Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma.

In a family with Familial Non-Medullary Thyroid Carcinoma (FNMTC), our investigation using Whole-Exome Sequencing (WES) uncovered a novel germline USP42 mutation [p.(Gly486Arg)]. USP42 is known for regulating p53, cell cycle arrest, and apoptosis, and for being reported as overexpressed in breast and gastric cancer patients. Recently, a USP13 missense mutation was described in FNMTC, suggesting a potential involvement in thyroid cancer. Aiming to explore the USP42 mutation as an underlying cause of FNMTC, our team validated the mutation in blood and tissue samples from the family. Using immunohistochemistry, the expression of USP42, Caspase-3, and p53 was assessed. The USP42 gene was silenced in human thyroid Nthy-Ori 3-1 cells using siRNAs. Subsequently, expression, viability, and morphological assays were conducted. p53, Cyclin D1, p21, and p27 proteins were evaluated by Western blot. USP42 protein was confirmed in all family members and was found to be overexpressed in tumor samples, along with an increased expression of p53 and cleaved Caspase-3. siRNA-mediated USP42 downregulation in Nthy-Ori 3-1 cells resulted in reduced cell viability, morphological changes, and modifications in cell cycle-related proteins. Our results suggest a pivotal role of USP42 mutation in thyroid cell biology, and this finding indicates that USP42 may serve as a new putative target in FNMTC.

Glioblastoma Microenvironment and Cellular Interactions.

The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell-cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.

Multiple Faces of the Glioblastoma Microenvironment.

The tumor microenvironment is a highly dynamic accumulation of resident and infiltrating tumor cells, responsible for growth and invasion. The authors focused on the leading-edge concepts regarding the glioblastoma microenvironment. Due to the fact that the modern trend in the research and treatment of glioblastoma is represented by multiple approaches that target not only the primary tumor but also the neighboring tissue, the study of the microenvironment in the peritumoral tissue is an appealing direction for current and future therapies.

Adrenal Gland Primary Neuroblastoma in an Adult Patient: A Case Report and Literature Review.

Neuroblastoma (NB) is an undifferentiated malignant tumor of the sympathetic ganglia, occurring in children under 5 years of age. However, it is a rare histology in adult patients, occurring once per every 10 million patients per year. We present the case of a 68-year-old male patient presented to our department for right lumbar pain, asthenia, loss of weight and altered general status. The contrast-enhanced abdominal computer tomography revealed bilateral adrenal tumoral masses of 149 mm and 82 mm on the right and left sides, respectively, with invasion of the surrounding organs. The patient underwent right 3D laparoscopic adrenalectomy and right radical nephrectomy. The pathological result concluded that the excised tumor was a neuroblastoma of the adrenal gland. The patient followed adjuvant oncological treatment; however, due to disease progression, he passed away 22 months after the surgery. To our knowledge, less than 100 cases of adrenal NB in adult patients have been published, the eldest case being diagnosed at 75 years of age; meanwhile, the largest reported tumor measured 200 mm, and was excised through open surgery. Minimally invasive techniques have been limited so far to smaller, organ-confined diseases, thus making the present case the largest adrenal NB removed entirely laparoscopically. Neuroblastoma in the adult population is a rare finding, with worse prognosis compared to pediatric patients. The available literature does not provide enough data for standardized, multimodal management, as the patients are treated following adapted pediatric protocols, thus reinforcing the need for international, multidisciplinary boards for rare tumors.

Combined Systematic and MRI-US Fusion Prostate Biopsy Has the Highest Grading Accuracy When Compared to Final Pathology.

Background and objectives: Systematic prostate biopsy (SB) has a low Gleason group (GG) accuracy when compared to final pathology. This may negatively impact the inclusion of patients into specific risk groups and treatment choice. The aim of our study was to assess the GG accuracy of magnetic resonance imaging-ultrasound (MRI-US) fusion prostate biopsy. Materials and Methods: Of a cohort of minimally invasive radical prostatectomy (RP), we selected all patients who were diagnosed with prostate cancer (PCa) via MRI-US fusion biopsy (n = 115). Results: Combined biopsy had the highest rate for GG concordance (61.7% vs. 60.4% for SB vs. 45.3% for MRI-US fusion biopsy) and the lowest for upgrading (20.9% vs. 24.5% for SB vs. 34.9% for MRI-US fusion biopsy), p < 0.0001. No clinical data were predictive for upgrading or downgrading at final pathology. Locally advanced PCa was associated with a high Prostate Imaging-Reporting and Data System (PIRADS) score (p = 0.0014) and higher percentages of positive biopsy cores (PBC)/targeted (p = 0.0002) and PBC/total (p = 0.01). Positive surgical margins were correlated with higher percentages of PBC/systematic (p = 0.003) and PBC/total (p = 0.009). Conclusions: Pre-biopsy prostate MRI improves GG concordance between biopsy and RP. Combined biopsy provides the highest grading accuracy when compared to final pathology. Targeted and systematic biopsy data are predictive for adverse pathologic outcomes.

Different clinical significance of ASAP/HGPIN pattern in systematic vs. MRI-US fusion guided prostate biopsy.

Atypical small acinar proliferation (ASAP) and high grade intraepithelial neoplasia (HGPIN) patterns identified at prostate biopsy yield an important clinical significance, their presence signaling an increased likelihood of future oncological development or underdiagnosed PCa. MRI and MRI-TRUS fusion prostate biopsy have recently become the standard for the diagnosis of prostate cancer. Thus, we aimed to assess the role of ASAP/HGPIN pattern in the context of these recent developments as compared with the standard systematic biopsy. The present study included 400 patients who underwent MRI-TRUS fusion prostate biopsy. A subgroup of these patients had a history of prior systematic biopsy and their results were also included in the analysis. We observed that ASAP/HGPIN pattern diagnosed at systematic biopsy is suggestive of a high-volume clinically-significant disease, most probably located outside the standard sampling area. On the contrary, ASAP/HGPIN at MRI-TRUS fusion biopsy has clinical features more similar to benign prostate hyperplasia, thus suggesting a more incipient disease, if present. No relation between concurrent ASAP/HGPIN and PCa was observed in our study.

Systematic sampling during MRI-US fusion prostate biopsy can overcome errors of targeting-prospective single center experience after 300 cases in first biopsy setting.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy have become an integral part of the diagnosis of prostate cancer (PCa), as recommended by the European Association of Urology Guidelines. The aim of the current study was to evaluate the performance of MRI and MRI-transrectal ultrasound (TRUS) fusion prostate biopsy as first biopsy setting in a tertiary center. METHODS: A cohort of 300 patients was included in the current analysis. All patients presented with clinical or biochemical suspicion of PCa and harbored at least one suspect lesion on mpMRI. MRI-TRUS fusion prostate biopsy, followed by 12 core systematic prostate biopsy were performed by the same operator using a rigid registration system. RESULTS: The mean age of the patients was 64 years (IQR: 58-68.5 years) and the mean PSA was 6.35 ng/mL (IQR: 4.84-9.46 ng/mL). Overall cancer and csPCa diagnosis rates were 47% and 40.66%. Overall PCa/csPCa detection rates were 20.4%/11.1%, 52%/45% and 68.5%/66.7% for PI-RADS lesions 3, 4 and 5 (P<0.001/P<0.0001). Larger lesion diameter and lesion volume were associated with PCa diagnosis (P=0.006 and P=0.001, respectively). MRI-TRUS fusion biopsy missed PCa diagnosis in 37 cases (of whom 48.6% ISUP 1) in comparison with 9 patients missed by systematic biopsy (of whom 11.1% ISUP 1). In terms of csPCa, systematic biopsy missed 77.7% of the tumors located in the anterior and transitional areas. The rate of csPCa was highest when targeted biopsy was associated with systematic biopsy: 86.52% vs. 68.79% for targeted biopsy vs. 80.14% for systematic biopsy, P=0.0004. In 60.6% of cases, systematic biopsy was positive for PCa at the same site as the targeted lesion. Of these patients, eight harbored csPCa and were diagnosed exclusively on systematic biopsy. CONCLUSIONS: MRI-TRUS fusion prostate biopsy improves the diagnosis of csPCa. The main advantage of an MRI-guided approach is the diagnosis of anterior and transitional area tumors. The best results in terms of csPCa diagnosis are obtained by the combination of MRI-TRUS fusion with systematic biopsy. The systematic biopsy performed during MRI-targeted biopsy could have an important role in overcoming errors of MRI-TRUS fusion systems.