Porth's Essentials of Pathophysiology, 4e

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Cell and Tissue Function

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Malignant Neoplasms In contrast to benign tumors, malignant neoplasms tend to grow rapidly, invade and infiltrate nearby tissue, and spread to other parts of the body. They lack a well-defined capsule and their margins are not clearly separated from the normal surrounding tissue. 2,3 Because of their rapid rate of growth, malignant tumors may compress blood vessels and outgrow their blood supply, causing ischemia and tissue injury. Some malignancies secrete hormones and/or cytokines, liberate enzymes and toxins, and/or induce an inflammatory response that injures normal tis- sue as well as the tumor itself. There are two categories of malignant neoplasms— solid tumors and hematologic cancers. Solid tumors initially are confined to a specific tissue or organ. As the growth of the primary solid tumor progresses, cells detach from the original tumor mass, invade the sur- rounding tissue, and enter the blood and lymph system to spread to distant sites, a process termed metasta- sis . Hematologic cancers involve cells normally found within the blood and lymph, thereby making them dis- seminated diseases from the beginning. Cancer in situ is a localized preinvasive lesion. For example, in ductal carcinoma in situ of the breast, the malignant cells have not crossed the basement mem- brane. Depending on its location, an in situ lesion usu- ally can be removed surgically or treated so that the chances of recurrence are small. For example, cancer in situ of the cervix is essentially 100% curable. Tumor Cell Characteristics Whether a tumor is benign or malignant is determined by an examination of its cells. Typically, such an examination includes macroscopic (naked eye) inspection to determine the presence or absence of a tumor capsule and inva- sion of the surrounding tissue, supplemented by micro- scopic examination of histologic sections of the tumor. Additional information may be obtained from electron

microscopy, immunochemistry techniques, chromosomal studies, and DNA analysis. The growth and behavior of tumor cells may be studied using culture techniques. Differentiation and Anaplasia. Differentiation refers to the extent to which the parenchymal (specific organ versus supportive tissue) cells of a tumor resemble their normal forbearers morphologically and functionally. 2,3 Malignant neoplasms that are composed of poorly dif- ferentiated or undifferentiated cells are described as being anaplastic, anaplasia literally means to “form backward” to an earlier dedifferentiated state. On histo- logic examination, benign tumors are composed of cells that resemble the tissue from which they have arisen. By contrast, the cells of malignant tumors are character- ized by wide changes of parenchymal cell differentiation from well differentiated to completely undifferentiated. Undifferentiated cancer cells are marked by a number of morphologic changes. Both the cells and nuclei dis- play variations in size and shape, a condition referred to as pleomorphism . 2,3 Their nuclei are variable in size and bizarre in shape, their chromatin is coarse and clumped, and their nucleoli are often considerably larger than normal (Fig. 7-2A). Characteristically, the nuclei con- tain an abundance of DNA and are extremely dark staining. The cells of undifferentiated tumors usually display a large number of mitoses, reflecting a higher rate of proliferation. They also display atypical, bizarre mitotic figures, sometimes producing tripolar, tetrapo- lar, or multipolar spindles (Fig. 7-2B). Highly anaplas- tic cancer cells, whatever their tissue of origin, begin to resemble undifferentiated or embryonic cells more than they do their tissue of origin. Some cancers display only slight anaplasia and others marked anaplasia. The cytologic/histologic grading of tumors is based on the degree of differentiation and the number of proliferating cells. The closer the tumor cells resemble comparable normal tissue cells, both morpho- logically (structurally) and functionally, the lower the

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FIGURE 7-2. Anaplastic features of malignant tumors. (A) The cells of this anaplastic carcinoma are highly pleomorphic (i.e., they vary in size and shape).The nuclei are hyperchromatic and are large relative to the cytoplasm. Multinucleated tumor giant cells are present (arrows). (B) A malignant cell in metaphase exhibits an abnormal mitotic figure. (From Strayer DS, Rubin E. Neoplasia. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2012:162.)