{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:10:56Z","timestamp":1787847056831,"version":"build-2784847793"},"reference-count":36,"publisher":"BMJ","issue":"4","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K27385"],"award-info":[{"award-number":["23K27385"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2026,1,10]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Histological features of conventional malignant peripheral nerve sheath tumour (C-MPNST) resemble those of neurotrophic tropomyosin or tyrosine receptor kinase gene (\n                      <jats:italic>NTRK<\/jats:italic>\n                      )-rearranged spindle cell neoplasm, a new entity of soft-tissue tumour. Pan-TRK immunohistochemistry has recently become popular for detecting\n                      <jats:italic>NTRK<\/jats:italic>\n                      rearrangements cost-effectively, but its positivity can also reflect neural differentiation. We investigated what pan-TRK positivity truly indicates in a large case series of neurogenic tumours.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Pan-TRK, S100, SOX10 and histone 3 lysine 27 trimethylation (H3K27me3) immunohistochemical analyses were performed on 99 C-MPNSTs, 17 malignant triton tumours, 8 epithelioid MPNSTs (E-MPNSTs), 2 atypical neurofibromatous neoplasms with uncertain biologic potential (ANNUBPs) and 1 glandular MPNST. For pan-TRK-positive cases,\n                      <jats:italic>NTRK<\/jats:italic>\n                      rearrangements were examined by molecular methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      15 cases (11 C-MPNSTs, 3 E-MPNSTs and 1 ANNUBP) were positive for pan-TRK. Clinically, the positivity rates were significantly higher in older patients (\u226550 years, 21.3% vs &lt;50 years, 3.0%; p=0.0014) and sporadic cases (17.6% vs 5.1%; p=0.0287). In histological analyses, the positivity rate was significantly higher in E-MPNSTs than in C-MPNSTs (37.5% vs 11.1%; p=0.0333). Immunohistochemically, the expression of both S100 and SOX10 was significantly correlated with pan-TRK positivity (p=0.0310\u2009and 0.0145, respectively). Although DNA-based sequencing was successfully performed for 11 cases, no evident\n                      <jats:italic>NTRK<\/jats:italic>\n                      rearrangements were detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study suggests that pan-TRK immunostaining may be useful for confirming neural differentiation in MPNST. However, whether its positivity reflects\n                      <jats:italic>NTRK<\/jats:italic>\n                      rearrangements or neural differentiation must be carefully assessed in combination with various immunohistochemical and molecular tests.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2025-210513","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T18:20:26Z","timestamp":1769106026000},"page":"250-256","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of pan-TRK immunostaining in malignant peripheral nerve sheath tumours: does its positivity indicate\n                    <i>NTRK<\/i>\n                    rearrangements or neural differentiation?"],"prefix":"10.1136","volume":"79","author":[{"given":"Taro","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"},{"name":"Division of Diagnostic Pathology, Kyushu University Hospital, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Tomonaga","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"},{"name":"Division of Diagnostic Pathology, Kyushu University Hospital, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"},{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"},{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Kyushu University Beppu Hospital, Beppu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Momosaki","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Hospital Organisation Kyushu Medical Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Hospital Organisation Kyushu Medical Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kobe City Medical Center General Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Kohashi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Osaka Metropolitan University, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuharu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-1182","authenticated-orcid":false,"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"},{"name":"Division of Diagnostic Pathology, Kyushu University Hospital, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"2026031905050587000_79.4.250.1","unstructured":"Nielsen GP , Chi P . Malignant peripheral nerve sheath tumour. In: World Health Organization Classification of Soft Tissue and Bone Tumours. 5th edn. Lyon, 2020: 254\u20137."},{"key":"2026031905050587000_79.4.250.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02671-0"},{"key":"2026031905050587000_79.4.250.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0113-0"},{"key":"2026031905050587000_79.4.250.4","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.3390\/ijms25042366","article-title":"NTRK Therapy among Different Types of Cancers","volume":"25","author":"Theik","year":"2024","journal-title":"Review and Future Perspectives Int J Mol Sci"},{"key":"2026031905050587000_79.4.250.5","unstructured":"Suurmeijer AJH , Antonescu CR . NTRK-rearranged spindle cell neoplasm (emerging). In: World Health Organization Classification of Soft Tissue and Bone Tumours. 5th edn. Lyon: IARC Press, 2020: 287\u20139."},{"key":"2026031905050587000_79.4.250.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0324-7"},{"key":"2026031905050587000_79.4.250.7","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41379-020-0495-2","article-title":"NTRK3 overexpression in undifferentiated sarcomas with YWHAE and BCOR genetic alterations","volume":"33","author":"Kao","year":"2020","journal-title":"Mod Pathol"},{"key":"2026031905050587000_79.4.250.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-00657-x"},{"key":"2026031905050587000_79.4.250.9","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/s41379-021-01005-3","article-title":"Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements","volume":"35","author":"Tsai","year":"2022","journal-title":"Mod 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