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IKCS 2019: Histopathologic Changes Associated With Immunotherapy for Kidney Cancer

By: Lauren Harrison, MS
Posted: Thursday, November 21, 2019

Immune checkpoint inhibitors such as nivolumab and ipilimumab induce vascular changes, including fibrin deposition in vessel walls, capillary endothelial hyperplasia, and nuclear shrinkage, on histologic examination of renal cell carcinomas. This work was presented at the 2019 International Kidney Cancer Symposium in Miami by Sasan Setoodeh, MD, of The University of Texas Southwestern Medical Center, Dallas.

“Due to the shrinkage in nuclear size, the tumors will likely be undergraded post–immune checkpoint inhibitor therapies. Use of tumor histologic characteristics may help better patient selection for higher response rates,” concluded the study authors.

Samples from 12 patients who had undergone post–immune checkpoint inhibitor nephrectomy at The University of Texas Southwestern Medical Center Kidney Cancer Program were the focus of the study; they were compared with 10 random nephrectomy samples from patients who had not had neoadjuvant therapy. Both tumors and non-neoplastic kidney sections were evaluated for histopathologic changes. Of the 12 patients who had received immune checkpoint therapy, 3 received at least 12 cycles of immune checkpoint blockade as well as other prior therapies, whereas 9 patients had received 1 to 2 cycles of immune checkpoint inhibition before nephrectomy.

On histologic examination, the most obvious findings included (1) reduction/shrinkage of the tumor cell cytoplasmic and nuclear grade; (2) prominent fibrin deposition in vessel walls with capillary endothelial hyperplasia, endotheliitis, and fibrosis; and (3) prominent fibrous scarring and collagenization. None of these features were seen in any of the samples from patients who had not been treated with immune checkpoint inhibitors. Of note, two patients who had either papillary renal cell carcinoma or TFEB-rearranged renal cell carcinoma did not show these same morphologic changes. In the non-neoplastic sections of the kidneys, there was marked interstitial chronic inflammation, interstitial fibrosis, and tubular atrophy.

Disclosure: For full study authors, visit

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