Well Differentiated: Definition

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Well differentiated describes tumor cells that look very similar to the normal cells of the tissue where the tumor started. A pathologist uses this term after comparing the tumor cells with normal cells under the microscope. Well differentiated tumors usually grow more slowly than tumors whose cells look less normal. Your report may also write the term as “well-differentiated.”

Well differentiated is a description of the tumor cells, not a diagnosis on its own. It appears most often in the grade of a cancer, where it usually means a low-grade tumor. This article explains what well differentiated means, how pathologists recognize it, and how it relates to grade and prognosis.

What does well differentiated mean?

Differentiation is the process that turns young, unspecialized cells into mature cells with a specific job. A mature gland cell makes mucus, for example, and a mature skin cell makes a tough protein called keratin. Pathologists use the word differentiated to describe how much a tumor still resembles this mature tissue.

In a well differentiated tumor, the cells keep most of the features of the normal tissue. They have a similar size and shape, and they arrange themselves in a similar pattern. In a poorly differentiated tumor, the cells have lost most of these features. Pathologists call a tumor undifferentiated when its cells no longer resemble any normal tissue.

What does a well differentiated tumor look like under the microscope?

A pathologist recognizes a well differentiated tumor by how closely it copies the normal tissue. The features the pathologist looks for depend on the type of tumor:

Well differentiated adenocarcinoma. An adenocarcinoma starts from gland-forming cells. When it is well differentiated, most of the tumor still forms well-shaped glands that resemble normal glands.
Well differentiated squamous cell carcinoma. A squamous cell carcinoma starts from flat squamous cells. When it is well differentiated, the cells mature in layers and make large amounts of keratin, much like normal skin.
The cell nucleus. In a well differentiated tumor, the nuclei of the cells are usually similar in size and shape. They show only mild nuclear atypia, meaning they look only slightly abnormal.
Dividing cells. Well differentiated tumors usually contain few dividing cells, called mitotic figures, which fits with their slower growth.

How does well differentiated relate to tumor grade?

Pathologists use differentiation to assign a grade to many types of cancer. The grade describes how abnormal the cancer cells look, and it helps predict how the tumor will behave. Many reports use a three-level system based on differentiation:

Well differentiated (grade 1). The cancer cells look very similar to normal cells. Pathologists call these tumors low grade, and they tend to grow slowly.
Moderately differentiated (grade 2). The cancer cells look somewhat different from normal cells, and pathologists call these tumors intermediate grade.
Poorly differentiated (grade 3). The cancer cells look very different from normal cells. Pathologists call these tumors high grade, and they tend to grow and spread faster.

Some cancers use their own grading systems instead of these three words. Examples include the Gleason score for prostate cancer, the Nottingham grade for breast cancer, and the FNCLCC grade for sarcomas. Differentiation still forms part of each of these systems. Your report will name the system your pathologist used.

Is a well differentiated tumor cancer?

A well differentiated tumor can be either benign (noncancerous) or malignant (cancerous). Benign tumors are almost always well differentiated. However, many cancers are also well differentiated, so this term alone does not tell you whether a tumor is cancer.

To make that decision, the pathologist looks for features that only cancers show. The most important is invasion, which means tumor cells have grown into the surrounding tissue. Spread to lymph nodes or other organs, called metastasis, also confirms cancer. Your final diagnosis tells you whether the tumor is benign or malignant.

When is well differentiated part of the diagnosis name?

For a few tumors, well differentiated is part of the diagnosis itself rather than a grade. In these tumors, the term names a separate tumor type, as in these two common examples:

Well differentiated neuroendocrine tumor. A well differentiated neuroendocrine tumor starts from hormone-producing cells. The World Health Organization (WHO) classification, 5th edition, grades these tumors as grade 1, 2, or 3 by how fast the cells divide. A well differentiated neuroendocrine tumor can therefore be grade 3.
Well differentiated liposarcoma. Well differentiated liposarcoma is a cancer that starts from fat cells. When it grows in the arms or legs, pathologists may call it an atypical lipomatous tumor instead.

In these cases, read well differentiated as part of the tumor’s name. Your doctor can explain how this tumor type usually behaves.

What does well differentiated mean for prognosis?

A well differentiated cancer usually has a better prognosis than a poorly differentiated cancer of the same type. The cells grow more slowly and are less likely to spread early, and doctors weigh this finding when they plan treatment and follow-up.

Differentiation is only one part of the picture. The stage of the cancer describes its size and how far it has spread. A well differentiated cancer can still be large or have spread to lymph nodes. Your care team considers the grade, the stage, and the other findings in your report together.

Questions to ask your doctor

Is my tumor well differentiated, moderately differentiated, or poorly differentiated?
What grade is my tumor, and which grading system was used?
Is the tumor benign or malignant?
Did the tumor invade the surrounding tissue?
What stage is my cancer?
How does the grade of my tumor affect my prognosis?
Does the grade change my treatment options?
What follow-up will I need?