{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:12:51Z","timestamp":1747185171031,"version":"3.40.5"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NV19\u201001\u201000435"],"award-info":[{"award-number":["NV19\u201001\u201000435"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>In somatotroph pituitary neuroendocrine tumours (adenomas), a pattern of cytokeratin (CK) 18 expression is used for tumour subclassification, with possible clinical implications. Rare somatotroph tumours do not express CK 18. We aimed to characterise this subset clinically and histologically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Clinical and pathological data for the study were derived from a previously published data set of a cohort of 110 patients with acromegaly. Data included serum levels of insulin\u2010like growth factor 1 (IGF1), growth hormone (GH), prolactin and thyroid\u2010stimulating hormone (TSH), tumour diameter, tumour invasion defined by Knosp grade and immunohistochemical data concerning the expression of Ki67, p53, E\u2010cadherin, somatostatin receptor (SSTR)1, SSTR2A, SSTR3, SSTR5 and D2 dopamine receptor. Additional immunohistochemical analysis (AE1\/3, CK 8\/18, vimentin, neurofilament light chain, internexin\u2010\u03b1) was performed. CK 18 was negative in 10 of 110 (9.1%) tumours. One of these tumours was immunoreactive with CK 8\/18 antibody, while the remainder expressed only internexin\u2010\u03b1 intermediate filament in patterns similar to CK 18 (perinuclear fibrous bodies). CK\u2010negative tumours showed no significant differences with respect to biochemical, radiological or pathological features. They showed significantly higher expression of SSTR2A compared to the sparsely granulated subtype and significantly lower expression of E\u2010cadherin compared to the non\u2010sparsely granulated subtypes of tumours. The tumours showed divergent morphology and hormonal expression: two corresponded to densely granulated tumours and three showed co\u2010expression of prolactin and morphology of either mammosomatotroph or somatotroph\u2013lactotroph tumours. Four tumours showed morphology and immunoprofile compatible with plurihormonal Pit1\u2010positive tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CK\u2010negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14366","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T06:28:51Z","timestamp":1616135331000},"page":"406-415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytokeratin 8\/18\u2010negative somatotroph pituitary neuroendocrine tumours (PitNETs, adenomas) show variable morphological features and do not represent a clinicopathologically distinct entity"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7169-4386","authenticated-orcid":false,"given":"Jiri","family":"Soukup","sequence":"first","affiliation":[{"name":"The Fingerland Department of Pathology Faculty of Medicine Hradec Kralove University Hospital Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Cesak","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Faculty of Medicine Hradec Kralove University Hospital Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Hornychova","sequence":"additional","affiliation":[{"name":"The Fingerland Department of Pathology Faculty of Medicine Hradec Kralove University Hospital Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Manethova","sequence":"additional","affiliation":[{"name":"The Fingerland Department of Pathology Faculty of Medicine Hradec Kralove University Hospital Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludmila","family":"Michnova","sequence":"additional","affiliation":[{"name":"Department of Pathology Military University Hospital Prague Praha Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Netuka","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology 1st Medical Faculty Charles University Military University Hospital Prague Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Vitovcova","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics Faculty of Medicine Hradec Kralove Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Cap","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine Faculty of Medicine Hradec Kralove University Hospital Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-2280","authenticated-orcid":false,"given":"Ales","family":"Ryska","sequence":"additional","affiliation":[{"name":"The Fingerland Department of Pathology Faculty of Medicine Hradec Kralove University Hospital Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7053-3369","authenticated-orcid":false,"given":"Filip","family":"Gabalec","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine Faculty of Medicine Hradec Kralove University Hospital Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21765"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02655-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1385\/EP:16:3:201"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPAKB6JEBVMX5U"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2014-0020-OA"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-016-0748-8"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-008-9029-z"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0586"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.08.007"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-012-0445-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2011.04163.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/723432"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2013.09.003"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0832"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13851"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-020-09634-1"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16173"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1084-y"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1985.tb50418.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0167-7"},{"key":"e_1_2_7_22_1","first-page":"355","volume-title":"WHO classification of tumours of endocrine organs","author":"Lloyd RV","year":"2017"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0016-8"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1385\/EP:13:4:341"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.11.002"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.151"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.12.003"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.03065.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-014-0597-2"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000806"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0055-y"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2020.10.004"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-4449-8"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12352"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1760"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0779-5"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-008-9167-1"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.14366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T13:22:01Z","timestamp":1693315321000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.14366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1111\/his.14366"],"URL":"https:\/\/doi.org\/10.1111\/his.14366","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"type":"print","value":"0309-0167"},{"type":"electronic","value":"1365-2559"}],"subject":[],"published":{"date-parts":[[2021,5,21]]},"assertion":[{"value":"2021-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}