{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T07:33:23Z","timestamp":1771572803685,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,19]],"date-time":"2020-01-19T00:00:00Z","timestamp":1579392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2011-02350857"],"award-info":[{"award-number":["RF-2011-02350857"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>It is unclear whether the site of origin of papillary thyroid microcarcinoma (mPTC) with respect to the thyroid surface has an influence on clinicopathologic parameters. The objectives of the study were to: (i) Accurately measure the mPTC distance from the thyroid surface; (ii) analyze whether this distance correlates with relevant clinicopathologic parameters; and (iii) investigate the impact of the site of origin of the mPTC on risk stratification. Clinicopathologic features and BRAF mutational status were analyzed and correlated with the site of origin of the mPTC in a multicenter cohort of 298 mPTCs from six Italian medical institutions. Tumors arise at a median distance of 3.5 mm below the surface of the thyroid gland. Statistical analysis identified four distinct clusters. Group A, mPTC: size \u2265 5 mm and distance of the edge of the tumor from the thyroid capsule = 0 mm; group B, mPTC: size \u2265 5 mm and distance of the edge of the tumor from the thyroid capsule &gt; 0 mm; group C, mPTC: size &lt; 5 mm and distance of the edge of the tumor from the thyroid capsule = 0 mm; and group D, mPTC: size &lt; 5 mm and distance of the edge of the tumor from the thyroid capsule &gt; 0 mm. Univariate analysis demonstrates significant differences between the groups: Group A shows the most aggressive features, and group D the most indolent ones. By multivariate analysis, group A tumors are characterized by tall cell histotype, BRAF V600E mutation, tumor fibrosis, aggressive growth with invasive features, vascular invasion, lymph node metastases, and intermediate ATA risk. The mPTC clinicopathologic features vary according to the tumor size and distance from the thyroid surface. A four-group model may be useful for risk stratification and to refine the selection of nodules to be targeted for fine needle aspiration.<\/jats:p>","DOI":"10.3390\/cancers12010246","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T03:04:43Z","timestamp":1579575883000},"page":"246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Does the Site of Origin of the Microcarcinoma with Respect to the Thyroid Surface Matter? A Multicenter Pathologic and Clinical Study for Risk Stratification"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0113-6682","authenticated-orcid":false,"given":"Giovanni","family":"Tallini","sequence":"first","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna\u2013Molecular Diagnostic Unit, 40138 Azienda USL di Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-5135","authenticated-orcid":false,"given":"Antonio","family":"De Leo","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Repaci","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-8817","authenticated-orcid":false,"given":"Dario","family":"de Biase","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna\u2013Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-1542","authenticated-orcid":false,"given":"Maria Letizia","family":"Bacchi Reggiani","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doriana","family":"Di Nanni","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna\u2013Molecular Diagnostic Unit, 40138 Azienda USL di Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ambrosi","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna\u2013Molecular Diagnostic Unit, 40138 Azienda USL di Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cira","family":"Di Gioia","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0388-1283","authenticated-orcid":false,"given":"Giorgio","family":"Grani","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6326-8990","authenticated-orcid":false,"given":"Kerry Jane","family":"Rhoden","sequence":"additional","affiliation":[{"name":"Genetics Unit, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Solaroli","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Ospedale Maggiore, 40133 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7219","authenticated-orcid":false,"given":"Fabio","family":"Monari","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiano","family":"Filetti","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1791-5915","authenticated-orcid":false,"given":"Cosimo","family":"Durante","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1056\/NEJMp1409841","article-title":"Korea\u2019s thyroid-cancer \u201cepidemic\u201d\u2014Screening and overdiagnosis","volume":"371","author":"Ahn","year":"2014","journal-title":"N. 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