Table 1.

International TIL Working Group recommendations for assessing TILs in breast cancer

1)	TILs should be reported for the stromal compartment (=% stromal TILs). The denominator used to determine the % stromal TILs is the area of stromal tissue (i.e., area occupied by mononuclear inflammatory cells over total intratumoral stromal area), not the number of stromal cells (i.e., fraction of total stromal nuclei that represent mononuclear inflammatory cell nuclei).
2)	TILs should be evaluated within the borders of the invasive tumor.
3)	Exclude TILs outside of the tumor border and around DCIS and normal lobules.
4)	Exclude TILs in tumor zones with crush artifacts, necrosis, regressive hyalinization as well as in the previous core biopsy site.
5)	All mononuclear cells (including lymphocytes and plasma cells) should be scored, but polymorphonuclear leukocytes are excluded.
6)	One section (4–5 μm, magnification × 200–400) per patient is currently considered to be sufficient.
7)	Full sections are preferred over biopsies whenever possible. Cores can be used in the pretherapeutic neoadjuvant setting; currently no validated methodology has been developed to score TILs after neoadjuvant treatment.
8)	A full assessment of average TILs in the tumor area by the pathologist should be used. Do not focus on hotspots.
9)	The working group’s consensus is that TILs may provide more biological relevant information when scored as a continuous variable, since this will allow more accurate statistical analyses, which can later be categorized around different thresholds. However, in daily practice, most pathologists will rarely report for example 13.5% and will round up to the nearest 5%–10%, in this example thus 15%. Pathologist should report their scores in as much detail as the pathologist feels comfortable with.
10)	TILs should be assessed as a continuous parameter. The percentage of stromal TILs is a semiquantitative parameter for this assessment, for example, 80% stromal TILs means that 80% of the stromal area shows a dense mononuclear infiltrate. For assessment of percentage values, the dissociated growth pattern of lymphocytes needs to be taken into account. Lymphocytes typically do not form solid cellular aggregates; therefore, the designation ‘100% stromal TILs’ would still allow some empty tissue space between the individual lymphocytes.
11)	No formal recommendation for a clinically relevant TIL threshold(s) can be given at this stage. The consensus was that a valid methodology is currently more important than issues of thresholds for clinical use, which will be determined once a solid methodology is in place. Lymphocyte predominant breast cancer can be used as a descriptive term for tumors that contain ‘more lymphocytes than tumor cells’. However, the thresholds vary between 50% and 60% stromal lymphocytes.

Adopted from Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S. The evaluation of tumor infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014, Ann Oncol 2015; 26: 259-71, with permission of Oxford University Press [43].

TIL, tumor-infiltrating lymphocytes; DCIS, ductal carcinoma in-situ.