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Knowledge regarding the molecular genetic profile of this entity remains limited, with only two molecular studies conducted to date, which identified pathogenic mutations in the\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    gene and\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter mutations in all analyzable cases. A more aggressive biological potential than previously reported has been only recently unveiled as well. To further advance the understanding of pathogenic mechanisms of CNSET and to investigate the distinctiveness of this rare entity, we analyzed two cases using immunohistochemistry, next-generation sequencing (NGS), and methylation profiling. The latter was employed to compare the epigenetic landscape of CNSET with that of clinicopathologically similar entities, such as hepatoblastoma and solid pseudopapillary neoplasm (SPN) of the pancreas. Both CNSET cases occurred in women (aged 24 and 23\u00a0years) and measured 24\u00a0cm and 16\u00a0cm in diameter, respectively. Both cases showed similar histological features, being composed of organoid nests of bland spindled to epithelioid cells embedded in myofibroblastic stroma. Both cases were immunohistochemically positive for CD56, WT1, and CAM5.2 and negative for hepatocellular and neuroendocrine markers. Case 2 showed aberrant nuclear expression of \u03b2-catenin, while in case 1, there was cytoplasmic positivity only. Using Illumina TruSight Oncology 500 NGS panel, case 1 revealed a pathogenic mutation in the\n                    <jats:italic>WT1<\/jats:italic>\n                    gene and a\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter mutation, and case 2 had a\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    mutation. DNA methylation analysis showed that CNSET forms a distinct cluster, separate from other reference entities. Follow-up in case 2 revealed a disease-free status 21\u00a0months after partial hepatectomy. This study showed that the molecular landscape of CNSET of the liver is characterized by\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    ,\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter, and\n                    <jats:italic>WT1<\/jats:italic>\n                    gene mutations, with the latter representing a novel alteration. Similarly to\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    , the\n                    <jats:italic>WT1<\/jats:italic>\n                    gene plays a significant role in the Wnt signaling pathway. Given the metastatic potential and chemotherapy resistance of CNSET, understanding its molecular background is important for potential alternative targeted treatment. Methylation profiling confirms CNSET as a distinct entity, separate from hepatoblastoma and SPN of the pancreas.\n                  <\/jats:p>","DOI":"10.1007\/s00428-025-04281-5","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:31:32Z","timestamp":1759959092000},"page":"801-810","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Calcifying nested stromal-epithelial tumor of the liver: Report of two cases revealing novel WT1 mutation and distinct epigenetic features"],"prefix":"10.1007","volume":"488","author":[{"given":"Andrea","family":"Strakova-Peterikova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Fedeli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Rychly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Soukup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Michal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Martinek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Grendar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaheh","family":"Mosaieby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"Ptakova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryna","family":"Slisarenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Michal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3231-6870","authenticated-orcid":false,"given":"Kvetoslava","family":"Michalova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"4281_CR1","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1038\/s41379-021-00822-w","volume":"34","author":"DJ Papke Jr","year":"2021","unstructured":"Papke DJ Jr, Dong F, Zhang X et al (2021) Calcifying nested stromal-epithelial tumor: a clinicopathologic and molecular genetic study of eight cases highlighting metastatic potential and recurrent CTNNB1 and TERT promoter alterations. 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