Nuclear protein in testis (NUT) carcinoma, formerly referred to as NUT midline carcinoma, is an exceptionally rare and aggressive malignancy. Evidence guiding radiotherapy-based management is limited, especially for nasal primary tumors with neuroaxis and systemic dissemination.

A 40-year-old woman was referred after resection of a nasal cavity malignancy. During the subsequent course, she experienced orbital pain, headache, visual impairment, severe lumbar and radicular pain, bilateral lower-limb paralysis, urinary retention, malignant pleural effusion, and widespread metastatic disease.

Pathologic consultation supported nasal NUT carcinoma, with positive NUT immunostaining and a Ki-67 index of approximately 70%. External molecular testing was reported to confirm a NUTM1 rearrangement, although the original report could not be obtained for review, and the assay platform and fusion partner could not be independently verified.

After surgery, the patient received postoperative VMAT/IMRT to 70 Gy in 35 fractions with concurrent cisplatin. Following leptomeningeal, cauda equina, and extensive osseous dissemination, she received palliative helical IMRT/Tomotherapy craniospinal irradiation to 15 Gy in 10 fractions. A later VMAT plan delivered 30 Gy in 10 fractions to one lumbar and 2 hepatic targets. Pembrolizumab, bevacizumab, temozolomide, pleural drainage, and intrapleural therapy overlapped with different treatment phases.

During the first course, headache severity decreased from 8/10 to 2.5/10 on a visual analog scale, and clinically recorded Snellen visual acuity improved from 20/200 to 20/50. Pain relief was documented after craniospinal irradiation and after the third treatment course. Serial imaging was contemporaneously interpreted as indicating interval reduction in selected lesions after radiation-containing multimodal treatment phases, although uniform retrospective remeasurement was not feasible. According to telephone follow-up with the patient's family, the patient died approximately 12 months after surgery.

Repeated clinical and imaging responses were observed following multiple phases of multimodal treatment incorporating radiotherapy. Because systemic therapies were administered during overlapping periods, the independent contribution of radiotherapy could not be isolated. Radiotherapy may provide clinically meaningful local or palliative benefit as part of individualized multimodal treatment in selected patients.

Coinfection with Pneumocystis jirovecii and Aspergillus fumigatus in immunocompromised patients carries high mortality. More importantly, paradoxical clinical and radiological responses during treatment remain poorly understood.

A 66-year-old male with mantle cell lymphoma who had received prolonged corticosteroid therapy after suspected rituximab-associated lung injury presented with progressive pulmonary symptoms.

Concurrent pulmonary infection with P jirovecii and A fumigatus was confirmed by bronchoalveolar lavage combined with metagenomic next-generation sequencing.

The patient was treated with trimethoprim-sulfamethoxazole and voriconazole.

Clinical symptoms improved markedly; however, chest imaging showed paradoxical progression, possibly reflecting an immune reconstitution inflammatory syndrome-like inflammatory response.

bronchoalveolar lavage combined with metagenomic next-generation sequencing enables rapid diagnosis of concurrent opportunistic pulmonary infections. Paradoxical radiographic worsening despite clinical improvement may suggest an immune reconstitution inflammatory syndrome-like inflammatory response, although persistent or progressive infection cannot be excluded.

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal manifestation of non-Hodgkin lymphoma (NHL) that can closely resemble breast carcinoma clinically and radiologically. This overlap may delay accurate diagnosis and appropriate treatment. We report a case of PB-DLBCL in a postmenopausal woman whose initial multimodal imaging findings were suspicious for breast carcinoma, but whose final diagnosis was established by core needle biopsy with immunohistochemical and molecular evaluation.

A 59-year-old postmenopausal woman presented with a painless, palpable mass in the right breast that had been present for approximately 3 weeks.

Breast ultrasonography, mammography, magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) demonstrated a suspicious right breast mass with ipsilateral axillary lymphadenopathy, initially raising concern for breast carcinoma. Ultrasound-guided core needle biopsy showed diffuse infiltration by atypical lymphoid cells. Immunohistochemistry confirmed a B-cell phenotype, and fluorescence in situ hybridization (FISH) showed no MYC, BCL2, or BCL6 rearrangements. Bone marrow biopsy showed no evidence of marrow involvement. The final diagnosis was PB-DLBCL, non-germinal center B-cell-like (non-GCB) subtype, Ann Arbor stage IIE.

The patient received 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy. No breast-directed surgery, consolidative radiotherapy, or central nervous system prophylaxis was administered.

At 6 weeks after completion of R-CHOP therapy, PET/CT showed complete metabolic resolution of the right breast lesion, with only a residual punctate calcified focus measuring approximately 0.4 × 0.4 × 0.3 cm. The Deauville score decreased from 5 at baseline to 1 after treatment, meeting Lugano criteria for complete response. No clinically significant treatment-related adverse events were documented.

PB-DLBCL can closely mimic breast carcinoma on multimodal imaging. Suspicious breast imaging findings do not exclude lymphoma. Tissue diagnosis with adequate immunophenotypic and molecular evaluation is essential before definitive treatment planning to avoid misdiagnosis and unnecessary surgery.

Dedifferentiated endometrial carcinoma (DEC) is a rare and aggressive subtype of endometrial cancer comprising undifferentiated carcinoma and a low-grade endometrioid component. Although POLE-mutated tumors usually show favorable outcomes owing to their ultramutated and immunogenic nature, the clinical relevance of POLE mutations in DEC remains unclear. In particular, the therapeutic effects of immune checkpoint inhibitors in POLE-mutated DEC with brain metastases have not been well characterized.

Here, we report the case of a 58-year-old woman with POLE-mutated DEC who presented with headache, dizziness, and generalized weakness due to multiple brain and pulmonary metastases. The clinical course, pathological and genomic findings, multidisciplinary treatment, and treatment outcomes were evaluated.

Endometrial biopsy confirmed dedifferentiated carcinoma. Genomic profiling identified a pathogenic POLE exonuclease domain mutation (V411L) and a high tumor mutational burden (49.7 mutations/Mb).

The patient underwent urgent cerebellar resection, followed by radiotherapy, during which a new intracranial lesion developed.

Systemic therapy with carboplatin, paclitaxel, and pembrolizumab resulted in marked regression of uterine and pulmonary lesions. Her symptoms resolved completely, and the Eastern Cooperative Oncology Group performance status improved from 2 to 0. During maintenance pembrolizumab therapy, further tumor regression was observed, and durable disease control was maintained thereafter. At 14 months, the patient remained progression-free without significant adverse events.

This case demonstrated a dramatic and sustained response following multidisciplinary treatment, including surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitor therapy, in POLE-mutated DEC with brain metastases. This highlights the importance of molecular profiling in identifying patients who may benefit from immunotherapy, even in aggressive and widely metastatic disease.

Laryngeal paraganglioma (LP) is a rare neuroendocrine tumor with limited evidence on its metastatic behavior. This case is unique because it describes the diagnostic process, therapeutic decisions, and clinical outcome of LP with multisystem metastases, contributing to a better understanding of its aggressive course and management challenges.

The patient presented with progressive dysphagia, which was later accompanied by hoarseness and dyspnea.

Clinical examination and imaging revealed a mass involving the larynx. Histopathological and immunohistochemical analyses confirmed LP.

The patient underwent tracheostomy after declining partial laryngectomy. Due to tumor progression 5 months post-surgery and dysphagia, partial laryngectomy with extensive tumor resection was performed.

Four months postoperatively, recovery was uneventful, with no local recurrence and successful tracheostomy tube removal. However, at 13 months after initial diagnosis (November 22, 2020), multiple systemic metastases were detected in the lungs, pancreas, and subcutaneous tissues. The patient succumbed to systemic failure on February 9, 2021.

LP diagnosis relies on combined histopathological and immunohistochemical confirmation. Complete surgical resection is critical for preventing recurrence. Once metastasis develops, the prognosis remains poor, underscoring the importance of early diagnosis and multidisciplinary treatment.

Discontinuation of treatment by cancer patients is a complex decision driven by many factors that are not yet fully understood. Using a qualitative approach is the best way to explore this complexity in greater depth. Therefore, this study aimed to explore and synthesize the factors that influence the decision-making of cancer patients regarding withdrawal from treatment.

This is a qualitative systematic review and meta-synthesis, conducted using the six-step meta-synthesis method developed by Sandelowski and Barroso in 2007. Initially, a comprehensive systematic search was conducted in PubMed, Web of Science, Scopus, and CINAHL to identify relevant studies published between 2000 and 2024 according to our inclusion criteria. Subsequently, conventional content analysis was used to analyze the data extracted from qualitative studies. Initially, 348 studies were retrieved, and after screening, 18 studies were included in the meta-synthesis.

From 177 primary codes, one main theme, two categories (endogenous and exogenous factors), and eight sub-categories were extracted through the meta-synthesis process. The factors affecting withdrawal from treatment were: "financial and insurance challenges," "the communication role of the healthcare team," "cultural and social factors," "spiritual and religious beliefs," "family functioning," "personal attributes," "the role of emotions," and "medication side effects."

The decision to withdraw from treatment is a multifaceted process influenced by personal values, clinical considerations, and social dynamics. A deeper understanding of these factors enables healthcare providers, especially nurses, to design better support programs.

Digestive system malignancies remain a major cause of cancer mortality in the United States (US). Updated evidence through 2023 is needed to characterize recent trends, disparities, and cancer-site heterogeneity among adults aged 45 years or older. We conducted an ecological time-trend secondary analysis of publicly available, deidentified, aggregate mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause of Death database. US residents aged ≥ 45 years who died from digestive system malignancies (International Classification of Diseases, 10th Revision [ICD-10] C15-C26) during 1999 to 2023 were included. Age-adjusted mortality rates (AAMRs) per 1,00,000 were directly standardized to the 2000 US standard population, whereas age-group analyses used crude rates. Joinpoint regression estimated annual percent changes (APCs) and average annual percent changes (AAPCs), with Benjamini-Hochberg (BH) adjustment for multiple comparisons. Between 1999 and 2023, the number of deaths increased from 1,25,353 to 1,66,045, whereas the national AAMR declined from 131.59 to 108.28 per 1,00,000 population (AAPC = -0.89%; 95% confidence interval: -0.98 to -0.79; q < 0.001). The annual decline was smaller after 2008. Men consistently had higher AAMRs than women, and non-Hispanic Black adults had the highest mortality rate but the most rapid long-term decline (AAPC = -1.55%; q < 0.001). Recent numerical changes among women, non-Hispanic White adults, and adults aged 45 to 54 years were not statistically significant after BH adjustment. In 2023, state-level AAMRs ranged from 92.31 in Colorado to 133.42 per 1,00,000 in Mississippi. Under the consistent 2013 National Center for Health Statistics (NCHS) classification, the 2020 AAMR was higher in nonmetropolitan than metropolitan areas (117.23 vs 105.67 per 1,00,000). Cancer-site-specific patterns were heterogeneous: the largest absolute reductions in AAMRs occurred for colorectal and stomach cancers, whereas AAMRs increased for liver and intrahepatic bile duct, pancreatic, anal and anal canal, and small-intestinal cancers. Despite a modest long-term decline in age-adjusted mortality from digestive system malignancies, the absolute number of deaths increased, and substantial demographic, geographic, and cancer-site-specific heterogeneity persisted. Continued site-specific and equity-focused surveillance is needed to guide prevention, early detection, and resource allocation.

This study aimed to comprehensively investigate the molecular mechanisms of clear cell renal cell carcinoma (ccRCC), identify key cellular subpopulations and genes, develop an effective diagnostic model, and screen potential targeted therapies for ccRCC. We analyzed single-cell transcriptomic sequencing data to identify the major cellular subpopulations in ccRCC. High-dimensional weighted gene co-expression network analysis and multiple machine learning algorithms were used to identify key genes and develop a diagnostic model. Two-sample Mendelian randomization analysis was performed to assess causality. Molecular docking was used to identify a candidate therapeutic agent. Data processing was conducted using R and Python. The proportion of endothelial cells was significantly higher in ccRCC (P < .001). High-dimensional weighted gene co-expression network analysis showed that the pink module was closely associated with endothelial cells. Univariate logistic regression and Least Absolute Shrinkage and Selection Operator identified 11 key genes: WDR83OS, TMA7, PFDN5, DSTN, PHPT1, HMGN3, TMSB10, RPL27A, RPL23A, RPL15, and RPL27. Based on these genes, a diagnostic model for ccRCC was developed using multiple machine learning algorithms and achieved an area under the receiver operating characteristic curve of 0.960. In addition, 2-sample Mendelian randomization analysis supported a causal association between WDR83OS and ccRCC (inverse-variance weighted: odds ratio = 1.160, P = .033). Molecular docking indicated that oxyphenbutazone had a high binding affinity for WDR83OS, with a binding energy of -7.124 kcal/mol. By integrating multiple bioinformatic approaches, this study identified key cellular populations and genes in ccRCC, developed a reliable diagnostic model, and highlighted WDR83OS as a potentially important therapeutic target.

Type 2 (T2) biologics represent a promising treatment option for chronic obstructive pulmonary disease (COPD) patients with eosinophilic inflammation.

To evaluate the prevalence of stable COPD patients who may be eligible for T2 biologics.

Real-world, retrospective, monocentric study in COPD patients undergoing inpatient pulmonary rehabilitation.

Clinical, functional, and inflammatory data were collected. Patients were considered eligible for T2 biologic therapy whether they were receiving optimized inhaled therapy and had a history of ⩾2 moderate and/or ⩾1 severe exacerbations in the previous year, together with a blood eosinophil count ⩾300 cells/μL.

Among 441 patients, 21.5% had blood eosinophil counts ⩾300 cells/μL and 6.8% fulfilled the combined eligibility criteria. A high burden of respiratory and cardiometabolic comorbidities and increased cardiovascular risk was observed in the overall population.

Only a subgroup of patients seems eligible for biologics, treatment escalation should be based on optimized standard care management and patient phenotyping.

Environmental fungi play an important role in allergic respiratory diseases. Alternaria alternata sensitization has been associated with more severe respiratory phenotypes and poorer asthma control. Mediterranean agricultural environments may favor environmental exposure because of their climatic conditions and intensive agricultural activity.

To analyze the prevalence of sensitization to Alternaria alternata, evaluate its association with asthma control and quality of life, and describe household environmental findings in a Mediterranean agricultural population.

An observational, analytical, cross-sectional study with standardized collection of clinical, allergological, and environmental data was conducted in 100 consecutive adult patients (18-65 years) with allergic rhinitis/rhinoconjunctivitis, with or without associated asthma. Sensitization to Alternaria alternata was defined by a positive skin prick test and/or molecular determination against Alt a 1 (>0.35 kUA/L). Asthma control was assessed using the Asthma Control Test (ACT), quality of life using the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), and rhinitis control using the Spanish Rhinitis Questionnaire (SPRINT). Household environmental evaluation was performed in sensitized patients.

Sensitization to Alternaria alternata was observed in 29% of patients (95% CI: 20.1-38.8). Skin prick testing was positive in 25 patients, whereas molecular sensitization against Alt a 1 was observed in 20 patients. Sensitized patients showed poorer asthma control and greater quality-of-life impairment than non-sensitized patients. No significant differences in the polysensitization burden were observed. Among sensitized patients, household microbiological assessment demonstrated Alternaria alternata detection in 46.4% of indoor samples and 28.6% of outdoor samples.

Sensitization to Alternaria alternata was frequent in this Mediterranean agricultural population and was associated with poorer asthma control and greater quality-of-life impairment. Environmental findings support further investigation of fungal exposure in Mediterranean agricultural settings.