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Precancerous (Premalignant) Changes
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As noted in the previous chapter, the lag period encompasses that span of time between initiation of the carcinogenic process and the clinical detection of cancer. The sequential multiple hits that are an essential part of carcinogenesis occur during the first part of this period, extending from a few years through 3 or more decades, producing the first neoplastic cell. Repeated division of this cell and its progeny (the malignant clone), sufficient to produce a clinically detectable neoplasm (approximately 109 cells), occupies additional months or years constituting the remainder of the lag period. In most instances, no clinical or morphologic abnormalities are apparent throughout this time. However, in some cases, an intermediate abnormal, nonneoplastic growth pattern may be detected. Such an abnormality is a precancerous (preneoplastic) lesion.
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It is important to recognize precancerous lesions when they occur because surgical excision is curative (the potentially malignant tissue having been removed). While hyperplasias and metaplasias are not per se premalignant, if sustained they may progress to dysplasia, which does carry a high risk of conversion to malignancy. Most benign neoplasms progress to malignancy only rarely, but in some the risk is high (Table 19-1), and these then also are considered premalignant lesions. Again, the detection of dysplasia in a benign tumor is a warning sign.
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Invasive cancer is usually lethal, but progression of disease varies. Small prostatic cancers are found incidentally—ie, in patients who died of other causes without any clinical evidence of prostate cancer—at autopsy in about 30% of men over age 60 years. This figure rises to 90% of men over age 90 years. These cancers are called occult because they remained small and did not become manifest clinically during life.
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Another example of long-standing hidden cancer is delayed metastatic disease (occult metastases). Patients who have been treated for melanoma and breast cancer sometimes develop evidence of metastatic disease 15–20 years later. It has been proposed that occult cancers and delayed metastases may represent ...