Stephen E. Pautler

Aims: Sporadic renal cell carcinomas with fibromyomatous stroma (RCC FMS) with coexistent haemangioblastoma (HB)‐like morphology have been previously reported. Such morphology has not, however, been documented in patients with tuberous sclerosis complex (TSC). We evaluated clinicopathologic, immunohistochemical and molecular findings of RCC FMS with HB‐like features in three TSC patients.Methods and results: All three patients were females with confirmed germline mutations in TSC1 in the absence of VHL or other alterations. One patient had bilateral nephrectomy with six separate tumours (three in each kidney), and two patients had one tumour each, resected by partial nephrectomy. Prominent fibromuscular stroma was present at the tumoral periphery and surrounding clear cell nests forming tubules and papillary formations (RCC FMS areas), admixed with solid, clear to eosinophilic and spindle cell areas (HB‐like areas). HB‐like areas were variably represented in individual tumours, but in some, HB‐like features were almost exclusive. HB‐like areas were negative for CK7 and showed inhibin‐α and S100 reactivity, in contrast to typical RCC FMS areas, which were CK7 positive, while negative for inhibin‐α and S100. GPNMB, which is consistently expressed in TSC/mTOR altered tumours, was positive in both components. On follow‐up (10 months–21 years), all patients had an indolent course.Conclusions: HB‐like morphology found in RCC FMS in TSC patients represents part of the morphologic spectrum of RCC FMS, which is a previously underreported and underrecognized feature. RCC FMS with HB‐like areas show uniform GPNMB reactivity and are associated with TSC/MTOR alterations, but not with VHL alterations.

Background: Urinary tract infection (UTI) is a recognized complication of shock wave lithotripsy (SWL) for urolithiasis. Evidence guiding antibiotic prophylaxis remains of low certainty, contributing to substantial practice variation and conflicting guidelines. A well-powered, blinded randomized trial is essential to provide trustworthy evidence for clinical practice. Study Design: An international, multicentre, randomized controlled trial (the APPEAL trial) assessing the benefits and harms of a single dose of ciprofloxacin versus placebo before SWL in reducing post-procedure UTI. Patients, healthcare providers, data collectors, outcome adjudicators and statisticians blinded to treatment assignment. Endpoints: Appeal’s primary outcome is bacteriuria or symptomatic UTI (symptomatic UTI defined as symptomatic cystitis, pyelonephritis, or urosepsis) within approximately 7-14 days post-SWL. Other outcomes include pyelonephritis or urosepsis, and serious adverse events. Patients and Methods: Over 1,500 patients from high- and middle-income countries undergoing SWL for nephrolithiasis or ureterolithiasis. Exclusion criteria include a positive pre-SWL urine analysis for nitrites or urine culture, ongoing or planned antibiotic use, suspected struvite stones, urinary catheters or diversion, or a history of urosepsis. Imminent report of APPEAL will provide high-quality evidence on the role of antibiotic prophylaxis in SWL and identify subgroups that may benefit most. Trial Registration: ClinicalTrial.gov identifier (ID): NCT03692715 .