{
  "abstract": "Background/Objectives: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was reclassified as a non-malignant entity in 2016 to reduce overtreatment. A proportion of NIFTP-containing glands nonetheless harbour a synchronous differentiated thyroid carcinoma (DTC). We quantified its prevalence and pathological profile and assessed whether routinely collected pre-operative variables identify affected patients. Methods: A multicentre retrospective cohort of 1185 adults with NIFTP confirmed at second histological review, operated on between 2017 and 2023 in 22 centres. The outcome was a synchronous DTC in the surgical specimen. A weighted random forest and an elastic-net logistic regression based on 13 pre-operative predictors were evaluated with 20-times repeated five-fold cross-validation, with all data-driven steps nested within training folds, and with leave-one-centre-out and temporal validation. Results: A synchronous DTC was present in 61 patients (5.1%; 95% CI 4.0–6.6; 6.2% after review of the stored reports), with marked between-centre variation (none recorded in eight centres). Fifty-eight carcinomas (95%) were pT1a; none had gross extra-thyroidal extension or nodal metastasis (nodes examined in 27 patients), and none met the 2025 American Thyroid Association criteria mandating a more extensive operation. No pre-operative variable differed between groups after multiplicity adjustment. The cross-validated AUROC was 0.56 (95% CI 0.47–0.65) for the random forest and 0.58 (0.48–0.67) for the elastic net; the within-centre concordance was 0.48 and the temporal-validation AUROC 0.39, and decision-curve analysis showed no net benefit over default strategies. Conclusions: About one in twenty NIFTP-containing specimens harbours a synchronous DTC, usually a low-risk papillary microcarcinoma. Routinely available pre-operative variables do not identify these patients; management should be guided by the pathology of the carcinoma itself.",
  "abstract_shown": true,
  "affiliations": [
    "UCO Clinica Chirurgica, Department of Medicine, Surgery and Health Sciences, University of Trieste, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Cattinara Teaching Hospital, 34149 Trieste, Italy",
    "SS Endocrinologia, Department of Medicine, Surgery and Health Sciences, University of Trieste, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Cattinara Teaching Hospital, 34149 Trieste, Italy",
    "Department of Medicine and Surgery, Unit of General Surgery, University Hospital of Parma, 43126 Parma, Italy",
    "DAI Chirurgia Generale, Chirurgia Plastica e Ortopedia, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy",
    "Department of Surgical Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy",
    "SC Chirurgia Oncologica della Tiroide, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy",
    "Thyroid and Parathyroid Surgery Unit and Otolaryngology Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, Italy",
    "Ospedale Isola Tiberina, Gemelli Isola, Centro di Ricerca in Chirurgia delle Ghiandole Endocrine e dell’Obesità, Università Cattolica del Sacro Cuore, 00186 Rome, Italy",
    "Department of Thoracic and Endocrine Surgery and Faculty of Medicine, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland",
    "Endocrine Surgery Unit, Department of Surgery and Oncology, Verona University Hospital, P.le L.A. Scuro 10, 37134 Verona, Italy",
    "Unità Operativa Semplice Dipartimentale di Chirurgia Tiroidea, Azienda Ospedaliera Universitaria “Luigi Vanvitelli”, 80138 Naples, Italy",
    "Unit of Biostatistics, Epidemiology and Public Health, University of Padova, 35131 Padova, Italy",
    "UOC Endocrinochirurgia, AOU Dulbecco, 88100 Catanzaro, Italy",
    "Dipartimento MEPRE-J, Chirurgia Oncologica, Policlinico P. Giaccone, Università degli Studi di Palermo, 90127 Palermo, Italy",
    "UOC Chirurgia Generale Universitaria “V. Bonomo”, Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (DiMePRe-J), Università degli Studi di Bari, 70124 Bari, Italy",
    "Endocrine Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy",
    "Department of Precision and Regenerative Medicine and Jonic Area (DiMePRe-J), Section of Surgery, Laparoscopic and Emergency General Surgery Unit, Hospital University of Bari, 70124 Bari, Italy",
    "Servizio di Chirurgia, Ospedale Regione di Mendrisio—OBV, EOC, Via Alfonso Turconi 23, 6850 Mendrisio, Switzerland",
    "Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy",
    "Department of General, Emergency and New Technologies, University Hospital of Modena, Baggiovara Civil Hospital, 41126 Modena, Italy",
    "UOC Chirurgia Endocrina e Metabolica, Centro Dipartimentale di Chirurgia Endocrina e dell’Obesità, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy",
    "Unit of Endocrine Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via Liborio Giuffré 5, 90127 Palermo, Italy",
    "Division of Endocrine Surgery, Fondazione Istituto G. Giglio, 90015 Cefalù, Italy; Saint Camillus International University of Health Sciences (UniCamillus), 00131 Rome, Italy",
    "UOC Chirurgia Endocrina, Ospedale San Carlo di Nancy, 00165 Rome, Italy",
    "BIOSTAT-X, Institute of Pediatric Research (IRP) “Città della Speranza”, 35127 Padova, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 41,
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      "name": "Francesco Pennestrì",
      "orcid": "0000-0003-0865-700X"
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      "name": "Angela Pezzolla"
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      "name": "Esther Diana Rossi",
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  "bibtex": "https://research.draconitic.com/paper/2ctfs3vnwz78b.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18213505",
  "fulltext_url": null,
  "id": "2ctfs3vnwz78b",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/21/3505",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/2ctfs3vnwz78b.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:06Z",
      "native_id": "10.3390/cancers18213505",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/21/3505"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6694",
      "subfield": "oncology"
    }
  ],
  "title": "Synchronous Differentiated Thyroid Carcinoma in Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Prevalence, Pathological Profile, and Limits of Pre-Operative Risk Prediction in a Multicentre Cohort",
  "title_text": "Synchronous Differentiated Thyroid Carcinoma in Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Prevalence, Pathological Profile, and Limits of Pre-Operative Risk Prediction in a Multicentre Cohort",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T00:21:03Z",
  "url": "https://research.draconitic.com/paper/2ctfs3vnwz78b",
  "venue": "Cancers",
  "versions": []
}