Abbreviations & AcronymsBcl-2 = B-cell lymphoma 2 CD10 = cluster of differentiation 10 CD99 = cluster of differentiation 99 CN = cystic nephroma MESTK = mixed epithelial and stromal tumor of the kidney PSA = prostate-specific antigen SMA = smooth muscle actin Abstract: Mixed epithelial and stromal tumor of the kidney is a rare benign tumor that consists of both epithelial and stromal cells. To date, eight malignant cases have previously been reported in female patients only. We report the first case of malignant mixed epithelial and stromal tumor of the kidney in a male patient. A 67-year-old Japanese man receiving hormonal therapy for prostatic cancer was found to have a right renal cystic tumor and underwent right nephrectomy. Histologically, the tumor was composed of benign epithelial and stromal cells in addition to malignant undifferentiated stromal cells. Immunohistochemically, the malignant stromal component was positive for cluster of differentiation 99 and B-cell lymphoma 2, but no chimeric transcripts for synovial sarcoma were identified. Finally, a diagnosis of malignant mixed epithelial and stromal tumor of the kidney was recorded. Urologists and pathologists should recognize that malignant mixed epithelial and stromal tumors of the kidney might occur in male patients receiving hormonal therapy for prostatic cancer.

Cytology is widely conducted for diagnosis of urothelial bladder cancer; however, its sensitivity is still low. Recent studies show that liquid biopsies can reflect tumor genomic profiles. We aim to investigate whether plasma or urine is more suitable for detecting tumor‐derived DNA in patients with early‐stage urothelial bladder cancer. Targeted sequencing of 71 genes was carried out using a total of 150 samples including primary tumor, urine supernatant, urine precipitation, plasma and buffy coat from 25 patients with bladder cancer and five patients with cystitis and benign tumor. We compared mutation profiles between each sample, identified tumor‐identical mutations and compared tumor diagnostic sensitivities between urine and conventional cytology. We identified a total of 168 somatic mutations in primary tumor. In liquid biopsies, tumor‐identical mutations were found at 53% (89/168) in urine supernatant, 48% (81/168) in urine precipitation and 2% (3/168) in plasma. The high variant allele fraction of urine was significantly related to worse clinical indicators such as tumor invasion and cytological examination. Although conventional cytology detected tumor cells in only 22% of non‐invasive tumor, tumor diagnostic sensitivity increased to 67% and 78% using urine supernatant and precipitation, respectively. Urine is an ideal liquid biopsy for detecting tumor‐derived DNA and more precisely reflects tumor mutational profiles than plasma. Genomic analysis of urine is clinically useful for diagnosis of superficial bladder cancer at early stage.

Background : A study was conducted to evaluate our experience of ileal-conduit formation in tetraplegic patients with special reference to late complications due to upper urinary tract stones and pyocystis.Methods : Ileal-conduit formation was performed in 16 patients with tetraplegia to improve urinary management. The mean age at operation was 46 years (range 19-70) and the mean follow-up period was 8.7 years (range 2-17). We evaluated the results retrospectively from patients' medical records. Results : Two patients died 2 years after the procedure and one patient died 8 years after the ilealconduit formation. Five patients suffered from repeated renal or ureteral stone. In three of these cases, serious urinary tract infections developed whenever the stone caused an obstruction. Three patients received a cystectomy at the time of the ileal-conduit formation. Eight patients suffered from empyema of the bladder and in two of these cases a subsequent cystectomy was required. Conclusions : Ileal-conduit formation should be cautiously considered as an option in the urinary management of tetraplegic patients, particularly when more conservative management strategies have proved unsuccessful. However, an antirefluxing mechanism for the ileal conduit may be necessary, and a simultaneous cystectomy may improve the results.

Genomic profiling of tumors enables therapeutic decisions, and identifying drugmatched mutations will prolong survival and prognosis. Here, we generated a custom panel for detecting genetic alterations in 19 patients with urothelial bladder cancer. This panel targeted 71 genes associated with urological cancer. Targeted sequencing was performed on formalin-fixed paraffin-embedded tumor tissues. Paired patient-matched tumor and blood samples were subjected to this analysis. A total of 142 somatic mutations were detected in 19 tumor tissues. At least one non-synonymous mutation was detected in all tumor tissues, and KDM6A, KMT2D, TP53, KMT2C, PIK3CA, and ERCC2 were recurrently mutated. Chromatin remodeling and epigenetic modifier genes are frequently mutated. Of 142 mutations, 69 mutations (49%) were annotated to have oncogenic potential. Furthermore, 74% of patients were expected to receive targeted therapy due to drug-matched mutations being identified in their tumors. Among this cohort, a patient harbored an ERCC2 helicase domain mutation and would be expected to respond to platinum-based therapy. As expected, the patient received carboplatin-containing neoadjuvant therapy with a remarkable response. Furthermore, tumor-derived mutations in urine were rapidly decreased after neoadjuvant therapy. These results suggested targeted sequencing could help to detect drug-matched somatic mutations and indicate single or combination therapy for cancer patients.

In 2008, a familial noradrenergic pheochromocytoma (PCC) with a KIF1B germline mutation in exon 41 was reported in a 24-year-old female proband and her family. However, in 2020, the same research group reported that the cause of PCC in this family was a MAX germline mutation and was not due to the KIF1B mutation. In this study, we investigated the pathogenicity of a KIF1B germline mutation detected in a 26-year-old woman with juvenile-onset noradrenergic PCC. She was surgically treated and did not have a family history of PCC. We performed whole-exome sequencing, Sanger sequencing, and immunohistochemical and gene expression analyses of catecholamine-synthesizing enzymes. Three tumors with associated somatic mutations were used as the control group. Whole-exome sequencing revealed a p.V1529M KIF1B germline mutation in exon 41 in our patient, and no other associated germline and somatic mutations, including MAX, were detected. Sanger sequencing confirmed the presence of both mutant and wild-type alleles in the tumor. Among the catecholamine-synthesizing enzymes, the expression of phenylethanolamine-N-methyl transferase was suppressed. An in silico analysis of the p.V1529M mutation showed a score suggestive of pathogenicity. After evaluation with the international guideline for sequence variants, p.V1529M mutation was still classified as a variant with uncertain significance; however, our data, including the in silico analysis data, provided certain evidences that met the criteria supporting its pathogenicity. Therefore, this study can support future studies in proving the pathogenicity of the KIF1B p.V1529M mutation.