https://hdl.handle.net/20.500.14178/904 Mon, 18 May 2026 01:03:00 GMT 2026-05-18T01:03:00Z https://hdl.handle.net/20.500.14178/3806 SMARCA4-deficient carcinoma of the head and neck region: report of 8 new sinonasal and non-sinonasal cases and literature review Farkas, Mihaela; Agaimy, Abbas; Švajdler, Marián; Hauer, Lukáš; Martínek, Petr; Vaněček, Tomáš; Pivovarčíková, Kristýna; Prchlíková, Barbora; Simpson, Roderick H W; Gočárová, Klaudia; Vereš, Peter; Slavík, Petr; Behenská, Kristýna; Marjanovic, Ksenija; Michal, Michal; Skálová, Alena; Bradová, Martina Neoplasms with inactivating mutations in SWI/SNF chromatin remodeling complex subunits gained attention in the head and neck (H&N) region due to their poor clinical outcomes. The sinonasal tract is a recognized "hot-spot" for SMARCA4-deficient cancers, including SMARCA4-deficient sinonasal carcinomas, and most sinonasal teratocarcinosarcomas. To date, only two H&N SMARCA4-deficient carcinomas have been reported outside the sinonasal region. We identified eight cases of SMARCA4-deficient H&N carcinomas from the authors' files and reviewed their clinicopathological features. All cases with available tissue blocks were investigated by molecular genetic methods using next-generation sequencing (NGS). The cohort included four sinonasal and four non-sinonasal tumors involving the tongue, oral floor, the upper jaw submucosa, and the hypopharynx. The extra-sinonasal cases affected three males and one female (ages 61-81). Histologically, two cases showed poorly differentiated small cell morphology, one case resembled salivary duct carcinoma, and one case had a dedifferentiated squamous cell carcinoma phenotype. Regional lymph node metastases were documented in two cases. Sinonasal tumors showed spindle cell morphology, olfactory neuroblastoma-like features with glandular or squamoid differentiation areas, and an undifferentiated small cell pattern. This study expands the known anatomical distribution and histological spectrum of SMARCA4-deficient H&N carcinomas. Their occurrence outside the sinonasal tract is rare and poses a diagnostic challenge. These tumors are highly aggressive and often present at advanced stages. In the sinonasal region, they can mimic olfactory neuroblastoma, while in other H&N sites, they can resemble neuroendocrine carcinoma. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3806 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3803 Integrated Genomic and Phenotypic Analyses Reveal Convergent Resistance Patterns in Clinical Candida tropicalis Isolates Chedraoui, Christy; Fattouh, Nour; El Hachem, Setrida; Sourenian, Tsolaire; El Bitar, Louna; El Moheb, Lama; Sleiman, Anna-Souraya; Bitar, Ibrahim; Husni, Rola; Khalaf, Roy A BACKGROUND: The incidence of Candida tropicalis isolation is increasing in hospital settings. High azole resistance and mortality rates make it a pathogen that requires further analysis. METHODS: Fourteen azole resistant Candida glabrata clinical isolates were collected from a Lebanese hospital and analysed through whole genome sequencing for single nucleotide polymorphisms in key resistance and virulence genes, and for phylogenetic relatedness. Isolates were then characterised for pathogenicity related attributes. RESULTS: All isolates had Lys314Glu mutation in ERG20 with multiple isolates displaying numerous shared mutations, such as Glu291Lys in CDR2 and Ala16Thr in CDR3. With the exception of two isolates that clustered together, most isolates were over 99.6% identical based on a genomic heatmap, implying high relatedness consistent with localised clonal expansion, although SNP differences appeared too high to support this. However, the isolates exhibited increased ergosterol and chitin content, as well as upregulation of drug efflux pumps resulting in drug resistance. CONCLUSION: Our hospital isolates showed convergent resistant pathways, with many isolates having both shared and unique mutations and a high degree of genomic similarities. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3803 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3797 Diagnosis of prostate cancer in brothers with signs of detection bias and related consequences Hemminki, Kari Jussi; Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Akseli; Hemminki, Otto Background: Swedish nationwide family and cancer data offer an unbiased opportunity to study familial prostate cancer (PC) and allow an assessment of the possible diagnostic bias that might have been introduced in the prostate-specific antigen (PSA) era. We address this bias in a setting between brothers diagnosed with PC.Methods: Brothers were identified from year 1932 onwards until the end of the study 2021. Differences between diagnostic ages, incidence, TNM stage and survival were compared between brothers.Results: A total of 18317 brothers were diagnosed in brotherships of two or more PCs. If there were no bias in diagnostics between the brothers, the null hypothesis was that their diagnostic ages were equal. This was clearly refuted by the data: subsequent brothers were preferentially diagnosed within a year of the first brother. The bias for subsequent brothers was higher when the brothers lived in the same community, and it was highest for large cities, particularly Stockholm. Comparing incidence rates between the first and subsequent brothers, subsequent brothers showed higher rates except at very high age. Proportions of patients detected with PSA (stage T1c) were higher in subsequent brothers compared to the first ones; the proportions were reversed for stages T2-4. Subsequent brothers were diagnosed less frequently with metastases compared to first brothers. Subsequent brothers survived better than first, but the difference depended on age and time since diagnosis.Conclusions: The results between brothers, using objective measures of diagnostic age, incidence and stage of disease, confirmed the existence of detection bias which however appeared to weaken towards high age. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3797 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3796 Does Lung Adenocarcinoma Subtyping Offer Clinical Benefits? A Population-Based Study from Sweden Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Akseli; Kaaks, Rudolf; Hemminki, Kari Jussi Purpose: Classification of lung adenocarcinoma into subtypes is relatively recent and not universally practiced. Consequently, large representative studies describing clinical outcomes are rare, failing to pervasively present advantages of subtyping. We describe the situation in Sweden with focus on survival.Methods: Patient data were obtained from the Swedish cancer registry from 2005 to 2021 accounting for 1418 patients, less than 5% of the reference group 'adenocarcinoma not otherwise specifed (NOS)'. Non-parametric survival estimates were calculated using the Kaplan-Meier method and testing for linear consistency using Weibull modelling.Results: Survival was generally better for women compared to men and this was most prominent for early-stage cancers. Female 5-year survival decreased in order, lepidic (59%), papillary (51%), invasive mucinous (46%), colloid (36%) and adenocarcinoma NOS (24%). Male 5-year survival for lepidic (46%) and colloid subtypes (22%) was significantly lower than female survival. Survival slopes for T1, T2, N0, M0 cases of lepidic, papillary and adenocarcinoma NOS were almost linear, in agreement with Weibull modelling k-values of 1.00 or slightly higher, impling that mortality increased slowly with time.Conclusions: The results showed female survival advantage for all adenocarcinoma subtypes. Survival in T1 and T2 classes with N0 and M0 for lepidic, papillary and adenocarcinoma NOS was close to linear, suggesting that patients are homogeneously diagnosed and treated. Survival benefits of lepidic and papillary subtypes over adenocarcinoma NOS give justification for adenocarcinoma subclassification, and also an independent validation of the WHO 2021 adenocarcinoma grading classification specifying lepidic and papillary subtypes. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3796 2026-01-01T00:00:00Z