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Breast malignant, males, children

Miscellaneous

Staging of breast carcinoma


Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Definition
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● T and M (not N) are similar for clinical and pathologic staging
● Numerous changes were made in AJCC 7th edition - AJCC Cancer Staging Manual (7th ed)

Primary tumor (T)
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● Same definitions for clinical and pathologic classification, although T1 subclassification requires more than clinical examination

TX: primary tumor cannot be assessed (includes cases with tumor present at margin by macroscopic examination, because total extent of 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 NOT associated with invasive carcinoma or carcinoma in situ (DCIS or LCIS) in the underlying breast parenchyma; carcinomas in the breast parenchyma associated with Paget’s disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget’s disease should still be noted
T1: tumor 2 cm (20 mm) or less in greatest dimension
T1mic: tumor 1 mm or less in greatest dimension (if multiple foci of microinvasion, use largest focus and add a comment, don’t add sizes of individual foci)
T1a: tumor more than 1 mm, but 5 mm or less in greatest dimension
T1b: tumor more than 5 mm, but 10 mm (1 cm) or less in greatest dimension
T1c: tumor more than 1 cm, up to 2 cm in greatest dimension
T2: tumor more than 2 cm, up to 5 cm in greatest dimension
T3: tumor more than 5 cm in greatest dimension
T4: tumor of any size with direct extension to chest wall or skin as described below (invasion of dermis alone does not qualify as T4)
     ●T4a: extension to chest wall, not including only pectoralis muscle adherence / invasion
     ●T4b: ulceration or ipsilateral satellite nodules or edema (including peau d’orange) of the skin, which do not meet the criteria for inflammatory carcinoma
     ●T4c: both T4a and T4b
     ●T4d: inflammatory carcinoma (clinical diagnosis characterized by diffuse erythema and edema [peau d’orange] involving a third or more of the skin of the breast; skin changes are due to lymphedema caused by tumor emboli within dermal lymphatics, which may not be obvious in a small skin biopsy; however, tissue diagnosis is necessary to demonstrate an invasive carcinoma in the underlying breast parenchyma or at least in the dermal lymphatics; note that either tumor emboli in dermal lymphatics or locally advanced breast cancers directly invading the dermis or ulcerating the skin, without the clinical skin changes described above, do NOT qualify as inflammatory carcinoma; dimpling of the skin, nipple retraction or any other skin changes except those described under T4b and T4d may occur in T1-3 without changing the classification

Notes:
● Measure invasive component only, not DCIS
● T classification traditionally assumes there was no prior treatment; can stage after preoperative (neoadjuvant, primary) chemotherapy, but should indicate that prior treatment was received (J Natl Cancer Inst 2005;97:1137)
● pT classification requires pathologic examination of a primary carcinoma with no gross tumor at resection margins (but can classify if only microscopic tumor is present at resection margin)
● If tumor size is slightly less than or greater than a cutoff for a given T classification, it is recommended that the size be rounded to the millimeter reading that is closest to the cutoff
● Can attempt to reconstruct original tumor size if multiple biopsies / excisions; due to difficulties in adding sizes from two resections, may want to report “at least pT_, a more accurate estimate may be based on imaging studies”
● If there are multiple simultaneous, macroscopically measurable, ipsilateral invasive tumors, use largest size, don’t sum sizes (but add a comment)
● If there are multiple invasive carcinomas, the size, grade, histologic type and results of ER, PgR and HER2 should pertain to largest invasive carcinoma; if smaller invasive carcinomas differ in any of these features, include this information in “Comments”
● Tumor in pectoralis muscle should be measured with the breast tumor to determine the tumor size and T category
● Simultaneous bilateral breast carcinomas are staged as separate primaries in separate organs
● Gross measurement is recommended (either fresh or fixed); however if significant in situ disease is present or invasive tumor extends microscopically beyond the grossly measured mass, then microscopic measurements may be more accurate; using microscopic measurements only is discouraged because processing artifact may cause significant tissue expansion or shrinkage (Hum Pathol 2005;36:756)
● If a prior biopsy showed a larger area of invasion than excisional specimen, use dimension of invasive carcinoma in the prior specimen for T classification
● If patient received prior treatment and no invasive carcinoma is present in current specimen, classified as Tis if residual DCIS and T0 if there is no remaining carcinoma (but add comment)
● Grade corresponds to largest area of invasion; if there are smaller foci of invasion of a different grade, include this information under “Additional Pathologic Findings”
● Margin status is “positive” if there is ink on carcinoma (ie, the distance is 0 mm); if the margin is not positive, then a distance from the margin may be listed; distances can be specific measurements or expressed as greater than or less than a measurement

Regional lymph nodes (pN)
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Note: IHC means immunohistochemistry, ITC means individual tumor cells

pNX: regional lymph nodes cannot be assessed (e.g., previously removed or not removed for pathologic study)
pN0: no regional lymph node metastasis identified histologically
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 (detected by H&E or IHC including ITC)
pN0 (mol-): no regional lymph node metastases histologically, negative molecular findings (RT-PCR)
pN0 (mol+): positive molecular findings (RT-PCR), but no regional lymph node metastases detected by histology or IHC
pN1: micrometastases; or metastasis in 1-3 axillary lymph nodes; OR in internal mammary nodes with metastases detected by sentinel lymph node biopsy, but not clinically detected apparent
pN1mi: micrometastasis (greater than 0.2 mm or more than 200 cells, but none greater than 2.0 mm)
pN1a: metastasis in 1-3 axillary lymph nodes, at least one metastasis greater than 2.0 mm
pN1b: metastasis in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected
pN1c: metastasis in 1-3 axillary lymph nodes and in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected
pN2: metastasis in 4-9 axillary lymph nodes; or in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastasis
pN2a: metastasis in 4-9 axillary lymph nodes (at least one tumor deposit larger than 2.0 mm)
pN2b: metastasis in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases
pN3: metastasis in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive level I or II axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected; or in ipsilateral supraclavicular lymph nodes
pN3a: metastasis in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm); or metastasis to the infraclavicular (level III axillary) lymph nodes
pN3b: metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in 4 or more axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected
pN3c: metastasis in ipsilateral supraclavicular lymph nodes

Notes:
● Requires resection and examination of at least the low axillary lymph nodes (level I)
● “i” stands for isolated tumor cells (ITC); “i+” means small clusters of tumor cells detected by H&E or IHC that are 0.2 mm or less (Am J Surg Pathol 2005;29:136) or fewer than 200 cells in a single histologic cross-section); isolated tumor cells are not counted as a positive node below
● In practice, the distinction between ITC and micrometastases is often difficult and without prognostic significance (Cancer 2008;112:1672)
● Classification based solely on sentinel lymph node biopsy, without subsequent axillary lymph node dissection, is designated (sn) for “sentinel node”, for example: pN0(sn)
● “Clinically detected” is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy, or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination
● Tumor in axillary fat without evidence of residual lymph node tissue is classified as a positive axillary lymph node
● Lymph node ratio (LNR, the ratio of positive over excised lymph nodes) is suggested as an alternative to pN staging (J Clin Oncol 2009;27:1062)

Diagrams
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Various possible difficulties

Additional references
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Cancer 2003;98:2740, CA Cancer J Clin 2006;56:37, Cancer 2005;103:1319 (problems with assessing ITCs)


Distant Metastasis (M)
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M0: no clinical or radiographic evidence of distant metastases; includes M0(i+)
cM0(i+): no clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases
M1: distant detectable metastases as determined by classic clinical and radiographic means or histologically proven larger than 0.2 mm


Stage grouping
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Stage 0:   Tis   N0   M0
Stage IA:    T1   N0   M0
Stage IB:    T0-1   N1mi  M0
Stage IIA:   T0-1   N1   M0 or   T2 N0 M0
Stage IIB:   T2   N1   M0 or   T3 N0 M0
Stage IIIA:  T0-2  N2   M0 or   T3 N1-2 M0
Stage IIIB:  T4   N0-2  M0
Stage IIIC:  Any T   N3   M0
Stage IV:    Any T   Any N   M1

Notes:
● Stage designation may be changed post-surgery if (a) imaging studies within 4 months of diagnosis reveal the presence of distant metastases, (b) there has been no disease progression and (c) no preoperative therapy was given
● T1 includes T1mi
● T0 and T1 tumors with nodal micrometastases only are excluded from Stage IIA and are classified as Stage IB
● The designation pM0 is not valid; any M0 should be clinical


Additional references
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Arch Pathol Lab Med 2006;130:287, National Cancer Institute (USA), Updated CAP staging

End of Breast malignant, males, children > Miscellaneous > Staging of breast carcinoma


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