Clear cell renal cell carcinoma micrometastasis: Insights from an unconventional cutaneous presentation.

Clear cell renal cell carcinoma (ccRCC) is a highly lethal cancer known for its propensity to metastasise, yet the mechanisms underlying metastasis are not well defined. Cutaneous metastases from ccRCC are uncommon and typically occur within 3 years post-nephrectomy, predominantly affecting the scalp, chest or abdomen. Here, we present a unique case of a 75-year-old male, previously treated for ccRCC with right radical nephrectomy, who developed a singular skin lesion on the left side of the neck 19 years post-nephrectomy. The lesion was confirmed as metastatic ccRCC through histopathological analysis, despite negative imaging findings. Micrometastases, characterised by microscopic tumour cell foci in distant sites, pose a significant diagnostic challenge, frequently evading detection on conventional imaging modalities like computed tomography and magnetic resonance imaging. This case contributes to our understanding of ccRCC metastasis, emphasising the necessity for continued clinical vigilance and thorough diagnostic scrutiny, particularly concerning atypical metastatic sites.

Highly efficient CRISPR-targeting of the murine Hipp11 intergenic region supports inducible human transgene expression.

Safe harbor loci allow predicable integration of a transgene into the genome without perturbing endogenous gene activity and for decades have been exploited in the mouse to investigate gene function, generate humanised models and create tissue specific reporter and Cre recombinase expressing lines. Herein, we show that the murine Hipp11 intergenic region can facilitate highly efficient integration of a large transgene-the human CD1A promoter and coding region-by means of CRISPR-Cas9 mediated homology directed repair. The data shows that the single copy human CD1A transgene is faithfully expressed in an inducible manner in homozygous animals in both macrophage and dendritic cells. Our results validate the Hipp11 intergenic region as being a highly amenable target site for functional transgene integration in mouse.

New prostate cancer prognostic grade group (PGG): Can multiparametric MRI (mpMRI) accurately separate patients with low-, intermediate-, and high-grade cancer?

PURPOSE: Our objective is to determine the accuracy of multiparametric MRI (mpMRI) in predicting pathologic grade of prostate cancer (PCa) after radical prostatectomy (RP) using simple apparent diffusion coefficient metrics and, specifically, whether mpMRI can accurately separate disease into one of two risk categories (low vs. higher grade) or one of three risk categories (low, intermediate, or high grade) corresponding to the new prognostic grade group (PGG) criteria. METHODS: This retrospective, HIPAA-compliant, IRB-approved study included 140 patients with PCa who underwent 3 T mpMRI with endorectal coil and transrectal ultrasound-guided (TRUS-G) biopsy before RP. MpMRI was used to classify lesions using a two-tier (low-grade/PGG 1 vs. high-grade/PGG 2-5) or a three-tier system (low-grade/PGG 1 vs. intermediate-grade/PGG 2 vs. high-grade/PGG 3-5). Accuracy of mpMRI was compared against RP for each system. RESULTS: The predictive accuracy of mpMRI using the two-tier system is higher than when using three-tier system (0.77 and 0.45, respectively). There were similar rates of undergrading between mpMRI and TRUS-G biopsy compared to RP (16% & 21%; respectively); rate of overgrading was higher for mpMRI vs. TRUS-G biopsy compared to RP (42% & 17%, respectively). When mpMRI and TRUS-G biopsy are combined, rate of undergrading is 1.4% and overgrading is 11%. CONCLUSIONS: MpMRI predictive accuracy is higher when using a two-tier vs. a three-tier system, suggesting that advanced metrics may be necessary to delineate intermediate- from high-grade disease. Rates of under- and overgrading decreased when mpMRI and TRUS-G biopsy are combined, suggesting that these techniques may be complementary in predicting tumor grade.