Nuclear Grade: Definition

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Nuclear grade is a score that describes how abnormal the nuclei of tumor cells look under the microscope. The nucleus is the part of the cell that holds its genetic material. The more the nuclei differ from those of normal cells, the higher the nuclear grade.

Nuclear grade is most often reported for breast cancer and kidney cancer. It is usually given as a number, such as 1, 2, or 3, or as a word, such as low, intermediate, or high. This article explains what nuclear grade measures, how it relates to the overall grade of a tumor, and what it means in your pathology report.

What does nuclear grade measure?

To assign a nuclear grade, a pathologist compares the nuclei of the tumor cells with the nuclei of normal cells from the same organ. The features the pathologist looks at include:

Size. Nuclei in higher-grade tumors are usually larger than normal nuclei.
Shape and variation. Normal nuclei are similar to each other in size and shape. In higher-grade tumors, they vary a lot from cell to cell. Pathologists call this variation pleomorphism.
Color and texture. The genetic material inside the nucleus is called chromatin. In higher-grade tumors, the chromatin is often darker and coarser than normal. Darker nuclei are described as hyperchromatic.
Nucleoli. Nucleoli are small dots inside the nucleus. They are often larger and easier to see in higher-grade tumors.

Each cancer type that uses nuclear grade has its own rules for scoring these features.

How is nuclear grade different from overall tumor grade?

The grade of a tumor describes how different the tumor looks from normal tissue. Nuclear grade looks only at the nuclei. The overall grade may also consider how the cells are arranged and how quickly they are dividing.

In some cancers, nuclear grade is the whole grade. In others, it is one part of a larger grading system. For example, the Nottingham histologic grade for invasive breast cancer adds a nuclear score to two other scores to produce the final grade.

Which cancers are given a nuclear grade?

Nuclear grade is reported for several tumor types. The most common examples are:

Ductal carcinoma in situ of the breast. Ductal carcinoma in situ (DCIS) is graded mainly by nuclear grade. The report describes it as low (grade 1), intermediate (grade 2), or high (grade 3).
Invasive breast cancer. In invasive ductal carcinoma and other invasive breast cancers, the nuclei are scored from 1 to 3. Your report may call this the “nuclear grade” or the “nuclear pleomorphism score.” It is one of three scores that make up the Nottingham histologic grade.
Kidney cancer. Clear cell renal cell carcinoma and some other kidney cancers are given a WHO/ISUP grade from 1 to 4. Grades 1 to 3 are based mainly on the size of the nucleoli. Grade 4 is given when the nuclei are extremely abnormal, or the tumor contains certain high-risk patterns. This system replaced the older Fuhrman grade, which may still appear on older reports.

Not every tumor is given a nuclear grade. For example, chromophobe renal cell carcinoma is not graded this way, because its nuclei often look abnormal even though the tumor usually behaves favorably.

What does a high or low nuclear grade mean?

In general, a higher nuclear grade means the tumor cells look more abnormal. Tumors with a higher nuclear grade tend to grow faster. They are also more likely to come back after treatment or spread to other parts of the body. Tumors with a lower nuclear grade tend to grow more slowly.

Nuclear grade is only one of several factors that describe a tumor. Your doctors will consider it along with the tumor size, margins, stage, and other test results. For some tumors, such as DCIS, the nuclear grade is one of the factors considered when deciding on treatment after surgery.

Can nuclear grade change between a biopsy and surgery?

Yes. A biopsy removes only a small part of the tumor, and different areas of a tumor can have different nuclear grades. When the whole tumor is removed, the pathologist may find an area with a higher grade than the biopsy showed. In most systems, the pathologist reports the highest grade seen, even if it is present in only part of the tumor.

Questions to ask your doctor

What is the nuclear grade of my tumor?
Is my nuclear grade low, intermediate, or high?
Is the nuclear grade the same as the overall grade of my tumor?
Which grading system was used in my report?
How does the nuclear grade affect my treatment options?
Was the grade different on my biopsy and my surgical specimen?
How does my nuclear grade affect the chance that the tumor will come back?
What other features of my tumor are important to consider along with the grade?