Background: Multiple intracranial meningiomas account for <10% of all meningiomas. Familial multiple meningiomas have been linked to germline mutations in two genes: neurofibromatosis type 2 (NF2) and SWIch/Sucrose Non-Fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1). Sporadic multiple meningiomas have been associated with somatic NF2 mutations and, to date, there has been no case related to somatic SMARCB1 mutations. Here, we describe the first case. Case Report: A 45-year-old female suffered a head trauma while snowboarding. Subsequent to her injury, she experienced persistent headache, nausea, vomiting, dizziness, and flashing lights in the right eye. Magnetic resonance imaging (MRI) of her brain revealed multiple intracranial meningiomas. She underwent a two-staged craniotomy to remove frontal/parietal/temporal and occipital extra-axial tumors. Pathology confirmed the masses as meningiomas, WHO Grade I. Tumor genetic testing was positive for SMARCB1 mutation but blood genetic testing was negative for SMARCB1 mutation. Conclusion: In sporadic multiple meningiomas, somatic NF2 mutations are usually the suspected genetic alternations. Our case illustrates that somatic SMARCB1 mutation is another genetic risk factor for sporadic multiple meningiomas, albeit rare.

Background

Small renal mass (SRM) biopsy remains under-utilized due to stigma. Meanwhile, the alarmingly high benign findings in resected kidney masses highlight the need for improved preoperative diagnosis and patient selection.

Methods

The purpose of this study is to review the success rate of SRM biopsy and to evaluate its impact on patient management. A total of 168 percutaneous image-guided core needle biopsies (CNBs) of SRMs were retrieved at a tertiary academic center between 2015 and 2019. Subsequent treatment choices, side effects and outcomes were retrospectively reviewed.

Results

The diagnostic rate of CNB was 86.9%. Benign neoplasms accounted for a significant portion (14.3%) of SRM. Renal cell carcinomas (RCCs) were the most common diagnoses (69.6%) as expected. In biopsy-resection correlation, the positive predictive value of CNB was 100%. Tumor typing and subtyping by CNB were highly accurate, 100% and 98.3% respectively. Nuclear grading for clear cell RCC was accurate in 83.8% cases. The CNB results had significant impact on treatment. Most patients with RCCs underwent either resection (54.1%) or ablation (33.9%), in contrast to observation in benign neoplasms (90.5%). Most importantly, the benign resection rate (3.2%) in this series was much lower than the national average.

Conclusion

CNB provided accurate diagnoses for the majority of SRMs and revealed benign diagnoses in a subset of clinically suspicious lesions. Employment of CNB in suspicious SRM may help avoid overtreatment for benign lesions.

Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer.

Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38^lo luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38^lo luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay. Finally, the CD38^lo luminal phenotype and gene signature are associated with disease progression and poor outcome in prostate cancer. Our results suggest that prostate inflammation expands the pool of progenitor-like target cells susceptible to tumorigenesis.