Table 2 Pitfalls in sTIL assessment in breast cancer slides identified from cases showing the highest variation in 3 ring studies (RS)—heterogeneity of lymphocyte distribution.

From: Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Pitfall

Frequency seen

Recommendation

Heterogeneity

15/26 (58%)

 

Increased sTILs at the leading edge compared to central tumor (Fig. 4a)

RS1: 3/7 (43%)

RS2: 1/6 (17%)

RS3: 7/13 (54%)

Increased density of lymphocytes at the leading front should be included as long as the lymphocytes are within the boundary of the tumor. Scoring multiple areas and averaging the results can help with heterogeneous tumors.

Marked hterogeneity in sTIL density within the tumor (Fig. 4b)

RS1: 2/7 (29%)

RS2: 0

RS3: 0

All stroma within the boundary of a single tumor is included in sTIL assessment. Scoring multiple distinct areas encompassing the range of sTIL density and averaging the results can assist in providing a more reproducible overall sTIL score.

Variably spaced apart clusters of cancer cells with a dense tight lymphocytic infiltrate separated by collagenous stroma with sparse infiltrate (Fig. 4c)

RS1: 2/7 (29%)

RS2: 3/6 (50%)

RS3: 0

All stroma within a single tumor is included within the sTIL assessment. In this situation, both the higher density areas closely associated with (but not touching) epithelial clusters and the lower density areas located between epithelial clusters are included. [The exception is a central hyalinized scar, which is excluded from scoring.] Scoring multiple areas and averaging the results can help with heterogeneous tumors.

  1. RS1 Ring Study 1, RS2 Ring Study 2, RS3 Ring Study 3.