Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic “type 1 versus type 2” classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth. Type 2 tumors have been cleared out of several confounding entities, now regarded as independent tumors with specific clinical and molecular backgrounds. In this work we describe the prevalence and characteristics of emerging papillary tumor entities in two renal tumor cohorts (one consisting of consecutive papillary tumors from a single institute, the other consisting of consultation cases from several centers). After a review of 154 consecutive pRCC cases, 58% remained type 1 pRCC, and 34% type 2 pRCC. Papillary renal neoplasm with reversed polarity (1.3%), biphasic hyalinizing psammomatous RCC (1.3%), and biphasic squamoid/alveolar RCC (4.5%) were rare. Among 281 consultation cases, 121 (43%) tumors had a dominant papillary growth (most frequently MiT family translocation RCCs, mucinous tubular and spindle cell carcinoma and clear cell papillary RCC). Our data confirm that the spectrum of RCCs with papillary growth represents a major diagnostical challenge, frequently requiring a second expert opinion. Papillary renal neoplasm with reversed polarity, biphasic hyalinizing psammomatous RCC, and biphasic squamoid/alveolar RCC are rarely sent out for a second opinion, but correct classification and knowledge of these variants will improve our understanding of the clinical behavior of renal tumors with papillary growth.

Background.: Biopsy-based transcripts associated with antibody-mediated rejection (AMR) hold promise as substitutes for C4d positivity. However, their utility in cases with additional diagnoses other than rejection remains inadequately studied. Methods.: In our comprehensive analysis of 326 kidney allograft biopsies, assessed by histology and the Molecular Microscope Diagnostic System, we identified 68 cases characterized by additional pathologies, including pyelonephritis (n = 15), BK nephropathy (n = 20), acute interstitial nephritis (n = 5), and glomerular diseases (n = 28). Results.: Among cases with pyelonephritis, 7 of 15 cases (46%) showed a rejection-like signal, 4 above (16%) and 3 (20%) below diagnostic thresholds. Notably, the T cell–mediated rejection (TCMR) archetype score R2 (median, 0.13; interquartile range [IQR], 0.04–0.34) predominantly contributed to this observation. In BK nephropathy, 13 of 20 cases (65%) showed a rejection-like signal, 10 (50%) above and 3 (15%) below diagnostic thresholds. Elevated TCMR R2 (median, 0.07; IQR, 0.00–0.41) and all AMR archetype scores R4–6 (median, 0.23; IQR, 0.07–0.53) were driving factors. Among cases with acute interstitial nephritis, 3 of 5 cases (60%) showed TCMR-like signal with elevated R2 scores (median, 0.13; IQR, 0.00–0.54). Conversely, only 5 of 28 cases (18%) showed a rejection-like signal in glomerular disease cases, whereas 57% displayed all AMR archetype scores of ≥0.30. Conclusions.: Additional pathologies can affect the Molecular Microscope Diagnostic System output, giving a molecular rejection-like signal. The prevalence of rejection-like signals below diagnostic thresholds is noteworthy, warranting caution and prompting further investigation.

Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are at increased risk for the development of a secondary upper-urinary-tract urothelial carcinoma (UTUC). We aimed to assess the usefulness of routine upper-tract imaging surveillance during NMIBC follow-up in a patient cohort of a tertiary academic center. All routine upper-tract-imaging scans using computerized tomography urography (CTU) between 2003 and 2016 were assessed for UTUC detection. A total of 315 patients were analyzed. Initial tumor stage was Ta in 207 patients (65.7%), T1 in 98 patients (31.1%) and pure CIS in 10 patients (3.2%). A total of 149 (47.3%) presented with low-grade (LG), and 166 (52.7%) with high-grade (HG) disease. Median follow-up was 48 months (IQR: 55). Four patients (1.2%) were diagnosed with UTUC during follow-up. All four patients presented with initial Ta HG BC. Two of the patients (50%) were diagnosed by routine upper tract imaging. The other two patients were diagnosed after development of symptoms. The 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. UTUCs were detected exclusively in patients with initial HG disease, indicating that upper-tract surveillance might only be necessary in these patients.