, we turn to cancer diagnosis, focusing on new technologies that are helping to direct the use of cancer drugs that are targeted at specific molecular lesions. Throughout, we give examples of new analytic methods and therapies that are not only changing our approach to cancer treatment but also providing new insights into cancer pathophysiology.

NOMENCLATURE

Neoplasia means "new growth," and the collection of cells and stroma composing new growths are referred to as neoplasms. Tumor originally described swelling caused by inflammation but is now equated with neoplasm. Oncology (Greek oncos equals tumor) is the study of tumors. Although physicians know what they mean when they use the term neoplasm, it has been difficult to develop a precise definition. In the modern era, a neoplasm is defined as a disorder of cell growth that is triggered by acquired or, less commonly, inherited mutations affecting a single cell and its clonal progeny. As discussed later, these causative mutations alter the function of genes and give the neoplastic cells a growth advantage, resulting in excessive proliferation that is independent of physiologic growth signals and controls.

All tumors are composed of two components: (one) neoplastic cells that constitute the tumor parenchyma and (two) reactive stroma made up of connective tissue, blood vessels, and cells of the adaptive and innate immune system. The classification of tumors and their biologic behavior are based primarily on the parenchymal component, but their growth and spread are critically dependent on their stroma. In some tumors, connective tissue is scant, and the neoplasm is soft and fleshy. In others, parenchymal cells stimulate the formation of abundant collagenous stroma, referred to as desmoplasia. Some desmoplastic tumors-for example, some cancers of the female breast-are stony hard or scirrhous.