Appendix - Breast Cancer Guidelines for the Pathological Examination and Reporting of Breast Specimens

Quality Determinants of Organized Breast Cancer Screening Programs

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Dr. F. Alexander, Dr. J. Danyluk, Dr. M.P. Greeff, Dr. C. Hegedus, Dr. J. Hugh, Dr. M. O'Connor , Dr. D. Paslawski, Dr. V. Tron, Dr. D.Willans

When reporting on a specimen that contains cancer and/or its recognized precursors, the pathologist's role is to provide the most accurate diagnosis and all the data required to manage the patient's condition. The unique value of checklists in increasing the consistency of such reporting by pathologists has been recognized for almost a decade^1,2. Pathologists in many laboratories in Canada are using checklists and synoptic reporting. Others have been slow to embrace this quality improvement initiative, and many groups are continuing to develop their own guidelines for reporting on a local or regional basis.

The guidelines provided here are based on earlier guidelines developed by the consultant members of the Breast Tumor Panel of the Canadian Reference Centre for Cancer Pathology (March 1995)³, the National Coordinating Group for Breast Screening Pathology (1995)⁴, the European Guidelines for Quality Assurance in Mammography Screening (2001)⁵, the Association of Directors of Anatomic and Surgical Pathology (1996)⁶, the National Cancer Institute of Canada Consensus Conference on Synoptic Reporting (1998), and existing checklists from the British Columbia Cancer Agency and various laboratories across Canada.

The checklists presented can be used as the official report, or as an internal laboratory working guide from which the Synoptic Report is developed as the official report, or both can be used as the official report. If only a Synoptic Report is used, record present, absent, not evaluated, or the significant findings, as appropriate for each element. A standard checklist format is preferred by the clinical community, but it is the content that is of paramount importance.

Definitions are provided for the data elements where the meaning may be unclear (e.g. multifocal), as no definition is used universally. It is recognized that in such cases there is no correct definition, and thus a definition is provided on the checklist to enhance consistency, reproducibility and comparability. It is imperative that the clinician know that several data elements are used inconsistently in the literature and that he/she is interpreting the element in the way that is intended by the pathologist. It is also important that the clinician know whether or not the elements were defined in the same way in his/her literature derived knowledge base.

Pathologists are urged to adopt the generally applicable recommendations of the Association of Directors of Anatomic and Surgical Pathology relating to standardization of the surgical pathology report, demographic and specific information, gross and microscopic description and comment section⁶.

These guidelines have been developed through the Pathology Working Group of the Alberta Cancer Surgery Working Group with input from Dr. F. O'Malley, Dr. P. Barnes, Dr. B. Tetu, Dr. M. Hayes and members of the Section of Anatomic Pathology of the Canadian Association of Pathologists. They have been accepted by the surgeons and oncologists in Alberta as the minimum content required from a pathology report for proper staging (Appendix A) and for management of a patient with in-situ and/or invasive breast cancer. They are intended to be practical for everyday use. Their acceptance as Canadian guidelines is promoted by the Canadian Association of Pathologists to enhance and expedite patient care while avoiding the need for review of the pathology report to obtain missing data.

Pathology Requisition and Specimen Submission

Specimen Type(s)

The pathology requisition should include a summary of the "pertinent clinical history" and identify the laterality, the location of the tumor in the breast, and the surgical procedure(s) or specimen type(s) e.g.:

Incisional biopsy	core; mammotome; open
Excisional	wire localization* lumpectomy; segmental; mastectomy re-excision
Sentinel node axillary content	node level may be provided

For excisional specimens, the surgeon should make every effort to remove and submit the specimen containing the lesion in one piece, surrounded by a cuff of tumor free tissue, since tumor size and the distance to the nearest margin cannot be provided when more than one piece of tissue containing tumor is received. A pathologic stage for the tumor (pT) cannot be determined if the specimen edge contains tumor grossly^7,8. If more than one piece is provided the relation of each to the other should be clearly identified.

The surgeon should also orient the specimen, e.g. by using sutures to indicate two surfaces (medial or lateral, superior or inferior) when skin is not present, and one suture when skin is present.

* For (needle guided) wire localization specimens, close cooperation among the surgeon, radiologist and pathologist is essential. The preoperative mammograms should accompany the specimen. Whether the specimen is submitted to radiology or pathology for confirmation of removal of the mammographic lesion will depend on local circumstances. A radiologist should correlate the specimen radiograph with the preoperative mammograms. The specimen radiograph, with the radiologist's findings, should be available to the pathologist for radiologic-pathologic correlation

Checklist 1
Gross Examinations and Reporting of Excisional Breast Cancer Specimens

(70kb pdf format)

Checklist 2
Microscopic Examination of Excisional Breast Cancer Specimens

(66kb pdf format)

Synoptic Report 1
Invasive Breast Carcinoma in Excisional Specimens

(66kb pdf format)

Synoptic Report 2
DCIS, When No Invasive Carcinoma is Present in Excisional Specimens

(66kb pdf format)

Synoptic Report 3
Incisional Biopsy Specimens

(66kb pdf format)

Appendix A
TNM/AJCC staging^7,8,12

Primary Tumor (T, pT)

X Primary tumor cannot be assessed.
TO No evidence of primary tumor.
Tis Carcinoma in situ: Ductal or lobular carcinoma in situ, or Paget's disease of the nipple with no tumor.
T1 Tumor 2 cm or less in greatest dimension.
T1 mic Largest focus of invasion £ 0.1 cm in greatest dimension. (Do not sum individual foci.)
T1a Tumor more than 0.1 but not more than 0.5 cm in greatest dimension.
T1b Tumor more than 0.5 cm but not more than 1 cm in greatest dimension.
T1c Tumor more than 1 cm but not more than 2 cm in greatest dimension.
T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension.
T3 Tumor more than 5 cm in greatest dimension.
T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below.
T4a Extension to chest wall not including pectoralis muscle.
T4b Clinically/grossly detected edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast. (Foci only detected histologically or microscopic invasion of the dermis not included.)
T4c Both (T4a and T4b).
T4d Inflammatory carcinoma: When pathologically staging a clinical inflammatory carcinoma, if the skin biopsy is negative and there is no localized, measurable, primary cancer, the category is pTx.

Note: Paget's disease associated with a tumor is classified according to the size of the tumor.

Skin of Breast
Dimpling of the skin, nipple retraction, or any other skin change except those described under T4b and T4d may occur in T1, T2 or T3 without changing the classification.

Chest Wall
Chest wall includes ribs, intercostal muscles, and serratus anterior muscle but not pectoral muscle.

Regional Lymph (pN)*

pNX Regional lymph nodes cannot be assessed (not removed for study or previously removed).
pN0 No regional lymph node metastasis.**
pN1mi Micrometastasis (> 0.2 mm, but none> 2 mm in greatest dimension).***
pN1 Metastasis in 1-3 ipsilateral axillary lymph node(s), and/or in ipsilateral internal mammary nodes with microscopic metastasis detected by sentinel lymph node dissection but not clinically apparent.

pN1a Metastasis in 1-3 axillary lymph node(s), including at least one larger than 2 mm in greatest dimension. pN1b Metastasis in internal mammary lymph nodes with microscopic metastasis detected by sentinel lymph node dissection but not clinically apparent. pN1c Metastasis in 1-3 axillary lymph nodes and internal mammary lymph nodes with microscopic metastasis detected by sentinel lymph node dissection but not clinically apparent.

pN2 Metastasis in 4-9 ipsilateral axillary lymph nodes, or in clinically apparent ipsilateral internal mammary lymph node(s) in the absence of axillary lymph node metastasis.

pN2a Metastasis in 4 to 9 axillary lymph nodes (at least one tumor deposit greater than 2.0 mm). pN2b Metastasis in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastasis.

pN3 Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes; or in ipsilateral supraclavicular lymph nodes.

pN3a Metastasis in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm), or metastasis to the infraclavicular lymph nodes. pN3b Metastasis in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent. pN3c Metastasis in ipsilateral supraclavicular lymph nodes.

Stage Grouping

Stage 0	Tis	NO	MO
Stage I	T1*	NO	MO
Stage IIA	TO	N1	MO
	T1	N1	MO
	T2	N0	MO
Stage IIB	T2	N1	MO
	T3	NO	MO
Stage IIIA	TO	N2	MO
	T1*	N2	MO
	T2	N2	MO
	T3	N1	MO
	T3	N2	MO
Stage IIIB	T4	Any N	MO
	Any T	N3	MO
Stage IV	Any T	Any N	M1

*T1 includes T1 mic

Notes: *Intramammary lymph nodes are coded as axillary lymph nodes. An isolated tumor nodule in the axillary fat of a breast cancer patient is classified as a lymph node metastasis. For nodal metastases, the size of the metastasis, not the size of the lymph node, determines pN.

**Cases with only isolated tumor cells (ITC) in regional lymph nodes are classified as pNO. ITC are single tumor cells or small clusters of cells, not more than 0.2 mm in greatest dimension, usually detected only by immunohistochemistry or molecular methods but which may be verified on H&E stains. ITCs do not typically show evidence of metastatic activity, e.g. proliferation or stromal reaction. Classification based solely on sentinel lymph node dissection without axillary lymph node dissection is designated (sn) for "sentinel node."¹²

***Multiple micrometastases in one node should be added up and not considered micrometastasis if larger in sum than 0.2 cm.

Appendix B
Histologic Typing of Breast Carcinoma

Ductal Carcinoma in Situ

Microinvasive Carcinoma

Invasive Carcinoma

• ductal (no special type)
• lobular
• mixed
• tubular
• medullary
• mucinous
• cribriform
• papillary
• metaplastic
• other rare types

(Adenocystic, Apocrine, Clear cell [glycogen rich], Mucoepidermoid, Neuroendocrine, Secretory [juvenile], Squamous, etc.)

Appendix C
Tumor Size

It is important to correlate gross and microscopic tumor size. If the gross size is different from the microscopic invasive component, record the microscopically confirmed size of the invasive component in the synoptic report.

The following guideline is extracted from the European Guidelines for Quality Assurance in Mammography Screening, 3^rd ed (January 2001)⁵.

Maximum Diameter

All lesions should be measured in the fresh or fixed state and on the histological preparation. If the two measurements are discrepant then that obtained from histological examination should be recorded where tumours are small enough to be visualized in cross-section. This may give a small underestimation of size due to shrinkage of the tissue in processing. It is considered, however, that the slight but consistent underestimation in the size of all tumours is preferable to the larger and less predictable errors that may result from measuring poorly delineated tumours macroscopically. Clearly, sufficient blocks should be taken from the periphery of larger tumours to allow accurate estimates of their size to be made from combined histological and macroscopic examination. The largest dimension should be recorded to the nearest millimetre.

For non-invasive carcinomas, the maximum diameter should be entered in the 'Non-Invasive' section only where the tumour is of ductal type; lobular carcinoma in situ is not measured. For invasive carcinomas, only the invasive component needs to be recorded unless accompanying ductal carcinoma in situ extends more than 1 mm beyond the periphery of the infiltrative component, when the size of the infiltrative component and the overall size should be stated in the appropriate spaces of this section. This is to allow the identification of invasive carcinomas, where the in situ component forms a significant proportion of the lesion and may be important in determining the risk of recurrence after local excision. The largest dimension, to the nearest millimetre, is recorded in each case. The diagrams below illustrate whole and invasive tumour measurements in a variety of circumstances. Foci of lymphatic and blood vascular invasion are not included in the whole tumour measurement. If a carcinoma (either infiltrative or ductal in situ) is insufficiently delineated to measure reliably, give an approximate estimate of the maximum dimension of the area over which the changes extend. It may be necessary to use combined histological, macroscopic and radiological information to make a reliable estimate.

Tumour Size

Appendix D
Histologic Grade
Nottingham Method for Assessing Histologic Grade in Breast Carcinoma¹³

Tubular Formation Score	Score
> 75% of tumor examined shows well formed tubules	1
10-75% of tumor examined shows well formed tubules	2
< 10% of tumor examined shows well formed tubules	3
Nuclear Pleomorphism Score
Nuclei are small, with little increase or variation in size compared with breast epithelial cell nuclei, regular outlines, uniformity of nuclear chromatin.	1
Nuclei are larger than normal, more open vesicular chromatin with visible, usually single nucleoli.	2
Marked variation in size and shape of nuclei, vesicular chromatin, prominent enlarged nucleoli, multiple nucleoli.	3
Mitosis Score
(Assessed in most mitotically active area; count 10 fields; count only clear morphologic stages of mitosis.) Dependent on the microscope field area as per the following guide.	1-3
Grade
Grade I/III (well differentiated, score 3-5)
Grade II/III (moderately differentiated, score 6-7)
Grade III/III (poorly differentiated, score 8-9)

Reference

Based on Elston CW, Ellis IO (eds). Systemic Pathology, 3rd edition/vol. 13: The breast. Churchill Livingstone, 1998:368-377.

European Guidelines for Quality Assurance in Mammography Screening 3rd ed. Jan. 2001.

Mitoses

The size of high power fields is very variable and hence it is necessary to standardize the mitotic count using the graph below. In order to determine the mitotic count for an individual microscope, the following procedure should be adopted:

GRAPH OF MITOTIC COUNTS BY FIELD DIAMETER

References

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2. Rosai J and members of the Department of Pathology, Memorial Sloan-Kettering Cancer Institute. Standardized reporting of surgical pathology diagnoses for the major tumor types. Am J Clin Pathol 1993;100:240-55.
3. Guidelines for the pathologic examination and reporting of breast biopsy specimens. 1995. Prepared by the Members of the Breast Tumor Panel of the Canadian Reference Centre for Cancer Pathology.
4. National Coordinating Group for Breast Screening Pathology. Pathology reporting in breast cancer screening. NHSBSP publication no. 3, 1995. ISBN 1871997 22 4.
5. Perry NM, De Wolf CJM, Broeders M, et al (eds). European guidelines for quality assurance in mammography screening, 3rd ed. Luxembourg: Office for Official Publications of the European Communities, January 2001.
6. Association of Directors of Anatomic and Surgical Pathology (Connolly JL, chair) et al. Recommendations for the reporting of breast carcinoma. Mod Pathol 1996;9:77-81.
7. Green FL, Page DL, Fleming ID et al 7. AJCC (American Joint Committee on Cancer) cancer staging manual, 6th ed. New York: Springer, 2002:225.
8. UICC (International Union Against Cancer), Sobin LH, Wittekind C (eds). TNM classification of malignant tumors, 5th ed. New York: Wiley-Liss, 1997:172.
9. Association of Directors of Anatomic and Surgical Pathology (Kempson RL, chair). Standardization of the surgical pathology report. Am J Surg Path 1992;16:84-6.
10. Brown TA, Wall TW, Christensen ED, et al. Atypical hyperplasia in the era of stereotactic core needle biopsy. J Surg Onc 1998;67:168-73.
11. Purcell CA, Norris HJ. Intraductal proliferations of the breast: a review of histologic criteria for atypical intraductal hyperplasia and ductal carcinoma in situ, including apocrine and papillary lesions. Ann Diag Pathol 1998;2:135-45.
12. Green FL, Page DL, Fleming ID et al AJCC (American Joint Committee on Cancer) cancer staging manual, 6th ed. New York: Springer, 2002:227.
13. Elston CW, Ellis IO (eds). Systemic pathology, 3rd ed/vol 13: The breast. Churchill Livingstone, 1998:368-77.

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