Training Program SLN Micrometastasis vs ITC Roderick R. Turner, MD Adjunct Member, JWCI

Introduction ITC and micrometastasis are distinguished on the basis of the greatest dimension of the largest cluster of tumor cells. Each cluster or single cell is measured separately. The number of clusters or single cells does not change categorization; but, in clinical practice, an explanatory comment may be added to a report. Infrequently, small volume axillary disease may be seen only in perinodal soft tissue or afferent lymphatics; this is regarded as nodal metastasis and classified, as above, by cluster size.

Definitions - Cluster A cluster is a confluent focus of tumor cells touching other tumor cells. This is determined from the two-dimensional image of the microscopic section. Clusters or cells separated by a single benign cell or a spatial gap are measured as separate clusters, except when fibroblastic reaction to the tumor cells has caused the separation.

Definitions - Measurements Measurements are determined by the greatest dimension of the largest tumor cell cluster. Single cells are measured separately. A known field diameter (or ocular micrometer) should be utilized for consistent and reliable categorization. Measurements are made solely from the two- dimensional plane(s) of section(s) examined, H-E or IHC. In clinical practice, deeper sections and IHC are available options for further evaluation. Do not use the distance that separate clusters span, sum measurements of multiple clusters, or count/estimate tumor cell numbers.

Definitions – Isolated Tumor Cells Small cluster(s), largest cluster not greater than 0.20mm. Single cells, as in the dispersed lobular pattern, represent ITC; densely crowded cells when contiguous/touching are measured and classified by the largest group of contiguous/touching cells. A single cell may qualify as ITC, but only when cytologic and microanatomic features are supportive of a carcinoma cell. This may include a strongly positive immunoreaction. Cellular debris and contaminants are excluded. Mitotic activity (proliferation) is not considered. Microanatomic location is not a factor in classification; ITC may be found in nodal parenchyma, capsular or subcapsular spaces, or extranodal/afferent lymphatic vessels.

Definitions - Micrometastasis Largest cluster or confluent focus is greater than 0.20mm, but no greater than 2.0mm. Usually seen in nodal parenchyma; but,when found in perinodal tissue, it is classified as for nodal disease based on size of deposit. For borderline or indeterminate findings, at the two ends of this spectrum, select the lower N classification.

0.2 mm TC #1 (1 of 2) Mostly ITC clusters, micrometastasis on right. See next.

0.2 mm TC#1 (2 of 2) Small contiguous micrometastasis, 0.25mm

2.0 mm TC#2 (1 of 2) Clusters are separated by fibroblastic reaction; this is a small macrometastasis, 3.0mm. See next for better detail.

0.2 mm TC#2 (2 of 2) The clusters are separated by fibroblastic reaction; largest dimension seen on previous slide (macrometastasis) is appropriate

TC#3 Small micrometastasis, 0.35mm, and other ITC clusters

0.2 mm2.0 mm TC#4 (1 of 2) Lobular carcinoma, mostly single ITC. Upper right shows dense crowding. See next.

0.2 mm TC#4 (2 of 2) Contiguous grouping of touching tumor cells measures 0.22mm and qualifies as micrometastasis

0.2 mm TC#5 Small micrometastasis, 0.22mm, and ITC clusters

0.2 mm TC#6 (1 of 2). Few clusters of ITC in nodal parenchyma. See next.

0.2 mm TC#6 (2 of 2). Multiple ITC clusters in nodal parenchyma, largest 0.20mm.

0.2 mm TC#7. Multiple tiny clusters and a poorly cohesive, but contiguous, one at upper left. Small micrometastasis, 0.23mm.

, TC#8 (1 of 2) Tumor cell clusters in perinodal soft tissue/capsule with fibroblastic reaction. Micrometastasis 1.5mm. See next.

TC#8 (2 of 2). Closer view of fibrotic reaction between clusters.

0.2 mm TC#9 (1 of 2) Tubular pattern. Multiple clusters of ITC.

0.1 mm TC#9 (2 of 2). Largest ITC cluster 0.16mm

0.1 mm TC#10. Single cell, strongly CK-IHC (+), 3x diameter of lymphocytes. Minimally qualifies as ITC

TC#11. ITC, 3 cells, in parenchyma.

TC#12. Many ITC clusters and single cells.

0.1 mm TC#13. Several clusters of ITC, largest approx 0.09mm.

TC#14. Multiple clusters of ITC in subcapsular sinus.

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