Nottingham Grading System – Breast Carcinoma

The Bloom-Richardson grading system was refined in the Nottingham/Tenovus Primary Breast Cancer Study (1974) into what is now referred to as the Nottingham grading system.  This is a semi-quantitative evaluation with better inter-observer reproducibility and evaluation criteria.

Nottingham Grading System
  •   Tubule formation
    •  Majority of tumor (>75%) =  1
    •  Moderate degree (10–75%) = 2
    • Little or none (<10%) = 3
  •  Nuclear pleomorphism
    •  Small, regular uniform cells = 1
    •  Moderate increase in size and variability = 2
    •  Marked variation = 3
  •  Mitotic counts
    •  Dependent upon microscopic field area  (field area = 0.274 mm²)
      •  0–9 = 1
      • 10–19 = 2
      • >20 = 3
    • Scoring scale should be adjusted based on field of view area
      • Olympus BX series FN22 40X = 0.24 mm²
Tubule formation the evaluation is relatively straight forward.  Nuclear pleomorphism is more subjective and qualitative in nature.  If the nuclei appear very close in comparison to luminal epithelial cells of normal breast tissue, then 1 point is scored.    The score is increased to 2 when cells are larger with vesicular nuclei/visible nucleoli, and there is moderate variability in size and shape.  3 points would be assessed when there is marked variation in size and shape (particularly large and bizarre nuclei).  Nuclei in the 3 point group will often have prominent multiple nucleoli and vesicular chromatin.
 
Like the Bloom-Richardson grading system, the Nottingham grading system takes a summation of the 3 variables combines him into a  single score.
  • 3–5 points: Grade I – well-differentiated
  • 6–7 points: Grade II – moderately differentiated
  • 8–9 points: Grade III – poorly differentiated
References
BLOOM HJ, RICHARDSON WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. British Journal of Cancer. 1957;11: 359–377.
 
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19: 403–410.
 
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 2002;41: 154–161.
 
Dalton LW, Pinder SE, Elston CE, Ellis IO, Page DL, Dupont WD, et al. Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement. Mod Pathol. 2000;13: 730–735. doi:10.1038/modpathol.3880126
 
Sundquist M, Thorstenson S, Brudin L, Nordenskjöld B. Applying the Nottingham Prognostic Index to a Swedish breast cancer population. South East Swedish Breast Cancer Study Group. Breast Cancer Res Treat. 1999;53: 1–8.