Premalignant nonepithelial lesions: a biological classification.

Premalignant lesions occur early in neoplastic development, are often small and multiple, lack one or more of the properties of cancers, often regress, and are often easily treatable. Such lesions may be derived from epithelial or nonepithelial cell populations. Many epithelial premalignant lesions can be identified by their confinement by a basement membrane. Mesenchymal, hematologic, and lymphoid premalignant lesions are difficult to recognize as most of these lesions have no defining morphologic features or anatomic boundary that identifies their premalignant nature. We have devised a classification for nonepithelial premalignant lesions, based on biologic behavior rather than morphology, that includes neoplastic lesions that have some but not all of the properties generally attributed to developed cancers. The five categories of nonepithelial premalignant lesions are: (a) lesions delimited by a basement membrane (e.g., melanoma in situ); (b) nonepithelial neoplasms having a low rate of metastasis (e.g., giant cell tumor of bone); (c) early forms of nonepithelial malignancy (e.g., Kaposi's sarcoma, patch stage); (d) indolent neoplasms that regularly progress to malignancies (e.g., chronic lymphocytic leukemia); and (e) certain low-grade neoplasms derived from germ cells (e.g., Grade 1 immature teratoma). Formal classification of the nonepithelial premalignant lesions would allow the pathologist to diagnose these biologically distinct entities as something other than simply benign or malignant, and would direct tumor biologists to study the key molecular properties that control the premalignant phenotype.