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).
TILs should be evaluated within the borders of the invasive tumor.
Exclude TILs outside of the tumor border and around DCIS and normal
lobules.
Exclude TILs in tumor zones with crush artifacts, necrosis, regressive
hyalinization as well as in the previous core biopsy site.
All mononuclear cells (including lymphocytes and plasma cells) should be
scored, but polymorphonuclear leukocytes are excluded.
One section (4–5 µm, magnification ×200–400) per patient is currently
considered to be sufficient.
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.
A full assessment of average TILs in the tumor area by the pathologist
should be used. Do not focus on hotspots.
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.
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.
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.
