Breast cancer is often treated with tamoxifen, a drug that can cause ocular side effects, including toxic retinopathy. Multimodal imaging, particularly optical coherence tomography (OCT), has improved the detection of early lesions such as foveal pseudocysts, thus increasing the prevalence of this complication. We present a case of tamoxifen-induced retinopathy in a patient treated for four years who developed decreased visual acuity with irreversible retinal lesions in the right eye despite discontinuation of the treatment. OCT was essential in characterizing the lesions. The pathophysiology remains poorly understood, but involvement of Müller cells and glutamate accumulation in the retinal pigment epithelium are suspected. Toxicity depends on cumulative dose, duration of treatment, and individual factors. Initial ophthalmologic screening and regular OCT monitoring are recommended to detect retinal damage early. In case of lesions, substitution with an aromatase inhibitor is often considered to limit lesion progression and preserve vision.

Immunotherapy has become the treatment of choice in a lot of metastatic diseases including melanoma, improving the prognosis. However, there are a lot of specific and multisystemic side effects. We report the case of a 68-year-old woman treated with combined immunotherapy for a metastatic melanoma who presented a severe right eye sight loss due to a papillary edema.

Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathy characterized by mechanical hemolytic anemia, thrombocytopenia, and multiorgan dysfunction, resulting from a severe deficiency of ADAMTS13. Among its rare forms, paraneoplastic TTP remains poorly described. We report here the case of a patient in the intensive care unit presenting with paraneoplastic TTP associated with metastatic prostate cancer. This case illustrates the diagnostic challenge posed by the interplay of multiple mechanisms and allows discussion of the different therapeutic options according to the type of TTP, including the role of plasma exchange in paraneoplastic TTP.

Beyond established rare fusions, such as ALK and ROS1, emerging ultrarare fusions involving receptor tyrosine kinases or their ligands, including EGFR-SHC1, further guide us to uncover novel mechanisms of oncogenic activation and corresponding treatment strategies. Collectively, rare and ultrarare genomic events are driving precision oncology toward an increasingly individualized era of "ultraprecision" cancer therapy. See related article by Zheng et al., p. 1573.

Imatinib is the standard first-line therapy for chronic myeloid leukemia (CML) and is generally well tolerated. Gastrointestinal adverse effects are common; however, gastric antral vascular ectasia (GAVE) is an extremely rare complication. We report a 77-year-old woman with chronic-phase CML who developed severe upper gastrointestinal bleeding 1 month after the initiation of imatinib therapy. Endoscopy revealed classic features of GAVE, and no alternative etiology was identified. Discontinuation of imatinib resulted in complete clinical and endoscopic resolution. Clinicians should consider this rare complication in patients receiving imatinib who present with unexplained anemia or gastrointestinal bleeding.

Systemic sclerosis (SSc) is a complex autoimmune disease marked by vasculopathy, fibrosis, and multisystem involvement. Interstitial lung disease (ILD) and pulmonary hypertension (PH) are major mortality contributors. Importantly, SSc is associated with an increased risk of malignancy. This report presents a challenging case of SSc with severe Raynaud's phenomenon (RP), digital gangrene, calcinosis cutis, extensive ILD, severe PH, and right heart failure. The patient underwent mesenchymal stem cell therapy (MST), following which she developed breast cancer and chemotherapy-related complications, ultimately leading to death. This case highlights the need for timely intervention, screening for malignancy, and awareness of potential therapy-related risks in SSc.

The occurrence of dual primary malignancies is an uncommon clinical phenomenon. This case report details a 65-year-old female presenting with both uterine leiomyosarcoma (LMS) and pulmonary adenocarcinoma, initially misdiagnosed as a metastatic spindle cell tumor.

The patient presented with foul-smelling vaginal discharge, irregular menses, lower limb swelling, and a nonproductive cough. Imaging and biopsies revealed a necrotic uterine mass diagnosed as LMS and a left upper lobe lung mass identified as adenocarcinoma. Genetic testing of the lung tumor showed an epidermal growth factor receptor (EGFR) exon 19 deletion mutation. Treatment included chemotherapy targeting both malignancies, surgical resection of the uterine tumor, and targeted therapy for the lung adenocarcinoma.

This case underscores the importance of thorough diagnostic evaluation in patients with multiple tumors to distinguish between metastatic disease and dual primary malignancies, as treatment strategies differ significantly.

Differentiating radiation necrosis (RN) from tumor progression is challenging despite advanced neuroimaging techniques. We collected a consecutive series of surgically resected RN with presumptive diagnosis of recurrent/refractory brain metastasis (BM) after radiation therapy (RT) and performed a descriptive analysis of characteristics and clinical courses.

From 107 patients who underwent surgery to remove previously irradiated BM, we retrieved 18 patients with pathologically confirmed pure RN.

Sixteen patients (89%) had preoperative MRI suggesting recurrent/refractory BM in accordance with clinical suspicion, and 14 (78%) patients showed radiological response after RT before progression. The median time from RT to surgery was 28.5 months (range 6-94 months). RT doses varied from 1,800 cGy/single fraction to 8,300 cGy/21 fractions. Lobulated/irregular shape, central necrosis, and substantial increase of perilesional edema were dominant MRI features. Neurological symptoms improved or stabilized in 13 patients (72%) after surgery. Five cases of distant recurrences occurred in patients with uncontrolled systemic cancer, except for one patient with controlled small cell lung cancer who recurred as a leptomeningeal metastasis. One patient had multiple enhancing lesions along the surgical cavity, suggesting local recurrence. Median overall survival after surgical removal of RN was 34 months (range 4.3-132 months), and eight out of eleven patients with controlled systemic cancer remained alive at last follow-up.

RN frequently mimics recurrent BM despite advanced imaging. Surgical resection provides both definitive diagnosis and symptomatic benefit in selected patients. However, distant recurrence of BM could happen in patients with uncontrolled systemic cancer.

To conduct a meta-analysis assessing the effectiveness of cine MRI in evaluating tumor invasion of the chest wall, using surgical and histopathologic analysis as the reference standard.

This systematic review and meta-analysis was conducted following the recommendations of the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guidelines. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420250654330.

Five prospective studies comprising 190 patients with suspected chest wall invasion were included. The pooled sensitivity of cine MRI for detecting chest wall invasion was 99% (95% CI: 34%-100%), with a specificity of 74% (95% CI: 64%-82%), a negative predictive value of 100% (95% CI: 52%-100%), and a positive predictive value of 50% (95% CI: 39%-61%). No substantial heterogeneity was observed across studies.

Cine MRI showed high sensitivity and excellent negative predictive value for ruling out chest wall invasion in lung cancer. These findings suggest cine MRI may be a useful noninvasive tool for preoperative assessment, particularly in cases with inconclusive CT or static MRI; however, CIs were wide due to the limited evidence base. Conversely, when cine MRI suggests invasion, the modest specificity and positive predictive value highlight the importance of invasive confirmation before definitive therapeutic decisions. Further prospective, multicenter studies using standardized protocols are warranted to validate and expand its clinical application.

NTRK fusions drive the pathogenesis of a distinctive group of mesenchymal neoplasms with significant impact on classification and targeted therapy. However, unexpected NTRK fusions have been reported in other sarcoma entities, raising uncertainty over their specificity and clinical management. Herein, we investigate the incidence and structural variants of NTRK fusions among a large clinicopathologic and molecular sarcoma cohort. The goal was to distinguish primary driver NTRK fusions from potential passenger events and correlate with sarcoma histotypes. NTRK1-3 fusions were queried across a large spectrum of sarcomas, profiled by targeted DNA and/or RNAseq. Fusions were classified as oncogenic when NTRK was the 3' partner, in-frame, retained kinase domain (KD), and/or RNAseq confirmation; fusions of uncertain significance (FUS) when out-of-frame, lacking full KD, and/or RNAseq negative. We identified 48 cases with NTRK fusions, detected either by pathologist-initiated RNAseq for diagnosis (n = 27) or by clinician-initiated DNAseq for therapeutic target discovery (n = 21). For the latter subset, reflex RNAseq was activated for confirmation. Integrated review confirmed 33 (69%) oncogenic fusions. Remaining were FUS, apart from one indeterminate. In all except three cases, oncogenic fusions occurred in canonical NTRK-driven histotypes. In contrast, NTRK FUS were detected in various pathologic entities, including well-differentiated/dedifferentiated liposarcoma (n = 9, 60%), two osteosarcoma, and single cases of other subtypes. NTRK1 fusions were the most common in both oncogenic and FUS groups (61%, 67%). CDKN2A/B deletions were observed mostly in oncogenic NTRK1 fusions (71%), while MDM2/CDK4 amplifications in the NTRK1 FUS. The FUS group demonstrated lower NTRK mRNA expression, with a mean of -4.60, p < 0.001. Pan-TRK immunohistochemistry was positive in cases with oncogenic NTRK fusions, and negative in FUS cases. Only two-thirds of NTRK fusions detected were functional drivers, mostly from pathologist-driven testing of suggestive histotypes. In contrast, genomic profiling in complex sarcomas often yields passenger FUS, lacking functional impact.