Dysplastic epithelium is recognized by a loss in the uniformity of individual cells and in their architectural orientation. Dysplastic cells exhibit considerable pleomorphism and often possess abnormally large, hyperchromatic nuclei. Mitotic figures are more abundant than usual and frequently appear in abnormal locations within the epithelium. In dysplastic stratified squamous epithelium, mitoses are not confined to the basal layers, where they normally occur, but may be seen throughout the epithelium. In addition, there is considerable architectural anarchy. For example, the usual progressive maturation of tall cells in the basal layer to flattened squames on the surface may be lost and replaced by a disordered hodgepodge of dark basal-appearing cells. When dysplastic changes are severe and involve the entire thickness of the epithelium, the lesion is referred to as carcinoma in situ, a preinvasive stage of cancer (
Fig. 6.6
It is important to appreciate that dysplasia is not synonymous with cancer. Mild to moderate dysplasias that do not involve the entire thickness of the epithelium sometimes regress completely, particularly if inciting causes are removed. However, dysplasia is often noted adjacent to frankly malignant neoplasms (e.g., in cigarette smokers with lung cancer), and in general the presence of dysplasia marks a tissue as being at increased risk for developing an invasive cancer.
The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of surrounding tissues, whereas most benign tumors grow as cohesive expansile masses that remain localized to their sites of origin. Because benign tumors grow and expand slowly, they usually develop a rim of compressed fibrous tissue (
Figs. 6.7 6.8 ). This capsule consists largely of extracellular matrix that is deposited by stromal cells such as fibroblasts, which are activated by hypoxic damage to parenchymal cells resulting from compression by the expanding tumor. Encapsulation creates a tissue plane that makes the tumor discrete, moveable (non-fixed), and readily excisable by surgical enucleation. However, it is important to recognize that not all benign neoplasms are encapsulated. For example, the leiomyoma of the uterus is discretely demarcated from the surrounding smooth muscle by a zone of compressed and attenuated normal myometrium, but lacks a capsule. A few benign tumors are neither encapsulated nor discretely defined; lack of demarcation is particularly likely in benign vascular neoplasms such as hemangiomas, which understandably may be difficult to excise. These exceptions are pointed out only to emphasize that although encapsulation is the rule in benign tumors, the lack of a capsule does not mean that a tumor is malignant. Sadly, because of their uncivilized nature, tumor cells sometimes do not follow the rules set by humans. We will see such deviations many times in this chapter.
Fig. 6.7 Fibroadenomaofthebreast.Thetan-colored,encapsulatedsmalltumorissharplydemarcatedfromthewhiterbreasttissue.
Fig. 6.8 Microscopicviewoffibroadenomaofthebreastseenin
Fig.6.7 .Thefibrouscapsule(right) sharplydelimitsthetumorfromthesurroundingtissue.(Courtesy of Dr.Trace Worrell, Department of Pathology, University of Texas Southwestern Medical School, Dallas,Texas.) http://ebooksmedicine.net
Fig. 6.9 Cutsectionofinvasiveductalcarcinomaofthebreast.Thelesionisretracted,infiltratingthesurroundingbreastsubstance,andwasstony-hardonpalpation.
Next to the development of metastases, invasiveness is the feature that most reliably distinguishes cancers from benign tumors (