Tumor Differentiation
and
Grading

Differentiation refers to the extent to which neoplastic cells resemble the corresponding normal parenchymal cells, both morphologically and functionally.

In general, benign tumors are well differentiated .

The neoplastic cell in a benign adipocyte tumor—a lipoma—so closely resembles the normal cell that it may be impossible to recognize it as a tumor by microscopic examination of individual cells. Only the growth of these cells into a mass discloses the neoplastic nature of the lesion.

Malignant neoplasms are characterized by a wide range of parenchymal cell differentiation, from surprisingly well differentiated to completely undifferentiated.

Certain well-differentiated adenocarcinomas of the thyroid, for example, may form normal-appearing follicles, and some squamous cell carcinomas contain cells that do not differ cytologically from normal squamous epithelial cells .
Thus, the morphologic diagnosis of malignancy in well-differentiated tumors may sometimes be quite difficult.
In between the two extremes lie tumors that are referred to as moderately differentiated.

Malignant neoplasms that are composed of cells that are completely lack differentiation are said to be anaplastic.

Cellular pleomorphism
Size
shape
Abnormal nuclear morphology
Hyperchromasia
High nuclear cytoplasmic ratio
Chromatin clumping
Prominent nucleoli
Mitoses
Mitotic rate
Loss of polarity
tumor progression and is not simply a function of an increase in tumor size. Careful clinical and experimental studies reveal that increasing malignancy is often acquired in an incremental fashion. At the molecular level, tumor progression and associated heterogeneity most likely result from multiple mutations that accumulate independently in different cells, generating subclones with varying abilities to grow, invade, metastasize, and resist (or respond to) therapy .