{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:18:56Z","timestamp":1787771936747,"version":"build-2784847793"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>Well-differentiated neuroendocrine tumors of the appendix (A-WDNET) are the most common neoplasms of the appendix but are rare and incidental. INSM1 is a novel transcription factor marker with high sensitivity and specificity for neuroendocrine differentiation. It may display architecturally diverse tumor growth patterns including solid, nest, insular trabecular, and acinar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>The aim of this study was to determine the staining expression of INSM1 in A-WDNETs and detail the morphological tumor growth patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>INSM1 immunohistochemistry was performed on 35 A-WDNET patients. Tumors were histologically classified according to their growth patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Thirty-five patients, 60% of whom were male, had a mean age of 30 years at diagnosis and a mean tumor size of 0.9 cm. Eight percent of the tumors invaded the mucosa\/submucosa, 34.3% showed invasion into the muscularis propria, 57.1% showed invasion into the subserosa or mesoappendix, LN metastasis was observed in two patients, lymph-vascular invasion in two patients, and perineural invasion in five patients. Ninety-four percent of the tumors were grade 1, the mitotic rate was &gt;2% in two cases, and Ki-67 PI was &gt;3% in two cases. INSM1 was positive in all cases (100%), 1+ 8.6%, 2+ 5.7%, 3+ 17.1%, 4+ 68.6%, weak staining in 11.4%, moderate staining in 22.9%, and strong staining in 67.7%. Type A histological growth pattern was observed in 54.3%, type B in 31.4%, and type C in 14.3% architecturally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>INSM1 was positive in all A-WDNET morphological patterns and was 100% sensitive. INSM1 IHC can be used as an alternative to traditional neuroendocrine markers or in combination with the diagnosis of neuroendocrine tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijpm.ijpm_514_23","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:01:10Z","timestamp":1708495270000},"page":"282-288","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of immunohistochemical expression of novel neuroendocrine marker INSM1 and histological tumor growth pattern in well-differentiated neuroendocrine tumors of the appendix: 15-year single tertiary center experience"],"prefix":"10.4103","volume":"67","author":[{"given":"Ali","family":"Koyuncuer","sequence":"first","affiliation":[{"name":"Department of Pathology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolga","family":"Canbak","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Health Sciences University Umraniye Training and Research Hospital, \u0130stanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Acar","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Health Sciences University Umraniye Training and Research Hospital, \u0130stanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"R1-20240829","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ijsu.2017.11.028","article-title":"Surgical management of acute appendicitis in adults: A review of current techniques","volume":"48","author":"Sohn","year":"2017","journal-title":"Int J Surg"},{"key":"R2-20240829","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000443165","article-title":"ENETS consensus guidelines for neuroendocrine neoplasms of the appendix (excluding goblet cell carcinomas)","volume":"103","author":"Pape","year":"2016","journal-title":"Neuroendocrinology"},{"key":"R3-20240829","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1177\/10668969221095172","article-title":"Appendiceal well-differentiated neuroendocrine tumors: A single-center experience and new insights into the effective use of immunohistochemistry","volume":"31","author":"Shibahara","year":"2022","journal-title":"Int J Surg Pathol"},{"key":"R4-20240829","first-page":"1013640","article-title":"Identification of phosphohistone H3 cutoff values corresponding to original WHO grades but distinguishable in well-differentiated gastrointestinal neuroendocrine tumors","author":"Kim","year":"2018","journal-title":"Biomed Res Int 2018"},{"key":"R6-20240829","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s12022-022-09708-2","article-title":"Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms","volume":"33","author":"Rindi","year":"2022","journal-title":"Endocr Pathol"},{"key":"R7-20240829","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/ajcp\/aqaa014","article-title":"INSM1 is a highly specific marker of neuroendocrine differentiation in primary neoplasms of the gastrointestinal tract, appendix, and pancreas","volume":"153","author":"McHugh","year":"2020","journal-title":"Am J Clin Pathol"},{"key":"R8-20240829","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.path.2010.05.003","article-title":"Pathology of gastrointestinal neuroendocrine tumors: An update","volume":"3","author":"Moreira","year":"2010","journal-title":"Surg Pathol Clin"},{"key":"R10-20240829","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.humpath.2022.12.005","article-title":"Extraskeletal myxoid chondrosarcoma: A study of 17 cases focusing on the diagnostic utility of INSM1 expression and presenting rare morphological variants associated with non-EWSR1: NR4A3 fusions","volume":"134","author":"Lenz","year":"2023","journal-title":"Hum Pathol"},{"key":"R11-20240829","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/ajcp\/aqaa014","article-title":"INSM1 is a highly specific marker of neuroendocrine differentiation in primary neoplasms of the gastrointestinal tract, appendix, and pancreas: An immunohistochemical study of 179 cases","volume":"153","author":"McHugh","year":"2020","journal-title":"Am J Clin Pathol"},{"key":"R12-20240829","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.path.2019.08.007","article-title":"Neuroendocrine tumors of the gastrointestinal tract and pancreas","volume":"12","author":"Patel","year":"2019","journal-title":"Surg Pathol Clin"},{"key":"R13-20240829","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/1097-0142(196802)21:2<270::AID-CNCR2820210217>3.0.CO;2-9","article-title":"Carcinoid tumors of the vermiform appendix","volume":"21","author":"Moertel","year":"1968","journal-title":"Cancer"},{"key":"R14-20240829","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.mpdhp.2011.06.012","article-title":"The neoplastic appendix: A practical approach","volume":"17","author":"Lam-Himlin","year":"2011","journal-title":"Diagn Histopathol"},{"key":"R15-20240829","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/1097-0142(19920901)70:5<1081::AID-CNCR2820700512>3.0.CO;2-9","article-title":"A comparative immunohistochemical study of jejunoileal and appendiceal carcinoids. Implications for histogenesis and pathogenesis","volume":"70","author":"Moyana","year":"1992","journal-title":"Cancer"},{"key":"R16-20240829","doi-asserted-by":"crossref","first-page":"437","DOI":"10.5858\/arpa.2015-0314-RA","article-title":"Recent updates on neuroendocrine tumors from the gastrointestinal and pancreatobiliary tracts","volume":"140","author":"Kim","year":"2016","journal-title":"Arch Pathol Lab Med"},{"issue":"Suppl 1","key":"R17-20240829","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1007\/s00428-007-0461-0","article-title":"Site-specific biology and pathology of gastroenteropancreatic neuroendocrine tumors","volume":"451","author":"Kl\u00f6ppel","year":"2007","journal-title":"Virchows Arch"},{"key":"R18-20240829","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.soc.2019.11.010","article-title":"Neuroendocrine tumors of the appendix, colon, and rectum","volume":"29","author":"Hrabe","year":"2020","journal-title":"Surg Oncol Clin N Am"},{"key":"R19-20240829","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.humpath.2022.06.003","article-title":"Expression of novel neuroendocrine markers in breast carcinomas: A study of INSM1, ASCL1, and POU2F3","volume":"127","author":"Zhong","year":"2022","journal-title":"Hum Pathol"},{"key":"R20-20240829","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s00795-017-0167-6","article-title":"Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor","volume":"51","author":"Tanigawa","year":"2018","journal-title":"Med Mol Morphol"},{"key":"R21-20240829","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41379-018-0122-7","article-title":"Insulinoma-associated protein 1 (INSM1) is a sensitive and highly specific marker of neuroendocrine differentiation in primary lung neoplasms: An immunohistochemical study of 345 cases, including 292 whole-tissue sections","volume":"32","author":"Mukhopadhyay","year":"2019","journal-title":"Mod Pathol"},{"key":"R22-20240829","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/his.13899","article-title":"Insulinoma-associated protein 1 expression in primary and metastatic neuroendocrine neoplasms of the gastrointestinal and pancreaticobiliary tracts","volume":"75","author":"Gonz\u00e1lez","year":"2019","journal-title":"Histopathology"},{"key":"R23-20240829","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/labinvest.2015.138","article-title":"Loss of antigenicity with tissue age in breast cancer","volume":"96","author":"Combs","year":"2016","journal-title":"Lab Invest"},{"key":"R24-20240829","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/PAI.0000000000000172","article-title":"Decline in antigenicity of tumor markers by storage time using pathology sections cut from tissue microarrays","volume":"24","author":"Blows","year":"2016","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"R25-20240829","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00418-021-01987-w","article-title":"Methods for restoration of ki67 antigenicity in aged paraffin tissue blocks","volume":"156","author":"Grillo","year":"2021","journal-title":"Histochem Cell Biol"},{"key":"R26-20240829","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/cup.13902","article-title":"Insulinoma-associated 1: A sensitive marker of neuroendocrine differentiation in cutaneous and metastatic neuroendocrine tumors","volume":"48","author":"Cassarino","year":"2021","journal-title":"J Cutan Pathol"},{"key":"R27-20240829","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.3390\/diagnostics11122172","article-title":"INSM1, a novel biomarker for detection of neuroendocrine neoplasms: Cytopathologists'view","volume":"11","author":"Maleki","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"R28-20240829","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1309\/AJCPGZWXXBSNL4VD","article-title":"INSM1: A novel immunohistochemical and molecular marker for neuroendocrine and neuroepithelial neoplasms","volume":"144","author":"Rosenbaum","year":"2015","journal-title":"Am J Clin Pathol"},{"key":"R29-20240829","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/s41379-020-0517-0","article-title":"INSM1 expression in a subset of thoracic malignancies and small round cell tumors: Rare potential pitfalls for small cell carcinoma","volume":"33","author":"Tsai","year":"2020","journal-title":"Mod Pathol"},{"key":"R30-20240829","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/cncy.21972","article-title":"Insulinoma-associated protein 1 is a sensitive and specific marker of neuroendocrine lung neoplasms in cytology specimens","volume":"126","author":"Doxtader","year":"2018","journal-title":"Cancer Cytopathol"},{"key":"R31-20240829","doi-asserted-by":"crossref","first-page":"120","DOI":"10.14740\/gr1138","article-title":"Neuroendocrine markers insulinoma-associated protein 1, chromogranin, synaptophysin, and CD56 show rare positivity in adenocarcinoma ex-goblet cell carcinoids","volume":"12","author":"Yang","year":"2019","journal-title":"Gastroenterology Res"},{"key":"R32-20240829","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1053\/j.semdp.2004.11.004","article-title":"Neuroendocrine tumors of the appendix","volume":"21","author":"Carr","year":"2004","journal-title":"Semin Diagn Pathol"},{"key":"R33-20240829","first-page":"601","article-title":"Neuroendocrine Neoplasms of the appendix: A review of the literature","volume":"38","author":"Moris","year":"2018","journal-title":"Anticancer Res"},{"key":"R34-20240829","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/jso.21634","article-title":"The clinical utility of Ki-67 in assessing tumor biology and aggressiveness in patients with appendiceal carcinoids","volume":"102","author":"Liu","year":"2010","journal-title":"J Surg Oncol"},{"key":"R35-20240829","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1159\/000343801","article-title":"Current size criteria for the management of neuroendocrine tumors of the appendix: Are they valid?Clinical experience and review of the literature","volume":"98","author":"Grozinsky-Glasberg","year":"2013","journal-title":"Neuroendocrinology"}],"container-title":["Indian Journal of Pathology and Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_514_23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:21:28Z","timestamp":1787768488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_514_23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,19]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/ijpm.ijpm_514_23","relation":{},"ISSN":["0377-4929","0974-5130"],"issn-type":[{"value":"0377-4929","type":"print"},{"value":"0974-5130","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,19]]},"assertion":[{"value":"2023-06-26","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}