Case Report: A Case of Renal Cell Carcinoma Unclassified With Medullary Phenotype Exhibiting a Favorable Response to Combined Immune Checkpoint Blockade.

Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is an extremely rare variant of kidney cancer with poor prognosis. Recently, immune checkpoint inhibitors (ICIs) have been the mainstay of treatment for advanced clear cell renal cell carcinoma (RCC). However, the efficacy of ICI in the treatment of RCCU-MP remains unclear. Here, we report about a 63-year-old Japanese man who was referred to our hospital with a diagnosis of RCC of the left kidney with multiple-lymph node involvement (cT3aN1M1). The patient underwent nephrectomy with lymph node biopsy, which was histopathologically diagnosed as RCCU-MP. Thereafter, he received combined immune checkpoint blockade with nivolumab and ipilimumab. After induction therapy, follow-up computed tomography revealed shrinkage of the metastatic lymph nodes. Moreover, the patient was relieved of his subjective symptoms and his performance status improved. However, after 15 months, maintenance ICI therapy was discontinued because of disease progression, and the patient died 28 months after diagnosis. Longitudinal analysis of peripheral blood mononuclear cells revealed increased stem cell memory and central memory CD8+ T-cell subsets during response to therapy and enhanced expression of exhaustion markers on CD8+ T cells upon treatment resistance. Combined immune checkpoint blockade could be effective in the treatment of metastatic RCCU-MP.

[Testicular Preservation in a Patient with a Testicular Epidermoid Cyst Achieved by Preoperative Diagnosis : A Case Report].

Testicular epidermoid cysts are relatively rare, accounting for about 1% of all testicular tumors, and are often treated by high orchiectomy. We describe here the case of a testicular epidermoid cyst treated by testicle-sparing surgery due to a preoperative diagnosis. A 23-year-old man complained of a painless mass in the right scrotum. Physical examination revealed a firm little fingertip-sized smooth-surfaced mass in the right testis. Ultrasonography showed a hypoechoic lesion with an echogenic rim in the right testis. A T2-weighted magnetic resonance image showed a well-demarcated mass with a low signal outline. On the basis of a preoperative diagnosis of epidermoid cyst, intraoperative testicular frozen section was performed, and the mass was resected surgically while preserving the testis.

[A Case of Pelvic Unicentric Castleman Disease Treated by Preoperative Transcatheter Arterial Embolization and Tumor Complete Resection with Combined Lower Abdominal and Posterior Approach].

A 22-year-old woman was referred to our hospital for further examination of an incidentally discovered hypervascular pelvic tumor with a maximum diameter of 10 cm. Although Castleman disease was suspected based on the imaging findings and pathologic findings of the needle biopsy, a definitive diagnosis was not made. Preoperative transcatheter arterial embolization was performed to decrease intraoperative bleeding, and tumor resection was performed on the following day. As for posterior approach prior to anterior approach, the patient was placed in a prone position, and the dorsal aspect of tumor was approached through the dissection of gluteal muscles. Then, dilated branches of the internal iliac vein was found on the tumor capsule, which were safely ligated under direct vision with favorable visual field. Then, the patient was placed in a supine position, the tumor was completely resected by anterior approach without transfusion. Histopathological diagnosis was Castleman disease hyaline vascular type. The patient was discharged without complication and has been free from recurrence for 6 months after surgery.

[A Case of Small Cell Carcinoma of the Bladder].

A 74-year-old man presented with further treatment for muscle invasive small cell carcinoma of the bladder. After three courses of neoadjuvant chemotherapy with cisplatine + etoposide (EP), total cystectomy was performed. The pathological findings revealed small cell carcinoma of the bladder (ypT2N0M0). Eleven months after the operation, thoracoabdominal computed tomography (CT) showed right pelvic lymph node metastasis. He underwent 9 courses of EP chemotherapy, and everolimus, finally, Amrubicin was administered. Amrubicin might be useful for small cell carcinoma of the bladder.

[Deep and Durable Response After Discontinuation of Nivolumab/Ipilimumab Combination Therapy for Metastatic Renal Cell Carcinoma : A Case Report].

A 47-year-old man was referred to our hospital for epigastric pain and cough, and was given a diagnosis of left clear cell renal carcnoma with multiple pulmonary metastases based on the results of renal tumor biopsy (cT3aN0M1). He received nivolumab/ipilimumab combination therapy, but developed diarrhea (grade 3) on day71, and treatment was discontinued. However, a deep and durable response after discontinuation of treatment was shown, and we were able to perform nephrectomy on day336. He is undergoing nivolumab therapy for pulmonary metastases.

[Clinical Effect of Nivolumab on Advanced Renal Cell Carcinoma with Peritoneal Metastasis].

Peritoneal dissemination or metastasis is a relatively rare presentation of renal cell carcinoma. We report four cases of advanced renal cell carcinoma with peritoneal metastases treated with nivolumab. Three cases showed an objective response in the metastatic lesions including peritoneal sites. After nivolumab administration, the computed tomography scan showed a transient enlargement of peritoneal lesions in two cases, which could be considered as pseudoprogression. Temporal changes of neutrophil-tolymphocyte ratio, C-reactive protein, and eosinophil ratio during the clinical course reflected the treatment effect of nivolumab in these patients, indicating that these could be potential biomarkers of the response. To our knowledge, this is the first case series showing therapeutic activity of nivolumab against peritoneal metastases in patients with renal cell carcinoma.

[A Case of Late Onset Nivolumab-Induced Interstitial Nephritis in a Patient with Metastatic Renal Cell Carcinoma].

A 43-year-old man underwent nephrectomy for right renal cell carcinoma (cT3aN0M1 (PUL), clear cell carcinoma). Thereafter, he was treated with sunitinib for lung metastases as the first-line therapy for three months. Because lung metastases progressed and new bone metastases appeared, nivolumab was started for the second-line treatment. Although the cancer progression was suppressed by multidisciplinary treatment combined with systemic immunotherapy and local radiation therapy, he developed severe acute kidney injury with cortical swelling after eighteen months of nivolumab treatment. A diagnosis of acute interstitial nephritis induced by nivolumab was made based on biopsy findings. Treatment with prednisolone (1.0 mg/kg daily) led to a rapid improvement in renal function. We must consider the possibility of immunerelated adverse events, especially nivolumab-induced acute kidney injury, even after long-term treatment.