Background/Objectives: Anaplastic thyroid cancer (ATC) is a rare and highly aggressive thyroid malignancy with limited treatment options. Loss of the sodium/iodide symporter makes ATC resistant to radioactive iodine therapy, highlighting the need for alternative therapeutic targets. This study evaluated L-type amino acid transporter 1 (LAT-1) and vitamin D receptor (VDR) as potential targets in ATC. Methods: We examined LAT-1 (SLC7A5) and VDR gene expression using TCGA data from the UALCAN database. Protein expression was evaluated by immunohistochemistry in 28 formalin-fixed, paraffin-embedded ATC specimens from Loma Linda University Health. We assessed staining intensity and distribution and compared expression between male and female patients. Results: TCGA analysis showed significantly higher SLC7A5 expression in thyroid tumors compared with normal thyroid tissue (*p = 0.0115), while VDR was strongly increased in tumors (**p < 0.001) and across all tumor stages. All 28 ATC specimens expressed both LAT-1 and VDR, although staining intensity and distribution varied among tumors. LAT-1 was primarily localized to the membrane and cytoplasm of tumor cells, with additional expression in stromal and endothelial cells. VDR showed membranous, cytoplasmic, and occasional nuclear expression. LAT-1 expression did not differ significantly by sex (ns, not significant, p = 0.19), whereas VDR expression was significantly higher in females than males (**p = 0.0014). Conclusions: LAT-1 and VDR are broadly expressed in ATC despite substantial intratumoral heterogeneity. Their consistent expression supports further investigation as potential targets for radioligand or other ligand-directed therapies. The higher VDR expression observed in female patients also suggests a potentially important sex-associated difference that warrants validation in larger ATC cohorts.

Background/Objectives: Thyroid cancer spans indolent differentiated tumors to lethal poorly differentiated and anaplastic carcinomas, and histopathology and molecular testing do not capture the spatial organization of tumor, stromal, and immune compartments that underlies invasion, dedifferentiation, and treatment resistance. Spatial transcriptomics profiles gene expression in situ. We systematically reviewed its platforms, applications, and findings in thyroid cancer. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched, following PRISMA 2020 guidance and supplemented by citation chasing, for English-language primary studies applying spatially resolved transcriptomics to thyroid cancer tissue. Subtype, platform, complementary methods, and principal findings were extracted, and each study was appraised item by item with the design-matched Joanna Briggs Institute (JBI) checklist. Results: Of 104 records, 21 studies were included: 12 case series, four analytical cross-sectional studies, three single-case reports, and two reanalyses of one public dataset. Nineteen used capture-based whole-transcriptome platforms, predominantly 10x Visium, and two used GeoMx digital spatial profiling; papillary thyroid carcinoma predominated, and medullary carcinoma was not examined. Tumor-microenvironment remodeling accompanying dedifferentiation toward anaplastic carcinoma was replicated in five independent cohorts. Cancer-associated fibroblast activation was reported in three cohorts, although the SERPINE1-positive and POSTN-positive programs were each single-cohort; APOE-linked tumor states appeared in two cohorts with opposite directionality; and invasive-front extracellular-matrix dysregulation in follicular tumors was reported in two. Six studies reported functional perturbation and 12 protein-level validation; no biomarker had independent external validation. Methodological concern was low in four studies, moderate in seven, and high in 10: only one of 12 case series reported consecutive and complete inclusion, eight reported no outcomes for the profiled patients, and nine analyzed spots or cells rather than patients. Conclusions: Spatial transcriptomics has resolved reproducible microenvironmental remodeling during dedifferentiation, but its prognostic and mechanistic claims rest on small, selected cohorts without independent validation. Larger, consecutively enrolled, clinically annotated studies are needed.

Background/Objectives: Among endocrine malignancies, thyroid cancer is the most prevalent and encompasses a broad clinical spectrum, ranging from indolent differentiated tumors to highly aggressive poorly differentiated and anaplastic thyroid carcinomas. Histopathology and molecular testing incompletely capture the spatial organization of tumor, stromal, and immune compartments that drives invasion, dedifferentiation, and treatment resistance. Spatial transcriptomics preserves tissue architecture while profiling gene expression, mapping molecular programs onto histologic context. We systematically reviewed its platforms, applications, and biological insights in thyroid cancer. Methods: PubMed/MEDLINE, Scopus, and Web of Science Core Collection were searched for English-language studies combining spatial-transcriptomic and thyroid-cancer concepts, following PRISMA 2020 guidance. Primary studies that applied a spatially resolved transcriptomic method to thyroid cancer tissue and reported spatial gene-expression findings were included; data were extracted on subtype, platform, complementary methods, and principal findings. Results: Of 104 records (47 after de-duplication), 21 studies met the inclusion criteria. Most used capture-based whole-transcriptome profiling, particularly 10x Visium, while GeoMx digital spatial profiling supported FFPE-compatible biomarker studies. Recurrent findings included POSTN+ and SERPINE1+ cancer-associated fibroblast programs at invasive fronts, APOE-linked immunosuppressive states, organized immune-evasion niches, and progressive tumor-microenvironment remodeling accompanying dedifferentiation toward ATC. Spatial transcriptomics also clarified invasion, lymph node and distant metastasis, and cell–cell communication. Conclusions: Spatial transcriptomics is opening new avenues for dissecting thyroid cancer progression, but current evidence is limited by small cohorts, platform concentration, and variable validation. Larger, standardized, clinically annotated studies are needed to define reproducible spatial biomarkers.

Purpose: To evaluate whether intrarenal antibiotic-augmented irrigation with neomycin/polymyxin B during percutaneous nephrolithotomy (PCNL) in patients at high risk for infection was associated with lower postoperative infectious complications and reduced infection-related resource utilization. Materials and Methods: We performed a single-center, retrospective matched cohort study of adults undergoing PCNL who were at high risk for infection between January 2020 and December 2024. Fifty patients who received intrarenal neomycin/polymyxin B irrigation (1 mL GU irrigant per 3-L saline bag) were matched 1:1 to controls receiving standard saline irrigation by age, sex, diabetes, Charlson Comorbidity Index, and preoperative urinary drainage. The primary end-point was symptomatic urinary tract infection (UTI) within 30 days. Secondary outcomes included systemic inflammatory response syndrome (SIRS), sepsis during index hospitalization, infection-related prolonged hospitalization, emergency department visits for infection, and 30-day infection-related readmission. Results: Thirty-day UTI occurred in 3/50 patients (6.0%) in the GU group vs 17/50 (34.0%) in controls (number needed to treat 3.6; p = 0.001). SIRS occurred in 16.0% vs 48.0% ( p = 0.001), sepsis during index hospitalization in 0% vs 16.0% ( p = 0.006), and infection-related prolonged hospitalization in 0% vs 20.0% ( p = 0.001). In adjusted analysis ( n = 99), GU irrigation remained independently associated with lower 30-day UTI risk (adjusted OR 0.11, 95% CI 0.03–0.44; p = 0.002). Short-term renal safety outcomes were comparable between groups. Modeled economic analysis suggested potential net savings of approximately $7800 per patient. Conclusions: In this matched cohort of PCNL patients at high risk for infection, intrarenal neomycin/polymyxin B irrigation was associated with substantially lower postoperative infectious morbidity, including elimination of sepsis during index hospitalization, with comparable short-term renal safety outcomes.