Contemporary Evaluation of Breast Lymph Nodes in Anatomic Pathology

Beth T. Harrison, MD; Jane E. Brock, MBBS, PhD


Am J Clin Pathol. 2018;150(1):4-17. 

In This Article

The Sentinel Node Procedure

Although the method and accuracy of SLN biopsy are not a usual concern of pathologists, it is worth a brief mention. In 2005, the American Society of Clinical Oncology (ASCO) set a target false-negative rate of less than 5%.[3] However, the evidence from at least six RCTs suggests that the false-negative rate is currently higher in practice, ranging from 5.5% to 16.7% (9.2% weighted average).[9] Although breast surgeons have employed various definitions of false-negative SLNs, the most generally accepted definition is one that is disease free on initial pathologic assessment but is followed by identification of metastasis in another axillary lymph node at any time thereafter. Accuracy depends on a variety of factors, including the type of tracer and its injection site, the number of lymph nodes, the experience of the surgeon, and patient and tumor characteristics, among others.[10]

There are two different types of tracers: blue dye (isosulfan blue and methylene blue) and radioactive isotope-labeled colloid (technetium [99mTc] sulfur colloid in the United States and Canada and 99mTc-albumin nanocolloid in Europe). Dye particles are smaller than colloid particles and travel more rapidly to the SLN. Due to the difference in speed of travel, blue dye tracer is administered intraoperatively, while radioisotope-labeled colloid tracer is usually administered either the morning of or the day before surgery. A limitation to blue dye is that it may spread beyond the first-order lymph nodes, marking non-SLNs, including those higher within the axilla. Thus, even when two different tracers are injected at the same location, SLN labeling may be discordant due to particle size, accounting in part for "blue/not-hot" and "hot/not blue" lymph nodes.[11]

Most surgeons (90%) in the United States use both types of tracers according to a recent survey.[12] Injections are either superficial (intradermal/subdermal) or deep (peritumoral). All hot and blue nodes, as well as unlabeled but palpably suspicious nodes, are removed. This approach is supported by evidence from the ALMANAC trial, which reported a false-negative rate of 6.7% for blue dye and radioactive tracers vs 9.1% for dye alone and 10.9% for radioactive tracer alone.[4]

The anatomy of the lymphatic drainage of the breast comprises the superficial, deep, and perforating systems. The superficial system drains from the superficial breast and skin to the axilla, usually to a lymph node posterior to the pectoralis minor muscle. The deep system drains from the breast to the axilla and also anastomoses with the perforating system. The perforating system traverses the pectoralis muscles and drains into the internal mammary lymph nodes (IMNs). The superficial system does not connect with the perforating system Figure 1.[13]

Figure 1.

Lymphatic drainage of the breast. Superficial drainage passes from skin and breast to the axillary lymph nodes (blue). Deep drainage connects not only to the axilla but also to the internal mammary lymph nodes (IMNs) (green) via perforators. Approximately 30% of medially located tumors drain to the IMNs.

As a result of this lymphatic drainage pattern, superficial injections (subdermal/periareolar) do not localize to the IMNs. Only deep peritumoral injection will reveal extraaxillary drainage, such as drainage to the IMNs (20% of patients), intramammary nodes (6%), and interpectoral (Rotter's node; 2%) and infraclavicular (level III axillary nodes; 3%) nodes. Medially located tumors are more likely to drain to IMNs than laterally located tumors (28% vs 15%), and these have a worse prognosis. Despite this, identification of IMN drainage at diagnosis is not clinically indicated as IMN involvement is rarely symptomatic and does not change therapy decisions, and removal does not confer a survival benefit.[14,15]

It has been suggested that the false-negative SLN rate may have more to do with the clinicopathologic features of the breast carcinoma than the surgeon's skill or technique or the underlying anatomy. For example, Wei et al[10] demonstrated that false-negative SLNs are associated with partial or complete replacement of non-SLNs, lobular or poorly differentiated ductal subtypes, and estrogen receptor (ER) positivity.