System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print 5 citations

PubMed: 40513989 DOI: 10.1016/j.modpat.2025.100810

Deciphering Pseudoendocrine Sarcoma: A Clinicopathological, Molecular, and Epigenetic Study Suggesting Biological Links With Solid Pseudopapillary Neoplasm of the Pancreas.

Mod Pathol 38(10):100810

Authors: Juan Fernández-Pérez, Isabelle Pommepuy, Michael Michal, Michal Michal, Arjen H G Cleven, Corinne Bouvier, Anne Gomez-Brouchet, Noelle Weingertner, David J Papke, Vickie Y Jo, Jeremy Garcia, Abbas Agaimy, Rihab Azmani, Aurelien Bourdon, Isabelle Hostein, Isabelle Soubeyran, Melissa Alame, Valérie Velasco, Jean-Michel Coindre, François Le Loarer, Raul Ezequiel Perret

Affiliations

  • Department of Pathology, Bordeaux University Hospital, Bordeaux, France.
  • Department of Pathology, Limoges University Hospital, Limoges, France.
  • Department of Pathology, Faculty of Medicine in Plzen, Charles University, Pilsen, Czech Republic; Bioptical Laboratory Ltd. Plzen, Czech Republic.
  • Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Pathology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
  • Department of Pathology, La Timone University Hospital, Marseille, France.
  • Department of Pathology, Toulouse University Hospital, Toulouse, France.
  • Department of Pathology, Strasbourg University Hospital, Strasbourg, France.
  • Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
  • Institute of Pathology, Friedrich-Alexander-University Erlangen-Nurnberg, University Hospital, Erlangen, Germany.
  • Bioinformatics, Data and Digital Health Department, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France.
  • Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, F-33000, Bordeaux, France.
  • Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, F-33000, Bordeaux, France; University of Bordeaux, Talence, France.
  • Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, F-33000, Bordeaux, France; University of Bordeaux, Talence, France; INSERM U1218, ACTION, Institut Bergonié, Bordeaux, France.
  • Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, F-33000, Bordeaux, France; INSERM U1218, ACTION, Institut Bergonié, Bordeaux, France.

Abstract

Pseudoendocrine sarcoma (PS) is a recently described neoplasm of uncertain differentiation, characterized by recurrent CTNNB1 mutations, frequent paravertebral location, and a neuroendocrine-like histomorphology. In this study, we report the clinicopathologic, immunohistochemical, transcriptomic, and epigenetic findings of 12 PS cases. The tumors affected 7 men and 5 women with a median age of 66 years and were located in the paraspinal/paravertebral region (n = 11) and the thigh (n = 1). Median tumor size was 82 mm (range, 32-170 mm). Histologically, the tumors comprised sheets and nests of epithelioid-to-ovoid cells with uniform nuclei and speckled chromatin, frequently associated with extracellular hyaline globules and fibrovascular cords/septa. Uncommon findings included microcalcifications, myxoid stroma, pseudopapillary, pseudoglandular, microcystic or corded architecture, and lumen and rosette-like structures. Necrosis was absent, and mitotic activity was low. On immunohistochemistry, the tumors showed aberrant nuclear staining for beta-catenin (8/8) and expression of CD56 (7/7), S100 (8/8), desmin (2/6), and androgen receptor (1/4). Pankeratin (AE1/AE3), progesterone receptor, synaptophysin, chromogranin, and INSM1 were negative. All tested cases harbored CTNNB1 mutations. Using a customized cohort, methylation profiling revealed that PS formed a common cluster with solid pseudopapillary neoplasm of the pancreas (SPNP), distinct from all methylation classes from the Heidelberg sarcoma classifier and a subset of paragangliomas. Transcriptomic analysis showed that PS formed an independent cluster from a control group of tumors (including SPNP). Differential gene expression analysis showed enrichment in genes of the Wnt signaling pathway (HALLMARK gene sets) and biological processes related to sensory perception, among others (gene ontology - biological process [GO-BP]). Additionally, upregulated genes were related to various fetal cell types from the cell type signature data set (MSigDB), particularly of neuronal and epithelial lineage. Immunohistochemical assessment of potential markers identified through gene expression analysis revealed focal-to-diffuse expression of GLUT1 (6/6) and focal/multifocal expression of Brachyury (4/9) and HuD (3/7). Follow-up information, available for 10 cases (median duration of 18 months; range, 7-69 months), showed local recurrences and metastatic spread in 2 patients each. Evidence of response to radiotherapy was documented in one tumor. Altogether, this study expands knowledge on PS and suggests biological links with SPNP, including a potential shared cell of origin.

MeSH

Cells, Genes, Gene Expression Profiling, Neoplasms, Comparative Genomic Hybridization, Pathology, Sarcoma, Pancreas, Mutation, Gene Expression