Protocol for the Examination of Specimens From Patients With Invasive Carcinoma of the Breast

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the “Surgical Pathology Cancer Case Summary (Checklist)” portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.This protocol applies to all invasive carcinomas of the breast, including ductal carcinoma in situ (DCIS) with microinvasion. The 7th edition 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.Select a Single Response Unless Otherwise Indicated.* Data elements with asterisks are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management.Specimen (note A)__ Partial breast__ Total breast (including nipple and skin)__ Other (specify): ______ Not specifiedProcedure (note A)__ Excision without wire-guided localization__ Excision with wire-guided localization__ Total mastectomy (including nipple and skin)__ Other (specify): ______ Not specifiedLymph Node Sampling (select all that apply) (note B)__ No lymph nodes present__ Sentinel lymph node(s)__ Axillary dissection (partial or complete dissection)__ Lymph nodes present within the breast specimen (ie, intramammary lymph nodes)__ Other lymph nodes (eg, supraclavicular or location not identified) Specify location, if provided: ____Specimen Integrity (note C)__ Single intact specimen (margins can be evaluated)__ Multiple designated specimens (eg, main excision and identified margins)__ Fragmented (margins cannot be evaluated with certainty)__ Other (specify): ____Specimen Size (for excisions less than total mastectomy) (note C)Greatest dimension: __ cm* Additional dimensions: __ × __ cm__ Cannot be determinedSpecimen Laterality__ Right__ Left__ Not specified*Tumor Site: Invasive Carcinoma (select all that apply) (note D)*__ Upper outer quadrant*__ Lower outer quadrant*__ Upper inner quadrant*__ Lower inner quadrant*__ Central*__ Nipple* Position: __ o'clock* Other (specify): ____*__ Not specifiedTumor Size: Size of Largest Invasive Carcinoma (note E)__ Microinvasion only (≤0.1 cm)Greatest dimension of largest focus of invasion greater than 0.1 cm: __ cm* Additional dimensions: __ × __ cm__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Cannot be determined (see Comment)Note: The size of the invasive carcinoma should take into consideration the gross findings correlated with the microscopic examination. In some cases, it may be helpful to use information about tumor size from imaging studies. If multiple foci of invasion are present, the size listed is the size of the largest contiguous area of invasion. The size of multiple invasive carcinomas should not be added together. The size does not include adjacent DCIS.If there has been a prior core needle biopsy or incisional biopsy showing a larger area of invasion than in the excisional specimen, the largest dimension of the invasive carcinoma in the prior specimen should be used for T classification, if known.If there has been prior treatment and no invasive carcinoma is present, the cancer is classified as Tis if there is residual DCIS and T0 if there is no remaining carcinoma.Tumor Focality (note F)__ Single focus of invasive carcinoma__ Multiple foci of invasive carcinoma * Number of foci: __ * Sizes of individual foci: ______ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ IndeterminateNote: If there are multiple invasive carcinomas, size, grade, histologic type, and the results of studies for estrogen receptor (ER), progesterone receptor (PR), and HER2/neu should pertain to the largest invasive carcinoma. If smaller invasive carcinomas differ in any of these features, this information may be included in the “Comments” section.Macroscopic and Microscopic Extent of Tumor (select all that apply) (note G)Skin__ Skin is not present__ Invasive carcinoma does not invade into the dermis or epidermis__ Invasive carcinoma directly invades into the dermis or epidermis without skin ulceration__ Invasive carcinoma directly invades into the dermis or epidermis with skin ulceration (classified as T4b)__ Satellite skin foci of invasive carcinoma are present (ie, not contiguous with the invasive carcinoma in the breast) (classified as T4b)Nipple__ DCIS does not involve the nipple epidermis__ DCIS involves nipple epidermis (Paget disease of the nipple)Note: This finding does not change the T classification.Skeletal Muscle__ No skeletal muscle present__ Skeletal muscle is present and is free of carcinoma__ Carcinoma invades skeletal muscle__ Carcinoma invades into skeletal muscle and into the chest wall (classified as T4a)Note: Invasion into pectoralis muscle is not considered chest wall invasion, and cancers are not classified as T4a unless there is invasion deeper than this muscle.Ductal Carcinoma In Situ (note G)__ No DCIS is present__ DCIS is present __ Extensive intraductal component (EIC) negative __ EIC positive __ Only DCIS is present after presurgical (neoadjuvant) therapy*Size (Extent) of DCIS* Estimated size (extent) of DCIS (greatest dimension by using gross and microscopic evaluation) is at least __ cm* Additional dimensions: __ × __ cm* Number of blocks with DCIS: __* Number of blocks examined: __Note: The size (extent) of DCIS is an estimation of the volume of breast tissue occupied by DCIS. This information may be helpful for cases with a predominant component of DCIS (eg, DCIS with microinvasion) but may not be necessary for cases of EIC-negative invasive carcinomas.*Architectural Patterns (select all that apply)*__ Comedo*__ Paget disease (DCIS involving nipple skin)*__ Cribriform*__ Micropapillary*__ Papillary*__ Solid*__ Other (specify): ____*Nuclear Grade*__ Grade I (low)*__ Grade II (intermediate)*__ Grade III (high)*Necrosis*__ Not identified*__ Present, focal (small foci or single cell necrosis)*__ Present, central (expansive “comedo” necrosis)Lobular Carcinoma In Situ__ Not identified__ PresentHistologic Type of Invasive Carcinoma (note H)__ Ductal carcinoma in situ with microinvasion__ Lobular carcinoma in situ with microinvasion__ Ductal carcinoma in situ involving nipple skin (Paget disease) with microinvasion__ Invasive ductal carcinoma (no special type or not otherwise specified)__ Invasive lobular carcinoma__ Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)__ Invasive mucinous carcinoma__ Invasive medullary carcinoma__ Invasive papillary carcinoma__ Invasive micropapillary carcinoma__ Invasive tubular carcinoma__ Invasive cribriform carcinoma__ Invasive carcinoma, type cannot be determined__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Other(s) (specify): ____Note: The histologic type corresponds to the largest area of invasion. If there are smaller foci of invasion of a different type, this information should be included under “Additional Pathologic Findings.”Histologic Grade: Nottingham Histologic Score (note I)Glandular (Acinar)/Tubular Differentiation__ Score 1: >75% of tumor area forming glandular/ tubular structures__ Score 2: 10% to 75% of tumor area forming glandular/tubular structures__ Score 3: <10% of tumor area forming glandular/ tubular structures__ Only microinvasion present (not graded)__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Score cannot be determinedNuclear Pleomorphism__ Score 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size__ Score 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape__ Score 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms__ Only microinvasion present (not graded)__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Score cannot be determinedMitotic Count__ Score 1 (see Table 1)__ Score 2 (see Table 1)__ Score 3 (see Table 1)__ Only microinvasion present (not graded)__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Score cannot be determined* Number of mitoses per 10 high-power fields: __* Diameter of microscope field: __ mmOverall Grade__ Grade 1: scores of 3, 4, or 5__ Grade 2: scores of 6 or 7__ Grade 3: scores of 8 or 9__ Only microinvasion present (not graded)__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Score cannot be determinedNote: The grade corresponds to the largest area of invasion. If there are smaller foci of invasion of a different grade, this information should be included under “Additional Pathologic Findings.”Margins (select all that apply) (note J)__ Margins cannot be assessed__ Margins uninvolved by invasive carcinoma Distance from closest margin: __ mm * Specify margins: * Distance from superior margin: __ mm * Distance from inferior margin: __ mm * Distance from anterior margin: __ mm * Distance from posterior margin: __ mm * Distance from medial margin: __ mm * Distance from lateral margin: __ mm * Distance from other specified margin: __ mm * Designation of margin: ______ Margins uninvolved by DCIS (if present) Distance from closest margin: __ mm * Specify margins: * Distance from superior margin: __ mm * Distance from inferior margin: __ mm * Distance from anterior margin: __ mm * Distance from posterior margin: __ mm * Distance from medial margin: __ mm * Distance from lateral margin: __ mm * Distance from other specified margin: __ mm * Designation of margin: ______ Margin(s) positive for invasive carcinoma * Specify margin(s): ____ * Specify margin(s) and extent of involvement: *__ Superior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Inferior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Anterior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Posterior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Medial margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Lateral margin *__ Focal *__ Minimal/moderate *__ Extensive__ Margin(s) positive for DCIS * Specify margin(s): ____ * Specify margin(s) and extent of involvement: *__ Superior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Inferior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Anterior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Posterior margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Medial margin *__ Focal *__ Minimal/moderate *__ Extensive *__ Lateral margin *__ Focal *__ Minimal/moderate *__ Extensive*Treatment Effect: Response to Presurgical (Neoadjuvant) Therapy (note K)*In the Breast*__ No known presurgical therapy*__ No definite response to presurgical therapy in the invasive carcinoma*__ Probable or definite response to presurgical therapy in the invasive carcinoma*__ No residual invasive carcinoma is present in the breast after presurgical therapy*In the Lymph Nodes*__ No known presurgical therapy*__ No lymph nodes removed*__ No definite response to presurgical therapy in metastatic carcinoma*__ Probable or definite response to presurgical therapy in metastatic carcinoma*__ No lymph node metastases. Fibrous scarring, possibly related to prior lymph node metastases with pathologic complete response*__ No lymph node metastases and no prominent fibrous scarring in the nodes*Lymph-Vascular Invasion (note L)*__ Not identified*__ Present*__ Indeterminate*Dermal Lymph-Vascular Invasion*__ No skin present*__ Not identified*__ Present*__ IndeterminateLymph Nodes (required only if lymph nodes are present in the specimen) (note B)Number of sentinel lymph nodes examined: __Total number of lymph nodes examined (sentinel and nonsentinel): __Number of lymph nodes with macrometastases (>0.2 cm): __Number of lymph nodes with micrometastases (>0.2 mm to 0.2 cm and/or >200 cells): __Number of lymph nodes with isolated tumor cells (≤0.2 mm and ≤200 cells): __Size of largest metastatic deposit (if present): __Note: The sentinel node is usually the first involved lymph node. In the unusual situation in which a sentinel node is not involved by metastatic carcinoma, but a nonsentinel node is involved, this information should be included in a note.*Extranodal Extension*__ Present*__ Not identified*__ Indeterminate*Method of Evaluation of Sentinel Lymph Nodes (select all that apply)*__ Hematoxylin-eosin (H&E), 1 level*__ H&E, multiple levels*__ Immunohistochemistry*__ Sentinel lymph node biopsy not performed*__ Other (specify): ____Pathologic Staging (based on information available to the pathologist) (pTNM) (note M)TNM Descriptors (required only if applicable) (select all that apply)__ m (multiple foci of invasive carcinoma)__ r (recurrent)__ y (posttreatment)Primary Tumor (Invasive Carcinoma) (pT)__ pTX: Primary tumor cannot be assessed__ pT0: No evidence of primary tumor†__ pTis (DCIS): Ductal carcinoma in situ†__ pTis (LCIS): Lobular carcinoma in situ†__ pTis (Paget): Paget disease of the nipple not associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast parenchyma†pT1: Tumor ≤20 mm in greatest dimension__ pT1mic: Tumor ≤1 mm in greatest dimension (microinvasion)__ pT1a: Tumor >1 mm but ≤5 mm in greatest dimension__ pT1b: Tumor >5 mm but ≤10 mm in greatest dimension__ pT1c: Tumor >10 mm but ≤20 mm in greatest dimension__ pT2: Tumor >20 mm but ≤50 mm in greatest dimension__ pT3: Tumor >50 mm in greatest dimensionpT4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules). Note: Invasion of the dermis alone does not qualify as pT4.__ pT4a: Extension to chest wall, not including only pectoralis muscle adherence/invasion__ pT4b: Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d'orange) of the skin, which do not meet the criteria for inflammatory carcinoma__ pT4c: Both T4a and T4b__ pT4d: Inflammatory carcinoma‡† For the purposes of this checklist, these categories should only be used in the setting of preoperative (neoadjuvant) therapy for which a previously diagnosed invasive carcinoma is no longer present after treatment.‡ Inflammatory carcinoma is a clinical-pathologic entity characterized by diffuse erythema and edema (peau d'orange) involving one-third or more of the skin of the breast. The skin changes are due to lymphedema caused by tumor emboli within dermal lymphatics, which may or may not be obvious in a small skin biopsy. However, a tissue diagnosis is still necessary to demonstrate an invasive carcinoma in the underlying breast parenchyma or at least in the dermal lymphatics, as well as to determine biologic markers, such as ER, PR, and HER2 status. Tumor emboli in dermal lymphatics without the clinical skin changes described above do not qualify as inflammatory carcinoma. Locally advanced breast cancers directly invading the dermis or ulcerating the skin without the clinical skin changes and tumor emboli in dermal lymphatics also do not qualify as inflammatory carcinoma. Thus, the term inflammatory carcinoma should not be applied to neglected locally advanced cancer of the breast presenting late in the course of a patient's disease. The rare case that exhibits all the features of inflammatory carcinoma, but in which skin changes involve less than one-third of the skin, should be classified by the size and extent of the underlying carcinoma.Regional Lymph Nodes (pN) (choose a category based on lymph nodes received with the specimen; immunohistochemistry and/or molecular studies are not required).If internal mammary lymph nodes, infraclavicular nodes, or supraclavicular lymph nodes are included in the specimen, consult the AJCC Cancer Staging Manual1 for additional lymph node categories.Modifier (required only if applicable)__ (sn): Only sentinel node(s) evaluated. If 6 or more sentinel nodes and/or nonsentinel nodes are removed, this modifier should not be used.Category (pN)__ pNX: Regional lymph nodes cannot be assessed (eg, previously removed, or not removed for pathologic study)__ pN0: No regional lymph node metastasis identified histologically. Note: Isolated tumor cell (ITC) clusters are defined as small clusters of cells not greater than 0.2 mm or single tumor cells, or a cluster of fewer than 200 cells in a single histologic cross section.† ITCs may be detected by routine histology or by immunohistochemical (IHC) methods. Nodes containing only ITCs are excluded from the total positive node count for purposes of N classification but should be included in the total number of nodes evaluated.__ pN0 (i−): No regional lymph node metastases histologically, negative IHC__ pN0 (i+): Malignant cells in regional lymph node(s) no greater than 0.2 mm and no more than 200 cells (detected by H&E or IHC including ITCs)__ pN0 (mol−): No regional lymph node metastases histologically, negative molecular findings (reverse transcriptase–polymerase chain reaction [RT-PCR])__ pN0 (mol+): Positive molecular findings (RT-PCR), but no regional lymph node metastases detected by histology or IHC__ pN1mi: Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm)__ pN1a: Metastases in 1 to 3 axillary lymph nodes, at least 1 metastasis greater than 2.0 mm__ pN2a: Metastases in 4 to 9 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm)__ pN3a: Metastases in 10 or more axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm)† Approximately 1000 tumor cells are contained in a 3-dimensional 0.2-mm cluster. Thus, if more than 200 individual tumor cells are identified as single dispersed tumor cells or as a nearly confluent elliptical or spherical focus in a single histologic section of a lymph node, there is a high probability that more than 1000 cells are present in the node. In these situations, the node should be classified as containing a micrometastasis (pN1mi). Cells in different lymph node cross sections or longitudinal sections or levels of the block are not added together; the 200 cells must be in a single node profile even if the node has been thinly sectioned into multiple slices. It is recognized that there is substantial overlap between the upper limit of the ITC and the lower limit of the micrometastasis categories because of inherent limitations in pathologic nodal evaluation and detection of minimal tumor burden in lymph nodes. Thus, the threshold of 200 cells in a single cross section is a guideline to help pathologists distinguish between these 2 categories. The pathologist should use judgment regarding whether it is likely that the cluster of cells represents a true micrometastasis or is simply a small group of isolated tumor cells.Distant Metastasis (M)__ Not applicable__ cM0 (i+): No clinical or radiographic evidence of distant metastasis, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are ≤0.2 mm in a patient without symptoms or signs of metastasis__ pM1: Distant detectable metastasis as determined by classic clinical and radiographic means and/ or histologically proven and >0.2 mm*Additional Pathologic Findings (note N)* Specify: ____Ancillary Studies (note O)Estrogen Receptor (immunohistochemical results on invasive carcinoma performed on this specimen or a prior core needle biopsy or incisional biopsy)__ Performed on this specimen__ Performed on another specimen * Specify specimen (accession number): ______ Pending__ Not performed__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Other (specify): ____Results:__ Immunoreactive tumor cells present (≥1%) Quantitation: ______ Less than 1% immunoreactive cells present__ No immunoreactive tumor cells present__ Results unknown__ Other (specify): ____* and ____* Type of (if other than Receptor (immunohistochemical results for invasive carcinoma performed on this specimen or a prior core needle biopsy or incisional biopsy)__ Performed on this specimen__ Performed on another specimen * Specify specimen (accession number): ______ Pending__ Not performed__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Other (specify): ____Results:__ Immunoreactive tumor cells present (≥1%) Quantitation: ______ Less than 1% immunoreactive cells present__ No immunoreactive tumor cells present__ Results unknown__ Other (specify): ____* and for invasive carcinoma performed on this specimen or a prior core needle biopsy or incisional Performed on this specimen__ Performed on another specimen * Specify specimen (accession number): ______ Pending__ Not performed__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Other (specify): ____Results:__ Positive Other (specify): ______ Results and In Situ for Performed on this specimen__ Performed on another specimen * Specify specimen (accession number): ______ Pending__ Not performed__ No residual invasive carcinoma after presurgical (neoadjuvant) therapy__ Other (specify): ____Results:__ Not or to or to or * number of HER2 per __ * number of per __ * ____ Results unknown__ Other (specify): ____* of Studies for invasive carcinoma performed on this specimen or a prior core needle biopsy or incisional Performed on this Performed on another specimen * Specify specimen (accession number): ____* of ____* (select all that apply)*__ Not identified*__ in in invasive carcinoma*__ in in both carcinoma and (select all that apply) (note The breast findings for which this is performed finding *__ or *__ *__ Other (specify): ____*__ Other (specify): ____*__ of breast cancer * Specify and prior ____*__ presurgical (neoadjuvant) therapy for this diagnosis of invasive carcinoma * Specify of breast specimens and may be reported with the breast tissue without the of the breast. The nipple is usually not included with include specimens designated and If a is detected by or imaging a is to the location of the or may be used to the of the in the The specimen (if and the results of the evaluation should be available to the pathologist when imaging by or usually does not the if it clinically only detected by without excisions are performed for or to the nipple to nipple of all breast including the nipple and This of a total mastectomy without of axillary lymph This is a total mastectomy with of the nipple and only a of This is a total mastectomy without of skin or The tissue is examined and the nipple removed if involved by This of a total mastectomy with an axillary In the checklist, the breast and lymph node specimens are small portion of pectoralis muscle is This of a total mastectomy with of the pectoralis and pectoralis This type of specimen and can be on the checklist as checklist is intended for reporting the patient's specimen with the largest focus of invasive carcinoma. If additional margin excisions are performed in the same the findings for these specimens can be included in the margin If additional smaller foci of invasive carcinoma are present in the main excision or in margin the of these carcinomas (ie, size, histologic type, and should be under “Additional Pathologic Additional studies on smaller foci of carcinoma are if the carcinomas are of different histologic type or If additional margin excisions are performed in a (eg, on another and a larger area of invasive carcinoma is not present, the checklist not be a patient has 2 ipsilateral invasive carcinomas removed in 2 excisions the same the checklist should be used for the larger invasive carcinoma. The pathologic findings for the smaller cancer may be reported without using the If a patient has 2 ipsilateral invasive carcinomas removed in 2 excisions in on different the checklist should be used for the larger carcinoma and the AJCC T classification pertain to this carcinoma. If a patient has breast carcinomas, these be reported in information from other specimens is included in the checklist (eg, the results of from a prior core needle biopsy or the finding of lymph node metastases on a lymph node this must be in the “Comments” and the of the other cases should be of specimens should not be reported by using this small incisional (including core needle of a biopsy after of of the for specimens with invasive carcinoma has the The clinical or for which the performed must be examined If the is a imaging the specimen and/or additional studies may be necessary to the the or the area with the imaging should be in a for histologic If the specimen of DCIS with complete of the specimen, or at a the involved is to additional of invasion and/or other gross in the specimen must be designated margin must be evaluated for by invasive carcinoma and DCIS. If the specimen is received sectioned or this should be as this limit the to the of may be for studies or that do not involve the histologic of the tissue (eg, only when in such a as to not the evaluation of the invasive carcinoma and lymph nodes for and margin with invasive carcinoma lymph nodes of Lymph Sentinel lymph nodes are identified by the by of or or nonsentinel nodes may also be Axillary lymph nodes are removed by of axillary The nodes are into I lateral to the lateral of the pectoralis II between the medial and lateral of the pectoralis muscle and the lymph and III or infraclavicular medial to the medial margin