Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer.

BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.

[A case of Neuropsychiatric systemic lupus erythematosus with varying stenotic lesions in several cerebral major arteries and a vertebral artery aneurysm].

A 42 years old female suffered from systemic lupus erythematosus (SLE) about 20 years ago. While steroid was tapered for a steroid-induced psychiatric disorder, she presented with an acute confusional state and was diagnosed with neuropsychiatric SLE (NPSLE). MRI showed acute infarction mainly in the cortex of the right temporal lobe and MRA demonstrated dynamic subacute morphological changes such as stenosis and dilation in several major intracrainal arteries. The right vertebral artery diffusely dilated and subsequently formed an aneurysm in a week. Contrast-enhanced MRI vessel-wall imaging showed a remarkable enhancement of the aneurysm wall, which might indicate an unstable unruptured aneurysm. The prompt introduction of intravenous cyclophosphamide improved both clinical and radiological signs. Our case indicates that intensive immunosuppressive treatments should be considered in NPSLE patients with varying vasospasm and aneurysm, indicating exacerbated disease activity.

Derivative Chromosome 3 Loss from t(3;6)(q12;q14) Followed by Differential VHL Mutations Underlie Multifocal ccRCC.

BACKGROUND/AIM: The Von Hippel-Lindau (VHL) gene encodes a protein (pVHL) that plays an important role in proteasome degradation of hypoxia inducible factor α (HIFα) through E3 activation. Accumulation of HIFα by loss of functional pVHL promotes tumorigenesis, thus, VHL has tumor suppressor gene capability in clear cell renal cell carcinoma (ccRCC). VHL is the most frequently mutated gene in ccRCC. The complete loss of VHL is mainly achieved by loss of chromosome 3p, which has a VHL coding region in combination with mutation or hypermethylation of the remaining copy of VHL. Given the risk of constitutional chromosome 3 translocation for RCC, it is important to detect the translocation and understand the mechanism underlying the development of multifocal ccRCC. CASE REPORT: A 67-year-old female patient diagnosed with multifocal RCC underwent robot-assisted partial nephrectomy (RAPN) for three kidney tumors. A cancer gene panel test using next generation sequencing (NGS) detected differential VHL mutations (c.533T>G; p.L178R, c.465_466insTA; p.T157Ifs*3, c.343C>A; p.H115N), while VHL mutation was not detected in peripheral blood DNA. A tendency toward copy number loss of genes on der(3) was also detected in all tumors, but not in the germline one. A karyotype analysis revealed a germline translocation between 3 and 6, t(3;6)(q12;q14). CONCLUSION: Chromosome 3 translocation and loss of derivative chromosome containing 3p and subsequent somatic differential VHL mutations in this case strongly support the previously proposed three-step model to explain the development of familial conventional ccRCC.

[A Case of Metastasis of Gastric Cancer to the Bladder].

A 62-year-old woman was diagnosed with peritoneal dissemination of gastric cancer and was treated with anticancer drugs. Eleven months after the start of the treatment, follow-up computed tomography newly showed thickening of the bladder wall and left hydronephrosis even though the chemotherapy reduced peritoneal dissemination. Therefore, she was referred to our hospital for further evaluation. Cystoscopy and magnetic resonance imaging showed the tumor arising from the bladder neck to trigone. A few days later, she was admitted to our hospital because of bladder tamponade. Transurethral coagulation was carried out, and we resected part of the bladder tumor for pathological examination at the same time. As the pathological features of the bladder tumor were similar to those of the primary stomach cancer and peritoneal dissemination, the diagnosis of the bladder tumor was metastatic gastric adenocarcinoma. She died three months after visiting our hospital.

A case of malignant melanoma simultaneously found in the lung and small intestine.

Metastatic melanoma in the small bowel is a common cause of secondary intestinal tumors. We present a case of a 77-year-old man with melena resulting from melanoma in the small bowel that was simultaneously found with malignant melanoma in the lung. Abdominal contrast-enhanced computed tomography (CT) and position emission tomography (PET) revealed a 30 × 20 mm hypervascular lesion in the small bowel and a 9 × 9 mm right lobe lung mass with metastasis in the mediastinal and peritoneal lymph nodes, and the spleen. The bowel and lung tumor lesions were confirmed by enteroscopy and bronchoscopy, respectively, and were histologically diagnosed as malignant melanoma. In cases of small bowel malignant melanoma, an extraintestinal origin should always be suspected because intestinal melanomas are almost always metastatic. PET/CT is an effective tool for confirming intestinal melanomas because of its high sensitivity and specificity.

Declining hepatitis C virus (HCV) prevalence in pregnant women: impact of anti-HCV screening of donated blood.

BACKGROUND: Screening blood donors for hepatitis C virus (HCV) antibody has effectively mitigated transfusion transmission of HCV. We conducted a post hoc analysis to clarify the impact of donor screening on a general population of reproductive-age females and their offspring. STUDY DESIGN AND METHODS: Anti-HCV screening in Japan started in late-1989. In a cohort studied between May 1990 and November 2004, a total of 22,664 consecutive serum samples from pregnant women were screened for anti-HCV. Reactive samples were further tested for HCV RNA. Linear structural regression was applied to identify causal relationships. RESULTS: Anti-HCV-reactive rates declined significantly by two measures. First, among women known to have been transfused, rates fell from 14.8% to 3.1% with the implementation of anti-HCV screening (p < 0.01). Nevertheless, this is 10 times higher than the 0.3% reactive rate seen in a similar cohort of nontransfused women. Second, rates fell from 1.8% among women born in 1955 or before to 0.3% for women born in 1966 or later (p < 0.01). Among 103 anti-HCV-reactive women, 31 (30%) had been transfused and another 17 (17%) had other identifiable risk factors. The remaining 55 (53%) had no clear risk factor. Blood transfusion accounted for 19% of anti-HCV acquisition, by path analysis. Only one infant in this cohort was vertically infected with HCV. CONCLUSION: Anti-HCV screening of donated blood and hygienic improvements have markedly decreased HCV infection of pregnant women with a transfusion history; however, 70% of anti-HCV-reactive women were deemed to be infected via routes other than transfusion.