Age and gender were reported as significant parameters in DFS for thyroid cancer in some studies8–10. In our study, age and gender did not significantly associated with DFS. The critical reason may be the heterogeneous conditions of other studies; including all the differentiated thyroid cancers in the study other than papillary thyroid carcinoma.
American thyroid association (ATA) introduced a risk stratification system according to clinical outcomes following total thyroidectomy and radioiodine remnant ablation or adjuvant therapy. Intrathyroidal PTCs of all sizes were included in the ATA low-risk category, the risk of structural disease recurrence decreased from 8–10% in intrathyroidal PTC > 4 cm11, to 5–6% in 2–4 cm intrathyroidal PTC11, to 4–6% in multifocal papillary microcarcinomas and 1–2% in unifocal papillary microcarcinomas 12, 13. In our study, T stage classification not only included intrathyroidal PTCs, but also other parameters. Therefore, the significance of T stage in DFS may not be displayed, and this was in accordance with Yuksel UM et.al’s study14.
A highly prognostic grading approache for uterine cervix15, pulmonary16, and several squamous cell carcinomas was based on tumor budding and cell nest size. We also assessed these histopathological parameters in PTC. However, interobserver reproducibility between pathologists were not high, and probably due to glands features. A prognostic morphological factor that associated with DFS was collagen area in PTCs. Moderate and high collagen area associated with higher DFS than low’s (p = 0.028). Zeng R et al. reported that there is a positive assosiation between hashimoto's thyroiditis and PTC in children and adolescents. A prominent characteristic of hashimoto's thyroiditis is the presence of lymphatic follicles17. However, we did not found significant association between lymphatic follicles around tumor and DFS. Calcification could be found in PTC occassionally. Neither, this morphology feature showed association with survival in the cohort.
The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension18. With ipsilateral lymph node metastases, contralateral lymph node metastases are more prevalent19. However, it is not impossible that papillary thyroid carcinoma located in one lobe showing contralateral but not ipsilateral N1b. Based on N1a and N1b of American Joint Committee on Cancer, lympho node metastasis type were subdivided into 5 types in our study. Bilateral and contralateral lymph node metastasis type were significantly associated with shortened DFS (p = 0.029). This was inaccordance with Yuksel, U. M.’s study14. Two operative methods were included in this study: total thyroidectomy with lymph node dissection and subtotal thyroidectomy with lymph node dissection. This operative factor showed no association with DFS.
Knezević-Obad A et al. reported that positive cytologic examination played an important role in determing total thyroidectomy for patients20. To the best of our knowledge, no risk scheme could indicate a higher or lower DFS with collagen area morphological factor. Our risk scheme contained collagen area and metastasis type and showed as an independent prognostic factor for DFS in PTCs.
Our retrospective study is limited by the fact that our analyses contains a small sample size. The initial corhort included two patients who were died due to PTC recurrence. However, the sample was not enough for stastistical analysis.
Taken together, the novel risk scheme contains collagen area and metastasis type and is easy to implement. Our data underlines the assumption that tumor collagen area and lymph node metastases type have the potential to constitute the pillars of a highly prognostic DFS risk scheme in PTC.