Objective: To investigate the clinicopathological features, immunophenotype, molecular genetic alterations and differential diagnosis of undifferentiated sarcoma with NR1D1 rearrangement. Methods: The clinicopathological data of two undifferentiated sarcomas with NR1D1 rearrangement were collected at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from January 2023 to December 2025. Histopathological observation, immunohistochemical staining, and next-generation sequencing (NGS) were performed, combined with a literature review. Results: Both patients were male, aged 20 and 29 years, with tumors located in the soft tissues of left knee joint and right foot, respectively. Microscopically, the tumors were epithelioid/short spindle-shaped, with diffuse and sheet-like distribution. Some tumor cells presented clear cytoplasm, slightly vacuolated nuclei with prominent nucleoli, and frequent mitoses. Focal loose stroma with microcystic formation, small necrotic foci, and scattered neutrophil infiltration were observed. The tumor cells focally expressed CKpan and CD99 in both cases. One case was positive for SATB2, Syn and cyclin D1. Both cases were negative for ERG, CD34, NKX2.2, NKX3.1, S-100, SOX10, WT-1, HMB45, Melan A, FOSB, CgA, Desmin, and MyoD1. Loss of expression was not observed for H3K27me3, INI-1, and BRG1. The Ki-67 proliferation index ranged from 20% to 30%. NGS identified NR1D1::MAML1 gene fusion in both cases. Both patients received postoperative chemotherapy but experienced early recurrence and multifocal lung metastases, including one case complicated with lymph node metastases. They died at 13 and 25 months of follow-up, respectively. Conclusions: Undifferentiated sarcoma with NR1D1 rearrangement is a rare, newly recognized, and highly aggressive subtype of sarcoma. It predominantly occurs in the soft tissue of extremities in young adult males and presents characteristic histomorphology. Molecular detection confirming NR1D1::MAML1 fusion is its diagnostic hallmark. This tumor shows poor response to conventional chemotherapy and often has early recurrence and distant metastasis with high mortality.

Metastatic prostate cancer (PC) initially responds to androgen deprivation therapy (ADT) but often progresses to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) expression, partly regulated by promoter-associated CpG methylation, plays a pivotal role in disease progression and therapeutic resistance. In this study, 146 formalin-fixed, paraffin-embedded (FFPE) prostate-related tissue specimens representing five disease states-non-malignant prostate tissue, primary localized PC, hormone-naïve bone metastases, short-term castration metastases, and CRPC bone metastases-were evaluated. Genome-wide promoter methylation was profiled, and AR expression was quantified at transcript and protein levels. Nuclear AR H-score (0-300) was used as the principal protein-level measure. AR H-score differed across clinical states (one-way ANOVA, F = 13.72, p < 0.001). Using the cohort median promoter-methylation beta value (0.51195) as the binary cutpoint, the distribution of low versus high methylation did not differ significantly across the five clinical groups (χ[2] = 8.42, df = 4, p = 0.077), whereas continuous promoter methylation was inversely correlated with AR H-score (r = -0.480, 95% CI -0.596 to -0.344, p < 0.001). Among the 134 malignant cases included in survival analyses, the AR-high stratum showed longer observed median PFS and OS than the AR-low stratum, while the MCA Kaplan-Meier curves showed substantial overlap. Accordingly, the data support stage-related AR remodeling and an inverse AR-methylation relationship, but do not establish a simple adverse-prognostic effect of high AR expression. The MCA remains exploratory and requires independent validation.

Infections caused by nontuberculous mycobacteria (NTM), especially Mycobacterium kansasii, are characterized by nonspecific clinical manifestations. Moreover, their radiological features frequently overlap with those of both tuberculosis (TB) infections and lung cancer, which significantly complicates the differential diagnosis. We present a case of a patient with Parkinson's disease (PD) who was admitted with cough and sputum production and dyspnea. Chest computed tomography (CT) revealed atelectasis, multiple solid nodules, osteolytic lesions in multiple ribs, and pleural effusion. The initial diagnostic evaluation raised the suspicion of a lung cancer with multiple bone metastases. While acid-fast staining (AFS) of biopsy tissue was positive, polymerase chain reaction (PCR) for TB was negative. Ultimately, targeted next-generation sequencing (tNGS) of sputum detected M. kansasii, considering the diagnosis of pulmonary M. kansasii infection. This case highlights the need to consider M. kansasii infection in atypical imaging findings and the utility of tNGS for diagnosis when conventional tests are inconclusive.

To our knowledge, clinically meaningful restoration of radioiodine avidity in established radioiodine-refractory differentiated thyroid cancer has not been reported after multikinase inhibitor therapy, despite successful redifferentiation reported with selective kinase inhibitors targeting BRAF, RAS, RET or NTRK. We report a 53-year-old woman with invasive follicular variant papillary thyroid carcinoma and synchronous cervical lymph node, pulmonary and bone metastases who underwent six cycles of radioiodine therapy within 3 years after total thyroidectomy. Initially radioiodine-avid metastases gradually lost radioiodine avidity, as suggested by serial post-radioiodine therapy whole-body scans. Lenvatinib was initiated after 3 years of active surveillance. Restored radioiodine uptake was observed on rhTSH-assisted diagnostic whole-body scan after 9 months of lenvatinib treatment, allowing subsequent salvage radioiodine therapy. Subsequent post-radioiodine therapy whole-body scans showed increased uptake intensity and additional radioiodine-avid bone metastases, with a marked decrease in suppressed thyroglobulin. Reassessment of radioiodine avidity after prolonged multikinase inhibitor treatment warrants clinical consideration to determine the feasibility of salvage radioiodine therapy.

Bone metastases are a major cause of pain, skeletal complications, marrow compromise and mortality in advanced prostate cancer. The therapeutic biology of skeletal disease is heterogeneous: malignant epithelial cells expressing prostate-specific membrane antigen (PSMA) coexist with osteoblasts, osteoclasts, reactive mineralising bone and variable marrow infiltration. Radium-223 dichloride is a bone-seeking alpha emitter with randomised evidence of overall-survival benefit in selected men with metastatic castration-resistant prostate cancer (mCRPC), whereas PSMA-targeted radioligand therapy delivers radiation to PSMA-expressing tumour deposits in bone and soft tissues. Their mechanistic complementarity has motivated sequential and concurrent strategies, but complementary localisation does not itself establish clinical synergy. This review critically integrates ALSYMPCA, ERA-223, PEACE-3, VISION, TheraP, PSMAfore, RALU and AlphaBet, together with radiobiology, molecular imaging, marrow and skeletal toxicity, dosimetry and evolving therapeutic sequencing. The final 133-patient retrospective RALU report describes the safety and outcomes observed after radium-223 followed by lutetium-177-PSMA in selected heavily pretreated patients; AlphaBet reports preliminary safety and antitumour activity with concurrent lutetium-177-PSMA-I&T and radium-223 in a single-arm early-phase study. Neither provides randomised evidence of an incremental survival benefit for dual-radionuclide treatment. Conversely, PEACE-3 establishes an overall-survival benefit for radium-223 combined with enzalutamide under contemporary bone-protective practice, whereas ERA-223 underscores the fracture hazards of inappropriate combinations. Future trials must integrate lesion-level imaging, whole-body disease phenotype, marrow reserve, patient-reported outcomes, competing systemic treatments and personalised radiation exposure. The most defensible clinical strategy is evidence-weighted selection of radionuclide therapy according to disease distribution and treatment history, with concurrent dual-radionuclide approaches restricted to appropriately governed trials.

Ewing sarcoma is an aggressive bone cancer of children and young adults. Survivors face long-term complications from intensive chemotherapy and outcomes remain stubbornly poor for patients with metastases. There is an urgent need for improved treatments. Emerging evidence suggests Ewing sarcoma is particularly sensitive to perturbed iron homeostasis. As iron contributes to many critical processes, there are multiple mechanisms to disrupt iron metabolism. Several pre-clinical studies exploiting altered iron homeostasis in Ewing sarcoma report encouraging results. This review summarizes unique features of and ways to target iron metabolism in Ewing sarcoma, and the translational potential for these therapeutic strategies.

Bone metastases are a significant source of morbidity in advanced malignancy, particularly in prostate cancer, because osteoblastic metastases can cause pain, skeletal-related events, and quality-of-life impairment. Bone-targeting radionuclide drugs are also effective in the treatment of increased bone turnover and were first developed as β-emitters for palliation but have been developed in recent years as α-emitters with proven survival benefit. This review covers the biology, history, and mechanism of action of the approved bone-targeting radiopharmaceuticals ([89]Sr-chloride, [153]Sm-lexidronam, [223]Ra-dichloride). Special focus is placed on the only bone-targeting radiopharmaceutical currently approved in the United States-[223]Ra-dichloride-including patient selection, administration, radiation safety, and follow-up. [223]Ra, a calcium analog with a short α-particle path length, high linear energy transfer, and marrow-sparing properties, is valuable in the treatment of metastatic androgen pathway modulator-resistant prostate cancer (formerly metastatic castration-resistant prostate cancer) with bone-predominant disease and symptoms. The practical aspects of nuclear medicine are emphasized, such as imaging confirmation, laboratory value thresholds, written instructions, room preparation, contamination control, discharge instructions, and posttreatment monitoring. Bone-targeting radiopharmaceutical therapy has increasingly attractive options beyond palliation with new combination and sequencing treatment options involving prostate-specific membrane antigen-targeted therapy. The lessons learned from the shift from "β-blasts" to "α-bombs" provide a potential pathway to more effective current treatment and a new generation of targeted radiopharmaceutical therapy.