The impact of risk factors ascertained at the surgery of the primary tumor on metastasis appearance and outcome of patients with papillary thyroid microcarcinoma (PTMC).

Aim/Introduction: Most PTMCs with larger diameter of ≤10 mm have favorable long-term prognosis, but can also exhibit aggressive behavior when neck lymph node (LN) metastases are associated. However, the role of minimal extrathyroid tumor extension (mETE) is still discussed and it has been removed from AJCC 8th Edition because many authors reported no impact on metastasis appearance and disease-free survival (DFS). In PTMC patients, we investigated some risk factors influence on recurrences, metastases, and DFS during follow-up. Materials and Methods: We retrospectively enrolled 449 consecutive PTMC patients, 85 M and 364 F, 254 aged <55 and 195 ≥55 years who underwent total thyroidectomy and radioiodine ablation.Risk factors were present in 164/449 patients, such as neck LN metastases, mETE and multifocality/multicentricity (M/M). In every case, eventual metastases were detected during follow-up using 131I-whole body scan (WBS) and SPECT/CT, ultrasound, needle biopsy, and serum thyroglobulin assay. The lesions were confirmed by histology; when surgery was not feasible, metastases were confirmed during about a ten-year follow-up by aforementioned exams. Results: During follow-up, metastases were ascertained in 47/449 patients (10.5%), 6 M and 41 F, 29 aged <55 and 18 ≥55 years. Globally, 85 metastases were ascertained, 73 in the neck and 12 at distance (3 lung, 5 mediastinum, 4 bone). Risk factors were discovered during surgery in 27/47 (57.4%) of patients who developed metastases; mETE was globally present in 14 patients, neck LN metastases in 12 and M/M in 14. Among the 402/449 patients who did not develop metastases, risk factors were ascertained in 137/402 cases (mETE in 25 patients, LN in 13 and M/M in 117). Comparing the different variables, at Cox regression multivariate analysis, neck LN metastases (9.38 [95%CI 3.75-23.45] p<0.001) and mETE (5.97 [95% CI 2.69-13.24] p<0.001), but not M/M, gender and age, were significantly associated with an increased risk of metastasis during follow-up. DFS was significantly (p<0.001) lower in the patients with both these risk factors than patients without risk factors. Conclusion: In the present study, neck LN metastases and mETE proved significant risk factors for metastasis appearance and DFS reduction in PTMC patients during follow-up. The data confirmed that neck LN metastases are indicators of PTMC aggressiveness, as reported in numerous studies; however, the same results have been obtained by mETE suggesting a reflection on its previous removal from AJCC 8th Edition. Active surveillance in the follow-up of PTMC patients with mETE should be recommended.