bims-netuvo 2023-05-07 papers

Issue of 2023‒05‒07
eight papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

Histopathology. 2023 May 04.

Biopsy prostate cancer perineural invasion and tumour load are associated with positive posterolateral margins at radical prostatectomy: implications for planning of nerve-sparing surgery.

Anser Prostate Cancer Network

AIMS: Radical prostatectomy (RP) for prostate cancer is frequently complicated by erectile dysfunction and urinary incontinence. However, sparing of the nerve bundles adjacent to the posterolateral sides of the prostate reduces the number of complications at the risk of positive surgical margins. Preoperative selection of men eligible for safe, nerve-sparing surgery is therefore needed. Our aim was to identify pathological factors associated with positive posterolateral surgical margins in men undergoing bilateral nerve-sparing RP.METHODS AND RESULTS: Prostate cancer patients undergoing RP with standardised intra-operative surgical margin assessment according to the NeuroSAFE technique were included. Preoperative biopsies were reviewed for grade group (GG), cribriform and/or intraductal carcinoma (CR/IDC), perineural invasion (PNI), cumulative tumour length and extraprostatic extension (EPE). Of 624 included patients, 573 (91.8%) received NeuroSAFE bilaterally and 51 (8.2%) unilaterally, resulting in a total of 1197 intraoperative posterolateral surgical margin assessments. Side-specific biopsy findings were correlated to ipsilateral NeuroSAFE outcome. Higher biopsy GG, CR/IDC, PNI, EPE, number of positive biopsies and cumulative tumour length were all associated with positive posterolateral margins. In multivariable bivariate logistic regression, ipsilateral PNI [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.62-5.48; P < 0.001] and percentage of positive cores (OR = 1.18, 95% CI = 1.08-1.29; P < 0.001) were significant predictors for a positive posterolateral margin, while GG and CR/IDC were not.
CONCLUSIONS: Ipsilateral PNI and percentage of positive cores were significant predictors for a positive posterolateral surgical margin at RP. Biopsy PNI and tumour volume can therefore support clinical decision-making on the level of nerve-sparing surgery in prostate cancer patients.

Keywords: NeuroSAFE; percentage of positive biopsies; perineural invasion; prostate biopsy; prostate cancer; surgical margin

DOI: https://doi.org/10.1111/his.14934

Adv Biol (Weinh). 2023 May 02. e2300102

The Role of Opioid Receptors in Cancer.

Siddhant Bhoir, Megan Uhelski, Juan Jose Guerra-Londono, Juan P Cata.

Opioids are one of the most potent drugs for treating moderate to severe pain. Despite irrefutable clinical application in chronic pain management, the long-term use of opioids has been increasingly questioned due to undesired side effects that demand attention. Opioids such as morphine mediate clinically relevant effects primarily through the µ-opioid receptor that go beyond their classical role as analgesics, causing potentially fatal side effects such as tolerance, dependence, and addiction. Furthermore, there is growing evidence that opioids affect immune system function, cancer progression, metastasis, and recurrence. Though a biological plausibility, the clinical evidence for the action of opioids on cancer is mixed, revealing a more complex picture as researchers struggle to establish a vital link between opioid receptor agonists, cancer progression, and suppression, or both. Thus, in light of the uncertainty of opioid effects on cancer, in this review, a focused overview of the role of opioid receptors in modulating cancer progression, their underlying signaling mechanisms, and the biological activity of opioid receptor agonists and antagonists is provided.

Keywords: cancer; opiate analgesics; opioid receptors; opioids; signal transduction

DOI: https://doi.org/10.1002/adbi.202300102

Cancer Imaging. 2023 May 02. 23(1): 43

Three-dimensional analysis of human pancreatic cancer specimens by phase-contrast based X-ray tomography - the next dimension of diagnosis.

Diana Pinkert-Leetsch, Jasper Frohn, Philipp Ströbel, Frauke Alves, Tim Salditt, Jeannine Missbach-Guentner.

BACKGROUND: The worldwide increase of pancreatic ductal adenocarcinoma (PDAC), which still has one of the lowest survival rates, requires novel imaging tools to improve early detection and to refine diagnosis. Therefore, the aim of this study was to assess the feasibility of propagation-based phase-contrast X-ray computed tomography of already paraffin-embedded and unlabeled human pancreatic tumor tissue to achieve a detailed three-dimensional (3D) view of the tumor sample in its entirety.METHODS: Punch biopsies of areas of particular interest were taken from paraffin blocks after initial histological analysis of hematoxylin and eosin stained tumor sections. To cover the entire 3.5 mm diameter of the punch biopsy, nine individual tomograms with overlapping regions were acquired in a synchrotron parallel beam configuration and stitched together after data reconstruction. Due to the intrinsic contrast based on electron density differences of tissue components and a voxel size of 1.3 μm achieved PDAC and its precursors were clearly identified.
RESULTS: Characteristic tissue structures for PDAC and its precursors, such as dilated pancreatic ducts, altered ductal epithelium, diffuse immune cell infiltrations, increased occurrence of tumor stroma and perineural invasion were clearly identified. Certain structures of interest were visualized in three dimensions throughout the tissue punch. Pancreatic duct ectasia of different caliber and atypical shape as well as perineural infiltration could be contiguously traced by viewing serial tomographic slices and by applying semi-automatic segmentation. Histological validation of corresponding sections confirmed the former identified PDAC features.
CONCLUSION: In conclusion, virtual 3D histology via phase-contrast X-ray tomography visualizes diagnostically relevant tissue structures of PDAC in their entirety, preserving tissue integrity in label-free, paraffin embedded tissue biopsies. In the future, this will not only enable a more comprehensive diagnosis but also a possible identification of new 3D imaging tumor markers.

Keywords: Pancreatic cancer; Phase-contrast; Precursor lesion; Synchrotron; Virtual histology; X-ray based tomography

DOI: https://doi.org/10.1186/s40644-023-00559-6

Clin Endocrinol (Oxf). 2023 May 04.

Adrenal and juxta-adrenal schwannomas: A single-centre study.

Stacey Rolak, Prerna Dogra, Travis McKenzie, Michael Rivera, William F Young, Irina Bancos.

OBJECTIVE: Adrenal schwannomas and juxta-adrenal schwannomas are rare tumours. We aimed to summarise their clinical, biochemical and imaging characteristics.DESIGN: Single-centre retrospective study of eligible patients between 1995 and 2022.
PATIENTS AND MEASUREMENTS: Patients with a histopathologic diagnosis of adrenal or juxta-adrenal schwannoma.
RESULTS: Twenty-four patients were diagnosed with either primary adrenal schwannoma (8, 33%) or juxta-adrenal schwannoma (16, 67%). Most tumours (21, 88%) were discovered incidentally on imaging. All tumours were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumour size was 4 cm (range, 2-13 cm). Adrenal schwannomas were smaller when compared to juxta-adrenal schwannomas (median of 3.1 cm [range, 2-9 cm] vs. 4.6 cm [range, 2.3-13.3 cm], p = .037). On imaging, the tumours were round or oval in shape in 16 (70%), lobulated in 7 (30%), solid in 15 (68%), solid-cystic in 7 (32%), heterogeneous in 14 (61%) and homogeneous in 9 (39%). The median unenhanced computed tomography attenuation was 30 Hounsfield units (HU) (range, 12-38 HU). Of the 20 patients who underwent complete hormonal testing, all had nonfunctioning tumours. There was no recurrence or new tumour development in our cohort.
CONCLUSIONS: Adrenal and juxta-adrenal schwannomas are nonfunctioning benign tumours that present with indeterminate radiographic features, including large tumour size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumour is based on biopsy or resection.

Keywords: Hounsfield unit; adrenal gland neoplasm; computed tomography; diagnosis; neurilemmoma; phenotype

DOI: https://doi.org/10.1111/cen.14927

Rom J Morphol Embryol. 2023 Jan-Mar;64(1):64(1): 73-82

Primary de novo malignant peripheral nerve sheath tumor of the breast mimicking mastitis. Report of a case and review of the literature.

José Fernando Val-Bernal, Sandra Hermana, Fernando Hernanz, Germán Moreno.

Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor representing <0.1% of malignant breast tumors. Here, we report a case of sporadic MPNST of the breast in a 45-year-old woman with a fast-evolving painful mass in the right breast associated with edema, redness, and increased local temperature, simulating mastitis. This presentation has not been reported. A review of the literature since 1992 has revealed 15 MPNST cases, including the present one with sufficient data for analysis. All the cases were women. The ages ranged from 16-60 years (mean 40.5 years). Duration of symptoms varied from four days to 15 years (mean 2.7 years). Tumor size ranged from 2.5-30 cm (mean 10.9 cm). 64.3% of tumors were well-circumscribed. Tumors were graded as grade 1 (7.7%), grade 2 (38.5%), and grade 3 (53.8%). Three (20%) cases showed histopathological peculiarities. Simple mastectomy was performed in four (26.7%) cases, radical mastectomy in six (40%) cases, and simple excision in five (33.3%) cases. There were no metastases in the six cases where axillary dissection was performed. Seven (53.8%) patients received adjuvant therapy, including chemotherapy and∕or radiotherapy. Local recurrence was observed in two (16.7%) patients. Distant metastasis was detected in one patient (7.7%) affecting the lung 11 months after radical mastectomy. The follow-up was available for 10 patients (mean 2.2 years, median 1 year). One patient (10%) died of the disease. At the last follow-up, 80% of patients were still alive. The main differential diagnosis includes nonpleomorphic spindle cell tumors.

DOI: https://doi.org/10.47162/RJME.64.1.09

Urology. 2023 Apr 28. pii: S0090-4295(23)00375-8. [Epub ahead of print]

Solitary intrascrotal plexiform neurofibroma in a 10-year-old male: A case report.

David G Gelikman, Vishnu Bhupalam, Rhea J Birusingh, Pamela Ellsworth, Abhishek Seth.

Intrascrotal neurofibromas are extensive tumors that grow from peripheral nerves within the scrotum and are exceedingly rare among the benign extratesticular tumors. Though the risk is low, potential for malignancy and patient discomfort make diagnosis and surgical evaluation imperative. Pediatric neurofibromas are typically only associated with Neurofibromatosis type 1. However, herein, we describe a rare case of a benign, intrascrotal plexiform neurofibroma in a 10-year-old male who lacks any stigmata associated with this genetic disorder. Diagnostic and surgical challenges as well as histopathological findings are discussed.

DOI: https://doi.org/10.1016/j.urology.2023.04.015