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 these things out.

“Differentiation” actually has a slightly different (ha ha) meaning in pathology than you might think at first. We use the term differentiation 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 cell stage, the less differentiated it is said to be.

When talking about tumors, the word “differentiation” is used in a similar way. When we say a tumor is well-differentiated, we mean that it’s made up of cells that look very much like the cells from which they arose. If it’s a well-differentiated liver carcinoma, that means the tumor cells look very much like normal (mature, fully differentiated) liver cells.

A poorly-differentiated tumor is made up of cells that barely resemble the cells from which they arose. The cells of a poorly-differentiated tumor are usually pleomorphic (varying in size and shape), and it’s very hard to tell what cells they arose from (are they squamous cells? fibroblasts? lymphoid cells?). 

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.