{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:41:05Z","timestamp":1773924065613,"version":"3.50.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Nodular regenerative hyperplasia (NRH) is a rare vascular disorder of the liver. Clinically, patients present with portal hypertension with or without a cholestatic pattern of injury. Histologically, the liver parenchyma is composed of small nodules of hypertrophic hepatocytes surrounded by atrophic hepatocytes without significant fibrosis. Nodular regenerative hyperplasia is a difficult diagnosis on biopsy specimens, but biopsy remains the gold standard for diagnosis. In this retrospective review, cytokeratin 7 (CK7) immunohistochemistry (IHC) was used to aid in the diagnosis and further characterization of NRH and NRH-like changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The H&amp;E-stained slides, reticulin, and CK IHC were reviewed for 22 cases. The percentage of hepatocytes staining for CK7 (0%-100%), the location of staining (centrilobular hepatic progenitor cells vs periportal\/bile ductular reaction), and the pattern of staining distribution (patchy or diffuse) were recorded for comparison.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 22 cases, 9 were CK7 positive. Cases of NRH, however, expressed various degrees of CK7 positivity in centrilobular hepatic progenitor cells, unlike NRH-like changes, which were either CK7 negative or CK7 positive in periportal hepatocytes or in areas of bile ductular reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In cases with the appropriate clinical history and histology, CK7 immunohistochemistry can be performed to distinguish nodular regenerative hyperplasia (primary) and NRH-like changes (secondary). In difficult cases, CK7 positivity in centrilobular hepatic progenitor cells can help confirm the diagnosis of NRH. These data support NRH as a true entity with a distinct pathophysiology from NRH-like changes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajcp\/aqae110","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T20:40:44Z","timestamp":1723063244000},"page":"196-204","source":"Crossref","is-referenced-by-count":0,"title":["Nodular regenerative hyperplasia: The role of the CK7 immunohistochemistry pattern of expression in diagnosis"],"prefix":"10.1093","volume":"163","author":[{"given":"Brooke B","family":"Bartow","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL ,","place":["US"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepti","family":"Dhall","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL ,","place":["US"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL ,","place":["US"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjula","family":"Garapati","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL ,","place":["US"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chirag R","family":"Patel","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology, Mayo Clinic , Phoenix, AZ ,","place":["US"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameer","family":"Al Diffalha","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL ,","place":["US"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"issue":"3","key":"2026031904521350800_CIT0001","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/0270-9139(95)90324-0","article-title":"Terminology of nodular hepatocellular lesions","volume":"22","author":"International Working Party","year":"1995","journal-title":"Hepatology."},{"issue":"3","key":"2026031904521350800_CIT0002","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1699-0463.1953.tb01513.x","article-title":"Miliary hepatocellular adenomatosis","volume":"33","author":"Ranstrom","year":"1953","journal-title":"Acta Pathol Microbiol Scand"},{"issue":"5","key":"2026031904521350800_CIT0003","first-page":"943","article-title":"Nodular regenerative hyperplasia of the liver","volume":"35","author":"Steiner","year":"1959","journal-title":"Am J Pathol."},{"issue":"11","key":"2026031904521350800_CIT0004","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.3748\/wjg.v17.i11.1400","article-title":"Nodular regenerative hyperplasia: evolving concepts on underdiagnosed cause of portal hypertension","volume":"17","author":"Hartleb","year":"2011","journal-title":"World J Gastroenterol."},{"issue":"5","key":"2026031904521350800_CIT0005","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1002\/hep.1840110512","article-title":"Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules","volume":"11","author":"Wanless","year":"1990","journal-title":"Hepatology."},{"issue":"6","key":"2026031904521350800_CIT0006","doi-asserted-by":"publisher","first-page":"e0120299","DOI":"10.1371\/journal.pone.0120299","article-title":"Diagnosing nodular regenerative hyperplasia of the liver is thwarted by low interobserver agreement","volume":"10","author":"Jharap","year":"2015","journal-title":"PLoS One."},{"issue":"2","key":"2026031904521350800_CIT0007","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/s0016-5085(03)00938-7","article-title":"6-thioguanine can cause serious liver injury in inflammatory bowel disease patients","volume":"125","author":"Dubinsky","year":"2003","journal-title":"Gastroenterology."},{"issue":"11","key":"2026031904521350800_CIT0008","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1111\/j.1572-0241.2007.01530.x","article-title":"6-thioguanine associated nodular regenerative hyperplasia in patients with inflammatory bowel disease may induce portal hypertension","volume":"102","author":"Ferlitsch","year":"2007","journal-title":"Am J Gastroenterol."},{"issue":"8","key":"2026031904521350800_CIT0009","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1097\/QAD.0b013e3283389e26","article-title":"Noncirrhotic portal hypertension in HIV-infected patients: unique clinical and pathological findings","volume":"24","author":"Vispo","year":"2010","journal-title":"AIDS."},{"issue":"4","key":"2026031904521350800_CIT0010","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1002\/ajh.20024","article-title":"Nodular regenerative hyperplasia of the liver: an under-recognized cause of portal hypertension in hematological disorders","volume":"75","author":"Al-Mukhaizeem","year":"2004","journal-title":"Am J Hematol."},{"issue":"2","key":"2026031904521350800_CIT0011","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.jhep.2013.08.013","article-title":"Non-cirrhotic portal hypertension\u2014diagnosis and management","volume":"60","author":"Khanna","year":"2014","journal-title":"J Hepatol."},{"issue":"1","key":"2026031904521350800_CIT0012","doi-asserted-by":"publisher","first-page":"17","DOI":"10.4132\/jptm.2015.09.23","article-title":"Idiopathic noncirrhotic portal hypertension: an appraisal","volume":"50","author":"Lee","year":"2016","journal-title":"J Pathol Transl Med"},{"issue":"8","key":"2026031904521350800_CIT0013","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1111\/j.1440-1746.2012.07168.x","article-title":"Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension","volume":"27","author":"Bissonnette","year":"2012","journal-title":"J Gastroenterol Hepatol."},{"issue":"8","key":"2026031904521350800_CIT0014","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1097\/MEG.0b013e3283360021","article-title":"Nodular regenerative hyperplasia of the liver: survival and associated features in a UK case series","volume":"22","author":"Morris","year":"2010","journal-title":"Eur J Gastroenterol Hepatol."},{"issue":"1","key":"2026031904521350800_CIT0015","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/hep.21258","article-title":"Nodular regenerative hyperplasia: not all nodules are created equal","volume":"44","author":"Reshamwala","year":"2006","journal-title":"Hepatology."},{"issue":"4","key":"2026031904521350800_CIT0016","doi-asserted-by":"publisher","first-page":"152833","DOI":"10.1016\/j.prp.2020.152833","article-title":"Nodular regenerative hyperplasia\u2014an under-recognized vascular disorder of liver","volume":"216","author":"Bakshi","year":"2020","journal-title":"Pathol Res Pract."},{"issue":"6","key":"2026031904521350800_CIT0017","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1053\/j.semdp.2018.10.003","article-title":"Diagnostic histochemistry in hepatic pathology","volume":"35","author":"Iezzoni","year":"2018","journal-title":"Semin Diagn Pathol."},{"issue":"suppl 1","key":"2026031904521350800_CIT0018","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.1002\/cld.148","article-title":"Role of special stains in diagnostic liver pathology","volume":"2","author":"Krishna","year":"2013","journal-title":"Clin Liver Dis (Hoboken)"},{"issue":"5","key":"2026031904521350800_CIT0019","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1111\/j.1365-2559.2012.04278.x","article-title":"Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study","volume":"61","author":"Matsukuma","year":"2012","journal-title":"Histopathology."},{"issue":"5","key":"2026031904521350800_CIT0020","doi-asserted-by":"publisher","first-page":"876818","DOI":"10.3389\/fsurg.2022.876818","article-title":"Nodular regenerative hyperplasia after liver transplant; it\u2019s all in the presentation","volume":"9","author":"Chen","year":"2022","journal-title":"Front Surg"}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/163\/2\/196\/58979713\/aqae110.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/163\/2\/196\/58979713\/aqae110.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T08:52:21Z","timestamp":1773910341000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/163\/2\/196\/7746077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,30]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2,12]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqae110","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"value":"0002-9173","type":"print"},{"value":"1943-7722","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2024,8,30]]}}}