Masashi Nakayama

Introduction: Reactive lymphoid hyperplasia (RLH) is a rare benign lymphoproliferative disorder that rarely involves the kidney and has not been reported in association with regional lymphadenopathy. Case Presentation: A 70‐year‐old woman was incidentally found to have a left renal mass. Contrast‐enhanced computed tomography revealed a 20‐mm enhancing renal lesion with enlarged hilar lymph nodes, leading to a preoperative diagnosis of renal cell carcinoma with nodal metastasis (cT1aN1M0). Open radical nephrectomy with regional lymphadenectomy was performed. Histopathological analyses established a diagnosis of reactive lymphoid hyperplasia. No additional treatment was administered, and the patient has remained free of recurrence for 3 months. Conclusion: We report the first case of RLH accompanied by regional lymph node enlargement. Because RLH can closely mimic renal cell carcinoma on imaging, it should be considered in the differential diagnosis of renal masses when the clinical presentation is inconsistent with typical renal cell carcinoma.

Supplementary Table S3 shows the phased methylation of the GSTP1 promoter region across 908 alleles, or clones, classified by density of methylation.

Supplementary Table S2 shows the phased methylation of the GSTP1 promoter region across 102 lesions classified by density of methylation.

Supplementary Figure S2 shows the methylation rate by allele of the GSTP1 promoter region for partially methylated PIN alleles and demonstrates a hotspot of methylation around transcription factor binding sites and the transcription start site.

Supplementary Table S1 shows patient and tumor characteristics from the patients who underwent radical prostatectomies for this study.

Supplementary Figure S1 shows the phased methylation by allele of the GSTP1 promoter region classified by density of methylation.

Supplementary Figure S3 shows the GSTP1 promoter methylation and its corresponding GSTP1 immunohistochemistry expression for PIA and PIN lesions within an individual patient, and notably the heterogeneity of the PIA lesions.

Glutathione S-transferase pi 1 (GSTP1) is lowly expressed in normal prostate luminal cells and becomes induced in most proliferative inflammatory atrophy (PIA) lesions. GSTP1 becomes silenced in prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma (CaP) via cytosine-phospho-guanine (CpG) island promoter hypermethylation. However, GSTP1 methylation patterns in PIA and PIN, and their relationship to patterns in CaP are poorly understood. We used bisulfite genomic sequencing to examine patterns of GSTP1 promoter CpG island methylation in laser capture microdissected benign, PIA, PIN, and CaP regions from 32 subjects that underwent radical prostatectomy. We analyzed 908 sequence clones across 24 normal epithelium, 37 PIA, 18 PIN, and 23 CaP regions, allowing assessment of 34,863 CpG sites with allelic phasing. Normal and PIA lesions were mostly unmethylated with 0.52 and 1.3% of total CpG sites methylated, respectively. PIN and CaP lesions had greater methylation with 24% and 51% of total CpG sites methylated, respectively. The degree of GSTP1 methylation showed progression from PIA << PIN < CaP. PIN lesions showed more partial methylation compared with CaP lesions. Partially methylated lesions were enriched for methylation changes at AP1 and SP1 transcription factor binding sites. These results demonstrate that methylation density in the GSTP1 CpG island in PIN was intermediate relative to that in normal prostate epithelium/PIA and CaP lesions. These results are consistent with gradual spreading of DNA methylation centered at the SP1/AP1 transcription factor binding sites in precursor lesions, with subsequent spreading of methylation across the entire CpG island in transition to CaP.Prevention Relevance:DNA hypermethylation at the GSTP1 promoter progressively spreads from being unmethylated in normal prostate to intermediate levels in precursor lesions to extensive methylation in cancer. This molecular progression of GSTP1 promoter methylation patterns in early prostate carcinogenesis could be useful for identification and interception of prostate cancer precursors.

Background Systemic therapy for metastatic renal cell cancer (mRCC) has changed significantly due to randomized controlled trial results. We investigated whether these changes affect real-world outcomes and clarified factors associated with treatment outcomes in patients from a single institution outside of clinical trials. Methods We retrospectively reviewed records of mRCC patients treated at Osaka International Cancer Institute between January 2005 and May 2024. Between-group analysis of progression-free survival (PFS) and overall survival (OS) by Kaplan–Meier comparison and identification of survival-associated factors by univariate and multivariate analyses were performed. Patients assumed ineligible for clinical trials were analyzed in subgroups according to any of Eastern Cooperative Oncology Group performance status > 1, hemoglobin level < 9.0 g/dL, estimated glomerular filtration rate < 40 mL/min/1.73 m², platelet count < 100,000/μL, neutrophil count < 1500/μL, non-clear cell histology, or brain metastasis. Results In total, 320 patients were evaluated: 2005–2009, n = 58; 2010–2014, n = 77; 2015‒2019, n = 86; and 2020‒2024, n = 99. Significant between-group differences were observed for median PFS (7 vs. 8 vs. 12 vs. 20 months; p = 0.0048) and (35 vs. 38 vs. 67 vs. 52 months; p = 0.0206). Multivariate analysis revealed that first-line or subsequent-line immune checkpoint inhibitor (ICI) use was an independent factor for OS (HR: 0.28, p < 0.0001). Even among 112 (35%) trial-ineligible patients, multivariate analysis demonstrated that the use of first-line or subsequent-line ICI was an independent factor for OS (HR: 0.26, p < 0.0001). Conclusion Over time, treatment outcomes appeared to have improved with real-world treatment for mRCC, with use of ICIs being related to improvements in treatment outcomes.

Background Systemic therapy for metastatic renal cell cancer (mRCC) has changed significantly due to randomized controlled trial results. We investigated whether these changes affect real-world outcomes and clarified factors associated with treatment outcomes in patients from a single institution outside of clinical trials. Methods We retrospectively reviewed records of mRCC patients treated at Osaka International Cancer Institute between January 2005 and May 2024. Between-group analysis of progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier comparison and identification of survival-associated factors by univariate and multivariate analyses were performed. Patients assumed ineligible for clinical trials were analyzed in subgroups according to any of Eastern Cooperative Oncology Group performance status > 1, hemoglobin level < 9.0 g/dL, estimated glomerular filtration rate < 40 mL/min/1.73 m², platelet count < 100,000/µL, neutrophil count < 1500/µL, nonclear cell histology, or brain metastasis. Results In total, 320 patients were evaluated: 2005–2009, n = 58; 2010–2014, n = 77; 2015‒2019, n = 86; and 2020‒2024, n = 99. Significant between-group differences were observed for median PFS (7 vs. 8 vs. 12 vs. 20 months; p = 0.0048) and OS (45 vs. 38 vs. 67 vs. 52 months; p = 0.0206). Multivariate analysis revealed that first-line or subsequent-line immune checkpoint inhibitor (ICI) use was an independent factor for OS (HR: 0.28, p < 0.0001). Even among 112 (35%) trial-ineligible patients, multivariate analysis demonstrated that the use of first-line or subsequent-line ICI was an independent factor for OS (HR: 0.24, p < 0.0001). Conclusion Over time, treatment outcomes appeared to have improved with real-world treatment for mRCC, with use of ICIs being related to improvements in treatment outcomes.