Risk factors for central neck lymph node metastases in follicular variant vs. classic papillary thyroid carcinoma

Raffaelli, Marco; Crea, Carmela De; Sessa, Luca; Fadda, Guido; Lombardi, Celestino Pio; Bellantone, Rocco Domenico Alfonso

doi:10.1007/s12020-018-1607-3

Cited by 11 publications

(7 citation statements)

References 44 publications

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“…In distant metastases of various types of cancer, the interaction of platelets and tumor cells that is fostered by T4 may contribute to metastasis formation ( 37 ). It is not clear what the factors are that lead to local—particularly, central—lymph node metastases from differentiated thyroid cancers ( 51 ). We propose that local T4 production by thyroid cancer cells may be a factor that contributes to local, as well as distant, metastasis.…”

Section: Discussionmentioning

confidence: 99%

Actions of Thyroid Hormones on Thyroid Cancers

et al. 2021

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L-Thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3. The integrin is overexpressed and activated in cancer cells, rapidly dividing endothelial cells, and platelets. The biologic result is that T4 at physiological concentration and without conversion to 3,3’,5-triiodo-L-thyronine (T3) may stimulate cancer cell proliferation and cancer-relevant angiogenesis and platelet coagulation. Pro-thrombotic activity of T4 on platelets is postulated to support cancer-linked blood clotting and to contribute to tumor cell metastasis. We examine some of these findings as they may relate to cancers of the thyroid. Differentiated thyroid cancer cells respond to physiological levels of T4 with increased proliferation. Thus, the possibility exists that in patients with differentiated thyroid carcinomas in whom T4 administration and consequent endogenous thyrotropin suppression have failed to arrest the disease, T4 treatment may be stimulating tumor cell proliferation. In vitro studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts via the integrin to block T4 support of thyroid cancer and other solid tumor cells. Actions of T4 and tetrac or chemically modified tetrac modulate gene expression in thyroid cancer cells. T4 induces radioresistance via induction of a conformational change in the integrin in various cancer cells, although not yet established in thyroid cancer cells. The thyroid hormone receptor on integrin αvβ3 mediates a number of actions of T4 on differentiated thyroid cancer cells that support the biology of the cancer. Additional studies are required to determine whether T4 acts on thyroid cancer cells.

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Section: Discussionmentioning

confidence: 99%

Actions of Thyroid Hormones on Thyroid Cancers

et al. 2021

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“…The reasons for the difference are currently unknown. Interestingly, several studies have showed that compared with the classic variant, follicular variant of PTC is protective for lymph node metastasis [36,37]. The low expression of IL-18 in follicular variant is just right consistent with the reduced incidence of nodal metastasis in this variant.…”

Section: Discussionmentioning

confidence: 84%

Elevated Levels of Interleukin-18 are Associated with Lymph Node Metastasis in Papillary Thyroid Carcinoma

Chun,

Lu,

Chen

et al. 2024

Horm Metab Res

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Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates the Th1 immune response. IL-18 exhibits anticancer activity and has been evaluated in clinical trials as a potential cancer treatment. However, evidence suggests that it may also facilitate the development and progression of some cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not been investigated. In this study, we found that the expression of IL-18 was significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18 expression was closely associated with lymphovascular invasion and lymph node metastases. Furthermore, compared to PTC patients with no nodal metastasis, serum IL-18 levels were slightly increased in patients with 1–4 nodal metastases and significantly elevated in patients with 5 or more nodal metastases. The pro-metastatic effect of IL-18 may be attributed to the simultaneous increase in the expression of S100A10, a known factor that is linked to nodal metastasis in PTC. In addition, the activation of several pathways, such as the intestinal immune network for lgA production and Staphylococcus aureus infection, may be involved in the metastasis process. Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore, suppressing the function of IL-18 rather than enhancing it appears to be a reasonable strategy for treating aggressive PTC.

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“…Despite an adequate preoperative study generally is able to identify clinical evidence of extrathyroidal extension and/ or multifocality and/or lateral neck lymph nodes involvement in PTC patients, the N stage of the central neck is quite hard to define both preoperatively and intraoperatively since occult central nodal metastases occurred in 40-80% of PTC patients [11,[14][15][16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…An accurate preoperative work up could led to identify some suspicious characteristics (e.g., macroscopic evidence of multifocality or extrathyroidal extension; evidence of lateral neck lymph node metastases) [11,14,15,17], but it is well known that it is hard to reliably define the central neck nodal status pre-and even intra-operatively [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Modulating the extension of thyroidectomy in patients with papillary thyroid carcinoma pre-operatively eligible for lobectomy: reliability of ipsilateral central neck dissection

et al. 2020

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Purpose Pre-operative work-up and macroscopic intraoperative inspection could overlook occult central neck nodal metastases in patients with papillary thyroid carcinoma (PTC). An occult N1a status is able to change the initial risk stratification in small, clinically unifocal PTC potentially scheduled for thyroid lobectomy (TL) making total thyroidectomy (TT) the preferable option. We aimed to verified the reliability of an intraoperative management protocol based on frozen section examination (FSE) of ipsilateral central neck nodes (IpsiCND) to identify, among patients scheduled for TL, those who could benefit of a more extensive surgical resection (TT plus bilateral central neck dissection -CND-). Methods Thirty PTC patients preoperatively classified as T1N0 underwent TL plus IpsiCND-FSE (TL-group). In case of positive FSE, TT plus bilateral CND was accomplished during the same surgical procedure. A comparative analysis was performed between TL-group and a control group (C-group), who underwent TT plus IpsiCND-FSE, matched by a propensity score analysis. Results Nodal metastases (>2 mm) were found at final histology in 5/30 patients in the TL-group and in 6/30 in the C-group (p = 1.00). Micrometastases (≤2 mm) were retrieved in 5/30 TL-group patients and in 4/30 C-group patients (p = 1.00). Final histology staged as pN1a 10 (33.3%) patients for each group. FSE correctly identified five patients with occult nodal metastases >2 mm (16.6%) in TL-group, who underwent TT plus bilateral CND during the same surgical procedure. No permanent complications occurred. At a mean follow-up of 22.2 months, no local and/or nodal recurrence were observed. Conclusions Intraoperative assessment of N status obtained with IpsiCND plus FSE allows for an accurate risk stratification. IpsiCND plus FSE real time modulated thyroidectomy seems a safe and effective surgical strategy reducing the need of a subsequent completion surgery and, theoretically, the risk of local recurrence.

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Risk factors for central neck lymph node metastases in follicular variant vs. classic papillary thyroid carcinoma

Cited by 11 publications

References 44 publications

Actions of Thyroid Hormones on Thyroid Cancers

Actions of Thyroid Hormones on Thyroid Cancers

Elevated Levels of Interleukin-18 are Associated with Lymph Node Metastasis in Papillary Thyroid Carcinoma

Modulating the extension of thyroidectomy in patients with papillary thyroid carcinoma pre-operatively eligible for lobectomy: reliability of ipsilateral central neck dissection

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