Citations

Locally advanced basal cell carcinoma (BCC) is an uncommon and complex presentation of BCC. These tumors can present as extensive nonhealing ulcers and require skin biopsy to rule out other causes, including malignant, infectious, and inflammatory etiologies. In this case report, a 57-year-old female without significant past medical history presented with a 5-year history of a chronic progressive ulcer involving the neck and back. Histopathological study of the tissue identified nodular and infiltrative BCC, prompting further multidisciplinary treatment and management with vismodegib, radiation, and surgery.

Abstract Objectives Sarcomatoid urothelial carcinoma (sUC) is associated with poor clinical outcomes. Herein, we evaluated clinicopathologic features (including PD-L1 expression) for institutional cases. Methods Sixty-five patients with sUC treated by radical cystectomy were matched for age, sex, and pathologic stage to 190 patients with pure urothelial carcinoma (UC). Outcomes were evaluated using the Kaplan-Meier method. Immunohistochemistry (IHC) results for tumor-specific PD-L1 expression in sUC were quantified using H-scores (range, 0-300). Cases with constitutive PD-L1 expression (cPD-L1; H-score ≥240) were evaluated for amplification events using fluorescence in situ hybridization (n = 28), mate-pair sequencing (Mpseq; n = 6), RNA sequencing (n = 5), and targeted next-generation sequencing (n = 8). PD-L1 regulatory pathways were evaluated using gene set enrichment analysis in the Cancer Hallmark dataset. Results Most patients with sUC had advanced disease (≥pT2, 62/65, 95%), without significant differences in overall and cancer-specific survival, when matched to pure UC. Median PD-L1 H-scores using different clones were 100 (SP142), 120 (SP263), and 195 (22C3). cPD-L1 was seen in 43% (28/65) of cases of sUC that were enriched for TP53, TERT, and CDKN2A/B alterations. PD-L1 amplification was identified in 7 (of 28, 25%) of these cases. Bionformatics analysis consistently identified IL6-JAK-STAT3 and interferon α/γ signaling in sUC with cPD-L1 expression. Conclusions Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.

Abstract Context Evidence on the etiology and function of adrenal masses in younger adults is scarce. Objective This work aimed to characterize the clinical, imaging, and biochemical presentation of adrenal masses in 18- to 40-year-olds. Methods A retrospective cohort study was conducted January 2016 to December 2021 at a tertiary academic medical center. Participants included young adults (age 18-40 years) with adrenal masses identified through radiologic registry. Exclusion criteria included preexisting adrenal masses before 2016, hyperplasia, or masses smaller than 1 cm. Outcomes included adrenal mass diagnosis, as determined by reference standard of histopathology, radiologic surveillance, and biochemical evaluation. Results A total of 255 patients (women 142 [56%]; White 156 [61%]; median age 35 years [interquartile range 30-39 years]) were included. Comorbidities included genetic predisposition syndromes (16, 6.3%), preexisting malignancy (70, 27%), obesity (100, 48%), hypertension (89, 35%), and diabetes (25, 10%). The majority of adrenal masses were incidentally found (184, 72%) and median size was 1.9 cm (IQR 1.4-2.7 cm) on detection. Among adrenal masses in young adults, prevalence of malignancy and pheochromocytoma was 16% and 4%, respectively; among adrenal incidentalomas, 5% were malignant. Factors associated with malignancy or pheochromocytoma in multivariable analysis included nonincidental mechanism of discovery (odds ratio [OR] 15.5; 95% CI, 7.2-35.7; P < .001), and larger size (OR 1.5; 95% CI, 1.2-2.0; P < .001). Hormonal evaluation was performed in only 57 (22%) patients and was positive for hormone hypersecretion in 16 (28%) of tested individuals. Conclusion We demonstrated a high prevalence of malignancy and pheochromocytoma in our cohort of young adults with adrenal masses. Completion of appropriate hormonal work-up was infrequent, potentially missing patients with functioning adrenal adenomas.

BACKGROUND: Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard for evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. The aim of this observational study was to describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%. METHODS: Patients with aortic valve area ≤1.5 cm 2 underwent right heart catheterization at rest and during maximal exercise, measuring pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and the PCWP/CO-slope. Patients were stratified into 3 groups: discordant LG AS (aortic valve area ≤1.0 cm 2 and mean gradient <40 mm Hg); moderate AS (aortic valve area >1.0 cm 2 ); and high-gradient (HG) severe AS (aortic valve area ≤1.0 cm 2 and mean gradient ≥40 mm Hg). RESULTS: Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) HG severe AS. The median PCWP/CO-slope was significantly steeper in discordant LG (3.3 [interquartile range, 2.1–4.3] mm Hg/L/min) and HG severe AS (2.7 [1.9–3.4] mm Hg/L per minute) compared with moderate AS (1.9 [0.7–2.8] mm Hg/L per minute), P =0.004. In a regression model adjusted for age, sex, and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO-slope. Furthermore, patients with discordant LG AS had a leftward-upward shift in the PCWP/CO-curve. CONCLUSIONS: Discordant LG and HG severe AS had similar hemodynamic responses to exercise with steeper PCWP/CO-slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left upwards shift in PCWP/CO-curve for discordant LG compared with HG severe AS indicates that this group also has heart failure with preserved ejection fraction physiology. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04913870 and NCT02395107.

Background: Facial appearance influences social perception, with laypersons focusing on the central facial triangle; nasal differences may alter gaze patterns, but few studies have quantified this using eye-tracking. Objective: To evaluate how layperson gaze patterns shift in response to different nasal variations as measured by eye-tracking. Methods: In this prospective cohort study, facial images with 30 nasal differences were created using Photoshop to represent a range of phenotypes, such as dorsal hump, crooked nose, and pinched tip, alongside controls. Gaze data were captured via eye-tracking, and linear mixed-effects modeling assessed differences in time spent viewing defined areas of interest, adjusting for participant and image variables. Results: A total of 119 participants (53.8% female) were enrolled. The median age was 40 years, and 82% identified as Caucasian. Among the 30 nasal alterations, only the saddle nose resulted in significantly increased gaze time compared to controls (mean increase: 0.89 s; p < 0.001). Participant age, sex, and gender of the face in the image did not significantly influence gaze behavior. Conclusion: In this study, only the saddle nose attracted greater visual attention from lay observers compared with other nasal variants.

ABSTRACT Background Preoperative vascular embolization (PVE) is commonly used in managing juvenile nasopharyngeal angiofibroma (JNA) to improve outcomes. However, few studies have evaluated how embolization patterns and vascular features affect prognosis. Methods A 15‐year retrospective review was performed on 44 patients with JNA undergoing surgery at one institution. Data included demographics, vascular supply, embolization techniques, surgical outcomes, and recurrence. Results Forty‐three patients underwent PVE. Most tumors were embolized transarterially (93.0%) using polyvinyl alcohol‐based agents (79.1%). The internal maxillary artery was most commonly embolized (93.0%). Internal carotid artery supply was present in 34.9%, and more than two vessels were embolized in 23.3%. Postembolization tumor blush occurred in 60.5%, with a median of 5% of the pre‐embolization blush remaining after embolization. Neither internal carotid involvement, number of vessels embolized, nor residual blush significantly impacted operative time, surgical outcomes, or recurrence. Conclusion With effective embolization, vascular complexity might not affect JNA resection outcomes. Multicenter studies are required to confirm those findings.

Abstract Intro: The 70-gene MammaPrint (MP) assay is prognostic for distant recurrence and predictive of benefit from adjuvant chemotherapy (CT) benefit established on surgical tissue of systemically untreated patients (pts). The MP index range is from -1 to +1 with higher index indicating lower risk of early recurrence. Risk is categorized as MP High Risk, MP Low Risk, and MP UltraLow Risk, and results can guide treatment decisions. Pts with MP index &gt;0 are classified as Low Risk and derive little benefit from CT. There are clinical scenarios in which the only available tissue for MP or other genomic testing has been exposed to neoadjuvant endocrine therapy (NET). Few studies have investigated the impact of ET exposure on MP index. Methods: Pts were identified through the I-SPY Low Risk Registry (LRR), an observational sub-study which enrolled pts with hormone receptor positive (HR+)/HER2-negative early breast cancer ineligible for the I-SPY2 trial due to MP Low Risk or UltraLow Risk status, between 2010-2020. Pts were treated at the discretion of their provider. We conducted a retrospective analysis of MP index from paired tumor tissue obtained from systemically untreated diagnostic core biopsies and surgical specimens after NET. MP categories and index before and after NET were compared. Change in MP index was assessed for an association with changes in clinicopathologic factors obtained through the LRR using the paired-t test. Results: 28 pts with paired tumor samples were included in the analysis. Median age was 48 (range 31-75) and 18 (64%) were premenopausal. At baseline, 13 (46%) were clinically node-positive and 22 (76%) had ductal histology. Tumor grade was 1 in 6 pts (21%), 2 in 20 pts (71%), and 3 in 2 pts (7%). ER expression was &gt;95% in 25 pts (range 60-100%) and PR expression was &gt;90% in 14 pts (range 0-100%). NET regimens included tamoxifen +/- ovarian function suppression (OFS) in 3 pts (10.7%), aromatase inhibitor (AI) +/- OFS in 15 pts (53.6%), tamoxifen followed by or in combination with AI +/- OFS in 8 pts (28.6%), fulvestrant in 1 pt (3.6%) and OFS alone in 1 pt (3.6%). 11 (61%) of premenopausal pts received OFS. 96% (27/28) of pts were classified as Low Risk both pre- and post-NET. Only one pt had MP change from Low Risk to High Risk. Three pts had change from Low Risk to UltraLow Risk or vice versa. As a continuous variable, a small average increase in MP index was observed after NET; but, there was a range of responses. 19 pts (68%) had an increase in MP index after NET, while 9 pts (32%) had a decrease. In those with a decrease in MP index, the average ER expression decreased by -13.6%, whereas in those with an increase in MP index, ER expression was unchanged (-0.18%) (p=0.049). There was no significant difference in changes in PR expression between tumors with increased vs decreased MP indices. At a median follow-up of 35 months, 4 distant recurrences were observed. Of the 9 pts with a decrease in MP index, 3 pts (33%), including the one who changed from Low Risk to High Risk, experienced a distant recurrence. In contrast, in those with an increase in MP index, 1 of 19 (5%) experienced a distant recurrence. Conclusion: In pts with early-stage HR+/HER2- MP Low Risk or UltraLow Risk breast cancer, NET had minimal impact on the tumor MP classification. These data suggest that the MP assay could be used for tissue exposed to NET if untreated tissue is not available. Further investigation in larger cohorts is needed to validate these findings. The observation that there were more distant recurrences in pts with tumors that had an increase in MP after NET is hypothesis generating, and potentially clinically relevant if validated in a larger study. The potential of MP as a dynamic risk marker to stratify recurrence risk following NET is being evaluated in the ongoing I-SPY2 Endocrine Optimization Pilot. Citation Format: S. Jacob, C. Wu, A. Glas, C. Yau, L. Brown-Swigart, G. Hirst, T. Haddad, K. Giridhar, A. Elias, R. Mukhtar, L. Huppert, K. Albain, D. Yee, L. van’t Veer, L. Esserman, J. Chien. Impact of Neoadjuvant Endocrine Therapy on MammaPrint Index in Hormone Receptor-Positive, HER2-Negative MammaPrint Low Risk Early-Stage Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-05-28.