PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild-type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of the mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia (PML) protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 activity and senescence in ccRCC. Treatment with the FDA-approved PML inhibitor arsenic trioxide induced PML degradation and p53 accumulation and inhibited ccRCC expansion in vitro and in vivo. Therefore, by defining non-oncogene addiction to the PML gene, our work uncovers a novel ccRCC vulnerability and lays the foundation for repurposing an available pharmacological intervention to restore p53 function and chemosensitivity.

Leiomyoadenomatoid tumours of the epididymis: A new case report and review of the literature.

Benign tumours of the epididymis are rare, and the most common tumour types include adenomatoid tumours, representing more than half of all cases, and leiomyomas. Here, we reported a case of leiomyoadenomatoid tumours of the epididymis, a very rare, benign histological entity with only few cases described in the English literature, which have been reviewed and summarised. Clinically, the lesion presented as a solitary mass growing at the level of the tail of the right epididymis. After the intraoperative frozen section analysis revealed a benign adenomatoid lesion, the mass was enucleated with a conservative surgery sparing the testis. This case highlights the importance for both pathologists and urologists to be aware of these rare, but benign, tumours, to avoid misdiagnosis, especially in the setting of frozen intraoperative consultation, or primary radical surgical procedures, as radical orchiepididymectomy without frozen section consultation.

Prostate cancer testicular metastasis: Are they underestimated? Case report and analysis of the literature.

INTRODUCTION: We aim to present a rare case of a patient who developed a late testicular metastasis of PCa after radical prostatectomy. CASE DESCRIPTION: A 78 years old man presenting for left testicular swelling slowly increasing of size over the last 2 months. He underwent a retropubic radical prostatectomy and extended bilateral lymphadenectomy in 2007 for prostatic adenocarcinoma. At the time of the presentation the last PSA was 0.91 ng/mL. The patient underwent a standard left orchifunicolectomy in April 2019 without intra- or perioperative complications. The pathological analysis showed a testicular metastasis of acinar adenocarcinoma. CONCLUSIONS: In conclusion, testicular metastasis from PCa are uncommon conditions. PSA evaluation and physical examination of all sites of metastasis and accurate evaluation of all signs/symptoms during the clinical visit remains crucial to the diagnosis of recurrence.