Breast – Malignant, Males, Children

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Breast-malignant, males, children

Sentinel lymph nodes

Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.

Reviewer: Daniel Visscher, M.D., University of Michigan Hospitals, February 2009 (see Reviewers page)

Revised: 10 September 2009

Last major update: September 2009

Definition

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● Sentinel node is first node to which lymphatic drainage and metastasis from breast cancer occurs; usually an axillary node in central group of level I, but may be at level II (behind the pectoralis minor muscle), level III (infraclavicular) or be intramammary, interpectoral (Rotter's) or internal mammary node (Eur J Surg Oncol 2009;35:252); tumor is more likely at inflow junction of afferent lymphatic vessel (AJSP 2003;27:385)

Clinical

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● Sentinel node may have characteristics that prevent further tumor spread up the lymphatic chain (Int Semin Surg Oncol 2006;3:39)

● Procedure: surgeon injects blue dye or radioactive colloid around tumor, which travels to and identifies the first draining sentinel lymph node; extensive pathologic examination is performed of sentinel node (see below) to look for micrometastases

● If sentinel node(s) is negative, other nodes are negative in >95% of cases; axillary recurrence rate is only 0.3% at median 34 months (Eur J Surg Oncol 2008;34:1277)

● Considered a suitable replacement for axillary dissection for staging/diagnosis in T1 and T2 tumors, with reduced patient morbidity because fewer lymph nodes are removed (Ann Surg OncolM 2008;15:1996); may have a role in microinvasive disease (Breast J 2008;14:335)

● Intraoperative frozen section (World J Surg Oncol 2008;6:69), intraoperative imprint cytology (Eur J Surg Oncol 2009;35:16) or molecular assays may be useful (J Clin Oncol 2008;26:3338)

● Frozen section had 60% sensitivity and 100% specificity in one study, with “atypical” cases usually negative on permanent sections (Mod Path 2005;18:58); concentrated smear technique is more sensitive than direct smears (AJCP 2004;122:944)

● High risk (60%) of tumor in nonsentinel nodes if sentinel node has macroscopic tumor (2 mm or more) versus low risk (3%) if microscopic tumor (0.2 to 2 mm, Mod Path 2005;18:762)

● Micrometastases may not affect survival (Ann Oncol 2009;20:41, J Clin Oncol. 2009 Aug 31 [Epub ahead of print], but see J Am Coll Surg. 2009;208:333); in addition, cohesive cluster of malignant cells, 0.2 mm to 2.0 mm, may indicate significant axillary disease; smaller clusters are highly unlikely to be associated with significant residual metastasis or poor prognosis

● May be useful even after neoadjuvant [preoperative] chemotherapy (Acad Radiol 2009;16:551)

● In transit metastasis - metastases in lymph nodes other than sentinel node, that are associated with afferent lymph vessels to the sentinel node but not are typically removed during sentinel node procedure (J Clin Pathol 2008;61:1314)

● Memorial Sloan-Kettering Cancer Center nomogram is useful to surgeons to predict likelihood of non-sentinel lymph node axillary metastases (Ann Surg Oncol 2003;10:1140, J Am Coll Surg 2009;208:229)

● Recommendations for handling radioactive specimens at: AJSP 2000;24:1549

Isolated tumor cells

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● Single cells in lymph nodes interpreted as malignant; clinical significance has not yet been demonstrated

● Primary tumors associated with sentinel nodes with isolated tumor cells have more lymphovascular invasion and higher proliferative rate than primaries without nodal involvement, but less lymphovascular invasion, lower proliferative rate and smaller tumor size than primary tumors with micro- or macrometastases (Surgery 2008;144:518)

● May represent benign epithelium or degenerated malignant cells (Am J Surg Pathol 2009;33:106, Hum Pathol 2009;40:778)

Consensus recommendations

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References: Hum Path 2002;33:579:

● Submit entire node unless gross tumor

● Slice large nodes into 3-4 mm thick sections and submit all

Other possible protocols if examination of initial H & E stained section does not reveal metastases:

(1) Obtain 2 additional hematoxylin and eosin-stained sections and one pancytokeratin (AE1-AE3) stained section (AJSP 2002;26:377)

(2) Obtain 3 additional H & E stained sections (no immunohistochemistry since occult metastases have minimal predictive value, Mod Path 2002;15:641), or

(3) Cut into 2 mm slices, obtain 5 levels for each slice - 2 H&E, 3 AE1-AE3 (Arch Pathol Lab Med 2003;127:701, Arch Pathol Lab Med 2009;133:1437)

(4) Complete sectioning through block detects additional micrometastases, but raises cost effectiveness concerns (Am J Surg Pathol 2009 Aug 28 [Epub ahead of print])

Note: AE1-AE3 is better than CAM 5.2 since less staining of reticulum cells (Arch Pathol Lab Med 2000;124:1310)

False positives with cytokeratin

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● Wrong antibody (Arch Pathol Lab Med 2001;125:1497), nevus cells (Eur J Dermatol 2008;18:586), reticulum cells that are AE3+ (Arch Pathol Lab Med 2002;126:248, image; less of a problem with AE1-AE3), mesothelial cell inclusions, benign glandular inclusions (Am J Clin Pathol 2008;130:21), ectopic breast tissue (AJSP 2003;27:513), sclerosing adenosis (Arch Pathol Lab Med 2008;132:1439), benign epithelial cells associated with pre-sentinel biopsy breast massage (AJSP 2004;28:1641) or megakaryocytes (Arch Pathol Lab Med 2002;126:618, image)

Case reports

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● 45 year old woman with distinct populations of infiltrating ductal carcinoma and lobular carcinoma in both breast and sentinel lymph node (Arch Pathol Lab Med 2004;128:365)

● Level III sentinel node (World J Surg Oncol 2006;4:31)

Clinical images

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Blue stained axillary node

Micro images

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Micrometastases: H&E and keratin Clusters and single cells highlighted

with pan-keratin antibody

Fig 1: micrometastases-H&E Isolated tumor cells are AE1/AE3+

Fig 2: micrometastasis-AE1/AE3+

Fig 1: negative H&E Isolated tumor cells and micrometastasis

Fig 2: AE1/AE3 demonstrates micrometastasis

False positive cases Erroneous use of lamda light chain, which

stains plasma cells, instead of AE1/AE3

Sclerosing adenosis,

no tumor

Additional references

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● AJSP 2002;26:383 (other recommendations), AJSP 2003;27:842 (which micrometastases are significant), Wikipedia, eMedicineHealth

End of Breast – Malignant, Males, Children > Sentinel lymph nodes

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