Q. A question: why do you call a tumor “well-differentiated” when actually it is the LEAST different from the tissue of origin? Shouldn’t it be “low differentiated?”

A. That’s a great question. So many times in pathology we use terms without explaining them – you’re right to try to figure it out.

“Differentiation” actually has a slightly different (ha ha) meaning in pathology than you might at first think. We use the term to describe the way a cell progresses along whatever path it has chosen for itself. For example: a neutrophil starts out as a myeloblast (see above). Then it moves through several stages (promyelocyte, myelocyte, metamyelocyte, band) before reaching its fully “differentiated” self: a segmented neutrophil. The farther along the path the cell is, the more “differentiated” it is said to be. The earlier the stage, the less “differentiated” it is said to be.

This kind of makes sense when you think of a myeloblast in the bone marrow. Most of the time, you can’t tell what type of myeloid cell that blast is going to turn into – all myeloblasts look the same. But as it matures, it will eventually show its nature – its different-ness – and you’ll be able to tell what it is becoming. Early on, all myeloid cells look the same, but later, they all look different. So the more the cell matures, the more “differentiated” (“different”) it is said to be.

The same analogy works for a tumor. Really big, ugly, anaplastic cells are just really big, ugly, anaplastic cells – they don’t look that different from each other, whether they are part of a thyroid tumor, or a lymphoid tumor, or a breast cancer. As the cell acquires more characteristics of a mature thyroid cell (or lymphoid cell, or breast cell), it is said to be farther along the “differentiated” pathway, because you can see the difference between that cell and cells of a different lineage.