Moderately Differentiated: Definition

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Moderately differentiated describes tumor cells that look partly like normal cells and partly abnormal. It is the middle category in many grading systems. Pathologists also call it intermediate grade or grade 2. A moderately differentiated tumor usually behaves somewhere between a well differentiated and a poorly differentiated tumor.

This article explains what moderately differentiated means, how it fits with the other grades, and what it means in colorectal, lung, and breast cancer.

What does differentiation mean?

Differentiation describes how closely tumor cells resemble the normal cells they came from. A pathologist judges differentiation by examining the tumor under a microscope. The term appears most often in reports on carcinomas, such as adenocarcinoma and squamous cell carcinoma.

Pathologists usually sort tumors into three groups:

Well differentiated. The cells look much like normal cells. This is grade 1, or low grade.
Moderately differentiated. The cells keep some normal features but also look clearly abnormal. This is grade 2, or intermediate grade.
Poorly differentiated. The cells look very abnormal and have lost most normal features. This is grade 3, or high grade.

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

A moderately differentiated tumor still shows some normal tissue structure. The exact features depend on the type of tumor:

Adenocarcinoma. The tumor cells still form glands, but the glands are irregular, crowded, or incomplete.
Squamous cell carcinoma. The tumor cells still make some keratin, the tough protein in normal skin cells. They show more abnormal features than a well differentiated tumor.

The cell nuclei are usually larger and more irregular than normal. The pathologist may see more dividing cells, called mitotic figures, than in a well differentiated tumor.

How is moderately differentiated used in different cancers?

Moderately differentiated has a specific meaning in some cancers. Each cancer type has its own grading rules:

Colorectal cancer. Pathologists now often use a two-tier system for colon adenocarcinoma. This system groups moderately and well differentiated tumors together as low grade.
Lung adenocarcinoma. In lung adenocarcinoma, grade 2 means the tumor grows mainly in gland-like or finger-like patterns. Fewer than 20 percent of the tumor shows high grade patterns.
Breast cancer. In invasive breast carcinoma, the Nottingham histologic grade ranges from 3 to 9. A score of 6 or 7 is grade 2, or moderately differentiated.

Some tumors are not graded this way. Brain tumors, for example, use a separate grading system.

What does moderately differentiated mean for my prognosis?

A moderately differentiated tumor usually grows faster than a well differentiated tumor. It usually grows more slowly than a poorly differentiated tumor. The grade is only one part of the picture, however.

Your doctors combine the grade with the stage, the margins, and other findings. Together, these help predict how the cancer may behave and guide treatment.

Can a tumor have more than one grade?

Yes, parts of the same tumor can look different. One area may be moderately differentiated, while another is poorly differentiated. In colorectal cancer, for example, the pathologist assigns the grade based on the least differentiated area.

Questions to ask your doctor

What grading system did the pathologist use for my tumor?
Is my tumor described as grade 2, intermediate grade, or low grade?
Did any part of my tumor look poorly differentiated?
How does the grade affect my prognosis?
What is the stage of my cancer?
Does the grade change my treatment options?
Does my tumor need biomarker testing?