Frontiers in Oncology最新文献

Background: Mammary Paget's Disease (MPD) is a rare subtype of breast cancer, accounting for 1%-4% of all breast cancers. Controversy remains regarding whether sentinel lymph node biopsy (SLNB) is necessary for MPD patients undergoing breast-conserving surgery (BCS) when imaging studies fail to detect deep invasive carcinoma, and this controversy lacks support from specific case evidence.

Case summary: A patient presented with "recurrent left nipple fissure for 3 years and eczematous changes for 3 months." Preoperative biopsy at another hospital confirmed MPD; imaging showed no deep mass. Postoperative pathology revealed left breast MPD associated with multifocal microinvasive carcinoma, accompanied by metastases to left axillary lymph nodes (6/8), left subclavian lymph nodes (2/3), and left supraclavicular lymph nodes (1/3). The pathological stage was pT1mic pN3c cM0. No recurrence was observed 6 months after adjuvant therapy with the TCbHP regimen plus capecitabine consolidation therapy.

Conclusion: Although no definite mass was identified on breast magnetic resonance imaging (MRI) in this case, SLNB and subsequent pathology confirmed extensive lymph node metastasis (pN3c). Omission of SLNB could have led to understaging and compromised treatment decision-making. This single case may suggest that SLNB holds significant staging value for MPD patients with no obvious breast mass on imaging. It provides hypothesis-generating, practical evidence for addressing this controversial clinical issue, warranting further investigation in larger cohorts.

Background: The modified Glasgow Prognostic Score (mGPS), which reflects the degree of systemic inflammation and nutritional status, is associated with prognosis in various common malignancies. However, its association with 30-day unplanned readmission and 1-year mortality in stage III-IV lung cancer (LC) patients remains unvalidated. This study aimed to evaluate the prognostic value of mGPS in stage III-IV LC patients receiving immune checkpoint inhibitors (ICIs).

Methods: In this retrospective study, 209 patients diagnosed with stage III-IV LC who underwent ICI therapy between January 2023 and May 2024 were included. Patients were stratified based on mGPS scores into three risk categories: low-risk (0 points), intermediate-risk (1 point), and high-risk (2 points). Kaplan-Meier analyses, multivariate Cox proportional hazard regression, and subgroup analyses were employed to assess primary outcomes.

Results: Among the enrolled patients, the rates of 30-day unplanned readmission and 1-year mortality were 35.4% (74/209) and 11.0% (23/209), respectively. Kaplan-Meier analysis indicated significantly elevated cumulative incidences of 30-day unplanned readmission and 1-year mortality in the high-risk group relative to intermediate- and low-risk groups (log-rank p < 0.001). Adjusted multivariable Cox regression revealed that each 1-point increase in mGPS conferred a 72% higher risk of 30-day unplanned readmission (HR 1.72, 95%CI 1.25-2.38, p = 0.001) and a 117% higher risk of 1-year mortality (HR 2.17, 95%CI 1.15-4.10, p = 0.017). Additionally, compared with low-risk patients, those in the high-risk group experienced a 198% increase in the risk of 30-day unplanned readmission (HR 2.98, 95% CI 1.56-5.69, p = 0.001) and a 366% increase in 1-year mortality risk (HR 4.66, 95% CI 1.33-16.35, p = 0.017). Trend tests confirmed that the risk of adverse outcomes rose steadily with increasing mGPS risk category. Subgroup analyses demonstrated that the prognostic effect of mGPS was consistent across age, TNM stage, metastatic status, and nutritional condition (p for interaction > 0.05).

Conclusion: Higher mGPS scores significantly correlate with elevated risks of both 30-day unplanned readmission and 1-year mortality among LC patients receiving ICI therapy. Routine mGPS monitoring may warrants further evaluation in prospective multicenter validation studies to inform prophylactic interventions.

Non-alcoholic steatohepatitis (NASH), the inflammatory progression of non-alcoholic fatty liver disease (NAFLD), is a leading cause of hepatocellular carcinoma (HCC) amid rising obesity and metabolic syndrome. This review elucidates the immunometabolic interplay driving NASH-HCC pathogenesis. Immune cells, including Kupffer cells, monocyte-derived macrophages, and T-cell subsets, orchestrate chronic inflammation and fibrosis via cytokine cascades (TNF-α, IL-1β, TGF-β1) and polarization shifts. Metabolic dysregulation-including insulin resistance, lipid accumulation, and oxidative stress-exacerbates hepatocyte injury, disrupts the balance between apoptosis and compensatory proliferation, and promotes immune evasion through pathways such as β-catenin/TNFRSF19 signaling and hypoxia-inducible factor 1-alpha (HIF-1α). Gut-liver axis alterations further amplify inflammation. Therapeutic advances include immunotherapies (PD-1 inhibitors combined with anti-angiogenics), metabolic regulators (PPARα/FXR agonists, GLP-1RAs), and lifestyle interventions, though NASH-HCC shows reduced immunotherapy efficacy due to unique immunosuppressive microenvironments. Future directions emphasize novel immune targets (MDSCs, SLAMF1), metabolic reprogramming, and microbiota modulation for precision therapies. Integrating multimodal approaches holds promise for halting NASH-to-HCC progression and improving outcomes.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that primarily affects children and young adults. While typically found in the lungs, liver, and gastrointestinal tract, pelvic involvement is recognized but occurs less frequently than intra-abdominal IMT, particularly in pediatric patients. Here we report a case of a 2-year-old boy who presented with a brief history of vomiting and decreased appetite. Imaging revealed a cystic-solid mass in the pelvis with progressive enhancement of the solid component, leading to suspicion of a vascular soft tissue neoplasm. Surgical exploration identified a free-floating mass within the abdominal cavity supported by a long vascular pedicle originating from the splenic hilum, an atypical anatomical finding that added complexity to preoperative diagnosis. Complete surgical resection was performed, and postoperative examination was conducted. Histopathological analysis confirmed IMT, and fluorescence in situ hybridization (FISH) detected ALK gene rearrangement, which supported diagnostic confirmation of IMT in this case rather than guiding therapeutic intervention. The patient recovered uneventfully following surgery, with no evidence of recurrence during follow-up. This case supports considering IMT in pediatric pelvic masses and reinforces that complete surgical resection remains the primary treatment. Although ALK gene rearrangement was not associated with therapeutic intervention in the present case, its identification remains diagnostically relevant and may provide important insights into management decisions in selected clinical scenarios, such as recurrence or unresectable disease.

Ubiquitination is an important post-translational modification of proteins that precisely regulates protein stability and function through the coordinated actions of E3 ubiquitin ligases (E3s) and deubiquitinases (DUBs), participating in biological processes including protein degradation and signal transduction. In recent years, the role of ubiquitination modification in the carcinogenesis, progression, and treatment of renal cell carcinoma (RCC) has garnered increasing attention. This review summarizes the structural classifications of key enzymes in the ubiquitination process-E3s and DUBs-and to discuss their specific molecular mechanisms in RCC. Finally, we discuss the targeted therapeutic strategies focusing on these key ubiquitination-modifying enzymes in RCC.

Solitary plasmacytoma (SP) is seldom encountered. It can affect any bone in the body, but is more common in the spine, especially in the thoracic region, while SP in the tibia is relatively rare. Herein, we report the case of a 34-year-old woman who visited our hospital with right calf pain for over a month. The X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) revealed a tumor growing along the longitudinal axis of her right tibia, which was suspected to be malignant. The patient subsequently underwent a puncture biopsy, and the pathological results revealed a plasma cell myeloma. To further evaluate the extent of tumor involvement, the patient underwent single-phase technetium-99 labeled methylene diphosphonate (^99mTc-MDP) single photon emission computed tomography (SPECT) whole-body bone imaging, and the results showed no significant radioactive concentration in the entire body except for the right proximal tibia. Based on these imaging features and pathological results, the patient was diagnosed with SP. We summarized the clinical features and imaging findings of tibial SP based on our case and the published literature The results showed that SP is more likely to occur in young people. Its imaging has a certain specificity, which is characterized by a uniform low - density shadow growing along the longitudinal axis, without a sclerotic rim, and increased radioactive uptake on whole - body bone imaging. MRI showed long signals on T1 and T2, with significant enhancement on contrast-enhanced scans, but rarely breaking through the bone cortex to form soft tissue masses. The current study suggests that a thorough understanding of the clinical and imaging characteristics of the tibial SP can increase the likelihood of obtaining an accurate diagnosis before surgery.

Background: Pathogenic BRCA1 variants are established in hereditary breast and ovarian cancer (HBOC) and associated with pancreatic, prostate, and gastric cancers. Salivary gland tumors (SGTs) have been reported in BRCA1/2 carriers and suggested as part of an extended HBOC phenotype based on epidemiological associations. However, functional evidence is lacking, and homologous recombination deficiency (HRD)-the hallmark of BRCA-driven cancers-has not been systematically assessed in BRCA1-associated SGTs.

Case presentation: We report a Colombian family segregating the BRCA1 c.3331_3334delCAAG (p.Gln1111Asnfs*5) founder variant with phenotypic variability across four generations: gastric (31%), breast (37.5%), colorectal (19%), and thyroid cancers (12.5%). The proband, a 61-year-old woman, developed high-grade mucoepidermoid carcinoma of the parotid gland. Germline testing confirmed the familial BRCA1 variant. Tumor profiling revealed the same BRCA1 variant (VAF 56%) plus a pathogenic TP53 mutation (c.730G>T, p.Gly244Cys; VAF 32%), without BRCA1 loss of heterozygosity. HRD testing using shallow whole genome sequencing showed preserved homologous recombination function (Genomic Instability Score: 0.01, LGA: 11.40, LPC: 0), all below HRD-positive thresholds.

Conclusion: This represents the first SGT in a BRCA1 carrier evaluated with HRD testing. The absence of HRD argues against BRCA1-driven tumorigenesis despite clear familial segregation. These findings challenge the presumed causal relationship between BRCA1 variants and SGT development. Clinical implications are direct: SGTs in BRCA1 carriers should not be assumed eligible for PARP inhibitor therapy without HRD confirmation, and enhanced surveillance appears unwarranted. This case underscores that co-occurrence does not establish causation and highlights the critical importance of functional validation before expanding hereditary cancer spectra.

Background: Endocrine-related cancers pose an escalating challenge for reproductive-age women in the Asia-Pacific region, characterized by persistent socioeconomic disparities.

Methods: Using data from the Global Burden of Disease Study 2021, we analyzed the incidence, mortality, and DALYs of breast, ovarian, and thyroid cancers across 15 countries (1990-2021). Trends were quantified using EAPC, and mortality trajectories through 2050 were projected using GAM.

Results: Breast cancer exhibited a polarized pattern: mortality steadily declined in High-SDI nations but surged in Low-SDI regions. Thyroid cancer revealed a dichotomy of screening-driven overdiagnosis in High-SDI settings versus high lethality in Low-SDI areas. Ovarian cancer maintained the poorest prognosis in resource-limited settings. Crucially, primary risk drivers are shifting from traditional behavioral factors to metabolic factors.

Conclusion: With disparities projected to widen by 2050, stratified interventions are urgent. We recommend screening de-escalation for High-SDI nations and resource-adapted measures for Low-to-Middle SDI nations to bridge the growing equity gap. reproductive-age women.

Background: Clear cell renal cell carcinoma (ccRCC) most commonly metastasizes to the lungs, lymph nodes, bones, and liver. Metastasis to the breast is exceptionally rare, representing less than 0.5% of cases. Herein, we report an unprecedented case of triple metastasis with the longest recorded latency period.

Case presentation: An 86-year-old female presented with a painless left breast mass 25 years after undergoing radical nephrectomy for ccRCC. Multi-modality imaging (mammography, ultrasound, MRI) revealed a suspicious breast lesion. Subsequent chest CT and PET-CT identified synchronous metastatic nodules in the lungs and brain. Histopathological examination of the resected breast mass confirmed metastatic carcinoma. The diagnosis of ccRCC metastasis was substantiated by an immunohistochemical profile positive for PAX8, CAIX, and CD10, while negative for estrogen receptor, progesterone receptor, and HER2.

Conclusion: This case highlights breast metastasis as a rare but critical differential diagnosis in patients with a history of ccRCC, even decades after initial treatment. It underscores the necessity of lifelong follow-up for ccRCC survivors and demonstrates the integral role of imaging and pathological confirmation in guiding clinical diagnosis. Furthermore, the remarkable 25-year latency period challenges existing surveillance paradigms and provides a compelling rationale for the use of combined immunotherapy and targeted agents in managing ultra-late, multi-metastatic recurrences.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with a range of immune-related adverse events, including neurological complications. We report the case of a 64-year-old man diagnosed with small-cell lung cancer who developed AMPA2 antibody-positive autoimmune encephalitis after receiving tislelizumab combined with chemotherapy. The patient presented with a 3-week history of cognitive decline following the second cycle of treatment. Extensive testing confirmed the presence of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 2 (AMPA2) antibodies in the cerebrospinal fluid and serum. The patient was treated with corticosteroids and intravenous immunoglobulin, resulting in significant improvement within 1 month. This case highlights the potential of ICIs to induce autoimmune encephalitis, which is a rare but serious complication. This finding underscores the importance of early recognition and prompt intervention in patients undergoing immunotherapy.