Advancing the PD-L1 CPS test in metastatic TNBC: Insights from pathologists and findings from a nationwide survey.

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC.

Mesenchymal stem cells protective effect in adriamycin model of nephropathy.

Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity. The in vivo experimental approach was carried out in male Sprague-Dawley rats (overall 60 animals) treated with different ADR schemes to induce acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of 1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but protected the kidney from severe glomerulosclerosis when given concomitantly to ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage. Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify proteinuria and progression to renal failure, which implies lack of regenerative potential in this model.

Gastrointestinal stromal tumors: clinical pathological review of a personal series.

The Authors report their experience on the management of gastrointestinal stromal tumors (GISTs). In addition to recent cases immediately diagnosed as GISTs, a pathological review of stored material from non-epithelial tumors of the gastrointestinal tract operated on over the past 20 years was performed. Twenty-three out of a total of 31 cases were shown to be positive for the immunophenotypic characteristics (CD117/CD34) of GISTs. Most cases (approximately 60%) were symptomatic, with hemorrhage being the most common presenting sign, followed by occlusion, pain and perforation. Asymptomatic cases were detected incidentally during procedures for other conditions. Diagnostic techniques (ultrasound, endoscopy, endoscopic ultrasound, X-ray, CT, MRI) allowed only the detection of wall (extraluminal) involvement. Apart from differentiating between benign and malignant, preoperative biopsy was seldom valuable. All cases were treated surgically, with intervention tailored to location and anatomical/surgical and anatomical/pathological features. Long-term follow-up was conducted in all patients and for most is still ongoing: five patients died from recurrent disease at varying intervals after surgery (from 17 to 102 months). Relationships between observed aggressiveness and risk were studied. Parameters that may prove useful for the early detection and appropriate management of these lesions are discussed.