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Updated Protocol for the Examination of Specimens From Patients With Carcinomas of the Breast.

A Basis for Checklists

This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.

It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with the document. Should a physician choose an alternative approach owing to the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.

The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.

UPDATED PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH CARCINOMAS OF THE BREAST
I. Cytologic Material

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

d. Gender

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information (note A)

a. Relevant history

b. Physical or mammographic findings

c. Procedure (eg, fine-needle aspiration)

d. Anatomic site(s) of specimen(s) (eg, right
breast, upper outer quadrant, subareolar)

e. Type(s) of specimen(s) (eg, nipple discharge,
aspirate)

B. Macroscopic examination

1. Specimen

a. Unfixed/fixed (specify fixative)

b. Number of slides received, if appropriate

c. Quantity and appearance of fluid specimen,
if appropriate

d. Other (eg, cytologic preparation from tissue)

e. Results of intraprocedural consultation

2. Material submitted for microscopic evaluation
(eg, smear; cytocentrifuge, touch, or filter preparation;
cell block)

3. Special studies (specify)

C. Microscopic evaluation

1. Adequacy of specimen (if unsatisfactory for
evaluation, specify reason)

2. Tumor

a. Histologic type, if possible

b. Other features (eg, nuclear grade, necrosis)

3. Additional pathologic findings, if present

4. Results/status of special studies (specify)

5. Comments

a. Correlation with intraprocedural consultation,
as appropriate

b. Correlation with results of other specimens,
as appropriate

c. Correlation with clinical, information, as appropriate

II. Biopsy (Incisional, Core)

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

d. Gender

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information (note A)

a. Relevant history

b. Physical or mammographic findings

c. Clinical diagnosis, if known

d. Procedure (eg, percutaneous core biopsy; image-guided
core biopsy; incisional biopsy)

e. Operative findings, as appropriate

f. Anatomic site(s) of specimen(s) (eg, right
breast, upper outer quadrant, subareolar)

B. Macroscopic examination

1. Specimen

a. Unfixed/fixed (specify fixative)

b. Size (3 dimensions or number and size of
cores/fragments)

c. Descriptive features (eg, color, consistency)

d. Other features (eg, prior biopsy site)

e. Results of intraoperative consultation

2. Tissue submitted for microscopic evaluation

a. Submit entire specimen, including tissue
used for frozen section (unless saved for special
studies)

3. Special studies (specify) (note B)

C. Microscopic evaluation

1. Tumor

a. Histologic type(s) (note C)

b. Histologic grade (note D)

c. Mitotic figure count

d. Extent of any associated ductal carcinoma in
situ (note E)

e. Microcalcifications (note F)

f. Vascular invasion (note G)

2. Result/status of special studies

a. Hormonal receptors

b. Other(s) (specify)

3. Additional pathologic findings, if present

4. Comments

a. Correlation with intraoperative consultation,
as appropriate

b. Correlation with results of other specimens,
as appropriate

c. Correlation with clinical information, as appropriate

III. Complete Excision of Tumor Less Than Total Mastectomy
(With or Without Axillary Contents). Includes
Wire-Guided (Localization) Excision.

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

d. Gender

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information (note A)

a. Relevant history

b. Physical or mammographic findings

c. Clinical diagnosis, if known

d. Procedure (eg, excisional biopsy, tylectomy,
partial mastectomy, as specified by surgeon)

e. Operative findings, as appropriate

f. Anatomic site of specimen (eg, right breast,
upper outer quadrant, subareolar)

B. Macroscopic examination

1. Specimen

a. Unfixed/fixed (specify fixative)

b. Tissue(s) included

c. Received sectioned/unsectioned before receipt
(note H)

d. Size of specimen (3 dimensions if removed
in 1 piece)

e. Dimensions and description of skin, if included

f. Orientation (if specified by surgeon) and
margin designation (eg, ink) (note I)

g. Results of intraoperative consultation

2. Tumor

a. Size (single greatest dimension) (note J)

b. Descriptive features (eg, degree of circumscription,
consistency, mucoid appearance)

c. Correlation with imaging studies, including
specimen radiograph (note F)

d. Relation to surgical margins (note I)

3. Regional lymph nodes, if appropriate (note K)

a. Number identified, if possible

b. Location, if specified by surgeon

c. Size of the largest nodal metastasis, if visible

4. Additional pathologic findings (eg, prior biopsy,
prosthetic implant, fibrocystic changes), if
present

5. Tissue(s) submitted for microscopic evaluation
(note L)

a. Tumor (notes F and L)

b. Margin(s), as appropriate (note I)

c. Other lesion(s)

d. Lymph nodes (note K)

e. Frozen section tissue fragment(s) (unless
saved for special studies)

6. Special studies (specify) (note B)

C. Microscopic evaluation

1. Tumor

a. Histologic type(s) (note C)

b. Histologic grade (note D)

c. Mitotic figure count

d. Extent of any associated ductal carcinoma in
situ (notes E and I)

e. Microcalcifications (note F)

f. Verification of tumor size (notes J and M)

g. Extent of invasion (note M)

h. Vascular invasion (note G)

i. Involvement of skin, if possible (note M)

2. Status of surgical margins, as appropriate
(note I)

a. No tumor

b. Ductal carcinoma in situ at margin

c. Invasive carcinoma at margin (specify margin,
specify macroscopic or only microscopic)

3. Additional pathologic findings, if present

4. Regional lymph nodes (note K)

a. Total number examined (specify location if
indicated by surgeon)

b. Number involved by tumor (note extranodal
extension, if present)

c. Size(s) of the largest nodal metastasis

5. Distant metastasis (specify site[s]) (note M)

6. Results/status of special studies (specify)
(note B)

a. Hormonal receptors

b. Other(s) (specify)

7. Comments

a. Correlation with intraoperative consultation,
as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

IV. Mastectomy (Total, Modified Radical, Radical)

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

d. Gender

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information (note A)

a. Relevant history

b. Physical or mammographic findings

c. Clinical diagnosis, if known

d. Procedure (eg, simple mastectomy, modified
radical mastectomy)

e. Operative findings, as appropriate

f. Anatomic site of specimen (eg, right breast)

B. Macroscopic examination

1. Specimen

a. Unfixed/fixed (specify fixative)

b. Tissue(s) included

c. Size of breast

d. Dimensions and description of skin

e. Location of biopsy site or tumor (eg, quadrant,
relation to deep margin)

f. Results of intraoperative consultation

2. Tumor

a. Size (single greatest dimension) (note J)

b. Descriptive features (eg, degree of circumscription,
consistency, mucoid appearance)

c. Relation to surgical margins (note I)

3. Regional lymph nodes, if appropriate (note L)

a. Number identified, if possible

b. Location, if specified by surgeon

d. Size of the largest nodal metastasis, if visible

4. Additional pathologic findings (eg, prior biopsy,
prosthetic implant, fibrocystic changes), if
present

5. Tissues submitted for microscopic evaluation
(note L)

a. Tumor (notes F and L)

b. Biopsy site, needle track (if identified)

c. Margin(s), as appropriate

d. Nipple

e. Additional breast tissue (quadrants not involved
by tumor)

f. Other lesions

g. Lymph nodes (note K)

h. Frozen section tissue fragment(s) (unless
saved for special studies)

6. Special studies (specify) (note B)

C. Microscopic evaluation

1. Tumor

a. Histologic type(s) (note C)

b. Histologic grade (note D)

c. Mitotic figure count

d. Ductal carcinoma in situ, if present (note E)

e. Microcalcifications (note F)

f. Verification of tumor size (notes J and M)

g. Extent of invasion (note M)

h. Vascular invasion (note G)

i. Involvement of other tissues (eg, skin, chest
wall) (note M)

2. Regional lymph nodes, if appropriate (note K)

a. Total number examined (specify location if
indicated by surgeon)

b. Number involved by tumor (note extranodal
extension of tumor, if present)

c. Size(s) of the largest nodal metastasis

3. Additional pathologic findings, if present
(specify)

4. Distant metastasis (specify site[s]) (note M)

5. Results/status of special studies (specify)
(note B)

a. Hormonal receptors

b. Other(s)

6. Comments

a. Correlation with intraoperative consultation,
as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate


EXPLANATORY NOTES

A: Clinical Information.--The pathologist should have all relevant clinical information. Elements of the history that are important for breast cancer include family history, previous therapeutic irradiation to the breast, history of collagen vascular disease, nipple discharge, previous biopsy or other treatment, and whether the patient is currently pregnant or nursing.[1] It is important for the pathologist to know the physical and mammographic findings, such as whether the lesion was palpable or detected only by imaging studies, whether suspicious microcalcifications were seen, or whether the tumor is solid or cystic. Correlating the histologic features with the imaging studies is particularly important for image-guided core biopsies to ensure that the mammographic abnormality has been sampled and examined microscopically.

B: Special Studies.--Fresh tissue should not be used for special studies (eg, hormone receptor analysis by ligand-binding assay) unless the neoplasm is of sufficient size that histologic evaluation will not be compromised. When needed, hormone receptor analysis by immunohistochemistry and many other studies can be performed on routinely fixed, paraffin-embedded tissue. Besides a formal interpretation, each pathology report should specify the fixative used if other than formalin, the antibody clone and vendor, and results of control stains. Any deviation from the laboratory's standard staining and antigen-retrieval protocol should be mentioned. The percentage of positive cells should also be mentioned when clinically relevant.

C: Histologic Type.--This protocol applies to all carcinomas of the breast. The World Health Organization classification of breast carcinoma is presented below, although the protocol does not preclude the use of other classifications or histologic types, such as that published in the Armed Forces Institute of Pathology Fascicle on breast tumors.[2,3]

World Health Organization Classification of Carcinoma of the Breast
Noninvasive carcinoma (not otherwise specified [NOS])
 Ductal carcinoma in situ
 Lobular carcinoma in situ

Invasive carcinoma (NOS)
 Invasive ductal
 Invasive ductal carcinoma with an extensive intraductal
 component
 Invasive lobular(*)
 Mucinous[dagger]
 Medullary[daggers]
 Papillary[sections]
 Tubular
 Adenoid cystic
 Secretory (juvenile)
 Apocrine
 Cribriform
 Paget disease of the nipple
 with invasive carcinoma
 without invasive carcinoma
 Carcinoma with metaplasia
 Squamous type
 Spindle cell type
 Cartilaginous and osseous type
 Mixed type
 Inflammatory
 Other(s) (specify)


(*) Classic invasive lobular carcinoma, which has a better prognosis than invasive carcinoma, NOS, is diagnosed only when the tumor exhibits a single-file growth pattern, a monotonous population of small cells with very-low-grade nuclei, and low cell density. Tumors with a diffuse infiltrative growth pattern that do not fulfill these criteria should be reported by histologic grade with the suffix "with lobular features" (or "lobular variant"). Such tumors are identified separately because this growth pattern has been associated with extensive intramammary growth and distinctive patterns of metastasis.

([dagger]) The diagnosis of pure mucinous carcinoma requires the presence of low-grade nuclei and extracellular mucin in at least 90% of the tumor Tumors with less extensive mucin production should be reported by histologic grade with the suffix "with mucinous features."

([double dagger]) The diagnosis of medullary carcinoma requires strict adherence to diagnostic criteria: a sharply circumscribed tumor border, high histologic grade with patternless syncytial sheets of large undifferentiated tumor cells, a substantial and diffuse lymphoplasmacytic infiltrate between cellular nests, and scant fibrous stroma. Tumors lacking all of these features should be reported by histologic grade.

([section]) The diagnostic category of papillary carcinoma should always be qualified as to invasive or noninvasive.

D: Histologic Grade.--All invasive breast carcinomas with the exception of medullary carcinoma (as defined in note C) should be graded. The grading system used must be specified in the report, and the Nottingham combined histologic grade (Elston-Ellis modification of Scarff-Bloom-Richardson grading system) is recommended.[4,5] Grading of large-core needle biopsies may be done when the quantity of tissue available is sufficient. Within each stage grouping there is a relation between histologic grade and outcome.[6]

The Nottingham combined histologic grade depends on the extent of tubule formation, the extent of nuclear pleomorphism, and the mitotic count. Each variable is given a score of 1, 2, or 3, and the scores are added to produce a grade. The mitotic score is determined by the number of mitotic figures found in 10 consecutive high-power fields in the most mitotically active part of the tumor Only clearly identifiable mitotic figures (eg, cells in prophase, metaphase, or anaphase) should be counted; hyperchromatic, karyorrhectic, or apoptotic nuclei are excluded. Because of variations in field size, the high-power field size must be determined for each microscope and the appropriate point score determined accordingly. Using a micrometer to measure the field diameter of the microscope is recommended.

The following tabulation relates to the use of x 25 objective with a field diameter of 0.59 mm and a field area of 0.274 [mm.sup.2].[5]
 Feature Score

Tubule formation
 Majority of tumor: >75% 1
 Moderate: 10% to 75% 2
 Minimal: <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)
 <10 mitoses per 10 high-power fields (HPF) 1
 10-20 mitoses per 10 HPF 2
 >20 mitoses per 10 HPF 3

For a x40 objective with a field diameter of 0.44 mm
(area = 0.152 [mm.sup.2]), the equivalent scoring of mitotic
activity is as follows:

0-5 mitoses per 10 HPF 1
6-10 mitoses per 10 HPF 2
>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


E: Ductal Carcinoma In Situ (DCIS).--The following histologic features of DCIS should be included in the pathology report[7]:

1. Nuclear grade
Grade 1: Monotonous nuclei, 1.5-2.0 red blood cell
 (RBC) diameters, with finely dispersed chromatin
 and only occasional nucleoli

Grade 2: Neither nuclear grade 1 nor nuclear grade 3

Grade 3: Markedly pleomorphic nuclei, usually >2.5
 RBC diameters, with coarse chromatin and
 multiple nucleoli


2. Presence or absence of necrosis

3. Architectural pattern(s) Comedo Cribriform Papillary Micropapillary Solid

Although not required for pT classification and stage assignment, the extent (size) of DCIS is an important factor in patient management. Mammographic assessment of DCIS, usually based on distribution of calcifications, frequently underestimates the size of DCIS? While precise measurement may be impossible on nonpalpable, grossly inapparent lesions, the pathologist should estimate the size or extent of DCIS and include this in the report. Methods for estimating the extent of DCIS include directly measuring the lesion when confined to a single histologic slide, determining size by submitting the entire specimen in sequence and in sections of uniform thickness, and estimating the percentage of tissue involved in relation to the total specimen.[9]

In breast carcinomas with both invasive and in situ components, the pathology report should specify whether an extensive intraductal component is present. An extensive intraductal component is identified when DCIS comprises a substantial portion of the main tumor mass (approximately 25%) and extends into the surrounding breast parenchyma. Cases in which the lesion is primarily DCIS with foci of invasion are also classified as having an extensive intraductal component.[10] This finding is associated with an increased risk of local recurrence when the surgical margins are not evaluated or are focally involved.[11] The finding appears to have less significance when DCIS does not extend close to any of the margins following careful histologic evaluation.

F: Microcalcifications.--If the biopsy is done for micro-calcifications, their presence in the specimen must be confirmed by specimen radiography and microscopy. Ultimately, the pathologist must be satisfied that the lesion responsible for the calcifications is present in the specimen and that it has been examined microscopically. The location f the calcifications in relation to the tumor or other lesions should also be indicated.

If calcifications can be seen in the specimen radiograph but not in the initial histologic sections, deeper levels should be examined. If needed, radiographs of the paraffin block(s) may be obtained to see if calcifications remain in the block(s). If microcalcifications cannot be confirmed by routine microscopic evaluation, polarized light may be helpful since calcium oxalate crystals are birefringent but unstained in hematoxylin-eosin sections. On rare occasions calcifications do not survive tissue processing.

G: Vascular or Lymphatic Invasion.--Peritumoral vascular invasion should be noted because it has been associated with local failure and reduced overall survival.[12,13] Distinguishing lymphatic channels from blood vessels is unnecessary. While sometimes difficult to identify in skin biopsies, documenting the presence of dermal lymphatic invasion is particularly important because of its strong association with inflammatory breast carcinoma.[14]

H: 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 n as well as ascertaining the dimensions of the specimen or tumor. Evaluation of margins does not apply to a diagnostic incisional biopsy.

I: Orientation and identification of surgical margins.--Whenever feasible, the specimen should be oriented so the pathologist can identify specific margins. This is particularly important for excisions less than total mastectomy, where each margin (eg, superior, inferior, medial lateral deep) may be important. Identification of surgical margins accomplishes 2 primary goals: to specifically identify margins (if any) that are involved by tumor and to measure the distance from the tumor to specific margins. 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 an extensive intraductal component? Correlating mammograms with the pathologic findings and assessing surgical margins are particularly important procedures when dealing with patients with an extensive intraductal component.[16]

Orientation may be signified by sutures or clips placed on the specimen surface, or by other means of communication between surgeon and pathologist, and should be documented in the pathology report. Margins can be identified in several ways, including the use of multicolored inks, by submitting the margins in specific cassettes, or by the surgeon submitting each margin as a separately excised specimen. If inks are used, care should be taken to avoid penetration deep into the specimen.

Macroscopic or microscopic involvement of surgical margins by invasive carcinoma or DCIS should be noted in the report. If the specimen is oriented, the specific site(s) of involvement (eg, superior) should also be reported. When possible, the pathologist should report the distance from the tumor to the closest margin. 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.

J: Tumor Size.--Tumor size is a powerful predictor of tumor behavior? The tumor should be measured in at least 2 dimensions, and the single greatest dimension of the invasive component should be used for determining tumor stage. The size of the tumor, as measured by gross examination, must be verified by microscopic examination. If there is a discrepancy between gross and microscopic tumor measurement, the microscopic measurement of the invasive component takes precedence and should be used for tumor staging. For pT1 lesions or those with an extensive in situ component, measurement of tumor size on the histologic slide is more accurate than gross measurement. For tumors with both invasive and in situ components, only the invasive component is included in the tumor measurement for pT classification and stage assignment (see note M below). When 2 or more distinct invasive tumors are present, each is measured and reported separately; they are not combined into a single larger size. Determination of tumor size may not be possible with a core or incisional biopsy.

K: Lymph Nodes.--Grossly uninvolved nodes should be submitted in their entirety for histologic examination, whereas representative sections of grossly positive nodes may be submitted. Small nodes may be submitted intact, but larger nodes should be sectioned for proper fixation and examination.

The pathology report should clearly state the total number of lymph nodes examined, the total number of involved nodes, and the greatest dimension of the largest metastatic focus. A single microscopic section from each lymph node block is considered sufficient for routine evaluation. The presence of extranodal tumor extension should be included in the pathology report, since it may be associated with a higher frequency of axillary recurrence.

A solitary focus of tumor in a single node that is visualized by routine histologic examination and measures [is less than or equal to] 2 mm in greatest dimension is classified as a micrometastasis. While the prognosis for patients with a solitary micrometastasis has been reported to be better than that for patients with larger metastatic deposits, the significance of multiple micrometastases in one node or multiple lymph nodes with metastases of that size is unknown. We recommend that these be classified as pN1a. The number of nodes that contain micrometastases should be clearly specified in the pathology report, since this may affect treatment.

The significance of cells found exclusively by immunohistochemistry or molecular methods is unsettled. We recommend that these findings be reported separately from histologically detected micrometastases and classified as pN0.

L: Specimen Sample.--The number of sections submitted varies with the size and character of the specimen, the nature of the underlying neoplastic process, and whether the surgical margins need to be assessed. If the biopsy is performed because of a mammographic abnormality, the entire mammographic lesion (not necessarily the entire specimen) should be submitted when practical. For excisions less than total mastectomy, blocking of tissue includes evaluating the resection margins.

M: 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.[18,19] 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 (cTNM). Pathologic classification is based on gross and microscopic examination. Therefore, pT entails resection of the primary tumor or a biopsy adequate to evaluate the highest pT Category, pN entails removal of axillary lymph nodes, and pM requires microscopic examination of distant lesions. Clinical classification is usually carried out by the clinician before treatment or when pathologic classification is not possible.
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 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([dagger])

 T1a Tumor >0.1 cm but not >0.5 cm in
 greatest dimension

 T1b Tumor >0.5 cm but not >1 cm in greatest
 dimension

 T1c Tumor >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([double dagger])


(*) Paget disease associated with a tumor is classified according to the size of the tumor.

([dagger]) 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.

([double dagger]) 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 staging a clinical inflammatory carcinoma pathologically (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 (eg, 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

 N1biii Extension of tumor beyond the
 capsule of a lymph node, metastasis
 <2 cm in greatest dimension

 N1biv Metastasis to a lymph node [is greater than
 or equal to] 2 cm 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([dagger]) M0
 T2 N0 M0

Stage IIB T2 N1 M0
 T3 N0 M0

Stage IIIA T0 N2 M0
 T1(*) N2 M0
 T2 N2 M0
 T3 N1, N2 M0

Stage IIIB T4 Any N M0
 Any T N3 M0

Stage IV Any T Any N M1


(*) T1 includes T1mic.

([dagger]) The prognosis of patients with pN1a is similar to that of patients with pN0.

Tumor remaining in a patient after curative therapy (eg, surgical resection) is categorized by a system known as R classification, shown below. This classification may be used by the surgeon to indicate the known or assumed status of the completeness of the surgical resection. For the pathologist, the R classification is relevant only to the margins of surgical resection specimens; patients with tumor involving the resection margins on pathologic examination may be assumed to have residual tumor. Such patients may be classified as to whether the involvement is macroscopic or microscopic.
RX Presence of residual tumor cannot be assessed
R0 No residual tumor
R1 Microscopic residual tumor
R2 Macroscopic residual tumor


Tumor remaining in a resection specimen following previous (neoadjuvant) treatment of any type (radiation therapy alone, chemotherapy therapy alone, or any combined modality treatment) is codified by the TNM using a prescript "y" to indicate the posttreatment status of the tumor (eg, ypT1). The classification of residual disease may be a predictor of postoperative outcome. In addition, the ypTNM classification provides a standardized framework for the collection of data needed to accurately evaluate new neoadjuvant therapies.

Tumor that is locally recurrent after a documented disease-free interval following surgical resection is classified according to the TNM categories but modified with the prefix "r" (eg, rpT1).

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.

References

[1.] Winchester DP, Cox JD. Standards for diagnosis and management of invasive breast carcinoma. CA Cancer J Clin. 1998;48:83-107.

[2.] Rosen PP, Oberman HA. Tumors of the Mammary Gland. Washington, DC: Armed Forces Institute of Pathology, American Registry of Pathology; 1993. Atlas of Tumor Pathology; 3rd series, fascicle 7.

[3.] Histological Typing of Breast Tumours. 2nd ed. Geneva, Switzerland: World Health Organization; 1981. International Classification of Tumours.

[4.] Bloom HJG, Richardson WW. Histological grading and prognosis in breast carcinoma: a study of 1049 cases of which 359 have been followed for 15 years. Br J Cancer. 1957;11:359-377.

[5.] Elston CW, Ellis JO. Pathological prognostic factors in breast cancer: experience from a long study with long-term follow-up. Histopathology 1991;19:403-410.

[6.] Henson DE, Ries L, Freedman LS, Carriaga M. Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. Cancer. 1991;68:2142-2149.

[7.] Schwartz GF, Lagios MD, Carter D, et al. Consensus conference on the classification of ductal carcinoma in situ. Cancer. 1997;80:1798-1802.

[8.] Holland R, Hendriks JHCL, Verbeek ALM, et al. Extent, distribution, and mammographic/histological correlations of breast ductal carcinoma in situ. Lancet. 1990;335:519-522.

[9.] Winchester DP, Strom EA. Standards for diagnosis and management of ductal carcinoma in situ (DCIS) of the breast. CA Cancer J Clin. 1998;48:108-128.

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Accepted for publication January 1, 2000.

From Good Samaritan Hospital, Los Angeles, Calif (Dr Fitzgibbons); Georgetown University Medical Center, Washington, DC (Dr Connolly); and Vanderbilt University Medical Center, Nashville, Tenn (Dr Page).

This protocol was originally published in Arch Pathol tab Med. 1997; 121:27-33.

This protocol was developed by the Cancer Committee of the College of American Pathologists and submitted for editorial review and publication. It represents the views of the Cancer Committee and is not the official policy of the College of American Pathologists.

Reprints: Joe Schramm, College of American Pathologists, 325 Waukegan Rd, Northfield, IL 60093-2750.

Patrick L. Fitzgibbons, MD; James L. Connolly, MD; David L. Page, MD; for the Members of the Cancer Committee, College of American Pathologists
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Author:Fitzgibbons, Patrick L.; Connolly, James L.; Page, David L.
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Statistical Data Included
Geographic Code:1USA
Date:Jul 1, 2000
Words:5955
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