Distribution Patterns of Micrometastases and Isolated Tumor Cell Clusters (ITC) in Sentinel Lymph Nodes from the NSABP B-32 Trial
Sharif R Nankoe, Joan M Skelly, Takamaru Ashikaga, Seth P Harlow, David N Krag, Donald L Weaver. University of Vermont College of Medicine, Burlington, VT
Background: ITCs and micrometastases in sentinel nodes were independent prognostic variables in the analysis of NSABP B-32 data; however, differences in overall survival were minimal: 0.6% and 2.4%, respectively (NEJM 2011;364:412-421). Other factors associated with metastases may have predictive value.
Design: 174 of 616 (28%) occult metastasis positive cases from B-32 were reviewed to discover and quantify potential prognostic variables including: ITC pattern (P1, single afferent; P2, two afferents; P3, >2 afferents or subcapsular clusters >5 linear mm or >33% circumference); micrometastasis pattern (P5, one subcapsular; P6, one parenchymal; P7, two supcapsular; P8, one subcapsular and one parenchymal; P9, two parenchymal; P10, >2 foci); area of involvement of close clusters (A0, n/a; A1, up to 1mm; A2, >1 up to 2mm; A3, >2 up to 3mm); maximum depth from capsule (mm); and ITC total cell count. For pattern (P) assessment, at least 2.2 mm of uninvolved nodal parenchyma was required between cluster groups to be considered separate afferents. Micrometastasis patterns with single cells surrounding a larger cluster (eg P5s) were noted.
Results: 106 of 143 (74%) ITCs were single afferent (P1) pattern and 24 of 31 (77%) micrometastases were single subcapsular (P5) pattern. For tightly clustered groups, area of involvement was up to 1mm (n=10), >1 up to 2mm (n=2), >2 up to 3mm (n=2) or not relevant (n=160). Depth from capsule was <0.1mm (n=40; 23%), 0.1-0.5mm (n=93; 53%), 0.6-1.0mm (n=19; 11%), 1.1-2.0mm (n=17; 10%), and >2.0mm (n=5; 3%). Maximum total cell counts for ITCs in a single node cross section were <100 cells (n=121), 100-200 cells (n=17), >200 cells (n=5).
Conclusions: ITCs are most likely to be associated with a single afferent lymphatic while micrometastases are most likely to be a single subcapsular focus; other patterns identified may indicate higher prognostic risk. Depth from capsule was widely distributed and may represent a prognostic variable worth further investigation. Tightly grouped ITC clusters with an area of involvement in the micrometastasis range are infrequent (8%) and unlikely to assist in N-classification. Similarly, ITC cases with >200 cells in a single node cross section were infrequent.
|Pattern||Number of Cases||Percent||Percent of ITCs||Percent of Micromets|