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BREAST CANCER GRADING at LEXINGTON MED. CTR.
the Elston modification of the Scarf-Bloom-Richardson
system
introduction
The GRADE of any cancer is one of the 3
most important pieces of information needed by physicians who treat cancer. Since breast cancer is
often diagnosed through a series of procedures (the least invasive tissue diagnostic attempt being
fine-needle-aspiration cytology [FNA]), one has to remember that there are insurmountable limits on
certainty of information yielded. For example, an FNA may obtain cells which are not diagnosable as
cancer; and that is not the same as declaring your tumor to be benign. With this minimal procedure,
our pathology group's unexpressed intention is to communicate: a "positive" [cancer] diagnosis is
[99.99% of the time] positive [certain], but negative is not negative (negative is
probably better viewed as "indeterminate" [it may fail to reveal the cancer in maybe 15% of
instances of FNA]). When initial efforts are made to assign "grade", there is a somewhat similar
limitation on dependability of grade assignment. When we assign grade to a specimen that is less
than 60% of the entire tumor mass, then what we REALLY mean is that the grade is "no better than"
whatever we see on that incomplete specimen (rarely, one will get a better grade upon being able to
evaluate the whole tumor [LMC-05-7403]; but usually the grade will be the same or worse. That is,
the true, final grade is the worst that we find on evaluation of the greatest amount of the tumor
ever given to us (which is not always the entire tumor...neoadjuvant chemo may make the rest of the
tumor disappear). Unlike prostate cancer, tumor grade, however, tends to be vastly most commonly
homogeneously the same throughout a breast cancer. Yet the visual discrimination and discernment of
the several grading parameters becomes more and more clear as one sees more and more of the entire
tumor. So, an initial large-core needle biopsy
procedure of the breast can sometimes undergrade or overgrade breast cancers (I'd guess 2-10% of
cases).
The 15 or so types of breast
cancer (as with the types of song-birds) vary in natural, biological behavior
characteristics. Each type...ductal, lobular, mucinous, tubular, colloid, medullary,
etc...tends to possess an innate grade (or state of aggressiveness). Of the world-wide
variety of canine (dog-like) animals, there are various degrees of aggressiveness...from calm
lap dog to vicious timber wolf. Cancer grading is an imperfect attempt (see Wikipedia) to assign a value for
aggressiveness or dangerousness. The grading system we use (widely recommended around the
world) is the "Elston grade" [short for "Elston modification of the Bloom-Richardson grading
system"...MSBR...also related to the Nottingham grading system for invasive breast cancer], and it is applied most successfully to cases of "invasive ductal carcinoma [or
adenocarcinoma], NOS [not otherwise specified]".
preparing a
sample for grading
Think of organ tissue cells as being, in the living state, like millions of tiny
raw eggs, each in its individual delicate "shell" [but not hard like a hard, calcific egg
shell]. The tissue sample must be chemically treated so that the cells become "fixed"...made
"hard"...for proper slicing just like we make raw eggs hard by boiling so that they can be
thin sliced.
So, from the time of the surgical or biopsy
procedure onward, the tissue specimen must be properly handled (no squeezing or pressing
which might distort the microscopic features), properly fixed, properly sliced (if a
lumpectomy), and portions trimmed to proper size and thickness (so that the various
processing chemicals will be able to optimally perform each of their jobs), properly
chemically processed (water and fat-based tissues must be dehydrated and de-fatted in a
carefully graded series of chemical treatments so as to be properly infiltrated with paraffin
wax [which will allow the tissue to be sliced into tissue ribbons 4-6 microns in thickness]),
expertly and carefully microtome-sectioned into those tissue ribbons, ribbons properly
mounted on slides, and then those slide-mounted tissue ribbons carefully passed through a
chemical series which removes the wax and rehydrates the tissues, so that the slides can be
expertly and carefully stained with water-soluble dyes. THEN, the slides of
the tissue sample are ready to be diagnosed and graded by a qualified pathologist. If tissues
are roughly handled, cut too thick, or over-stained with dye, overgrading becomes a risk. If
improperly defatted and dehydrated prior to wax infiltration, or if wax is insufficiently
removed prior to staining, and/or understained, undergrading becomes a risk. Pathologists,
pathologist assistants (PAs), and histotechnologists form the team who combine forces to
perform this series of activities.
here are the IDC grading
parameters
The "Elston grade" is arrived at (by pathologists) by evaluating the cancer for
the following three parameters in order to "sum" or add-up the designated points in order to
produce an Arabic numerical sum score. Score ranges equate to Roman-numeral grades, there
being three grades.
- TUBULES: (a
pattern or architectural parameter assessing cellular organization...the tumor's ability
to maintain some semblance of normal order...how bad the tissue organization looks)
1 point, if lots of tubule formation (greater than 75%
"tubularity"/"glandularity")
2 points, if moderate " " (10-74% " "
)
3 points, if sparse to no " " ( 0-9% " "
)
- NUCLEAR
[size/shape/chromatin texture] VARIATION: (a cytological/cellular parameter...how bad the
cells look)
1 point, if only mild nuclear enlargement, no/mild darkening of
chromatin [nuclear DNA/chromosomes], no/mild variation of nuclear shapes and sizes.
2 points, if moderate such
changes.
3 points, if nuclei quite
large, or bizarre, or have prominent nucleoli, and are quite dark
[hyperchromatic]
- MITOTIC ACTIVITY:
(a growth-rate parameter which is
determined in the tumor area showing the fastest growth rate, usually the tumor
periphery, counting the number of mitotic figures in ten high-power microscopic fields
[hpf]...ours is with a 40x objective)
1 point, 0-9 mitotic figures in ten high-power fields.
2 points, 10-19 " " " " "
3 points, 20 or more " " " "
now the
assignment of grade
Now, having assigned the points for the three
parameters, one simply adds them up and compares to the following list. For example: a tumor
has 5% tubules (3 points), moderate nuclear abnormalities (2 points), and 18 mitotic figures
per 40x hpf (2 points)...a total of 3 pt. plus 2 pt. plus 2 points equals a total 7 points.
This assigning of numerical values adds a sort of discipline to the pathologist's
estimations.
- from 3-5 total points is defined as Elston grade I
- from 6-7 total points is defined as Elston grade II
- from 8-9 total points is defined as Elston grade III
commentary
qualification
Pathologists with long
experience in cancer diagnosis of all types and organs develop a "feel", a "sense", a "gestalt"
about the microscopic "look" of badness of cancers (sort of an intuitive Broders grade...developed
by Dr. A. C. Broders about 1920). There is almost an infinite variety of parameters which are yet
to be carefully and officially evaluated around the world to the point of universal expert
agreement. So, if we are struck that a cancer "looks" worse than the Elston grade indicates, we may
feel the need to express this in the pathology report as a personal opinion of discrepancy or
discordance with the Elston grade. Now emerging is an even greater interest in the "growth rate"
[proliferative status] of the breast cancer...our pathologists assess this by means of both mitotic
activity and the percentage of nuclei positively stained by the Ki67 (MIB-1) cell-cycle
proliferative marker (which ADDITIONALLY marks non-mitotic, proliferating cell nuclei...plus the
already-visualized mitotic cells). Some are evaluating a grading system which ignores tubule
formation and adds extra emphasis to the proliferative activity of the tumor, the
MSBR system. The pathology transcriptionist carefully types the report information into the
written pathology report, the report being carefully reviewed and then electronically
approved by the pathologist responsible for that particular breast
case.
Some Official
References
- Elston, CW. Grading of invasive carcinoma of
the breast. In: Page DL and Anderson TJ. eds. Diagnostic Histopathology of the
Breast [a textbook]. Churchill Livingstone. pages 300-311,
1987.
-
Elston CW and Ellis IO. Pathological prognostic factors in breast
cancer. The value of histological grade in breast cancer.
Histopathology [a journal]. 19:403-410,
1991.
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(posted 2 December 2000; latest update 10 October
2016)
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