Complete Pathologic Responses With Immunotherapy in Metastatic Renal Cell Carcinoma: Case Reports

Abstract

Immunotherapy-based combinations have become standard of care in advanced renal cell carcinoma (RCC). Despite the potential for complete radiographic response, complete pathologic responses have been rarely reported. We present two cases of confirmed complete pathologic response to immunotherapy despite residual radiographic abnormalities. The first case describes a 68-year-old female with metastatic RCC who was treated with upfront pembrolizumab plus axitinib. She underwent nephrectomy after 15 doses of pembrolizumab with pathology revealing no evidence of viable tumor. To our knowledge, this is the first reported case of a complete pathologic response with pembrolizumab in metastatic RCC. The second case describes a 64-year-old female with metastatic RCC who was treated with second-line nivolumab after progression on cabozantinib. After 13 doses of nivolumab, she underwent nephrectomy with pathology revealing no evidence of viable tumor. These cases highlight the potential for scar tissue, fibrosis, and necrosis to persist radiographically after treatment with immunotherapy despite the absence of viable tumor cells.

Keywords: case reports; immunotherapy; kidney neoplasms; pathologic complete responders; pembrolizumab.

Figure 1

Computerized tomography scans before and after immunotherapy in Case #1 Initial CT scan showing large left sided renal mass in April of 2019 (A) compared to CT scan in March of 2020 (B) showing substantially decreased mass.

Figure 2

Representative pathologic images from Case #1 Hematoxylin and eosin (H&E) stained slides at low-power (A) and high-power (B) magnification showing extensive hyalinized fibrosis with scattered chronic inflammation and hemosiderin laden macrophages in the area of tumor regression. The fibrosis extends into the adjacent fibroadipose tissue (C). Chronic tubulointerstitial nephritis and globally sclerosed glomeruli are present in the adjacent residual benign renal parenchyma (D).

Figure 3

Computerized tomography scans before and after immunotherapy in Case #2 Initial CT scan in July of 2018 showing large right renal mass (A) and pulmonary metastases (B) compared to CT scan in December of 2019 showing substantially decreased mass (C) and resolution of pulmonary metastases (D).

Figure 4

Representative pathologic images from Case #2 H&E stained slides at low-power (A) and high-power (B) magnification showing a massive infiltration of chronic inflammatory cells and foamy macrophages in the area of tumor regression. Areas of tumor regression also showed necrotizing granulomatous inflammation (C). Chronic tubulointerstitial nephritis, globally sclerosed glomeruli, and hemosiderin laden macrophages are present in the adjacent residual benign renal parenchyma (D).