Nothing is more important to the patient with a tumor than being told “It is benign.” In most instances such a prediction can be made with remarkable accuracy based on long-established clinical and anatomic criteria, but some neoplasms defy easy characterization. Certain features may indicate innocence, and others may indicate malignancy. These problems are not the rule, however, and there are four fundamental features by which benign and malignant tumors can be distinguished. These are differentiation and anaplasia, rate of growth, local invasion, and metastasis. (Robbins Pathology, 8th eddition)
Differentiation and Anaplasia
Differentiation and anaplasia refer only to the parenchymal cells that constitute the transformed elements of neoplasms. The differentiation of parenchymal cells refers to the extent to which they resemble their normal forebears morphologically and functionally. The stroma carrying the blood supply is crucial to the growth of tumors but does not aid in the separation of benign from malignant ones. The amount of stromal connective tissue does determine, however, the consistency of a neoplasm. Certain cancers induce a dense, abundant fibrous stroma (desmoplasia), making them hard, so-called scirrhous tumors.
Benign neoplasms are composed of well-differentiated cells that closely resemble their normal counterparts. A lipoma is made up of mature fat cells laden with cytoplasmic lipid vacuoles, and a chondroma is made up of mature cartilage cells that synthesize their usual cartilaginous matrix-evidence of morphologic and functional differentiation. In well-differentiated benign tumors, mitoses are extremely scant in number and are of normal configuration.
Malignant neoplasms are characterized by a wide range of parenchymal cell differentiation, from surprisingly well differentiated to completely undifferentiated. For example, well-differentiated adenocarcinomas of the thyroid may contain normal-appearing follicles. Such tumors sometimes may be difficult to distinguish from benign proliferations. Between the two extremes lie tumors loosely referred to as moderately well differentiated.