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

Special Circumstances: Evaluation of the Axilla After Neoadjuvant Therapy

Neoadjuvant chemotherapy is increasingly employed in the management of breast cancer. Several studies have shown that posttreatment nodal status is an important determinant of DFS and OS regardless of response within the breast.[47–49] SLNB or ALND may be performed for lymph node staging in patients who have received neoadjuvant chemotherapy. The accuracy of SLNB is still under investigation, especially in patients with clinically positive nodes prior to treatment, as high false-negative rates (ranging from 10%-30%) have been previously reported in this population.[50–53]

The recent ACOSOG Z1071 trial[54] investigated the false-negative rate of SLNB following neoadjuvant chemotherapy. In this trial, women who received neoadjuvant chemotherapy for clinical T0-4 N1-2 M0 breast cancer were enrolled and subjected to both SLNB and ALND. In patients with cN1 disease and at least two SLNs identified (n = 525), the pathologic complete response rate was 41.0% and the false-negative rate was 12.6%. The false-negative rate was significantly affected by the type of mapping technique employed (10.8% for dual agent vs 20.3% for single agent) and the number of lymph nodes evaluated (7% for three or more SLNs vs 10% for two SLNs and 18% for one SLN). Since the overall false-negative rate in this subgroup exceeded the prespecified acceptability threshold of 10%, the authors originally concluded that SLNB should not be used as an alternative to ALND until changes in the approach and patient selection resulted in greater sensitivity.[54]

A subsequent analysis of the Z1071 trial data showed that identification and resection of clipped lymph nodes decrease the false-negative rate of SLNB to 6.8%.[55] Other studies have demonstrated that ultrasound-guided wire or radioactive seed localization significantly improves the success rate of surgical removal of clipped lymph nodes and the accuracy of SLNB after neoadjuvant therapy.[56,57] Therefore, a recommended protocol for management of the axilla in the neoadjuvant setting includes core needle biopsy of suspicious lymph nodes with clip placement followed by a localization procedure with confirmation of clip removal.

Pathologic evaluation of SLNs and axillary lymph nodes is similar to that employed for nonneoadjuvant specimens with some notable exceptions. The size of the largest metastatic deposit and the presence of extranodal extension should be reported. Posttreatment metastatic deposits are often characterized by single cells and small clusters of cells within an area of fibrosis, histiocytes, and other chronic inflammation consistent with treatment effect. In this context, the size of the entire area even partly involved by tumor should be measured rather than simply the size of the largest tumor cluster Image 3. As micrometastases and isolated tumor cells found after neoadjuvant therapy are predictors of worse survival, specimens with these findings should not be designated as having a pathologic complete response.[58]

Image 3.

Following neoadjuvant chemotherapy, if the metastatic tumor cells involve the lymph node as separate clusters within an area of fibrosis consistent with treatment effect/tumor bed, the entire area of involvement is measured to define the size of the metastasis (arrows) (H&E, x10).

Appropriate management of low-volume disease in posttreatment SLNs is still a matter of debate as evidence from recent trials in support of omission of completion ALND does not apply to the neoadjuvant setting.