{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:39:18Z","timestamp":1777999158928,"version":"3.51.4"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>The hobnail variant (HV) of papillary thyroid carcinoma (PTC) is an unusual entity recently proposed as an aggressive variant of PTC. We describe the pathologic and molecular features of 2 cases of HV of PTC. Both tumors presented in stage III (pT3 pN1a M0). The first case was diagnosed in a 62-year-old man, whereas the second was in a 53-year-old woman. Both patients were treated with total thyroidectomy and radioactive iodine. The primary tumors showed a hobnail\/micropapillary pattern in \u226550% of the neoplasm, and positivity for TTF-1, TTF-2, thyroglobulin (TG), cyclin D1, and p53. The Ki-67 index was 4.6% and 5%, respectively. In case 1, the tumor disclosed<jats:italic toggle=\"yes\">BRAFV600E<\/jats:italic>and<jats:italic toggle=\"yes\">TERT C228T<\/jats:italic>(124:G&gt;A) promoter gene mutation, negativity for<jats:italic toggle=\"yes\">NRAS<\/jats:italic>,<jats:italic toggle=\"yes\">HRAS<\/jats:italic>, and<jats:italic toggle=\"yes\">KRAS<\/jats:italic>mutations, and negativity for<jats:italic toggle=\"yes\">RET\/PTC1<\/jats:italic>,<jats:italic toggle=\"yes\">RET\/PTC3<\/jats:italic>, and<jats:italic toggle=\"yes\">PAX8\/PPAR\u03b3<\/jats:italic>rearrangements. After 11 years the patient died with cervical lymph node, bone, and liver metastases. In the liver metastasis, the tumor displayed columnar cell PTC areas (positive for TTF-1, TG, and<jats:italic toggle=\"yes\">BRAFV600E<\/jats:italic>) merging with undifferentiated carcinoma (UC) areas (positive for TTF-1 and<jats:italic toggle=\"yes\">BRAFV600E<\/jats:italic>; negative for TG). In case 2, the patient died 6 years after treatment with local recurrence and disseminated metastases to the lung, pleura, bone, and liver. The tumor recurrence showed a UC component (positive for cyclin D1 and p53; negative for TTF-1 and TG) with a residual HV of PTC (positive for cyclin D1, p53, TTF-1, and TG). No<jats:italic toggle=\"yes\">BRAF<\/jats:italic>,<jats:italic toggle=\"yes\">TERT<\/jats:italic>,<jats:italic toggle=\"yes\">NRAS<\/jats:italic>,<jats:italic toggle=\"yes\">HRAS<\/jats:italic>, nor<jats:italic toggle=\"yes\">KRAS<\/jats:italic>mutations were detected in the primary tumor or recurrence in case 2. Our findings suggest that p53-positive HV is a very aggressive form of PTC prone to progression to UC.<\/jats:p>","DOI":"10.1097\/pas.0000000000000793","type":"journal-article","created":{"date-parts":[[2016,12,25]],"date-time":"2016-12-25T12:56:57Z","timestamp":1482670617000},"page":"854-860","source":"Crossref","is-referenced-by-count":41,"title":["Hobnail Variant of Papillary Thyroid Carcinoma"],"prefix":"10.1097","volume":"41","author":[{"given":"Jos\u00e9 M.","family":"Cameselle-Teijeiro","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology, Clinical University Hospital, Servicio Gallego de Salud (SERGAS), Health Research Institute of Santiago de Compostela (IDIS)"},{"name":"Department of Anatomic Pathology, Medical Faculty, University of Santiago de Compostela, Santiago de Compostela"}]},{"given":"Irene","family":"Rodr\u00edguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Hospital HM Puerta del Sur, M\u00f3stoles, Madrid, Spain"}]},{"given":"Ricardo","family":"Celestino","sequence":"additional","affiliation":[{"name":"Institute of Research and Innovation in Health (i3S), University of Porto"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto"}]},{"given":"Catarina","family":"Eloy","sequence":"additional","affiliation":[{"name":"Institute of Research and Innovation in Health (i3S), University of Porto"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto"}]},{"given":"Magal\u00ed","family":"Piso-Neira","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Clinical University Hospital, Servicio Gallego de Salud (SERGAS), Health Research Institute of Santiago de Compostela (IDIS)"}]},{"given":"Ihab","family":"Abdulkader-Nallib","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Clinical University Hospital, Servicio Gallego de Salud (SERGAS), Health Research Institute of Santiago de Compostela (IDIS)"}]},{"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"Institute of Research and Innovation in Health (i3S), University of Porto"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto"},{"name":"Medical Faculty, University of Porto"}]},{"given":"Manuel","family":"Sobrinho-Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Institute of Research and Innovation in Health (i3S), University of Porto"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto"},{"name":"Medical Faculty, University of Porto"},{"name":"Department of Pathology, Hospital de S. 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Cases"],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1097\/pas.0000000000000793","relation":{},"ISSN":["0147-5185"],"issn-type":[{"value":"0147-5185","type":"print"}],"subject":[],"published":{"date-parts":[[2017,6]]}}}