Side: Right/Left (note - if bilateral please describe each side individually).
FNA, Needle Core Biopsy
Surgical Biopsy (incisional/excisional), Wide Excision/ Partial Mastectomy
Total Mastectomy +/- sentinel node biopsy/axillary dissection
Measurement of Specimen: Largest piece
Presence or Absence of Tumour
Number of Tumours: solitary/ multiple
Size of Tumour: 3 dimensions if possible
Gross Relationship of Tumour to Margins: measurement to closest margin
Gross Involvement of Skin or Skeletal Muscle.
Histological Diagnosis: State any specific type of carcinoma.
Size: check if greater than gross estimate; use a micrometer if possible. Greatest dimension.
Grade: note - see below
Lymphatic Invasion Outside the Tumour: Yes/ No
Venous Invasion: Yes/ No
Margins (Invasive ca.):
Distance to Closest Margin
State Which Margin If Possible
Look for deep fascia
Skeletal Muscle: State If Invaded.
Dermal Lymphatic Invasion
Estrogen Receptor Status: see below
Her-2 neu Status
Pattern of DCIS (Type)
Grade of DCIS
EIC Pattern: Yes /No (note - see below)
For DCIS Alone, Measurement of Size is Important.
Margin Status: - measure distance of DCIS to closest margin.
ER status now required
Calcification in the Tumour (or DCIS): Yes/ No
Number of sentinel nodes removed
Number of sentinel nodes positive for metastases
Number of non-sentinel nodes removed
Number of non-sentinel nodes positive for metastases
Size of Biggest Metastasis
Extranodal Extension - measure distance from capsule
Pathological TNM Stage: see below.
Grading System for Invasive Carcinoma of Breast
- The system is applicable to all invasive carcinomas.
- Special subtypes of breast carcinoma (lobular, tubulolobular, tubular, papillary, mucinous, cribriform, medullary, adenoid cystic, sarcomatoid (metaplastic), squamous, adenosquamous) should be noted separately but should also be assigned an overall grade. Strict criteria should be used to recognise these special types of breast cancer which have prognostic significance (Ellis 1992; Tavassoli 1992; Rosen 1993).
- Since the term "differentiation" used in the context of breast carcinoma is an ambiguous term, it is recommended that grades 1, 2 or 3 be used instead of, or at least in addition to, the terms "well, moderately, or poorly differentiated".
- Grading cannot be performed adequately on material that has been frozen for the purposes of "frozen section" or "quick section". Well-fixed, well-cut, and optimally stained H&E sections are essential.
- The Nottingham modification of the Bloom and Richardson method of grading is used most widely and is recommended for BC Cancer. The system described below incorporates modifications suggested by Elston, Contesso, and Helpap. The three separate parameters are scored independently as follows:
(I) Nuclear Grade
Nuclear score 1: Nuclei are small to medium-sized, relatively uniform in size and shape, and lacking clumped chromatin or prominent nucleoli. Nuclei may have small, inconspicuous nucleoli. Uniformity of size and shape are the most important features.
Nuclear score 2: Nuclei are medium to large in size but exhibit only moderate variability in size, shape and intensity and pattern of staining. Nucleoli may be quite prominent as long as the nuclei are relatively monotonous in appearance. Nucleoli with irregular outlines, giant or "macronucleoli" are absent. Bizarre giant cells are absent.
Nuclear score 3: Nuclei are large and vesicular and/or contain coarse clumps of chromatin. There is considerable variation in the size and shape of nuclei. Typically, nucleoli are very large, often multiple and may have irregular outlines. Giant nuclei, polylobated nuclei and multinucleate tumour giant cells may be present. Karyorrhexis, karyolysis and pyknosis of nuclei are often encountered.
Note: The above descriptions are given as guidelines, which may be supplemented by study of illustrations of the different nuclear grades in the references, cited below. Furthermore, since there is a morphological continuum in the nuclear appearance in breast carcinomas, the extremes of the spectrum are easily recognised but, in some cases, the scoring of nuclei is to some extent subjective and differences of interpretation between pathologists are to be expected. It must be stressed that it is impossible to assign a nuclear score based on the frozen section or post-frozen paraffin embedded material.
(II) Tubule Formation
The assessment of tubular differentiation or tubule formation applies to the neoplasm overall and requires examination of several sections at scanning magnification. A reliable tubular score cannot be assigned when only needle biopsies or small pieces of the tumour are examined.
Tubule score 1: >75% of the neoplasm is composed of tubular structures with visible lumina. Solid trabecula, vacuolated single cells, alveolar nests and solid sheets of cells comprise less than 25% of the tumour.
Tubule score 2: 10-75% of the tumour has a tubular pattern.
Tubule score 3: <10% tubule formation.
(III) Mitosis Score
The mitosis score is assessed in the peripheral areas of the neoplasm and not the sclerotic central zone. The neoplasm is scanned at intermediate magnification to determine the area in which mitoses are most abundant (usually areas of poor tubule formation where cells are arranged in sheets or large nests). Only definite mitotic figures are counted with care to avoid including pyknotic nuclei in the count. Although the Nottingham grading system uses a scoring system based on the number of mitoses per 10HPF's, the Oncologic Standards Committee considers that a mitotic count per square millimetre is most accurate. Mitoses are only counted in the invasive component of the lesion.
Score 1: <4 mitoses per square mm.
Score 2: 4-7 mitoses per square mm.
Score 3: >7 mitoses per square mm.
Alternatively the number of mitoses in 10 high power fields (HPFs) is counted. Using a Nikon Labophot microscope with a 40X objective lens (i.e. X400) and a field surface area of 0.152mm2, the scores are as follows :-
Score 1: 0-5 mitoses
Score 2: 6-10 mitoses
Score 3: >10 mitoses
In practice, Contesso's method of scoring of mitoses is quicker and easier to perform especially on small biopsies (e.g. Core biopsies). At least 20HPF's of the same area as stated above are assessed and scored as follows :-
Score 1: No field contains more than 1 mitosis.
Score 2: Two mitoses present in any one HPF.
Score 3: Three or more mitoses present in any one HPF.
The scores for the three separate parameters (tubules, nuclei and mitoses) are summated and the overall grade of the neoplasm is determined as follows :-
Grade 1: 3-5 points.
Grade 2: 6-7 points.
Grade 3: 8 or 9 points.
Pathology of Ductal Carcinoma In Situ (DCIS)
The following patterns of DCIS are recognized:
- Micropapillary - papillary structures lack fibrovascular cores.
- Papillary - fibrovascular cores present within papillary structures.
- Comedocarcinoma - defined as DCIS with extensive central necrosis (>2/3 the diameter of the duct). The latest consensus committee abandoned the requirement for high nuclear grade in combination with necrosis.
- Apocrine DCIS.
- Signet ring cell DCIS
- Low-grade endocrine DCIS
Grading of DCIS
Low Grade (Grade 1): Grade 1 or 2 nuclei and no zonal necrosis.
Intermediate grade (Grade 2): Grade 1 or 2 nuclei with zonal necrosis
High grade (Grade 3): Grade 3 nuclei with or without necrosis
Quantitation: In addition to the maximal linear size of the DCIS, a rough estimate of the volume of DCIS relative to the overall tumour should be given as a percentage. "Extensive intraduct component (EIC)" is used to qualify invasive carcinomas with DCIS, which may take two forms as follows :
- Prominent DCIS within the invasive tumour mass (comprising 25% or more of the volume) AND DCIS in adjacent breast ducts and/or lobules extending clearly beyond the boundaries of the invasive carcinoma.
- Widespread DCIS with microscopic stromal invasion is also placed in the EIC category.
This assessment is important because EIC carcinomas treated with breast conservation have a higher risk of local recurrence within the breast unless the margins are well clear.15
Grading of Invasive Lobular Carcinoma
In general, it is possible to grade lobular carcinoma. Usually, classical lobular carcinoma will attain a total score of 5 (tubules 3; nuclei 1; mitoses 1) giving the tumour an overall grade 1. Although some of the data are somewhat inconclusive, histological variants of lobular carcinoma are thought to differ in their degree of aggressiveness as follows:
- Good Prognosis (Grade 1): Tubulolobular carcinoma. This variant features tubular structures that are lined by very uniform small cells resembling those of classical lobular carcinoma. Single-file strands of identical cells are also present. Some authorities would regard this variant as a ductal carcinoma (tubular type).
- Fairly good Prognosis (Grade 1): (marginally better than that of ductal carcinoma NOS.) Classical lobular carcinoma. Criteria include:
Intermediate prognosis (Grade 2):
- Small uniform cells; grade 1 nuclei
- Single-file rows in a fibrous stroma
- Targetoid (concentric, "bull's-eye") pattern around pre-existing ducts
Poor prognosis patterns (Grade 3):
- Classical pattern with Grade 2 nuclei
- Alveolar variant - round and oval nests of uniform small cells
- Large cell variant
- Mixed patterns of lobular carcinoma
- Solid variant - large sheets of uniform small cells with round nuclei
- Pleomorphic lobular carcinoma - pattern resembles classical lobular carcinoma but the nuclei are grade 2-3, mitoses are easily identified, apocrine change is common, and ER is often negative.
- Signet-ring cell variant (>20% of cells should be signet-ring type)
Only invasion of lymphatics beyond the advancing edge of the tumour is important.
If in doubt call it negative.
Please state if there is extensive lymphatic/vascular invasion (>10 lymphatics involved).
Large calibre, thick-walled blood vessels containing tumour emboli either within the tumour in the surrounding tissue are included.
Neural invasion has been shown not to be of prognostic significance in most studies. This is confirmed in a recent analysis of BC Cancer data.
Tumour cells must be outside the nodal capsule.
Please state if "minimal" extra nodal spread (<1mm from capsule) or extensive infiltration of perinodal tissues with "matting" of nodes.
Breast markers on invasive carcinoma should be done on the core biopsy sample where relevant. Only if the results appear incongruous with the histology, should the markers be repeated on the excision specimen.
DCIS should be stained for ER in the excision specimen. PR and Her2-neu status of DCIS is not relevant for management of the patient.
1) Estrogen Receptors
Please select a block containing invasive carcinoma and normal breast tissue if possible.
Immunostains are graded subjectively on a scale 0-3+.
0 :- Negative nuclear staining; positive internal control staining. Allred scores 0(1,2)
1+ :- Allred scores 3-4
2+ :- Allred scores 5 and 6
3+ :- Allred scores 7 and 8
Allred Score: Percentage of nuclei staining + Intensity + Total score
|% Nuclei staining||Score|
2) Progesterone Receptors: Recommended on all invasive breast cancers.
PR is graded as for ER using the Allred (UKNEQUAS) scoring method.
3) Her-2neu: Required on all invasive breast cancers.
Pathological TNM Stage and UICC Stage Groupings
pTX : unable to assess size
pTis: Carcinoma In Situ
pT1mic: <0.1 mm microinvasive
pT1a: Tumour diameter 0.1-5mm
pT4a: Tumour spread to chest wall, but not pectoral muscle
pT4b: Skin involvement
pT4c: Both T4a + T4b
pT4d: Inflammatory breast cancer
Nodes – please see official TNM publication for details of complicated classes.
pNX: Nodal Status Unknown
pN0: Negative Nodes
pN0i+: <0.2mm metastases (single cells or isolated tumour cell clusters)
pN1mi: micrometastases 0.2-<2mm diameter
pN1a: 1-3 positive nodes, metastases >2mm diameter
N1b: Internal mammary LN positive not clinically apparent
pN1c: Internal mammary LN +ve (clinically occult) plus 1-3 axillary nodes +ve.
pN2a: 4-9 axillary nodes +ve.
pN2b: Internal mammary nodes +ve, axillary nodes negative
pN3a: >10 axillary nodes +ve or infraclavicular nodes +ve
pN3b: clinically detected ipsilateral internal mammary LN in presence of > 1 axillary LN +ve
pN3c: Supraclavicular node +ve
pMX : Unknown Status
pM0 : No Distant Metastases
pM1: Distant Metastases Present
UICC Stage Grouping