https://hdl.handle.net/20.500.14178/904 Mon, 06 Jul 2026 10:34:40 GMT 2026-07-06T10:34:40Z https://hdl.handle.net/20.500.14178/3863 Familial cancers associated with cancers of the breast, prostate, colorectum and lung in Sweden Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Hemminki, Akseli; Försti, Asta; Hemminki, Kari Jussi Available epidemiological evidence shows that many cancers share familial risks, and this is increasingly confirmed by data on shared pathogenic germline gene variants between cancers. We decided to harness the world's largest resource on familial cancer to assess discordant familial risks for female breast (BC), prostate (PC), colorectal (CRC) and lung (LC) cancers with any of 22 different cancers in first-degree relatives (proband cancers). Familial relative risk was calculated as standardized incidence ratio (SIR) when either one proband or 2 or more (2+) probands were found in a family to distinguish low- and high-risk associations. Discordant familial associations of BC were significant for 15 1-proband and 6 2+ proband cancers. For PC the numbers were 10 and 4, for CRC they were 9 and 3 and for LC they were 14 and 5. The results with large case numbers showed that BC, CRC and LC associated with each other but the familial association between PC and LC was negative. Many novel associations with possible genetic causes were found, including lobular BC with stomach cancer, PC with kidney cancer, CRC with squamous cell skin, brain and thyroid cancers, and LC with gallbladder and endocrine tumors, the most common of which were parathyroid adenomas. Also, LC associations with esophageal and cervical cancers were unlikely to be due to smoking alone and require additional explanations. In conclusion, 2/3 of discordant associations could suggest low-risk genetic and environmental causation and 1/3 high-risk genetic causation, both waiting for experimental proof. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3863 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3845 An Updated Conceptual Framework for Myoepithelial Tumors of Soft tissues and Bone: Toward a Molecularly Informed Classification Michal, Michael; Dermawan, Josephine K. Myoepithelial tumors (MET) of soft tissue and bone comprise a rare group of neoplasms unified by partially overlapping morphology and so called myoepithelial immunophenotype. Historically, MET have long posed diagnostic and prognostic challenges. Grading and risk stratification have relied largely on the presence of cytologic atypia. Recent molecular and epigenetic studies have fundamentally revised this concept, demonstrating that MET represent a biologically heterogeneous family rather than a single disease entity. Soft tissue (mostly deep-seated) and osseous MET frequently harbor recurrent gene fusions, most commonly involving FET family genes (EWSR1 or less often FUS) with partners such as POU5F1, PBX1, PBX3, KLF15, KLF17 , and ZNF444 , and more rarely non-FET fusions including SS18::POU5F1 . These fusion types correlate with reproducible clinicopathologic patterns and, in emerging outcome datasets, with subtype-specific differences in behavior. In contrast, superficially located adnexal tumors with ductal differentiation - representing true cutaneous mixed tumors/myoepitheliomas - typically lack EWSR1/FUS rearrangements and instead show PLAG1 rearrangements, supporting a bona fide myoepithelial origin and close relationship to PLAG1 -driven salivary gland counterparts. Additional complexity arises from SMARCB1-deficient, fusion-negative tumors and a small subset lacking identifiable recurrent drivers, as well as substantial overlap in morphology and immunophenotype with multiple MET mimics, contributing to diagnostic misclassification when using morphology and immunohistochemistry alone. To address these issues, we synthesize clinicopathologic, molecular, methylomic and pooled outcome data across major MET subgroups from recent multi-institutional cohorts, highlighting pronounced epigenetic and clinical heterogeneity and providing practical diagnostic guidance for surgical pathologists. We propose a molecularly informed classification framework that improves diagnostic precision, clarifies terminology - particularly distinguishing PLAG1 -rearranged cutaneous salivary-gland analogs from fusion-associated soft tissue/bone sarcomas with myoepithelial-like phenotype - and lays a foundation for refined prognostic stratification and future therapeutic studies. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3845 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3836 Context-Dependent Prognostic Role of Neutrophils and Mast Cells in Primary Colorectal Cancer and Liver Metastases Ye, Wenjing; Sobhe Abdelhamid Mahmoud, Esraa; Pavlov, Sergii; Červenková, Lenka; Ambrożkiewicz, Filip; Vyčítal, Ondřej; Hošek, Petr; Daum, Ondřej; Liška, Václav; Hemminki, Kari Jussi; Trailin, Andriy BACKGROUNDColorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Liver metastases (LM) are a major prognostic factor affecting survival and treatment outcomes. Distinguishing between synchronous and metachronous metastases is clinically important due to differences in tumor biology, immune contexture, and prognosis. Polymorphonuclear neutrophils (PMNs) and mast cells (MCs) are innate immune effectors that influence CRC progression and metastasis. However, their distribution across primary tumors (pCRC), nontumor mucosa (NM), and liver metastases (LM), and prognostic relevance remain incompletely understood.AIMTo evaluate distribution and prognostic value of PMNs and MCs in NM, pCRC, and LM in synchronous and metachronous CRC.METHODSThis exploratory retrospective cohort study included patients undergoing resection of pCRC with NM and synchronous LM (stage IV, n = 55) or metachronous LM (stage I-III, n = 44). CD66b+ PMNs and CD117+ MCs were assessed using immunohistochemistry, whole-slide imaging, and QuPath-based quantification across NM, tumor center (TC), inner (IM) and outer margins (OM), and peritumor zone (PT) of pCRC and LM. Cell densities were compared by site, region, and timing of metastatic presentation, and associated with disease-free survival (DFS).RESULTSPMNs were enriched in pCRC compared to NM, whereas MCs predominated in NM. Greater densities of PMNs and MCs were found in LM and pCRC, respectively. High PMNs in OM (HR=2.40, 95%CI: 1.14-5.04, p=0.021) and PT (HR=2.58, 95%CI: 1.22-5.46, p=0.013) of synchronous LM and OM of pCRC in stage I-III (HR=2.59, 95%CI: 1.11-6.02, p=0.027) correlated with shorter DFS, whereas high PMNs in TC of metachronous LM predicted longer DFS (HR=0.48, 95% CI: 0.24-0.99, p=0.048). High MCs densities in TC of pCRC in stage I-III predicted shorter DFS (HR=2.34, 95%CI: 1.05-5.23, p=0.038).CONCLUSIONPMNs density increased from NM to LM, while MCs decreased. MCs showed protumor prognostic associations in pCRC; PMNs were protumor in stage I-III pCRC and synchronous LM, but antitumor in metachronous LM. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3836 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3827 Evolving Concepts in Salivary Duct Carcinoma: A Narrative Review Masalunga, Marvin C; Bradley, Patrick J; van Herpen, Carla; Nagao, Toshitaka; Stenman, Göran; Vander Poorten, Vincent; Hellquist, Henrik; Di Palma, Silvana; Bradová, Martina; Leivo, Ilmo; Ferlito, Alfio; Skálová, Alena Salivary duct carcinoma (SDC) is an aggressive neoplasm that typically involves the major salivary glands. This rapidly growing tumor is known to recur and metastasize to the neck nodes and to distant sites. Given its poor prognosis, researchers have focused on identifying factors and driver genomic alterations that may account for its behavior, ultimately yielding potential therapeutic targets. This review summarizes the growing body of knowledge on SDC since the publication of the latest WHO Classification of Tumors of the Head and Neck. Updates on emerging subtypes, immunohistochemical profiles, molecular alterations, and potential therapeutic targets are succinctly presented. Findings from studies on tumor immune microenvironment (TIME), which may have implications for the treatment and prognosis of SDC, are also discussed in this narrative review. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3827 2026-01-01T00:00:00Z