A 59-year-old woman presented with a four-month history of progressive visual loss and floaters in her left eye. Her medical history included hypothyroidism, psoriasis, and type 2 diabetes. Fundus examination revealed choroidal folds, an amelanotic lesion temporal to the fovea, and an exudative retinal detachment. Optical coherence tomography (OCT) demonstrated a choroidal mass without subretinal fluid, while indocyanine green angiography (ICGA) showed a hypocyanescent lesion with no intrinsic vascularity. B-scan ultrasonography revealed an inhomogeneous choroidal mass with retrobulbar fluid (positive T-sign). Blood tests revealed elevated C-reactive protein (CRP) and liver enzymes levels, together with positive antinuclear antibodies (ANA), while the chest X-ray was normal. The overall clinical and imaging findings were consistent with nodular granulomatous scleritis. Choroidal melanoma, uveal lymphoma, primary vitreoretinal lymphoma, and choroidal hemangioma were excluded based on their imaging characteristics. Treatment with systemic corticosteroids resulted in rapid visual improvement and complete resolution of the lesion. This case demonstrates how inflammatory choroidal lesions can mimic intraocular tumors. Recognizing characteristic multimodal imaging features (choroidal folds, preserved choroidal vasculature on ICGA, positive T-sign on ultrasonography) can enable a confident diagnosis without biopsy, avoiding unnecessary treatment and delays in cancer diagnosis.

WNK2 is a known tumor suppressor in a set of solid tumors, including glioblastoma multiforme and pancreatic ductal adenocarcinoma. WNK2 functions are largely unknown beyond the kinase domain (KD)-dependent inhibition of ERK1/2 signaling. Waldenström's Macroglobulinemia (WM) is an indolent, yet incurable, B cell lymphoma characterized by highly recurrent MYD88 (MYD88[MUT]) and CXCR4 (CXCR4[MUT]) mutations that trigger sustained NF-κB and ERK1/2 signaling. Although not expressed in healthy B cells, WNK2 is a top dysregulated gene in MYD88[MUT] WM. To study WNK2 regulation and signaling, we performed multi-omics analyses, including bulk and PacBio Iso-Seq RNA-Seq and methylome, in 264 untreated WM and functional studies in cell lines and primary WM cells. Aberrant expression of WNK2 emerged as a near universal feature of early-stage WM and a hallmark of plasma cell-like MYD88[MUT] WM. We identified novel isoforms that carried a shared aberrant splicing event, either contained or lacked the KD and were highly expressed by the tumor cells, unlike the canonical full-length isoforms. Functionally, WNK2/S-NK1, the most expressed of the KD-lacking isoforms in WM, triggered a pro-inflammatory cascade that activated ERK1/2 and NF-κB signaling. We observed a similar, cancer-specific upregulation of WNK2 in a set of solid tumors, including the highly aggressive cholangiocarcinoma. Our findings reveal an undocumented oncogenic function for WNK2 driven by novel, cancer-specific isoforms and provide a framework for its further investigation as a determinant of disease progression in MYD88[MUT] WM and a novel therapeutic target in hematological and solid tumor oncology.

<p><strong>Introduction: </strong>Although genetic mutations have been reported in neuroendocrine carcinomas of unknown primary (NECs-UP), no scientifically validated targeted therapies are currently available. Moreover, cancer genomic profiling tests remain underutilized in clinical practice. These issues highlight the urgent need to elucidate the genomic landscape of NECs-UP and its potential therapeutic relevance.</p><p><strong>Aim:</strong> This study aimed to characterize the mutational profile of recurrent and/or metastatic NEC-UP.</p><p><strong>Materials and methods: </strong>Data were analyzed for 122 consecutive patients with NECs-UP registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and August 2025. Genetic mutations were determined by next-generation sequencing. Survival of patients was determined by log-rank test and a Cox proportional hazards model.</p><p><strong>Results: </strong>The top 10 mutations in NECs-UP were <em>TP53</em> (71.3%), <em>RB1</em> (49.2%), <em>KMT2D</em> (24.6%),<em> NOTCH1</em> (20.5%), <em>CDKN2A</em> (18.0%), <em>SPEN</em> (15.6%), <em>ARID1A</em> (15.6%), RICTOR (15.6%), <em>CIC</em> (14.8%), <em>SDHA</em> (14.8%), with 16.3 7.1 (mean SD) mutations/individual. Mutation in TP53 (p = 0.0474) and CIC (p = 0.0322) were associated with a significantly worse prognosis, as determined by log-rank test. The hazard ratios for cases with this mutation was 2.0550 (95% CI, 1.0540-4.006, p = 0.03455) for <em>CIC</em>.</p><p><strong>Conclusions: </strong>This study delineated the mutational spectrum of recurrent and/or metastatic NECs-UP. Even in advanced disease, prognostically relevant mutations were identified, emphasizing the clinical importance of cancer genomic profiling tests.</p&gt.

As the primary receptor of oxidized low-density lipoprotein (ox-LDL), LOX-1 is a putative therapeutic target for atherosclerotic disorders including ischemic stroke (IS), whereas the regulatory mechanism of LOX-1 remains largely unknown in IS. We employed computational algorithms to screen candidate miRNAs, followed by integrative analysis of differentially expressed miRNA profiles derived from blood cells of 25 acute IS cases and 25 controls matched with age and gender. MiR-187-3p-mediated regulation of LOX-1 was confirmed by a dual-luciferase reporter assay and Western Blot in THP-1 derived macrophages. Elevated blood levels of miR-187-3p were observed both in IS patients and the atherosclerotic mice. In a case-control study enrolling 279 IS cases and 279 controls, we found that miR-187-3p level was significantly associated with the occurrence of IS (adjusted OR = 1.204; 95% CI: 1.086-1.335; p < 0.001). Similar results were replicated in another coronary heart disease case-control population. In vivo, systemic delivery of agomiR-187-3p significantly reduced atherosclerotic plaque burden alongside decreased plasma lipids and suppressed inflammation. In vitro, miR-187-3p over-expression attenuated foam cell formation induced by ox-LDL and down-regulated pro-inflammatory mediators in macrophages. Conversely, miR-187-3p inhibition exacerbated these effects, which were partially rescued by LOX-1 inhibitor BI-0115. This study establishes miR-187-3p as a novel epigenetic regulator of LOX-1 and provides critical evidence supporting its therapeutic potential for modulating IS progression.

Somatostatin receptor (SSTR) imaging is the preferred modality for staging well-differentiated neuroendocrine tumors (NETs) and detecting unknown primary NETs. If SSTR imaging is negative, 18F-FDG PET/CT may be done to rule out tumor heterogeneity. We report a case of a 36-year-old woman with a well-differentiated grade I NET, who initially presented with severe right hypochondriac pain and vomiting. Standard diagnostic workup with 68Ga-DOTANOC followed by 18F-FDG PET/CT was negative; however, 68Ga-FAPI-04 PET/CT demonstrated intense tracer-avid lesions in pancreatic primary and liver metastases.