Detection of Occult Metastases in Sentinel Lymph Nodes: Comparison of a Limited Widely Spaced and a Comprehensive Narrowly Spaced Paraffin Block Sectioning Strategy
UP Le, K Weaver, SL Dupuis, T Ashikaga, DN Krag, S Harlow, DL Weaver. University of Vermont and Fletcher Allen Health Care, Burlington, VT
Background: The NSABP B-32 protocol is examining whether patients with initially negative sentinel lymph nodes (SLNs) who have occult metastases detected on deeper levels and cytokeratin (CK) immunohistochemical stains are at risk for regional or distant metastases. For all initially negative SLNs, the experimental B-32 sectioning protocol examines H+E and CK stains approximately 0.5 and 1.0 mm deeper into the paraffin blocks (2 levels; wide spacing) and was designed to detect virtually all metastases larger than 1.0 mm; smaller metastases may be missed. This pilot quality assurance study compares detection using the experimental B-32 protocol to a more comprehensive sectioning protocol designed to detect virtually all metastases larger than 0.2 mm (multilevel; narrow spacing).
Design: All SLNs were sectioned grossly at close to 2.0 mm and all sections embedded in paraffin blocks. For clinical treatment, a single H+E section was examined from each block. For 50 cases with 1-4 SLNs and all SLNs negative, additional sections were evaluated every 0.18 mm through the block until no tissue remained. All sections were stained with CK and sections at 0.5mm and 0.9mm were also stained with H+E.
Results: 7 of 42 (16.7%) cases harbored occult metastases; 5 cases (11.9%) were detected with the B-32 protocol and 2 additional cases (4.8%) were detected on sections that would not have been evaluated (p=0.25; correlated proportions). The largest metastasis in each case was 0.03, 0.04, 0.15, 0.5, and 0.6 mm for the B-32 strategy and 0.15 and 0.3 mm for the two cases detected only by the more comprehensive strategy. Median number of levels examined per block on the comprehensive protocol was 11 (range 1-20); the B-32 protocol was fixed at 2 levels (median 2; range 1-2). Median thickness of node sections in the block was 2.1 mm (range 0.3-3.7 mm).
Conclusions: The B-32 protocol with two widely spaced levels detected 5 of the 7 cases with occult metastases identified. To detect the two additional cases, 11 narrowly spaced levels completely through the paraffin block were required. Although more comprehensive sectioning of SLNs detects additional micrometastases, the data suggest diminishing returns and reduced cost effectiveness for the comprehensive strategy. The limited number of occult metastasis positive cases limits statistical power; however, large scale studies comparing these two strategies are prohibitively expensive.
Tuesday, March 10, 2009 8:45 AM
Platform Session: Section B, Tuesday Morning