25 Breast 25

25 Breast

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SUMMARY OF CHANGES

• Micrometastases are distinguished from isolated tumor cells on the basis of size and histologic evidence of malignant activity.

• Identifiers have been added to indicate the use of sentinel lymph node dissection and immunohistochemical or molecular techniques.

• Major classifications of lymph node status are designated according to the number of involved axillary lymph nodes as determined by routine hematoxylin and eosin staining (preferred method) or by immunohistochemical staining.

• The classification of metastasis to the infraclavicular lymph nodes has been added as N3.

• Metastasis to the internal mammary nodes, based on the method of detection and the presence or absence of axillary nodal involvement, has been reclassified.

Microscopic involvement of the internal mammary nodes detected by sentinel node dissection using lymphoscintigraphy but not by imaging studies or clinical examination is classified as N1. Macroscopic involvement of the internal mam- mary nodes as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination is classified as N2 if it occurs in the absence of metastases to the axillary lymph nodes or as N3 if it occurs in the presence of metastases to the axillary lymph nodes.

• Metastasis to the supraclavicular lymph nodes has been reclassified as N3 rather than M1.

INTRODUCTION

This staging system for carcinoma of the breast applies to infiltrating (includ- ing microinvasive) and in situ carcinomas. Microscopic confirmation of the diagnosis is mandatory, and the histologic type and grade of carcinomas should be recorded

ANATOMY

Primary Site. The anatomic subsites of the breast are illustrated in Figure 25.1.

The mammary gland, situated on the anterior chest wall, is composed of glan- dular tissue with a dense fibrous stroma. The glandular tissue consists of lobules that group together into 15–25 lobes arranged approximately in a spoke-like pattern. Multiple major and minor ducts connect the milk-secreting lobular

C50.0 Nipple

C50.1 Central portion of the breast

C50.2 Upper inner quadrant of breast C50.3 Lower inner quadrant

of breast

C50.4 Upper outer quadrant of breast C50.5 Lower outer quadrant

of breast C50.6 Axillary tail of breast

C50.8 Overlapping lesion of breast

C50.9 Breast, NOS

units to the nipple. Small milk ducts course throughout the breast, converging into larger collecting ducts that open into the lactiferous sinus at the base of the nipple. Most cancers form initially in the terminal duct lobular units of the breast. Glandular tissue is more abundant in the upper outer portion of the breast; as a result, half of all breast cancers occur in this area.

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

Regional Lymph Nodes. The regional lymph nodes of the breast are illus- trated in Figure 25.2. The breast lymphatics drain by way of three major routes:

axillary, transpectoral, and internal mammary. Intramammary lymph nodes are coded as axillary lymph nodes for staging purposes. Supraclavicular lymph nodes are classified as regional lymph nodes for staging purposes. Metastasis to any other lymph node, including cervical or contralateral internal mammary lymph nodes, is classified as distant (M1).

The regional lymph nodes are as follows:

1. Axillary (ipsilateral): interpectoral (Rotter’s) nodes and lymph nodes along the axillary vein and its tributaries that may be (but are not required to be) divided into the following levels:

a. Level I (low-axilla): lymph nodes lateral to the lateral border of pectoralis minor muscle.

b. Level II (mid-axilla): lymph nodes between the medial and lateral borders of the pectoralis minor muscle and the interpectoral (Rotter’s) lymph nodes.

c. Level III (apical axilla): lymph nodes medial to the medial margin of the pectoralis minor muscle, including those designated as apical.

2. Internal mammary (ipsilateral): lymph nodes in the intercostal spaces along the edge of the sternum in the endothoracic fascia.

3. Supraclavicular: lymph nodes in the supraclavicular fossa, a triangle defined by the omohyoid muscle and tendon (lateral and superior border), the

C50.6

C50.2

C50.0 C50.1

C50.3 C50.4

C50.5 C50.8

FIGURE 25.1. Anatomic sites and subsites of the breast.

internal jugular vein (medial border), and the clavicle and subclavian vein (lower border). Adjacent lymph nodes outside of this triangle are consid- ered to be lower cervical nodes (M1).

Metastatic Sites. Tumor cells may be disseminated by either the lymphatic or the blood vascular system. The four major sites of involvement are bone, lung, brain, and liver, but tumor cells are also capable of metastasizing to many other sites.

DEFINITIONS Primary Tumor (T)

Definitions for classifying the primary tumor (T) are the same for clinical and for pathologic classification. If the measurement is made by physical examina- tion, the examiner will use the major headings (T1, T2, or T3). If other meas- urements, such as mammographic or pathologic measurements, are used, the subsets of T1 can be used. Tumors should be measured to the nearest 0.1 cm increment.

TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ

Tis (DCIS) Ductal carcinoma in situ Tis (LCIS) Lobular carcinoma in situ

Tis (Paget’s) Paget’s disease of the nipple with no tumor (Figure 25.3)

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Low axillary,

level I Mid-axillary,

level II High axillary, apical,

level III

Supraclavicular

Pectoralis minor muscle

Internal mammary

FIGURE 25.2. Schematic diagram of the breast and regional lymph nodes.

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

T1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 0.1 cm or less in greatest dimension (Figure 25.4) T1a Tumor more than 0.1 cm but not more than 0.5 cm in greatest dimen-

sion (Figure 25.5)

T1b Tumor more than 0.5 cm but not more than 1 cm in greatest dimen- sion (Figure 25.5)

T1c Tumor more than 1 cm but not more than 2 cm in greatest dimension (Figure 25.5)

T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension (Figure 25.6)

Non-invasive Paget’s disease Tis

FIGURE 25.3. Tis (Paget’s) is defined as Paget’s disease of the nipple with no tumor.

T1mic(m) or T1mic(3)

T1mic

£0.1 cm

£0.1 cm

£0.1 cm

£0.1 cm

FIGURE 25.4. T1mic is defined as microinvasion 0.1 cm or less in greatest

dimension. The presence of multiple tumor foci of microinvasion (top of diagram)

should be noted in parentheses.

T3 Tumor more than 5 cm in greatest dimension (Figure 25.6) 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 (Figure 25.7) T4b Edema (including peau d’orange) or ulceration of the skin of the

breast, or satellite skin nodules confined to the same breast (Figures 25.8A, B)

T4c Both T4a and T4b (Figure 25.9) T4d Inflammatory carcinoma (Figure 25.10)

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T1

>1-2 cm=T1c

>0.5-1 cm=T1b

>0.1-0.5 cm=T1a

FIGURE 25.5. T1 is defined as a tumor 2 cm or less in greatest dimension.

T1a is defined as tumor more than 0.1 cm but not more than 0.5 cm in greatest dimension; T1b is defined as tumor more than 0.5 cm but not more than 1 cm in greatest dimension; T1c is defined as tumor more than 1 cm but not more than 2 cm in greatest dimension.

T2

T3

>2-5 cm

>5 cm

FIGURE 25.6. T2 (above dotted line) is defined as tumor more than 2 cm but not

more than 5 cm in greatest dimension and T3 (below dotted line) is defined as

tumor more than 5 cm in greatest dimension.

T4a

FIGURE 25.7. T4 is defined as a tumor of any size with direct extension to chest wall, not including pectoralis muscle.

T4b

Satellite nodule

A

B

FIGURE 25.8. A. T4b, illustrated here as satellite skin nodules, is defined as edema (including peau d’orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast. B. T4b illustrated here as edema (including peau d’orange).

T4c

FIGURE 25.9. T4c is defined as both T4a and T4b.

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed (e.g., previously removed) N0 No regional lymph node metastasis

N1 Metastasis in movable ipsilateral axillary lymph node(s) (Figure 25.11) N2 Metastases in ipsilateral axillary lymph nodes fixed or matted, or in

clinically apparent

ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis

N2a Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures (Figure 25.12)

N2b Metastasis only in clinically apparent

ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metas- tasis (Figure 25.13)

N3 Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent

ipsilateral

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T4d

Inflammatory carcinoma

FIGURE 25.10. T4d, inflammatory carcinoma.

N1

FIGURE 25.11. N1 is defined as metastasis in movable ipsilateral axillary lymph

node(s).

internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicu- lar lymph node(s) with or without axillary or internal mammary lymph node involvement

N3a Metastasis in ipsilateral infraclavicular lymph node(s) (Figure 25.14) N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary

lymph node(s) (Figure 25.15)

N3c Metastasis in ipsilateral supraclavicular lymph node(s) (Figure 25.16)

FIGURE 25.12. N2a is defined as metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures.

N2b

FIGURE 25.13. N2b is defined as metastasis only in clinically apparent

ipsilateral

internal mammary nodes and in the absence of clinically evident axillary lymph

node metastasis.

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FIGURE 25.14. N3a metastasis in ipsilateral

infraclavicular lymph node(s) without axillary or internal mammary lymph node involvement.

N3b

pN3c

FIGURE 25.15. N3b metastasis in

ipsilateral internal mammary lymph node(s) and axillary lymph node(s).

FIGURE 25.16. N3c is defined as metastasis

in ipsilateral supraclavicular lymph node(s).

Regional Lymph Nodes (pN)

pNX Regional lymph nodes cannot be assessed (e.g., previously removed, or not removed for pathologic study)

pN0 No regional lymph node metastasis histologically, no additional examination for isolated tumor cells (ITC)

pN0(i

) No regional lymph node metastasis histologically, negative IHC pN0(i

) No regional lymph node metastasis histologically, positive IHC, no

IHC cluster greater than 0.2 mm (Figure 25.17)

pN0(mol

) No regional lymph node metastasis histologically, negative molec- ular findings (RT-PCR)

pN0(mol

) No regional lymph node metastasis histologically, positive molec- ular findings (RT-PCR)

pN1 Metastasis in 1 to 3 axillary lymph nodes, and/or in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent

pN1mi Micrometastasis (greater than 0.2 mm, none greater than 2.0 mm) (Figure 25.18)

pN1a Metastasis in 1 to 3 axillary lymph nodes (Figure 25.18) pN1b Metastasis in internal mammary nodes with microscopic disease

detected by sentinel lymph node dissection but not clinically apparent

(Figure 25.19)

pN1c Metastasis in 1 to 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent

(Figure 25.20) pN2 Metastasis in 4 to 9 axillary lymph nodes, or in clinically appar-

ent

internal mammary lymph nodes in the absence of axillary lymph node metastasis

£0.2 mm pN0(i+)

FIGURE 25.17. pN0(i

) is defined as regional lymph node metastasis histologically,

positive IHC, no IHC cluster greater than 0.2 mm.

pN2a Metastasis in 4 to 9 axillary lymph nodes (at least one tumor deposit greater than 2.0 mm) (Figure 25.18)

pN2b Metastasis in clinically apparent

internal mammary lymph nodes in the absence of axillary lymph node metastasis (Figure 25.21) pN3 Metastasis in 10 or more axillary lymph nodes, or in infraclavicu-

lar lymph nodes, or in clinically apparent

ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axil- lary lymph nodes; or in more than 3 axillary lymph nodes with clinically negative microscopic metastasis in internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes

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>0.2-2 mm pN1mi

pN1a:1-3 nodes

pN2a:4-9 nodes (at least one tumor deposit >2.0 mm)

pN3a:≥10 nodes (at least one tumor deposit >2.0 mm)

FIGURE 25.18. Illustrated definition of pN1mi, defined as micrometastasis greater

than 0.2 mm with none greater than 2.0 mm, as well as pN1a, pN2a, and pN3a.

pN1b ^SNB+

FIGURE 25.19. pN1b with isolated tumor cells in a single internal mammary node, sentinel lymph node positive.

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 (Figure 25.18)

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

SNB+

pN1c

FIGURE 25.20. pN1c illustrating 3 positive axillary lymph nodes with isolated

tumor cells in a single internal mammary lymph node, sentinel lymph node

positive.

sentinel lymph node dissection but not clinically apparent

(Figure 25.22A, B)

pN3c Metastasis in ipsilateral supraclavicular lymph nodes (Figure 25.16)

Distant Metastasis (M)

MX Distant metastasis cannot be assessed M0 No distant metastasis

M1 Distant metastasis

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pN2b

FIGURE 25.21. pN2b illustrating clinically apparent metastasis in 2 positive internal mammary nodes with no axillary lymph node involvement.

pN3b

A

FIGURE 25.22. A. pN3b illustrated as clinically apparent metastasis in 2 positive

internal mammary nodes in the presence of 3 positive axillary lymph nodes.

STAGE GROUPING

0 Tis N0 M0

I T1

N0 M0

IIA T0 N1 M0

T1

N1 M0

T2 N0 M0

IIB T2 N1 M0

T3 N0 M0

IIIA T0 N2 M0

T1

N2 M0

T2 N2 M0

T3 N1 M0

T3 N2 M0

IIIB T4 N0 M0

T4 N1 M0

T4 N2 M0

IIIC Any T N3 M0

IV Any T Any N M1

Note: Stage designation may be changed if post-surgical imaging studies reveal the presence of distant metastases, provided that the studies are carried out within 4 months of diagnosis in the absence of disease progression and provided that the patient has not received neoadjuvant therapy.

NOTES

1. Clinically apparent is defined as detected by imaging studies (excluding lym- phoscintigraphy) or by clinical examination or grossly visible pathologically.

SNB+

pN3b

B

FIGURE 25.22. B. pN3b illustrated as clinically apparent metastasis in 6 positive

axillary lymph nodes with isolated tumor cells in one internal mammary lymph

node, sentinel lymph node positive.

2. Classification is based on axillary lymph node dissection with or without sentinel lymph node dissection. Classification based solely on sentinel lymph node dissec- tion without subsequent axillary lymph node dissection is designated (sn) for

“sentinel node,” e.g., pNO(i +)(sn).

3. Isolated tumor cells (ITC) are defined as single tumor cells or small cell clusters not greater than 0.2 mm, usually detected only by immunohistochemical (IHC) or molecular methods but which may be verified on H&E stains. ITCs do not usually show evidence of metastatic activity (e.g., proliferation or stromal reaction).

4. RT-PCR: reverse transcriptase/polymerase chain reaction.

5. Not clinically apparent is defined as not detected by imaging studies (excluding lym- phoscintigraphy) or by clinical examination.

6. If associated with greater than 3 positive axillary lymph nodes, the internal mammary nodes are classified as pN3b to reflect increased tumor burden.

7. T1 includes T1mic.

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