{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:54:49Z","timestamp":1776873289694,"version":"3.51.2"},"reference-count":63,"publisher":"Georg Thieme Verlag KG","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>According to the WHO classification 2017 of Pituitary Tumors adenomas are classified not only by structure and immunostaining for pituitary hormones but also by expression of the pituitary transcription factors Pit-1, T-pit and SF-1. By these factors, three cell lineages can be identified: Pit-1 for the GH-, Prolactin- and TSH-cell lineage, T-pit for the ACTH-cell lineage, and SF-1 for the gonadotrophic cell lineage. By this principle, all GH and\/or Prolactin producing and all TSH producing adenomas must be positive for Pit-1, all corticotrophic adenomas for T-pit, and all gonadotrophic for SF-1. In adenomas without expression of pituitary hormones immunostainings for the transcription factors have to be examined. If these are also negative the criteria for an endocrine inactive null cell adenoma are fulfilled. If one transcription factor is positive the corresponding cell lineage indicates a potential hormonal activity of the adenoma. So Pit-1 expressing hormone-negative adenomas can account for acromegaly, hyperprolactinemia, or TSH hyperfunction. T-pit positive hormone negative adenomas can induce Cushing\u2019s disease, and SF-1 positive hormone negative tumors indicate gonadotrophic adenomas. Instead of the deleted atypical adenoma of the WHO classification of 2004 now (WHO classification 2017) criteria exist for the identification of aggressive adenomas with a conceivably worse prognosis. Some adenoma subtypes are described as aggressive \u201cper se\u201d without necessity of increased morphological signs of proliferation. All other adenoma subtypes must also be designated as aggressive if they show signs of increased proliferation (mitoses, Ki-67 index&gt;3\u20135%, clinically rapid tumor growth) and invasion. By these criteria about one third of pituitary adenoma belong to the group of aggressive adenomas with potentially worse prognosis. The very rare pituitary carcinoma (0.1 % of pituitary tumors) is defined only by metastases. Many of them develop after several recurrences of Prolactin or ACTH secreting adenomas. The correlation of clinical findings and histological classification of pituitary adenomas is very important since every discrepancy has to be discussed between clinicians and pathologists. Based on data of the German Registry of Pituitary Tumors a table for examinations of correlations is shown in this review.<\/jats:p>","DOI":"10.1055\/a-1310-7900","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T23:33:58Z","timestamp":1615332838000},"page":"146-156","source":"Crossref","is-referenced-by-count":9,"title":["Clinical Implications of the New WHO Classification 2017 for Pituitary Tumors"],"prefix":"10.1055","volume":"129","author":[{"given":"Wolfgang","family":"Saeger","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology of the University of Hamburg, UKE, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arend","family":"Koch","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.beem.2009.05.008","article-title":"The epidemiology and genetics of pituitary adenomas","volume":"23","author":"A F Daly","year":"2009","journal-title":"Best Practice & Research Clinical Endocrinology & Metabolism"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/cncr.20412","article-title":"The prevalence of pituitary adenomas - A systematic review","volume":"101","author":"S Ezzat","year":"2004","journal-title":"Cancer"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1530\/JOE-18-0446","article-title":"Germline and mosaic mutations causing pituitary tumours: genetic and molecular aspects","volume":"240","author":"S Pepe","year":"2019","journal-title":"Journal of Endocrinology"},{"key":"ref4","first-page":"S 29","article-title":"Subclinical adenomas in postmortem pituitaries: classification and correlation to clinical data","volume":"114","author":"H Buurman","year":"2006","journal-title":"Exper clin Endocr Metab"},{"key":"ref5","first-page":"343","volume-title":"Classification and immunohistology of clinically silent adenomas in postmortem pituitaries","author":"W Saeger","year":"1994","edition":"Vol. 2"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1093\/ajcp\/111.6.817","article-title":"Pituitary adenomas and granular cell tumors - Incidence, cell type, and location of tumor in 100 pituitary glands at autopsy","volume":"111","author":"T Tomita","year":"1999","journal-title":"Am J Clin Pathol"},{"key":"ref7","first-page":"2172","article-title":"Epidemiology of pituitary adenoma: results of the first Swiss study","volume":"5","author":"E Fontana","year":"2009","journal-title":"Revue Medicale Suisse"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s11102-019-00940-4","article-title":"Pituitary incidentalomas in paediatric age are different from those described in adulthood","volume":"22","author":"P Souteiro","year":"2019","journal-title":"Pituitary"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1055\/s-0037-1621738","article-title":"Pediatric Craniopharyngiomas: A Primer for the Skull Base Surgeon","volume":"79","author":"C S Graffeo","year":"2018","journal-title":"Journal of Neurological Surgery Part B-Skull Base"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/oxfordjournals.epirev.a036232","article-title":"Epidemiology of pituitary adenomas","volume":"3","author":"E Gold","year":"1981","journal-title":"Epidemiol Rev"},{"key":"ref11","first-page":"11","volume-title":"Tumours of the pituitary gland","author":"R Osamura","year":"2017","edition":"Ed.4th"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1017\/cjn.2015.301","article-title":"Sellar Masses: An Epidemiological Study","volume":"43","author":"K Al-Dahmani","year":"2016","journal-title":"Canadian Journal of Neurological Sciences"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s12022-008-9029-z","article-title":"Clinicopathological features of growth hormone-producing pituitary adenomas: Difference among various types defined by cytokeratin distribution pattern including a transitional form","volume":"19","author":"A Obari","year":"2008","journal-title":"Endocr Pathol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1023\/A:1009903603495","article-title":"Estrogen receptors in prolactinomas: a clinico-pathological study","volume":"1","author":"G J Kaptain","year":"1999","journal-title":"Pituitary"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.humpath.2013.08.007","article-title":"Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies","volume":"45","author":"L Chinezu","year":"2014","journal-title":"Hum Pathol"},{"key":"ref17","first-page":"1604","article-title":"Prognostic and therapeutic consequences of G(s)alpha mutations in somatotroph adenomas","volume":"83","author":"A Barlier","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s11102-007-0058-2","article-title":"Analysis of GNAS mutations in 60 growth hormone secreting pituitary tumors: Correlation with clinical and pathological characteristics and surgical outcome based on highly sensitive GH and IGF-I criteria for remission","volume":"10","author":"P U Freda","year":"2007","journal-title":"Pituitary"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1210\/jcem-71-6-1416","article-title":"Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein","volume":"71","author":"C A Landis","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000095524","article-title":"Pathology of acromegaly","volume":"83","author":"E Horvath","year":"2006","journal-title":"Neuroendocrinology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1210\/jcem.86.9.7819","article-title":"Surgical management of GH-secreting pituitary adenomas: An outcome study using modern remission criteria","volume":"86","author":"J Kreutzer","year":"2001","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1210\/jc.2006-1668","article-title":"High prevalence of pituitary adenomas: A cross-sectional study in the province of Liege, Belgium","volume":"91","author":"A F Daly","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1750-3639.2012.00599.x","article-title":"Clinicopathological Correlations in Pituitary Adenomas","volume":"22","author":"O Mete","year":"2012","journal-title":"Brain Pathology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1053\/j.semdp.2013.06.002","article-title":"Therapeutic implications of accurate classification of pituitary adenomas","volume":"30","author":"O Mete","year":"2013","journal-title":"Semin Diagn Pathol"},{"key":"ref25","first-page":"31","article-title":"Calcospherites in pituitary prolactinomas. A hypothesis for their formation","volume":"108","author":"S Lipper","year":"1984","journal-title":"Arch Pathol Lab Med"},{"key":"ref26","first-page":"183","article-title":"Amyloidablagerungen in Hypophysenadenomen. Polarisationsoptische, immunhistologische und elektronenmikroskopische Untersuchungen","volume":"4","author":"W Saeger","year":"1983","journal-title":"Pathologe"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3109\/01913129409016287","article-title":"Ultrastructural Markers in the Pathologic Diagnosis of Pituitary Adenomas","volume":"18","author":"E Horvath","year":"1994","journal-title":"Ultrastruct Pathol"},{"key":"ref28","first-page":"1","volume-title":"Tumors of the pituitary gland","author":"S L Asa","year":"1998"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s12020-016-0863-3","article-title":"Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management","volume":"52","author":"F G Amlashi","year":"2016","journal-title":"Endocrine"},{"key":"ref30","first-page":"91","volume-title":"Pathology of pituitary adenomas and pituitary hyperplasia","author":"B W Scheithauer","year":"2001","edition":"Ed.1"},{"key":"ref31","first-page":"245","volume-title":"The adenohypophysis","author":"E Horvath","year":"1991"},{"key":"ref32","first-page":"99","article-title":"Pituitary adenoma secondary to primary hypothyroidism Two case reports","author":"J Y Du","year":"2020","journal-title":"Medicine"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/0002-9343(84)90302-4","article-title":"Pituitary thyrotropic adenoma associated with congenital hypothyroidism. Report of two cases","volume":"76","author":"V Fatourechi","year":"1984","journal-title":"Amer J Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1023\/A:1012909500847","article-title":"Cushing\u2019s disease: A surgical view","volume":"54","author":"D K L\u00fcdecke","year":"2001","journal-title":"J Neurooncol"},{"key":"ref35","first-page":"1","volume-title":"Surgical pathology of the pituitary gland","author":"R V Lloyd","year":"1993"},{"key":"ref36","first-page":"587","volume-title":"Hypophyse","author":"W Saeger","year":"2015","edition":"Ed.3. Aufl"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1097\/00000478-200310000-00005","article-title":"Crooke\u2019s cell adenoma of the pituitary - An aggressive variant of corticotroph adenoma","volume":"27","author":"D H George","year":"2003","journal-title":"Amer J Surg Pathol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1507\/endocrj.EJ18-0547","article-title":"Successful reduction of ACTH secretion in a case of intractable Cushing\u2019s disease with pituitary Crooke\u2019s cell adenoma by combined modality therapy including temozolomide","volume":"66","author":"S Tanaka","year":"2019","journal-title":"Endocrine Journal"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/BF00705414","article-title":"Alpha-subunit-producing pituitary adenomas. Immunocytochemical and ultrastructural studies","volume":"409","author":"A M Landolt","year":"1986","journal-title":"Virchows Arch A Pathol Anat Histopath"},{"key":"ref40","first-page":"1","volume-title":"Pathology and genetics: Tumours of endocrine organs (World Health Organization classification of tumours)","author":"R A DeLellis","year":"2004","edition":"Ed. 1"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11102-017-0855-1","article-title":"Histopathological classification of non-functioning pituitary neuroendocrine tumors","volume":"21","author":"E Manojlovic-Gacic","year":"2018","journal-title":"Pituitary"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s11102-019-00981-9","article-title":"Clinical, pathologic, and imaging characteristics of pituitary null cell adenomas as defined according to the 2017 World Health Organization criteria: a case series from two pituitary centers","volume":"22","author":"J P Almeida","year":"2019","journal-title":"Pituitary"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12022-014-9347-2","article-title":"Null Cell Adenomas of the Pituitary Gland: an Institutional Review of Their Clinical Imaging and Behavioral Characteristics","volume":"26","author":"J A Balogun","year":"2015","journal-title":"Endocr Pathol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s004280050421","article-title":"Immunohistochemical demonstration of oncocytes in nongonadotrophic pituitary adenomas","volume":"435","author":"H Nishioka","year":"1999","journal-title":"Virchows Archiv"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00701-013-1890-y","article-title":"Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature","volume":"156","author":"F T Rasul","year":"2014","journal-title":"Acta Neurochirurgica"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/01913120500323514","article-title":"Silent adenoma subtype 3 of the pituitary - Immunohistochemical and ultrastructural classification: A review of 29 cases","volume":"29","author":"E Horvath","year":"2005","journal-title":"Ultrastruct Pathol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1365-2265.2008.03514.x","article-title":"Silent subtype 3 pituitary adenoma: a clinicopathologic analysis of the Mayo Clinic experience","volume":"71","author":"D Erickson","year":"2009","journal-title":"Clin Endorin"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1530\/eje.1.02326","article-title":"Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry","volume":"156","author":"W Saeger","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3171\/2010.8.JNS10290","article-title":"Atypical pituitary adenomas: incidence, clinical characteristics, and implications Clinical article","volume":"114","author":"G Zada","year":"2011","journal-title":"J Neurosurg"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40478-015-0229-8","article-title":"Histological criteria for atypical adenomas: data from German Pituitary Tumor Registry suggest modifications","volume":"3","author":"C P Miermeister","year":"2015","journal-title":"acta neuropath communications"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1530\/EJE-18-0749","article-title":"Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre","volume":"180","author":"S Asioli","year":"2019","journal-title":"Eur J Endocrin"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1210\/jc.2017-00773","article-title":"Risk of Recurrence in Pituitary Neuroendocrine Tumors: A Prospective Study Using a Five-Tiered Classification","volume":"102","author":"G Raverot","year":"2017","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3810\/pgm.2009.03.1989","article-title":"Multimodality Treatment for Invasive Pituitary Adenomas","volume":"121","author":"M Hornyak","year":"2009","journal-title":"Postgraduate Medicine"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.wneu.2016.09.092","article-title":"Aggressive Pituitary Adenomas: The Dark Side of the Moon","volume":"97","author":"S M Priola","year":"2017","journal-title":"World Neurosurgery"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrendo.2014.64","article-title":"Aggressive pituitary adenomas-diagnosis and emerging treatments","volume":"10","author":"A Di Ieva","year":"2014","journal-title":"Nature Reviews Endocrinology"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1365-2990.2009.01043.x","article-title":"Silent subtype 3 carcinoma of the pituitary: a case report","volume":"36","author":"F Roncaroli","year":"2010","journal-title":"Neuropathology and Applied Neurobiology"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-17-0796","article-title":"European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas","volume":"178","author":"G Raverot","year":"2018","journal-title":"Eur J Endocrin"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00134-016-4587-x","article-title":"Bilateral adrenal hemorrhage","volume":"43","author":"H Fakih","year":"2017","journal-title":"Intensive Care Medicine"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1365-2265.2008.03487.x","article-title":"Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours","volume":"71","author":"A I McCormack","year":"2009","journal-title":"Clin Endorin"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1227\/NEU.0b013e318230ac63","article-title":"O-6-Methylguanine-DNA Methyltransferase (MGMT) Immunohistochemical Expression in Pituitary Corticotroph Adenomas","volume":"70","author":"F Salehi","year":"2012","journal-title":"Neurosurgery"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"99-+","DOI":"10.1016\/j.ecl.2014.10.008","article-title":"Invasive, Atypical and Aggressive Pituitary Adenomas and Carcinomas","volume":"44","author":"A Sav","year":"2015","journal-title":"Endocrinology and Metabolism Clinics of North America"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1227\/NEU.0000000000001319","article-title":"Ectopic Adrenocorticotropic Hormone-Secreting Pituitary Adenomas: An Underestimated Entity","volume":"80","author":"U J Knappe","year":"2017","journal-title":"Neurosurgery"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1365-3083.1990.tb02756.x","article-title":"apo-SAA1\/apo-SAA2 isotype ratios during casein- and amyloid- enhancing-factor-induced secondary amyloidosis in A\/J and C57BL\/6J mice mice","volume":"31","author":"L Hebert","year":"1990","journal-title":"Scand J Immunol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccell.2019.11.002","article-title":"Pangenomic Classification of Pituitary Neuroendocrine Tumors","volume":"37","author":"M Neou","year":"2020","journal-title":"Cancer Cell"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1310-7900.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T23:54:24Z","timestamp":1617926064000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1310-7900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":63,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2021,3,9]]},"published-print":{"date-parts":[[2021,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1310-7900","relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]}}}