Table 4 Pitfalls in sTIL assessment in breast cancer slides identified from cases showing the highest variation in 3 ring studies (RS)—scoring wrong area or cells.
From: Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Pitfall | Frequency seen | Recommendation |
|---|---|---|
Scoring wrong area or cells | 12/26 (46%) | |
Defining tumor boundary and scoring outside of tumor (Fig. 6a) | RS1: 0 RS2: 2/6 (33%) RS3: 2/13 (15%) | Do not include fibrous scars (image; yellow arrow) or lymphoid aggregates (blue arrow) beyond the invasive front of the tumor. |
Including lymphocytes surrounding DCIS (Fig. 6b) | RS1: 2/7 (29%) RS2: 1/6 (17%) RS3: 0 | Lymphocytes surrounding DCIS are excluded from assessment of sTILs. Myoepithelial stains can be used if there is doubt as to whether a particular focus is invasive or in situ. |
Including lymphocytes associated with encapsulated papillary carcinoma (Fig. 6c) | RS1: 1/7 (14%) RS2: 0 RS3: 0 | Only score sTILs associated with conventional invasive carcinoma. Similar to DCIS, lymphocytes associated with encapsulated papillary carcinoma should not be included in the sTIL assessment of the invasive component. |
Including lymphocytes surrounding benign glands (Fig. 6d) | RS1: 1/7 (14%) RS2: 0 RS3: 0 | Lymphocytes associated with benign lobules or ducts should be excluded from sTIL counts when carcinoma surrounds benign structures. Similar lymphocytic infiltrates outside of the tumor boundary can identify these as not tumor-related. |
Including intratumoral TILs (iTILS) (Fig. 7a) | RS1: 2/7 (29%) RS2: 1/6 (17%) RS3: 0 | Certain cases show dense lymphocytic infiltrates within the tumor epithelial nests, sometimes obscuring the boundary between tumor cells and stroma. It is important to be aware that intratumoral TILs are excluded from the assessment, which only includes TILs within the intervening stroma. If necessary, a cytokeratin stain may assist with defining tumor from stroma. |
Including neutrophils (Fig. 7b) | RS1: 1/7 (14%) RS2: 0 RS3: 0 | Only lymphocytes and plasma cells are included in sTIL evaluation. Pathologists should assess slides at a sufficiently high power to be able to differentiate between types of immune cells. Neutrophils, eosinophils, basophils, and histiocytes/ macrophages are all excluded from sTIL assessment. |
Including histiocytes (Fig. 7c) | RS1: 1/7 (14%) RS2: 0 RS3: 0 | Only lymphocytes and plasma cells are included in sTIL evaluation. Pathologists should assess slides at a sufficiently high power to be able to differentiate between types of immune cells. Neutrophils, eosinophils, basophils, and histiocytes/ macrophages are all excluded from sTIL counts. |
Misinterpreting apoptotic cells as lymphocytes (Fig. 7d) | RS1: 1/7 (14%) RS2: 0 RS3: 0 | At low power apoptotic cells can mimic lymphocytes. Pathologists should assess slides at a sufficiently high power to differentiate this mimic. |
Artifactual falling apart of cells mimicking TILs Fig. 7e) | RS1: 1/7 (14%) RS2: 0 RS3: 0 | Artifactual falling apart of tumor cells is more common in biopsy specimens, particularly along the edge. At low power discohesive tumor cells can mimic lymphocytes. Pathologists should assess slides at a sufficiently high power to differentiate this mimic. |
