{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:17:38Z","timestamp":1760231858976,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research C","doi-asserted-by":"publisher","award":["JP20K07408"],"award-info":[{"award-number":["JP20K07408"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>To investigate useful cytological features for differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), this study cytologically compared HCC to ICC using image analysis software. Touch smear specimens of surgically resected specimens were obtained from a total of 61 nodules of HCC and 16 of ICC. The results indicated that the major\/minor axis ratio of ICC is significantly larger than that of HCC (1.67 \u00b1 0.27 vs. 1.32 \u00b1 0.11, p &lt; 0.0001) in Papanicolaou staining. This result means that the nucleus of HCC is close to round and the nucleus of ICC is close to an oval. This significant difference in the major\/minor axis ratio between ICC and HCC was consistently observed by the same analyses using clinical samples of cytology (4 cases of HCC and 13 cases of ICC) such a fine-needle aspiration, brushing and ascites (ICC: 1.45 \u00b1 0.13 vs. HCC: 1.18 \u00b1 0.056, p = 0.004). We also confirmed that nuclear position center-positioned nucleus (p &lt; 0.0001) and granular cytoplasm (p &lt; 0.0001) are typical features of HCC tumor cells compared to ICC tumor cells. The research study found a significant difference in the nuclear morphology of HCC (round shape) and ICC (oval shape) in Papanicolaou-stained cytology specimens. This simple and objective finding will be very useful for the differential cytodiagnosis of HCC and ICC.<\/jats:p>","DOI":"10.3390\/cancers14092301","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:46:39Z","timestamp":1651805199000},"page":"2301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytological Comparison between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Image Analysis Software Using Touch Smear Samples of Surgically Resected Specimens"],"prefix":"10.3390","volume":"14","author":[{"given":"Sho","family":"Kitamura","sequence":"first","affiliation":[{"name":"Department of Pathology, Saga University Hospital, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-2598","authenticated-orcid":false,"given":"Keita","family":"Kai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saga University Hospital, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuo","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saga University Hospital, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Ide","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Noshiro","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eisaburo","family":"Sueoka","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinich","family":"Aishima","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saga University Hospital, Saga 849-8501, Japan"},{"name":"Department of Pathology and Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1111\/j.1872-034X.2010.00731.x","article-title":"Report of the 18th follow-up survey of primary liver cancer in Japan","volume":"40","author":"Ikai","year":"2010","journal-title":"Hepatol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2169\/internalmedicine.53.1410","article-title":"Hepatitis B and C virus infection is a risk factor for the development of cholangiocarcinoma","volume":"53","author":"Matsumoto","year":"2014","journal-title":"Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jhep.2012.02.022","article-title":"Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma","volume":"57","author":"Palmer","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Zhao, Y., Li, B., Huang, J., Wu, L., Xu, D., Yang, J., and He, J. (2012). Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: Evidence from a meta-analysis. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-289"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.semradonc.2018.06.010","article-title":"Hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Imaging for diagnosis, tumor response to treatment and liver response to radiation","volume":"28","author":"Lo","year":"2018","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.3748\/wjg.v24.i22.2348","article-title":"Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis","volume":"24","author":"Jiang","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.3748\/wjg.v13.i20.2775","article-title":"Positron emission tomography\/computer tomography: Challenge to conventional imaging modalities in evaluating primary and metastatic liver malignancies","volume":"13","author":"Sun","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/hep.29487","article-title":"Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis","volume":"67","author":"Roberts","year":"2018","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.3748\/wjg.v18.i43.6197","article-title":"Current endoscopic approach to indeterminate biliary strictures","volume":"18","author":"Victor","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/cyt.12565","article-title":"SurePath\u00ae\u00ae LBC improves the diagnostic accuracy of intrahepatic and hilar cholangiocarcinoma","volume":"29","author":"Naito","year":"2018","journal-title":"Cytopathology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4103\/0970-9371.86344","article-title":"Value of ultrasonography-guided fine needle aspiration cytology in the investigative sequence of hepatic lesions with an emphasis on hepatocellular carcinoma","volume":"28","author":"Swamy","year":"2011","journal-title":"J. Cytol."},{"key":"ref_12","first-page":"587936","article-title":"Fine-needle aspiration biopsy of hepatocellular carcinoma and related hepatocellular nodular lesions in cirrhosis: Controversies, challenges, and expectations","volume":"2011","author":"Wee","year":"2011","journal-title":"Patholog. Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1365-2303.2011.00882.x","article-title":"Fine needle aspiration biopsy of hepatocellular carcinoma and hepatocellular nodular lesions: Role, controversies and approach to diagnosis","volume":"22","author":"Wee","year":"2011","journal-title":"Cytopathology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1111\/j.1440-1746.2007.04924.x","article-title":"Fine-needle aspiration cytology to distinguish dysplasia from hepatocellular carcinoma with different grades","volume":"23","author":"Lin","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1159\/000326879","article-title":"Fine needle aspiration biopsy of hepatic focal fatty change. A report of two cases","volume":"46","author":"Zeppa","year":"2002","journal-title":"Acta Cytol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/cncr.20409","article-title":"Cytopathologic grading of hepatocellular carcinoma on fine-needle aspiration","volume":"102","author":"Kulesza","year":"2004","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/cncr.20000","article-title":"Cytologic features and histologic correlations of microacinar and microtrabecular types of well-differentiated hepatocellular carcinoma in fine-needle aspiration biopsy","volume":"102","author":"Yang","year":"2004","journal-title":"Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/(SICI)1097-0142(19991025)87:5<270::AID-CNCR6>3.0.CO;2-L","article-title":"Cytodiagnosis of well differentiated hepatocellular carcinoma: Can indeterminate diagnoses be reduced?","volume":"87","author":"Segal","year":"1999","journal-title":"Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/cyt.12009","article-title":"Micronucleus scoring in liver fine needle aspiration cytology","volume":"24","author":"Wen","year":"2013","journal-title":"Cytopathology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"448","DOI":"10.5812\/hepatmon.5954","article-title":"Cytologic comparison between malignant and regenerative nodules in the background of cirrhosis","volume":"12","author":"Geramizadeh","year":"2012","journal-title":"Hepat. Mon."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1159\/000351169","article-title":"Fine needle aspiration cytopathology of liver masses: 101 cases with cyto-\/histopathological analysis","volume":"57","year":"2013","journal-title":"Acta Cytol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"174103","DOI":"10.1155\/2013\/174103","article-title":"Role of FNA and core biopsy of primary and metastatic liver disease","volume":"2013","author":"McGahan","year":"2013","journal-title":"Int. J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/cncr.21155","article-title":"Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy: Case series and review of the literature","volume":"105","author":"Chaudhary","year":"2005","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/cncr.21842","article-title":"Pancreatic and bile duct brushing cytology in 1000 cases: Review of findings and comparison of preparation methods","volume":"108","author":"Volmar","year":"2006","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/cncy.21509","article-title":"Strategies for improving diagnostic accuracy of biliary strictures","volume":"123","author":"Salomao","year":"2015","journal-title":"Cancer Cytopathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/(SICI)1097-0339(200006)22:6<359::AID-DC6>3.0.CO;2-I","article-title":"Proliferating ductules are a diagnostic discriminator for intrahepatic cholangiocarcinoma in FNA biopsies","volume":"22","author":"Sampatanukul","year":"2000","journal-title":"Diagn. Cytopathol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/9\/2301\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:43Z","timestamp":1760137603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/9\/2301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["cancers14092301"],"URL":"https:\/\/doi.org\/10.3390\/cancers14092301","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,5,5]]}}}