Queries and consensus-building using the Delphi method
| No. | Query | Result of vote |
|---|---|---|
| Definition | ||
| 1 | Lymphatic vessel invasion is defined as invasion of tumour cells into lymphatic vessels | Agreement (100%) |
| 2 | Blood vessel invasion is defined as invasion of tumour cells into blood vessels | Agreement (100%) |
| Assessment of BLI | ||
| 1 | Scanning at 4× magnification should be used to identify suspected lesion. Then further assessment should be made at higher magnification | Agreement (87.5%) |
| 2 | BLI should not be determined in lesions presenting desmoplastic reaction | No agreement (50.0%) |
| 3 | BLI should not be determined in lesions with spicula in the space between tumour nest and stroma | Agreement (87.5%) |
| 4 | Lymphatic fluid, macrophage or blood cells in the space between tumour nests and stroma should be determined as BLI | No agreement (50.0%) |
| 5 | A tumour cluster with space around the cluster, but with vague periphery should not be determined as BLI | No agreement (25.0%) |
| 6 | Assessment of BLI should be performed in the invasive front of tumour | No agreement (50.0%) |
| 7 | Assessment of BLI should be performed with largest section containing the deepest invasive area of tumour | No agreement (50.0%) |
| Staining for assessment of BLI | ||
| 1 | Histochemical staining for assessment of blood vessel invasion should be performed with a whole section from the largest slice containing the deepest invasive area of the tumour | No agreement (50.0%) |
| 2 | Histochemical staining for assessment of blood vessel invasion should be performed with a section representative of the tumour | No agreement (25.0%) |
| 3 | Immunohistochemical staining for assessment of blood vessel invasion should be performed with a whole section from the largest slice containing the deepest invasive area of the tumour | No agreement (50.0%) |
| 4 | Histochemical staining for assessment of blood vessel invasion should be performed with a section representative of the tumour | No agreement (25.0%) |
| Assessment of blood vessel invasion | ||
| 1 | Elastica-stained internal elastic membrane without space around the tumour cluster should be determined as blood vessel invasion | Agreement (87.5%) |
| 2 | Elastica-stained internal elastic membrane without vascular endothelium around the tumour cluster should be determined as blood vessel invasion | Agreement (87.5%) |
| 3 | In elastica staining, thick arteries surrounded by the tumour cluster should be identified. If elastica-stained internal elastic membrane covering more than half of the circumference surrounding the tumour cluster is observed, the lesion should be diagnosed as blood vessel invasion | Agreement (87.5%) |
| 4 | Even without the presence of arteries, if elastica-stained internal elastic membrane covering more than half of the circumference surrounding the tumour cluster is observed, the lesion should be determined as blood vessel invasion | Agreement (87.5%) |
| 5 | Elastica-stained internal elastic membrane covering more than half of the circumference surrounding the tumour cluster without other vascular structure (ie, smooth muscle) is determined as blood vessel invasion | Agreement (87.5%) |
| 6 | Elastica-stained internal elastic membrane covering more than half of the circumference surrounding the tumour cluster without endothelial cells in H&E staining should not be determined as blood vessel invasion | No agreement (12.5%) |
| 7 | Tumour invasion into the elastica-stained vessel should be determined as blood vessel invasion | Agreement (100%) |
| 8 | Elastica-stained internal elastic membrane not covering the circumference surrounding the tumour cluster should not be determined as blood vessel invasion | No agreement (12.5%) |
| Assessment of lymphatic vessel invasion | ||
| 1 | An indistinguishable lesion should not be determined as lymphatic vessel invasion | Agreement (100%) |
| 2 | A tumour extending along Auerbach's neural plexus should not be determined as lymphatic vessel invasion | No agreement (75.0%) |
| 3 | A lumen with mucin should not be determined as a lymphatic vessel in case of mucinous carcinoma | No agreement (37.5%) |
| 4 | Lymphatic vessel invasion should not be determined in a lesion with small cancer cell cluster and desmoplastic reaction | No agreement (50.0%) |
| 5 | Small vessels indistinguishable between lymphatic and blood vessels should be determined as lymphatic vessel, if a thick vascular wall cannot be identified | No agreement (50.0%) |
| 6 | D2-40 positive vessel should be interpreted as lymphatic vessel regardless of the presence of endothelium | No agreement (37.5%) |
| 7 | D2-40 positive vessel without endothelium should not be interpreted as lymphatic vessel | No agreement (12.5%) |
| 8 | D2-40 negative vessel suspected as a lymphatic vessel in H&E staining should be interpreted as lymphatic vessel | No agreement (37.5%) |
| 9 | D2-40 positive cells covering all of the circumference surrounding the tumour cluster is the requirement for lymphatic vessel invasion | No agreement (0%) |
| 10 | D2-40 positive cells covering more than half of the circumference surrounding the tumour cluster is the requirement for lymphatic vessel invasion | No agreement (62.5%) |
| 11 | D2-40 positive endothelial cells covering all of the circumference surrounding the tumour cluster is the requirement for lymphatic vessel invasion | No agreement (0%) |
| 12 | D2-40 positive endothelial cells covering more than half of the circumference surrounding the tumour cluster is the requirement for lymphatic vessel invasion | Agreement (87.5%) |
| 13 | Tumour invasion into the D2-40- stained vessel is determined as lymphatic vessel invasion | Agreement (100%) |
BLI, blood and lymphatic vessel invasion.