{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:09:01Z","timestamp":1778573341814,"version":"3.51.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>While neuroendocrine markers such as chromogranin can be used to distinguish pheochromocytomas (positive) from adrenal cortical lesions (negative), other neuroendocrine markers such as synaptophysin can be positive in both entities. Insulinoma-associated protein 1 (INSM1) is a relatively novel marker often used in the diagnostic assessment of neuroendocrine tumors but with unexplored sensitivity\/specificity in distinguishing between pheochromocytomas and adrenal cortical lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Herein, semi-quantitative immunohistochemical expression for INSM1 was investigated in 35 pheochromocytomas and 64 adrenal cortical lesions (4 adrenal rests, 6 adrenal cortical hyperplasias, 43 adrenal cortical adenomas, 4 adrenal cortical neoplasms of uncertain malignant potential, 7 adrenal cortical carcinomas) and compared to relatively more traditional markers chromogranin and GATA3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>INSM1 demonstrated diffuse strong nuclear staining in all pheochromocytomas (100%) and focal weak nuclear staining in rare adrenal cortical lesions (8%). Substratification showed INSM1 positivity in a subset of adrenal cortical hyperplasias (17%) and adrenal cortical adenomas (9%). For pheochromocytomas, overall sensitivity (and specificity compared to adrenal cortical lesions) was 100% (92%) for INSM1, 91% (97%) for GATA3, and 100% (100%) for chromogranin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>When attempting to distinguish pheochromocytomas from adrenal cortical lesions, INSM1 and GATA3 can be effective immunohistochemical tools with excellent sensitivity and specificity. However, while they may be helpful adjuncts in diagnostically challenging cases, chromogranin remains the gold-standard marker with even higher sensitivity and specificity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajcp\/aqag034","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:43:32Z","timestamp":1773330212000},"source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic sensitivity and specificity of INSM1 in pheochromocytomas versus adrenal cortical lesions"],"prefix":"10.1093","volume":"165","author":[{"given":"Douglas Jian-Xian","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pathology, Stanford Medical Center , Stanford, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anandi","family":"Lobo","sequence":"additional","affiliation":[{"name":"Kapoor Centre of Urology and Pathology Department of Pathology, , Raipur,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"McKenney","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cleveland Clinic , Cleveland, OH,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankur R","family":"Sangoi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford Medical Center , Stanford, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"2026051203155919000_aqag034-B1","doi-asserted-by":"crossref","first-page":"15252","DOI":"10.1016\/S0021-9258(18)42173-4","article-title":"A novel human insulinoma-associated cDNA, IA-1, encodes a protein with \u201czinc-finger\u201d DNA-binding motifs","volume":"267","author":"Goto","year":"1992","journal-title":"J Biol Chem"},{"key":"2026051203155919000_aqag034-B2","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1096\/fj.08-125971","article-title":"Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation","volume":"23","author":"Lan","year":"2009","journal-title":"FASEB J"},{"key":"2026051203155919000_aqag034-B3","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1002\/cne.21629","article-title":"Transient expression of the conserved zinc finger gene INSM1 in progenitors and nascent neurons throughout embryonic and adult neurogenesis","volume":"507","author":"Duggan","year":"2008","journal-title":"J Comp Neurol"},{"key":"2026051203155919000_aqag034-B4","doi-asserted-by":"publisher","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":"2026051203155919000_aqag034-B5","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s13402-020-00505-9","article-title":"Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors","volume":"43","author":"Mahalakshmi","year":"2020","journal-title":"Cell Oncol (Dordr))"},{"key":"2026051203155919000_aqag034-B6","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1177\/10668969241311524","article-title":"Aberrant cytoplasmic INSM1 expression in erythroid cells: a potential diagnostic pitfall versus neuroendocrine neoplasms","volume":"33","author":"Wu","year":"2025","journal-title":"Int J Surg Pathol"},{"key":"2026051203155919000_aqag034-B7","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1097\/PAS.0b013e3181cfb506","article-title":"A tissue microarray-based comparative analysis of novel and traditional immunohistochemical markers in the distinction between adrenal cortical lesions and pheochromocytoma","volume":"34","author":"Sangoi","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"2026051203155919000_aqag034-B8","first-page":"424","article-title":"Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas. 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