-
Universally offered germline testing in upper tract urothelial carcinoma.1 week agoUpper tract urothelial carcinoma (UTUC) is a common extracolonic manifestation of Lynch syndrome (LS) characterized by mismatch repair deficiency (MMR-D) and microsatellite instability (MSI). LS detection in UTUC relies on tissue- and clinical-based screening, which can fail to detect pathogenic germline variants (PGVs). We sought to determine the prevalence and spectrum of PGVs in UTUC through universally offered germline testing.
In this retrospective, single-institution cohort, between 2020 and 2025, UTUC patients were universally offered germline testing, at no cost, irrespective of hereditary cancer suspicion. Concordance between germline findings and immunohistochemistry (IHC), MSI status, and screening criteria was assessed.
Of patients referred, 46% (128 of 281) completed testing. LS-associated MMR PGVs were detected in 3.1% (n = 4) and overall PGVs in 6.3% (n = 8). PGVs included MSH6 (n = 3), MSH2 (n = 1), BRCA1 (n = 2), CHEK2 (n = 1), and monoallelic NTHL1 (n = 1). Of MMR PGV carriers, NCCN LS screening criteria identified 50% (2 of 4), Amsterdam II identified none, and 1 patient scored below the PREMM5 ≥ 2.5% threshold. IHC was discordant in 78% (7 of 9) of MMR-D patients who lacked a germline MMR PGV; 50% (2 of 4) of MMR PGV carriers had intact MMR expression. One MSH6 PGV carrier was not detected by any screening strategy.
LS-associated PGV prevalence in UTUC mirrors colorectal and endometrial cancer cohorts undergoing universal genetic testing, where LS testing is standard, supporting liberalized referral for germline testing.CancerCare/Management -
Clinical characterization of cutaneous mucormycosis in patients receiving Bruton tyrosine kinase inhibitor therapy with Ibrutinib: A new case report and comparative discussion.1 week agoMucormycosis are invasive fungal infections caused by fungi of the order Mucorales that classically affect profoundly immunosuppressed patients. Recently, cases have emerged in patients receiving Bruton tyrosine kinase inhibitors like Ibrutinib, used for chronic lymphocytic leukemia (CLL).
We report a 58-year-old man with CLL on Ibrutinib and Venetoclax who developed a rapidly progressing necrotic ulcer on his leg after minor trauma. Histopathology revealed angioinvasive, non-septate hyphae; Rhizopus spp. was confirmed by culture. He was treated with surgical debridement, liposomal amphotericin B, and isavuconazole, with good outcome. We also reviewed published cases of cutaneous mucormycosis in Ibrutinib-treated patients.
Including our case, seven patients were identified. Most presented with single necrotic limb lesions after minor trauma. Median age was 69.5 years; median Ibrutinib exposure was 3 years. Liposomal amphotericin B was the most used antifungal; surgery was performed in over half of the patients.
Cutaneous mucormycosis is an emerging complication in Ibrutinib-treated patients. Early diagnosis and combined antifungal and surgical treatment are crucial.CancerCare/Management -
The diagnostic power of gross examination in bone and soft tissue pathology.1 week agoGross examination of surgical pathology specimens is a foundational component of pathology training and remains essential for the accurate evaluation of resection specimens. Bone and soft tissue tumors represent a rare and diagnostically challenging group of neoplasms that often require specialized expertise and subspecialty training for proper classification. Although definitive diagnosis typically relies on the careful integration of clinical, radiologic, histologic, immunophenotypic, and molecular findings; gross (macroscopic) features can provide valuable early diagnostic clues regarding tumor type, surgical adequacy, and biologic behavior. Despite their diagnostic value, the gross features of bone and soft tissue tumors are often underappreciated, in part due to the relative rarity of these neoplasms. In this review, we highlight selected bone and soft tissue tumors to emphasize the practical importance of careful gross examination in the evaluation and diagnosis of musculoskeletal neoplasia.CancerCare/Management
-
Associated factors regarding systemic anticancer therapy use prior to death among patients with metastatic non-small cell lung cancer: A multicentre retrospective cohort study.1 week agoSystemic anticancer therapy (SACT) near the end of life among patients with metastatic non-small cell lung cancer (NSCLC) is considered a population-level quality indicator of potentially inappropriate end-of-life care. We investigated factors associated with SACT in the final 6 weeks of life among patients diagnosed with metastatic NSCLC to optimise end-of-life care.
A multicentre retrospective cohort study was conducted among patients with metastatic NSCLC across 7 hospitals in the Dutch Santeon network. Data were extracted from electronic health records. The primary outcome was the receipt of SACT (immunotherapy and/or chemotherapy) within 6 weeks before death. Variables included relevant demographics, clinical and tumour characteristics, palliative care team involvement, emergency department (ED) visits, and hospitalisations. A multivariable logistic regression with backward selection was employed to identify associated variables.
Among 365 included patients, 37 % received SACT in the last 6 weeks of life. Notably, these patients were significantly more likely to die in a hospital (44.1 % vs 9.6 %), to visit the emergency department (77.9 % vs 32.8 %) or to be hospitalised in the last 6 weeks of life (80.1 % vs 37.1 %). Hospitalisations before last treatment were independently associated with SACT use in the last 6 weeks of life (OR 2.673 (CI 1.317-5.427), p = 0.006) whereas ED visits were retained in the final model but were not statistically significant (OR 1.688, 95 % CI 0.861-3.311; p = 0.128).
This study highlights the importance of better understanding potentially inappropriate care near the end of life among patients with metastatic NSCLC, specifically when focusing on previous hospitalisations or emergency department visits.CancerCare/Management -
Depression, intoxication, suicide attempt, suicide and the use of anxiolytics, hypnotics, sedatives and antidepressants following a diagnosis of non-small cell lung cancer. A population-based study (Sweden).1 week agoA cancer diagnosis affects quality of life, including psychological wellbeing. The risk of depression and suicide has been found to be increased in cancer patients, especially in cancers with poor prognosis. The aim of this study was to examine a broad range of indicators of psychological distress pre- and post-diagnosis in patients with non-small cell lung cancer (NSCLC).
We used data in a population-based lung cancer research database to compare diagnostic events of depression, anxiety, intoxication, suicide attempt and suicide as well as filled prescriptions for anxiolytics, hypnotics, sedatives and antidepressants between patients with NSCLC and individuals free of lung cancer (comparators).
The study population encompassed 47,625 patients diagnosed with NSCLC between January 2006 and May 2022 and 236,492 lung cancer free individuals. Diagnostic rates indicating psychological distress (depression, intoxication, suicide attempt, suicide) were higher in NSCLC patients after diagnosis. Already three months prior to diagnosis, fillings of prescriptions for anxiolytics, hypnotics and sedatives were more common in patients with NSCLC than in comparators and remained higher in the cases during the first year post diagnosis. Following diagnosis, rates of prescriptions for antidepressants were also higher in cases. For all medications except antidepressants, rates of filled prescriptions correlated with severity of disease.
We found evidence of increased rates of both diagnostic events related to psychological distress and use of psychiatric medications after a diagnosis of NSCLC. Our findings underscore the importance of symptom monitoring post-diagnosis and preparedness to provide adequate support and treatment.CancerCare/Management -
Gamma Knife Radiosurgery-Induced Acute Facial Palsy in Vestibular Schwannoma: A Case Report.1 week agoStereotactic radiosurgery (SRS) is an established treatment for vestibular schwannoma, offering high tumor control rates and a favorable safety profile. SRS-induced facial palsy is typically a late-onset complication, with acute-onset cases being exceedingly rare. We report the case of a 42-year-old man with a left-sided Koos grade I vestibular schwannoma who underwent single-fraction Gamma Knife radiosurgery with a prescription dose of 11 Gy to the 50% isodose line. Baseline facial nerve function was intact. Seventy-two hours post-treatment, the patient developed House-Brackmann (HB) grade V peripheral facial palsy, accompanied by severe vestibular symptoms. Magnetic resonance imaging obtained on post-treatment day 6 demonstrated reduced contrast enhancement, partial capsular breakdown, and central hypointensity within the tumor, suggestive of acute necrotic change. Vestibular symptoms improved rapidly following corticosteroid therapy; however, facial palsy recovery was gradual, improving to HB grade II at 12 months, with persistence at final follow-up (20 months). The tumor remained radiologically stable. Acute-onset facial palsy following SRS for vestibular schwannoma is extremely rare, with only four previous cases reported in the literature. This is the first reported case to occur following a relatively low margin dose-11 Gy-in contrast to the 13-14 Gy doses prescribed in earlier reports.CancerCare/Management
-
Safety of glucagon-like peptide-1 receptor agonists in neuroendocrine neoplasms.1 week agoGlucagon-like peptide-1 receptor agonists (GLP-1RAs) have been in use for twenty years. There have been concerns about their safety in patients with neuroendocrine neoplasms (NENs). The reports of GLP-1 receptor (GLP-1R)-driven proliferation of C-cell neoplasms in rodent studies had led to the black-box warning against their use in patients with medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2). In this review, we have attempted to evaluate the physiological and pathological expression of GLP-1 receptors (GLP-1R) in various endocrine organs and summarise the preclinical and clinical evidence regarding the effect of GLP-1RA exposure and risk of NENs. GLP-1R expression has not only been found in nonneoplastic tissues such as neurohypophysis, duodenal glands and pancreatic islets but also in neuroendocrine tumours (NETs). Preclinical studies have demonstrated the proliferative effects of GLP-1RA in cell lines representing pancreatic NETs (panNETs) and small intestinal NETs. The available data from retrospective studies, randomized trials and cancer registries provide conflicting data and does not support a generalized increase in NENs with the use of GLP-1RA. Some epidemiological studies have even shown survival benefits associated with GLP-1RA use. In addition, significant gaps in evidence remain, such as lack of data regarding certain tumour subtypes, long-term prospective studies with NENs as the clinical endpoint and uncertainty regarding patients with multiple endocrine neoplasia type 1 (MEN1). Hence, the initiation of GLP-1RA therapy in patient with predisposition to NEN where a contraindication does not exist, should be approached cautiously with careful monitoring for long-term adverse effects.CancerCare/Management
-
Past achievements and future perspectives of personalized vaccines and the role of dendritic cells.1 week agoPersonalized vaccines provide the advantage of patient-specific antigen selection to optimize immune responses, a strategy extensively explored in oncology through neoantigen-targeted peptide, mRNA, and dendritic cell platforms. Peptide vaccines provide simplicity and stability though often elicit limited cytotoxic T-cell responses. What is more, mRNA vaccines lead to rapid, multiplexed neoantigen delivery, endogenous antigen processing and eventually improved immunogenic coverage. Dendritic cell-based vaccines have the potency to prime potent T-cells although this technology requires labor-intensive manufacturing and extensive production timelines. Integration with immune checkpoint inhibitors, adoptive cell therapies, and oncolytic viruses further enhances efficacy, suggesting that rational combinations may be more effective than single modalities. Recent advances in sequencing, computational epitope prediction, and bioinformatics pipelines have facilitated neoantigen prioritization and DC vaccine design, enabling more rapid and precise personalization. Hybrid vaccination strategies, such as ex-vivo mRNA-electroporated dendritic cells and in-vivo DC-targeted platforms, bridge the gap between manufacturing feasibility and potent immune activation. Emerging technologies, including AI-driven neoepitope prediction, receptor-targeted antigen delivery, biomaterial-based modulation, and distributed mRNA manufacturing, seem to be promising approaches to accelerate personalized vaccine development in future. From another point of view, lessons learned from the COVID-19 pandemic accelerated the development, large-scale deployment, and validation of mRNA vaccine platforms for infectious diseases. Host HLA diversity, prior immune history, and viral evolution create heterogeneity in immune responses, highlighting opportunities for semi-personalized or adaptive strategies. In this review, we provide a landscape of personalized vaccines, with a focus on DC-based platforms, and explore translational lessons for viral pathogens. A conceptual framework linking cancer immunotherapy and infectious disease preparedness is proposed, emphasizing hybrid personalization approaches, rapid manufacturing, and AI-enabled epitope selection. This perspective highlights how convergence of immunology, computational biology, and advanced vaccine technologies could expand the scope of personalized vaccination, from oncology to future epidemic and pandemic scenarios as well as the current challenges.CancerChronic respiratory diseaseCare/Management
-
An unusual cranial manifestation of B-cell precursor lymphoblastic lymphoma in 10-year-old girl.1 week agoPediatric B-cell precursor lymphoblastic lymphoma (BCP-LBL) is a rare subtype of non-Hodgkin lymphoma with a predominantly extramedullary presentation. Cutaneous and subcutaneous involvement, particularly in the head region, is a recognized manifestation; however, presentation as a solitary scalp mass mimicking a benign surgical lesion remains diagnostically challenging. A 10-year-old female patient presented to the Neurosurgery Department for a growing mass in the right frontal region of the scalp for the past 4 months. After excision, the mass was diagnosed as BCP-LBL and the patient was referred to oncologic treatment. This report aims to increase awareness among surgeons and physicians that persistent or progressive pediatric scalp lesions, even when clinically benign-appearing, may represent an underlying malignant hematologic disease requiring prompt histopathological verification and specialist referral.CancerCare/Management
-
Spontaneous regression of B-cell acute lymphoblastic leukemia with PAX5 alterations at relapse: a case report.1 week agoAcute lymphoblastic leukemia is the most common pediatric hematological disease representing less than 1% of hematological diseases in adults. The prognosis of ALL improved significantly in the last decades. Almost all patients require a therapy at the time of diagnosis. Rare cases of spontaneous remission of ALL have been described. We report a case of B-ALL that underwent spontaneous remission after an episode of infection and describe the cytogenetic changes associated with this uncommon clinical presentation of B-ALL.CancerCare/Management