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Fibro-osseous tumors of the craniofacial bones are a heterogeneous group of lesions comprising cemento-osseous dysplasia (COD), cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF), psammomatoid ossifying fibroma (PsOF), fibrous dysplasia (FD), and low-grade osteosarcoma (LGOS) with overlapping clinicopathological features. However, their clinical behavior and treatment differ significantly, underlining the need for accurate diagnosis. Molecular diagnostic markers exist for subsets of these tumors, including GNAS mutations in FD, SATB2 fusions in PsOF, mutations involving the RAS-MAPK signaling pathway in COD, and MDM2 amplification in LGOS. Because DNA methylation and copy number profiling are well established for the classification of central nervous system tumors, we aimed to investigate whether this tool might be used as well for classifying fibro-osseous tumors in the craniofacial bones. We collected a well-characterized, multicenter cohort with available molecular data, including COD (n = 20), COF (n = 13), JTOF (n = 10), PsOF (n = 25), FD (n = 23), LGOS (n = 4), and high-grade osteosarcoma (HGOS; n = 11). Genome-wide DNA methylation and copy number variation data were generated using the Illumina Infinium Methylation EPIC array interrogating >850 000 CpG sites. DNA methylation profiling yielded evaluable results in 73/106 tumors, including 6 CODs, 12 COFs, 6 JTOFs, 19 PsOFs, 18 FDs, 2 LGOSs, and 10 HGOSs. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) revealed that FD, extragnatic PsOF, and HGOS formed distinct clusters. Surprisingly, COD, COF, JTOF, and mandibular PsOF clustered together, apart from other craniofacial bone tumors. LGOS did not form a distinct cluster, likely due to the low number of cases. Copy number analysis revealed that FD, COD, COF, JTOF, and PsOF were typically characterized by flat copy number profiles compared with LGOS with gains of chromosome 12 and HGOS with multiple heterogeneous copy number alterations. In conclusion, using DNA methylation and copy number profiles, benign fibro-osseous tumors can be separated from low-grade and HGOSs in the craniofacial bones, which is of diagnostic value in challenging cases with overlapping clinicopathological features., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC., Materials and Methods: Expression levels of these proteins were established on tissue microarrays containing 165 primary SDC tumor specimens. Association with survival was studied with Kaplan-Meier curves, and univariable and multivariable Cox regression models. Furthermore, association with lymph node status, AR and HER2 expression, and gender was studied., Results: We found that patients with high PSMA tumor expression showed a significantly longer overall survival (OS) (median 83 vs. 43 months, P = 0.022), a trend towards a longer DFS (median 51 vs. 22 months, P = 0.094), and significantly reduced hazard ratio for death in the univariable Cox regression model (HR 0.46, P = 0.034). In the multivariable model only a high number of tumor-positive lymph nodes and high age (>80) at diagnosis were prognostic for poor OS. High PSMA tumor expression was also significantly associated with low N-stage (P = 0.001) and expression was higher in women versus men (P = 0.029). High PSMA tumor expression and E-cadherin loss were significantly associated with strong and weak AR-expression, respectively (P = 0.033 and P = 0.007). None of the factors were significantly associated with HER2 expression., Conclusion: c-MET, E-cadherin, and tumor and neovascular PSMA expression are no independent prognostic factors in SDC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale : Treatment options for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC), major subtypes of salivary gland cancer, are limited. Both tumors often show overexpression of prostate-specific membrane antigen (PSMA). In prostate cancer, PSMA-ligands labeled with 68 Ga or 177 Lu are used for imaging and therapy, respectively. Primary aim of this study in R/M ACC and SDC patients was to systematically investigate 68 Ga-PSMA-uptake by PET/CT imaging to determine if PSMA radionuclide therapy could be a treatment option. Methods : In a prospective phase II study, PET/CT imaging was performed 1 h post injection of 68 Ga-PSMA-HBED-CC in 15 ACC patients and 10 SDC patients. Maximum standardized uptake values (SUV) were determined in tumor lesions. Immunohistochemical PSMA expression was scored in primary tumors and metastatic tissue. Standard imaging (MRI or CT) was performed for comparison. Results : In ACC patients, SUV max ranged from 1.1 to 30.2 with a tumor/liver-ratio >1 in 13 out of 14 evaluable patients (93%). In SDC patients, SUV max ranged from 0.3 to 25.9 with a tumor/liver-ratio >1 in 4 out of 10 patients (40%). We found a large intra-patient inter-metastatic variation in uptake of 68 Ga-PSMA, and immunohistochemistry did not predict ligand uptake in ACC and SDC. Finally, PSMA-PET detected additional bone metastases compared to CT in 2 ACC patients with unexplained pain. Conclusion : In 93% of ACC patients and 40% of SDC patients we detected relevant PSMA-ligand uptake, which warrants to study PSMA radionuclide therapy in these patients. Additionally, our data provide arguments for patient selection and treatment timing. Finally, PSMA-PET imaging has added diagnostic value compared to CT in selected patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)