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Define  area  for  TILs  evalua&on  

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Evalua&on  of  Tumor  Infiltra&ng   Lymphocytes  

(TILs)  

in  Endometrial  Carcinoma    

Guidelines  for  TILs  assessment  from  the  “Interna5onal   Immuno-­‐Oncology  Biomarker  Working  Group”    

Author:  Koen  van  de  Vijver1   1-­‐Netherlands  Cancer  Ins5tute  

(2)

Define  area  for  TILs  evalua&on  

Exclude  this  area   Evaluate  TILs  in  this  area  

Exclude  this  area  

Evaluate  TILs  in  this  area  

Evaluate  TILs  within  the  borders  of  the  tumor,   both  in  the  central  tumor  and  at  the  invasive   margin.    

(3)

Define  area  for  TILs  evalua&on  

Exclude  this  area   Evaluate  TILs  in  this  area  

(4)

Define  area  for  TILs  evalua&on  

PaPerns  of  myo-­‐invasion:    evaluate  TILs  in  the  connec5ve  5ssue  just  beneath  the   epithelial  layer  within  1mm  (invasive  margin)  

   

Broad  front  paPern   Adenomyo5c  paPern   Widely  separated  single-­‐glands  

Include  these  areas  

Exclude  this  area   Include  this  area  

Exclude  this  area   Exclude  this  area  

(5)

Define  area  for  TILs  evalua&on  

Immune  infiltrates  outside   of  the  tumor  borders  are   not  included.  

Exclude  this  area   Evaluate  TILs  in  this  area  

Do  not  include  perivascular  immune  infiltrates,   oUen  present  around  lymphovascular  space   invasion  (LVSI).  

Exclude  this  area  

(6)

Define  area  for  TILs  evalua&on  

Be  aware  of  tumor  present  in   adenomyosis:  small  endometrial   stromal  cells  may  mimic  immune   cells  

(7)

Define  area  for  TILs  evalua&on  

Do  not  use  areas  with  poor  fixa5on  

(8)

Determine  the  localiza&on  of  the  TILs  

Stromal  TILs   Intratumoral  TILs  

(9)

Determine  the  localiza&on  of  the  TILs  

Stromal  TILs  

(include  fibrovascular  cores  of  papillary  structures)   Intratumoral  TILs  

Exclude  areas   of  hemorrhage  

(10)

Determine  the  localiza&on  of  the  TILs  

Stromal  TILs  

Intratumoral  TILs   (spindled  growth   of  the  tumor)  

Be  aware  of  endometrial  carcinomas  with  a  spindled,  sarcomatoid  or  solid  growth    

(11)

Determine  type  of  inflammatory  infiltrate  

Include  only  mononuclear  infiltrate  

(lymphocytes  &  plasma  cells)   Exclude  areas  of  necrosis   for  evalua5on  of  TILs  

(12)

Determine  type  of  inflammatory  infiltrate  

Score  only  mononuclear  infiltrate:  a  MELF  paPern  of  invasion  is  oUen  accompanied  by  a                          neutrophilic  infiltrate:  exclude  this  area    

(MELF  =  microcys5c,  elongated  and  fragmented)  

Evaluate  TILs  in  this  area  

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