Sentinel Lymph Nodes in Classic Invasive Lobular Carcinoma of the Breast: Cytokeratin Immunostain Ensures Detection, and Precise Determination of Extent, of Involvement.

The assessment of sentinel lymph nodes (SLN) on hematoxylin and eosin (H&E)-stained sections in cases of classic type of invasive lobular carcinoma (cILC) is considered unreliable, particularly in cases with minimal involvement, that is by either isolated tumor cells (pN0i+) or micrometastases (pN1mi). Although the impact of minimal SLN involvement has been shown to be insignificant in most clinical trials (even though cILC was either under-represented or not separated in the respective cohorts), the results of MIRROR trial did emphasize the need for additional therapy in cases with minimally involved SLN to ensure improved disease-free survival. We sought to study the role of cytokeratin immunohistochemistry (CK-IHC) in evaluating SLN in cILC. A total of 582 cILC cases with SLN diagnosed over a 12-year period (2005 to 2016) were reviewed. In all, 394/582 (68%) cases had H&E(-)/CK(-) SLN. In total, 188/582 (32%) cases showed some degree of SLN involvement of which 143/582 (25%) cases had readily identifiable SLN involvement on H&E slides. Overall, 45/582 (7.7%) cases had H&E(-)/CK(+) SLN. The following data relate to the latter subset of 45 cases. Mean age of patients: 61 y (range: 32 to 86 y); right: 24 (53%), left: 21 (47%); multifocal and/or multicentric: 22 (49%); mean size: 2.0 cm (range: 0.25 to 4.4 cm); mean number of SLN: 2.5; mean number of involved SLN: 1.2; and cases with prior needle core or excisional biopsy: 45 (100%). CK(+) cells were identified in isolation or in loose clusters, either in subcapsular sinuses or nodal cortex or both. Overall, 30/45 (67%) showed ≤200 CK(+) cells (ie, pN0i+), and 15/45 (33%) showed >200 CK(+) cells (ie, pN1mi). In total, 15/45 (33%) cases underwent axillary lymph node dissection, of which 4/45 (9%) cases were positive. cILC recurred in 3/45 (7%) cases. On statistical analyses, the number of CK(+) cells (≤/>200) did not correlate with either axillary lymph node-positivity or with recurrence. Number of CK(+) cells (≤/>200) readily distinguished pN0i+ from pN1mi based on AJCC's numerical criteria. CK(+) cells could be quantified in linear terms (ie, AJCC's size criteria of pN0i+ and pN1mi was applicable) in only 2 cases. On the basis of these findings, the use of CK-IHC staining should be considered for SLN in cases of cILC to ensure detection, and precise determination of extent, of involvement; however, the prognostic significance of this procedure would have to await results of additional studies with long-term follow-up.