Combination of Nivolumab Plus Ipilimumab for Mucinous Tubular and Spindle Cell Carcinoma of the Kidney with Bone Metastases: The First Case Report

Abstract Background: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma (RCC) and generally considered a low-grade renal epithelial neoplasm composed of tubules, spindle cells, and extracellular mucin. MTSCC with distant metastases has been reported, with some cases showing a poor prognosis. While only a few case reports regarding the treatment of metastatic MTSCC have been reported, targeted agents and monotherapy of immune checkpoint inhibitors have shown some efficacy. To our knowledge, this is the first reported case of metastatic MTSCC of the kidney treated with combination therapy of nivolumab plus ipilimumab.Case presentation: A 26-year-old man consulted our hospital after a 72-mm tumor was detected at the upper pole of the left kidney with multiple osteolytic bone metastases by computed tomography (CT). A CT-guided biopsy of the renal tumor and bone metastases resulted in a diagnosis of MTSCC of the kidney with bone metastases (cT2aN0M1) and an ‘intermediate risk’ according to the International Metastatic Renal Cell Carcinoma Database Consortium criteria. He therefore received combination therapy of nivolumab plus ipilimumab therapy. After 4 cycles of combination nivolumab plus ipilimumab and 9 cycles of nivolumab monotherapy, he underwent cytoreductive nephrectomy because the tumor had shrunk, and sclerotic changes in the bone metastases were noted. In the excised specimen, the programmed cell death ligand 1 expression was higher in the spindle components than in the tubular components, but CD4- and CD8-positve T cells showed greater infiltration in the tubular components than in the spindle components. Furthermore, CD-4- and CD-8-positive T cells in both components of the resected specimen showed greater infiltration than they had at the pretreatment biopsy of the renal tumor and bone metastases.Conclusions: Combination immunotherapy of nivolumab and ipilimumab may be an effective treatment option for metastatic MTSCC of the kidney.