{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:50:49Z","timestamp":1782910249145,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073640"],"award-info":[{"award-number":["82073640"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U21A20389"],"award-info":[{"award-number":["U21A20389"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studies describing the clinical presentation and prognosis of patients with silent PIT1 (pituitary specific transcription factor)\u2010lineage pituitary neuroendocrine tumors (PitNETs) are rare. We identified patients with positive PIT1 tumor staining but without evidence of hormone hypersecretion at a tertiary center. Clusters were obtained according to cell morphology and immunostaining from each patient's digitally segmented whole slide image. We compared the clinical presentations, radiological features, and prognoses of the different clusters. We identified 146 patients (68 male, 42.9\u2009\u00b1\u200914.1\u2009years old) with silent PIT1\u2010lineage PitNETs. Morphology clustering suggested that tumors with large nuclei and apparent eccentricity were associated with a higher proportion of aggressiveness and a higher hazard of recurrence [hazard ratio (HR): 2.64, (95% CI, 1.06\u20136.55), <jats:italic>p<\/jats:italic>\u2009=\u20090.037]. Immunohistochemical clustering suggested that tumors with thyroid stimulating hormone (TSH) staining or all negative PIT1\u2010lineage hormones were associated with a higher proportion of aggressiveness and a higher risk of recurrence [HR: 12.4, (95% CI, 1.60\u201393.5), <jats:italic>p<\/jats:italic>\u2009=\u20090.015]. We obtained three\u2010tier risk profiles by combining morphological and immunohistochemical clustering. Patients with the high\u2010risk profile presented the highest recurrence rate compared with those in the medium\u2010risk and low\u2010risk profiles [HR: 3.54, (95% CI, 1.40\u20138.93), <jats:italic>p<\/jats:italic>\u2009=\u20090.002]. In conclusion, digital image analysis based on cell morphology and immunohistochemical staining allows objective stratification of patients with silent PIT1\u2010lineage tumors. Typical morphological characteristics of high\u2010risk tumors are large tumor nuclei and high eccentricity, and typical immunostaining characteristics are TSH staining or negative staining for all PIT1\u2010lineage hormones.<\/jats:p>","DOI":"10.1002\/cjp2.340","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T04:10:37Z","timestamp":1693800637000},"page":"488-497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Digital image analysis allows objective stratification of patients with silent <scp>PIT1<\/scp>\u2010lineage pituitary neuroendocrine tumors"],"prefix":"10.1002","volume":"9","author":[{"given":"Jiangyan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Institutes of Biomedical Sciences Fudan University  Shanghai PR 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