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

@article{dobrinja2026synchronous,
  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}},
  author = {Chiara Dobrinja and Manuela Mastronardi and Stella Bernardi and Elena Bonati and Marco Bononi and Pietro Giorgio Calò and Gian Luigi Canu and Federico Cappellacci and Maria Grazia Chiofalo and Loredana De Pasquale and Carmela De Crea and Marco Stefano Demarchi and Paolo Del Rio and Giacomo Di Filippo and Giovanni Docimo and Daniele Gasparini and Rita Gervasi and Giuseppa Graceffa and Angela Gurrado and Maurizio Iacobone and Eduardo Mercelo Iervolino and Nadia Innaro and Rita Laforgia and Giovanni Lazzari and Petra Makovac and Gabriele Materazzi and Fabio Medas and Eleonora Morelli and Barbara Mullineris and Piermarco Papini and Francesco Pennestrì and Angela Pezzolla and Marco Raffaelli and Esther Diana Rossi and Leonardo Rossi and Gregorio Scerrino and Luca Sessa and Mario Testini and Emanuela Traini and Nicolò de Manzini and Dario Gregori},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18213505},
  url = {https://www.mdpi.com/2072-6694/18/21/3505},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - 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
AU  - Chiara Dobrinja
AU  - Manuela Mastronardi
AU  - Stella Bernardi
AU  - Elena Bonati
AU  - Marco Bononi
AU  - Pietro Giorgio Calò
AU  - Gian Luigi Canu
AU  - Federico Cappellacci
AU  - Maria Grazia Chiofalo
AU  - Loredana De Pasquale
AU  - Carmela De Crea
AU  - Marco Stefano Demarchi
AU  - Paolo Del Rio
AU  - Giacomo Di Filippo
AU  - Giovanni Docimo
AU  - Daniele Gasparini
AU  - Rita Gervasi
AU  - Giuseppa Graceffa
AU  - Angela Gurrado
AU  - Maurizio Iacobone
AU  - Eduardo Mercelo Iervolino
AU  - Nadia Innaro
AU  - Rita Laforgia
AU  - Giovanni Lazzari
AU  - Petra Makovac
AU  - Gabriele Materazzi
AU  - Fabio Medas
AU  - Eleonora Morelli
AU  - Barbara Mullineris
AU  - Piermarco Papini
AU  - Francesco Pennestrì
AU  - Angela Pezzolla
AU  - Marco Raffaelli
AU  - Esther Diana Rossi
AU  - Leonardo Rossi
AU  - Gregorio Scerrino
AU  - Luca Sessa
AU  - Mario Testini
AU  - Emanuela Traini
AU  - Nicolò de Manzini
AU  - Dario Gregori
PY  - 2026
DA  - 2026/10/30
JO  - Cancers
DO  - 10.3390/cancers18213505
UR  - https://www.mdpi.com/2072-6694/18/21/3505
AB  - 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.
SN  - 2072-6694
ER  -