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While classical schwannomas have been well known for decades, HNS have only recently been described as a distinct histological pattern, composed of intermixed features typical of both schwannomas and neurofibromas. Differentiating HNS from pure neurofibroma (Nf) is critical, as misclassification may lead to an incorrect diagnosis of neurofibromatosis type 1 rather than SWN. The distinction of hybrid tumors (more precisely HNS) is especially important in SWN forms outside the neurofibromatosis type 2 (NF2) spectrum (NF2-SWN), where major diagnostic criteria are less well defined, making histological differentiation even more significant. At the molecular level, HNS frequently show alterations in the genes\n                    <jats:italic>NF2<\/jats:italic>\n                    ,\n                    <jats:italic>LZTR1<\/jats:italic>\n                    , and\n                    <jats:italic>SMARCB1<\/jats:italic>\n                    , often accompanied by characteristic losses of chromosome 22q. In addition, recurrent somatic mutations have been identified in genes such as\n                    <jats:italic>ERBB2<\/jats:italic>\n                    ,\n                    <jats:italic>RET<\/jats:italic>\n                    ,\n                    <jats:italic>KMT2A<\/jats:italic>\n                    , and\n                    <jats:italic>CTNNA3<\/jats:italic>\n                    . Methylation profiling classifies HNS within the schwannoma spectrum, supporting the hypothesis that they may be a morphological variant rather than a distinct entity, although this has not yet been conclusively confirmed. Histologically, HNS are characterized by a combination of mostly schwannoma-associated Antoni A patterns, collagen-rich neurofibroma-like areas, lymphocytic infiltrates, and, in some cases, plexiform growth. Given the diagnostic challenges, artificial intelligence-based image analysis, such as whole-slide imaging and radiomics, may offer valuable tools for more accurate identification of these tumors in the future. Initial studies in related fields have shown that such approaches can even surpass human-level accuracy. Nevertheless, an accurate histological and, if necessary, molecular evaluation remains essential\u2014particularly for the correct classification as SWN and for ensuring appropriate genetic counseling to affected individuals.\n                  <\/jats:p>","DOI":"10.1007\/s10689-025-00505-4","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:26:24Z","timestamp":1763357184000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hybrid neurofibroma\/schwannoma in schwannomatosis\u2014a diagnostically challenging benign peripheral nerve sheath tumour"],"prefix":"10.1007","volume":"24","author":[{"given":"Daniel","family":"Tippner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Anokhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Scheffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Hellmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan K.","family":"Plontke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Leisz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-2222","authenticated-orcid":false,"given":"Anja","family":"Harder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"505_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.05.007","author":"SR Plotkin","year":"2022","unstructured":"Plotkin SR et al (2022) Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: an international consensus recommendation. 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