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Breast malignant, males, children

Breast cancer

Histologic grading

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 10 November 2012, last major update January 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Grading system

● Most commonly used system is Elston/Nottingham modification of Bloom-Richardson system, based on (a) tumor tubule formation, (b) number of mitotic figures in most active areas, and (c) nuclear pleomorphism (Br J Cancer 1957;11:359, Histopathology 1991;19:403)
● Tumor should be graded based on representative portion of tumor, not the least differentiated part (Arch Pathol Lab Med 1983;107:411)

Tumor tubule formation:
1 point: > 75% of tumor
2 points: 10-75% of tumor
3 points: < 10% of tumor

Note: the overall appearance of the tumor must be taken into consideration in scoring tubule formation
Note: tubules must have clear central lumina to be counted

Number of mitotic figures in most active area, counting 10 high power fields:
               (a)     (b)     (c)
1 point:   0-5     0-9    0-11
2 points: 6-11   10-19 12-22
3 points: 11+    20+    23+

(a) Nikon or Labophot 40x objective or comparable with field diameter of 0.44 mm
(b) Leitz or Ortholux 25x objective or comparable with field diameter of 0.59 mm
(c) Leitz or Diaplan 40x objective or comparable with field diameter of 0.63 mm

(a) count mitotic figures at periphery of tumor in most mitotically active area; count 10 high power fields in the same area, but not necessarily contiguous; select fields with as much tumor as possible; avoid poorly preserved areas; ignore cells with hyperchromatic and pyknotic nuclei, which may be undergoing apoptosis
(b) quick scan mitotic impression is less accurate (Hum Pathol 2008;39:584)

Nuclear pleomorphism:
1 point: minimal nuclear variation in size and shape; small regular uniform cells
2 points: moderate nuclear variation in size and shape
3 points: marked nuclear variation in size and shape

Note: evaluate areas with greatest atypia
Note: for infiltrating lobular carcinoma, two tiered grading system for nuclear pleomorphism is recommended (Ann Diagn Pathol 2009;13:223)

3-5 points: well differentiated (grade I)
6-7 points; moderately differentiated (grade II)
8-9 points: poorly differentiated (grade III)

Criticisms of Nottingham Bloom Richardson grading system

● Grading has been criticized for low reproducibility (Mod Pathol 2005;18:1067, Virchows Arch 2007;450:627)
● The concept of a moderately differentiated category has been criticized (Pathobiology 2008;75:104, J Natl Cancer Inst 2006;98:262)
● Tumors with 3+3+1 pattern (i.e. <10% tubules, marked nuclear pleomorphism but few mitotic figures) may have low mitotic count due to failure to fix tumor immediately after excision, which allows tumor cells to complete cell division and leads to reduction in observed mitotic figures; Ki-67 may serve as surrogate for mitotic figure counting in these cases (Oncologist 2008;13:477)

Clinical description

● Histologic grade is a strong predictor of survival (J Clin Oncol 2008;26:3153)
● In US, blacks overall have higher grade tumors than whites (Cancer 2003;98:908)

Micro images

Tubule formation (AFIP Fascicle Third Series)
1 point (>75% tubules)     3 points (<10% tubules)

Nuclear pleomorphism
Mild                            Moderate                 Marked

Overall histologic grades
Low grade

Intermediate grade

Possibly high grade - see caption

High grade

Other images: high grade #1; #2; #3

End of Breast malignant, males, children > Breast cancer > Histologic grading

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