From: Margaret Keane (by way of Sara McKenna)
Subject: CAP - Breast Cancer Protocol
The following was taken from the College of American Pathologists website.
I hope it's helpful.
Margaret
Cancer Protocols - Breast Cancer Protocol
Breast Protocol
Explanatory Notes
A. Clinical Information
It is important for the pathologist to have relevant clinical information, especially whether the patient is currently pregnant or nursing or whether there has been any prior or current treatment, since this information may directly bear on the interpretation of the specimen. Radiation therapy or chemotherapy may alter the cellular features. Further more, tumor remaining after prior nonsurgical treatment is classified as residual disease (see Note P below).
B. Relevant Findings
It is important for the pathologist to know whether the mass or lesion is cystic or solid and whether it was palpable or detected only by imaging.
C. Tumor Size
The size of the invasive component is an important prognostic factor. Therefore, the greatest dimension of the tumor in centimeters should be recorded. The extent of invasion should also be measured microscopically, especially for small tumors. Determina tion of tumor size may not be possible with a core or incisional biopsy. Size of the invasive component is necessary for pT classification and for stage assignment (see Note P below).
In an invasive carcinoma with negative axillary lymph nodes that is 1 cm or less in greatest dimension, the combination of poor nuclear grade and the presence of lymphatic invasion is associated with an increased risk of tumor recurrence following purative resection. (1)
D. Special Studies
Fresh tissue should be removed and frozen for hormone receptor analysis by the cytosol assay technique only if the neoplasm is of sufficient size that histologic evaluation will not be compromised. Hormone receptor and DNA analyses can also be performed on routinely fixed, paraffin-embedded tissue.
E. Specimen Sample
The number of sections submitted varies with the size and character of the specimen and with the nature of the underlying neoplastic process. If a mammographic abnormality is identified in a specimen radiograph, the corresponding area of the pathology specimen should be uniquely identified.
F. Histologic Type
This protocol applies to all carcinomas of the breast. The World Health Organization (WHO) classification of breast carcinoma is presented below, although the protocol does not preclude the use of other systems of classification or histologic types, such as that published in the Armed Forces Institute of Pathology Fascicle on breast tumors. (2,3)
WHO Classification of Carcinoma of the Breast
* Noninvasive carcinoma (NOS)
o Ductal carcinoma in situ
o Lobular carcinoma in situ
* Invasive carcinoma (NOS)
o Invasive ductal
o Invasive ductal carcinoma with an extensive
intraductal component
o Invasive lobular
o Mucinous
o Medullary
o Papillary
o Tubular
o Adenoid cystic
o Secretory (juvenile)
o Apocrine
o Cribriform
o Paget's disease of the nipple
o with invasive carcinoma
o without invasive carcinoma
o Carcinoma with metaplasia
o Squamous type
o Spindle cell type
o Cartilaginous and osseous type
o Mixed type
o Inflammatory
o Other(s) (specify)
G. Histologic Grade
Pathologists should indicate the grading system used. The histologic grade applies only to the invasive component of the tumor. Grading is most reliable for ductal carcinomas. Within each stage grouping there is a relation between histologic grade and outcome.(4)
The Elston and Ellis approach to the Scarff Bloom Richardson method is generally considered useful.(5) The system depends on the extent of tubule formation, the extent of nuclear pleomorphism, and the mitotic count. Each variable is given a score from 1 through 3 and the scores added to produce a grade. For tubular, adenoid cystic, cribriform, and medul lary carcinomas, the histologic type replaces the grade. For mitotic counts, the field size of the microscope should be measured and the counts adjusted accordingly. (6) Mitotic counts are done in selected fields with the highest mitotic activity.
(The following tabulation relates to the use of 25x objective and a field area of 0.274 mm2).(6)
Feature Score
Tubule formation
Majority of tumor: greater than75% 1
Moderate: 10% to 75% 2
Minimal: less than 10% 3
Nuclear pleomorphism
Small regular nuclei 1
Moderate increase in size, etc. 2
Marked variation in size, nucleoli chromatin clumping, etc.3
Mitotic count (see also below)
less than10 mitoses per 10 HPF 1
10-20 mitoses per 10 HPF 2
more than 20 mitoses per 10 HPF 3
For a 40x objective with a diameter of 0.44 mm (area = 0.152 mm 2), the equivalent scoring of mitotic activity is as follows:
0-5 mitoses per 10 HPF 1
6-10 mitoses per 10 HPF 2
more than 11 mitoses per 10 HPF 3
The total score is then added and the grade assigned as follows.
Grade I 3 - 5 points
Grade II 6 - 7 points
Grade III 8 - 9 points
H. Carcinoma in situ
Ductal carcinoma in situ (DCIS) should be separated into "comedo" type, "non comedo" type or "other" patterns. Comedo type is defined by the presence of high nuclear grade (poor differentiation) in association with extensive necrosis.(7) Lobular carcinoma in situ is not graded.
Although not required for pT classification and stage assignment, the extent (size) of DCIS may play a significant role in patient management. Since mammography underestimates the extent of DCIS, the pathologist should attempt to assess it, even though precise measurements may be not be possible on non-palpable, grossly inapparent lesions.
I. Microcalcifications
If the specimen was removed because of mammographic identification of calcification, then the pathologist must be satisfied that the lesion(s) responsible for the mammographic abnormalities have either been identified or are not present in the specimen. Step sections may be required to identify the mammographic abnormality, especially if calcification can be demonstrated in the specimen or in a paraffin block by x-ray evaluation.
If microcalcifications cannot be confirmed by routine microscopic evaluation, polarized light may be helpful, since calcium oxalate is birefringent but unstained in hematoxylin-eosin sections. The location of the calcifications in relation to the tumor or other lesions should be indicated.
J. Lymphatic Invasion
Peritumoral lymphatic invasion should be noted because it may be associated with a less favorable outcome.(1,8) Dermal blood vessel or lymphatic invasion should be documented since its presence is essential for the diagnosis of inflammatory carcinoma. (9) However, while present in a great majority of cases, dermal lymphatic invasion may be difficult to identify and establish by biopsy alone.
K. Specimen Examination
It should be noted whether the tumor was sectioned prior to receipt, since this may preclude proper marking of the surgical margins of excision as well as ascertaining the dimensions of the specimen or tumor. Evaluation of margins [Idoes not apply to a diagnostic incisional biopsy.
L. Lymph Nodes
Identify all lymph nodes and submit representative sections of each in such a way that the number of nodes involved with metastatic carcinoma can be accurately enumerated in the report. Note whether the nodes are matted and whether tumor extends beyond the capsule. Extracapsular extension is associated with a higher frequency of axillary recurrence.
M. Orientation of Specimen
Occasionally the orientation is important (e.g. sutures marking superior and lateral margins). Orientation must be done by the surgeon and should be documented in the pathology report.
N. Margins of Excision
The margins of excision should be marked, usually with ink, taking care to avoid penetration of the ink deep into the specimen.
O. Reporting of Margins
Macroscopic or microscopic involvement of the surgical margin by invasive carcinoma or DCIS should be noted in the report. The site(s) of involve ment should be specified, if possible (e.g. superior). If the neoplasm is near the surgical margin, the distance from the margin should be reported. Blocking of tissue should be directed to evaluating the distance from the edge of the tumor to the resection margin, in addition to other sampling. Data indicate that the most significant predictors of local control after breast conservation treatment with lumpectomy and radiation are the status of the surgical margins and the presence or absence of extensive DCIS. (11)
P. TNM and Stage Groupings
The TNM Staging System for carcinoma of the breast of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended and shown below. (12, 13) Definitions for classifying the primary tumor (T) are the same for clinical and for pathologic classification. The telescoping method of classification can be applied. If the measurement is made by physical examination, the examiner will use the major headings (T1, T2, or T3). If other measurements, such as mammographic or pathologic, are used, the telescoped subsets of T1 can be used.
By AJCC/UICC convention, the designation "T" of the TNM classification refers exclusively to the first resection of a primary tumor. The prefix symbol "p" refers to the pathologic classification of the TNM (pTNM), as opposed to the clinical classification. Pathologic classification is based on gross and microscopic examination. Therefore, pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category; pN entails removal of nodes adequate to validate lymph node metastasis; and pM implies microscopic examina tion of distant lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.
The absence or presence of residual tumor following preoperative, non-surgical therapy (e.g., chemotherapy and/or radiation treatment) may be described by the symbol "R" and classified as follows:
RX Presence of residual tumor cannot be assessed
R0 No residual tumor
R1 Microscopic residual tumor
R2 Macroscopic residual tumor
If residual tumor is present, its extent may be documented by the TNM classification preceded by the symbol "y" (e.g., ypT1).
Local recurrence following a previous resection should be classified as above with the prefix "r" (e.g., rpT1).
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ, or Paget's disease of the nipple with no tumor*
T1 Tumor 2 cm or less in greatest dimension
T1mic Microinvasion 0.1 cm or less in greatest dimension**
T1a More than 0.1 cm but not > 0.5 in greatest dimension
T1b More than 0.5 cm but not >1 cm in greatest dimension
T1c More than 1 cm but not > 2 cm in greatest dimension
T2 Tumor > 2 cm but not > 5 cm in greatest dimension
T3 Tumor > 5 cm in greatest dimension
T4 Tumor of any size with direct extension to chest wall or skin.
T4a Extension to chest wall
T4b Edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast
T4c Both (T4a and T4b)
T4d Inflammatory carcinoma***
* Paget's disease associated with a tumor is classified according to the size of the tumor.
** Microinvasion is extension of cancer cells beyond the basement membrane into adjacent tissues with no focus more than 0.1 cm in greatest dimension. When there are multiple foci of microinvasion, the size of the largest focus only is used to classify the microinvasion: do not use the sum of all the individual foci. The presence of multiple foci should be noted, as with multiple larger invasive carcinomas.
*** Inflammatory carcinoma of the breast is characterized by diffuse, brawny induration of the skin with an erysipeloid edge, usually with no underlying mass. If the skin biopsy is negative and there is no localized measurable primary cancer, the T category is pTX when pathologically staging a clinical inflammatory carcinoma (T4d). Dimpling of the skin, nipple retraction or other skin changes, except those in T4b and T4d, may occur in T1, T2, or T3 without affecting the classification.
Regional Lymph Nodes (pN)****
NX Regional lymph nodes cannot be assessed (e.g. previously removed, or not removed for pathologic study)
N0 No regional lymph node metastasis
N1 Metastasis to movable ipsilateral axillary lymph node(s)
N1a Only micrometastasis (none > 0.2 cm in greatest dimension)
N1b Metastasis to lymph node(s), any > 0.2 cm in greatest dimension
N1bi Metastasis in 1 to 3 lymph nodes, any > 0.2 cm and all < 2 cm in greatest dimension
N1bii Metastasis to 4 or more lymph nodes, any > 0.2 cm and all < 2 cm in greatest dimension
N1biiiExtension of tumor beyond the capsule of a lymph node, metastasis less than 2 cm in greatest dimension
N1biv Metastasis to a lymph node 2 cm or more in greatest dimension
N2 Metastasis to ipsilateral axillary lymph node(s) fixed to one another or to other structures
N3 Metastasis to ipsilateral internal mammary lymph node(s)
****There are instances when the pathologist cannot make this determination because the complete staging procedure, such as a lymph node dissection, has not been performed or because information about a prior procedure is unavailable. In such situations an "X" is used rather than a number in the TNM designation.
Distant Metastasis (M)
MX Presence of distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis (includes metastasis to ipsilateral supraclavicular lymph node(s))
Stage Groupings
Stage 0 Tis N0 M0
Stage I T1* N0 M0
Stage IIA T0 N1 M0
T1* N1** M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIAT0 N2 M0
T1* N2 M0
T2 N2 M0
T3 N1, N2 M0
Stage IIIBT4 Any N M0
Any T N3 M0
Stage IV Any T Any N M1
* T1 includes T1mic.
** The prognosis of patients with pN1a is similar to that of patients with pN0.
Although the pathologist provides information about the individual pTNM categories based on examination of the surgical specimen, the referring physician usually has the responsibility for grouping the TNM categories into a stage of disease.
http://www.cap.org/html/lip/cancer_protocols/brst_explan.html#a