Dear Editor,
We read with great interest the paper by Cosme and co-workers about the differences between incidentally (ITC) and non-incidentally (NITC) diagnosed papillary thyroid carcinoma (PTC) (1). We congratulate the authors for the excellent work-up of the study cohort that comprised 122 ITCs and 103 NITCs. Intriguingly, the study revealed no significant difference between ITC and NITC groups regarding the pTNM staging, American Thyroid Association (ATA) recurrence risk, proportion of aggressive PTC subtypes, frequency of radioactive iodine (RAI) prescription, and RAI activity. Moreover, the diagnostic modality (incidental vs symptomatic) had no impact on disease persistence at the 5-year follow-up both on univariate and on multivariate analyses. Although ITCs were smaller and of lower pT status than NITCs (which was expected given the definition of the groups), a considerable proportion of ITCs (36%) were yet larger than 2 cm in size.
Based on these results, the authors are trying to address in their paper the ongoing debate as to whether the worldwide rise in TC incidence is mainly attributed to overdiagnosis (2) or to some objective factors like environmental exposures and lifestyle (3, 4). In particular, they conclude that ‘as even large tumours can be ITC, overdiagnosis is the most likely cause of increasing incidence of TC’. The authors seem to equate carcinomas found incidentally (ITC) with ‘overdiagnosis’. However, we believe this is not appropriate and actually not supported by the results of the study.
Overdiagnosis refers to a condition that, if unrecognized, would not cause symptoms or harm a patient during his or her life (5). In other words, an ‘overdiagnosed’ condition (including cancer) must be bothincidentaland harmless. True incidentalomas (i.e. TCs diagnosed incidentally at the histological examination of benign thyroid conditions) are the perfect example, as they almost never recur (6). This case of ‘overdiagnosis’ is, however, well recognized and does not lead to overtreatment, since most incidentalomas do not require any additional therapy (7). The ITCs in the study by Cosme and co-workers were, by contrast, not harmless, as only 61.5% of ITC patients were completely disease free at the 5-year follow-up and the course of the disease was not different from NITC patients. This finding is especially remarkable given the fact that true histologic incidentalomas were also included in the ITC group. Strictly speaking, the results of the study indicate that increased TC detection by clinical imaging is notoverdetection (which is the most frequent source of overdiagnosis (8)). Indeed, the study suggests that increased use of imaging may lead to the identification of clinically relevant tumors that could potentially harm the patient. Since the authors have included in the cohort ‘TC diagnosed incidentally at the histological examination of benign thyroid lesions’, they may want to analyze the clinicopathologic features of these tumors vs the incidental tumors found by imaging and the non-incidental ones.
The matter of TC overdiagnosis, however, is more complicated, as it includes, besides overdetection, overdefinition (8). The most prominent example of TC cancer overdefinition is certainly the ‘Non-invasive encapsulated follicular variant of PTC’. This entity has been routinely diagnosed by pathologists over decades as carcinoma in spite of its indolent nature. Only in 2017 – in the 4th edition of the WHO classification of endocrine tumors – it was downgraded to NIFTP, an essentially benign condition (9). This evidence-based terminology change alone may have reduced TC diagnoses by up to 20%, particularly in the United States (10, 11). It is not clear to what extent the study by Cosme and co-workers is affected by TC overdefinition because no histopathological review and re-classification of the cases were undertaken. In any case, the overdefinition of the non-invasive encapsulated follicular variant of PTC would have equally affected both ITC and NITC.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.
Funding
This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.
References
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Cosme I, Figueiredo A, Pinheiro S, & Leite V. Incidentally vs non-incidentally diagnosed papillary thyroid carcinoma: are there differences? European Thyroid Journal 2024 13 e240106. (https://doi.org/10.1530/ETJ-24-0106)
- 2↑
Vaccarella S, Franceschi S, Bray F, Wild CP, Plummer M, & Dal Maso L. Worldwide thyroid-cancer epidemic? The increasing impact of overdiagnosis. New England Journal of Medicine 2016 375 614–617. (https://doi.org/10.1056/NEJMp1604412)
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Kitahara CM, & Sosa JA. The changing incidence of thyroid cancer. Nature Reviews. Endocrinology 2016 12 646–653. (https://doi.org/10.1038/nrendo.2016.110)
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Kale MS, & Korenstein D. Overdiagnosis in primary care: framing the problem and finding solutions. BMJ 2018 362. (https://doi.org/10.1136/bmj.k2820)
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Mehanna H, Al-Maqbili T, Carter B, Martin E, Campain N, Watkinson J, McCabe C, Boelaert K, & Franklyn JA. Differences in the recurrence and mortality outcomes rates of incidental and nonincidental papillary thyroid microcarcinoma: a systematic review and meta-analysis of 21 329 person-years of follow-up. Journal of Clinical Endocrinology and Metabolism 2014 99 2834–2843. (https://doi.org/10.1210/jc.2013-2118)
- 7↑
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al.2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016 26 1–133. (https://doi.org/10.1089/thy.2015.0020)
- 8↑
Brodersen J, Schwartz LM, Heneghan C, O’Sullivan JW, Aronson JK, & Woloshin S. Overdiagnosis: what it is and what it isn’t. BMJ Evidence-Based Medicine 2018 23 1–3. (https://doi.org/10.1136/ebmed-2017-110886)
- 9↑
Lloyd RV, Osamura RY, Klöppel G & & Rosai J WHO Classification of Tumours of Endocrine Organs. In: WHO Classification of Tumours. p355. International Agency for Research on Cancer, World Health Organization, 2017.
- 10↑
Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LDR, Barletta JA, Wenig BM, Al Ghuzlan A, Kakudo K, et al.Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncology 2016 2 1023–1029. (https://doi.org/10.1001/jamaoncol.2016.0386)
- 11↑
Williams MD, Liu Z, Rossi ED, Agarwal S, Ryška A, Ghuzlan AA, Bychkov A, Baloch Z, Chernock R, Chiosea SL, et al. Seven years of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): rate of acceptance and variation of diagnostic approaches across different continents. Journal of Clinical Endocrinology and Metabolism 2024. (https://doi.org/10.1210/clinem/dgae354)
