The Nottingham Histologic Score (NHS) is a standardized system used by pathologists to assess the microscopic appearance and biological aggressiveness of an invasive breast cancer tumor. This grading system is also frequently referred to as the Modified Bloom-Richardson or the Elston-Ellis grading system. The resulting grade measures how much cancer cells deviate from normal breast cells and how quickly they appear to be dividing. The NHS describes the biological behavior of the tumor, which is separate from the cancer stage, which describes the tumor’s physical size and spread.
The Three Histologic Components
Pathologists use the Nottingham Histologic Score to evaluate three distinct morphological features of the tumor tissue under a microscope, assigning a score of 1 to 3 for each component. The first component, tubule formation, assesses the tumor cells’ attempt to organize into glandular structures, similar to the ducts and lobules of a healthy breast. A score of 1 is given if over 75% of the tumor forms these defined tubular structures, indicating a high degree of differentiation. Conversely, a score of 3 is assigned if less than 10% of the tumor shows any organized tubule formation, reflecting a highly disorganized and abnormal growth pattern.
The second criterion examined is nuclear pleomorphism, which measures the size, shape, and uniformity of the cancer cell nuclei. Variation in the nucleus’s appearance suggests greater cellular abnormality. A score of 1 means the nuclei are small, uniform, and closely resemble those of normal breast cells, while a score of 3 indicates pronounced differences, with large, irregularly shaped nuclei.
The final component is the mitotic count, which directly measures the rate of cell division, reflecting how quickly the tumor is growing. A pathologist counts the number of cells actively undergoing mitosis within a specific field of view on the slide. A low score of 1 is given when very few dividing cells are observed, suggesting a slow proliferation rate. A score of 3 is assigned when numerous mitotic figures are present, indicating rapid, uncontrolled cell growth.
How the Numerical Score is Determined
The total numerical Nottingham Histologic Score is calculated by adding the scores from the three individual components: tubule formation, nuclear pleomorphism, and mitotic count. Since each component is scored between 1 and 3, the minimum possible total score is 3, and the maximum possible score is 9. This total score then directly translates into one of three final histological grades.
A total score ranging from 3 to 5 is categorized as Grade 1, representing the lowest level of cellular abnormality. A total score of 6 or 7 results in a classification of Grade 2, signifying an intermediate level of differentiation. Finally, a total score of 8 or 9 is classified as Grade 3, indicating the highest degree of cellular deviation and proliferative activity.
What the Final Grade Indicates
The resulting histological grade indicates the tumor’s biological behavior and is used to predict the likely outcome for the patient. Grade 1 tumors, sometimes referred to as well-differentiated, closely resemble normal breast tissue and grow at the slowest rate. These low-grade cancers are associated with a more favorable long-term outlook and may require less aggressive systemic therapy.
Grade 2 tumors are considered moderately differentiated, exhibiting features between the well-organized Grade 1 and the highly abnormal Grade 3 tumors. These cancers show a moderate growth rate and carry an intermediate prognosis. Management often requires balancing the risk of recurrence with the potential side effects of treatment.
Grade 3 tumors are classified as poorly differentiated and represent the most aggressive form of breast cancer based on this scoring system. These high-grade tumors grow and divide rapidly, show the least resemblance to normal breast tissue, and carry a higher risk of recurrence and spread. Due to their aggressive nature, Grade 3 cancers often necessitate more intensive treatment plans, which may include chemotherapy in addition to surgery and radiation therapy. The grade is used by the care team, along with other factors like tumor size and hormone receptor status, to help determine the most appropriate course of action.