High-volume central node metastasis

This is an interesting manuscript demonstrating another nomogram that is primarily directed toward predicting high-volume central compartment lymph node metastasis in clinically node-negative papillary microcarcinoma. The incidence of microcarcinoma has risen 4- to 15-fold in the last two decades worldwide. The primary reason behind this is likely overdiagnosis and frequency of routine investigations. It is important to avoid overtreatment in these patients and maintain the best quality of life with the least complications. Central nodal metastasis is a concern in all thyroid carcinomas. The authors have described a nomogram in this manuscript based on their large series of patients and a thorough clinical and histological evaluation.

The word nomogram comes from the Greek word “nomos”. It represents the approximate computation of a mathematical function. The field of nomography was initially described in 1884 by the French engineer Philbert Maurice d’Ocagne (1). It was first used by engineers for vast graphical calculations of formulas. In the last three decades, the field of oncology has embraced various nomograms, primarily based on retrospective data and analysis of prognostic factors in oncology. These nomograms are quite helpful in defining prognostic indices for patients with various malignancies and in informing patients and their families about overall prognosis. Various nomograms have been published in the medical literature, especially in thyroid cancer, mainly related to overall prognosis. There are more than 1,300 publications in PubMed related to thyroid nomograms, with approximately 1,200 coming from China. Essentially, these represent risk-related analyses of a larger data set predicting various clinical features, such as risk of malignancy in thyroid nodules and incidence of central or lateral nodal metastasis. Interestingly, the authors in this manuscript have developed a nomogram for predicting high-volume central lymph node metastasis.

Nomograms also help patients to ascertain the treatment of choice between lobectomy or total thyroidectomy. The authors in this manuscript have reported the main prognostic factors as sex, age, tumor size, and multifocality (2). They used these parameters to analyze high-volume central lymph node metastasis. In their entire series, 4% of the patients had high-volume metastasis (more than 5 lymph nodes). They reported in their multivariate analysis that male patients younger than 50 years, tumor diameter greater than 8 millimeters, and multifocality are significantly associated with a higher likelihood of high-volume central lymph node metastasis. These are well-recognized prognostic factors for papillary microcarcinoma. Their data also showed no significant association between Hashimoto’s thyroiditis, extrathyroidal extension, or tumor location. It should be noted that extrathyroidal extension is generally considered a major risk factor for both central and lateral nodal metastasis. It is quite likely that the authors have a very small number of patients with extrathyroidal extension, and they have not divided this group between minor and major extrathyroidal extension. They have reported only 5% of the patients with extrathyroidal extension.

The commonality of central compartment nodal disease is very well known in thyroid carcinoma and micropapillary carcinoma. However, the clinical implication of small-volume metastasis such as fewer than 5 nodes and metastatic foci of less than 2 millimeters, is well defined in the literature. Since the initial publication of the American Thyroid Association (ATA) guidelines in 2006, there have been a large number of studies on prophylactic central compartment dissection (3). Shortly thereafter, it was recognized that this small-volume central compartment metastasis does not have major prognostic implications. However, routine surgical procedures did increase morbidity related to nerve injury and parathyroid issues. The second version of ATA guidelines recommended specific indications for prophylactic central compartment dissection, such as large tumors, gross extrathyroidal extension or aggressive histology (4). The pendulum then swung towards avoiding routine central compartment neck dissection. However, if the nodal metastases are large or obvious, selective nodal dissection of level VI and VII lymph nodes is routinely performed.

The authors have also reported multicentricity as an important parameter. However, this is not recognized until the surgery is completed, which may be a deficiency in the preoperative clinical evaluation. An ultrasound showing irregular margins is likely the most important radiological finding. The computed tomography (CT) scan may be more helpful in better preoperative radiological analysis.

It is interesting that the thrust of the manuscript is the analysis of papillary microcarcinomas, which are generally also considered for active surveillance. Our own experience and the experience reported by Miyauchi was quite convincing for the stability of the primary tumor and lymph nodes (5-7). The subsequent surgical intervention did not show major concerns about nodal involvement. The authors have highlighted individualized surgical decision-making while reducing overtreatment in low-risk patients. Their data appears to be in direct conflict with published reports on active surveillance. This is where the role of sonography showing irregular margins may be critical.

What remains unclear is what to do intraoperatively when the surgeon finds more than 5 positive lymph nodes or the final pathology report shows more than 5 positive lymph nodes. This issue is well analyzed in the 2025 ATA guidelines as the intermediate/high-risk group (8). The data show that the risk of recurrence in this group is probably less than 5 percent and whether completion thyroidectomy and radioactive iodine (RAI) would reduce this number remains unclear at this time. However, completion thyroidectomy does have direct implications on higher risk of complications and altered quality of life.

Preoperative evaluation is extremely critical, with dedicated ultrasound to define the primary tumor and possible nodal metastasis. Ultrasound is a good investigation for lateral nodal disease; however, it has limited value in evaluating the central compartment. We would consider a CT scan with contrast along with ultrasound for better evaluation of the central compartment. These two investigations are complementary and very helpful in preoperative evaluation. The crux of the surgical procedure is to evaluate the central compartment critically during each thyroid surgery, and if there are suspicious lymph nodes, to consider therapeutic central compartment dissection. Since there is a high incidence of enlarged lymph nodes in Hashimoto's thyroiditis, a frozen section evaluation is quite helpful. The authors have noted a 4% incidence of high-volume nodal metastasis, which aligns with many other publications in the literature. As the ATA has defined, gross extrathyroidal extension is an important prognostic factor both for the primary tumor and nodal metastasis; therefore, preoperative evaluation and intraoperative evaluation of gross extrathyroidal extension is critical.

The operating surgeon should make critical intraoperative decisions based on preoperative clinical and radiological findings, detailed analysis of the CT scan if performed, and clinical findings of the primary tumor (hardness, fixity to the surrounding structures, and gross extrathyroidal extension). The surgeon should be able to make a decision based on intraoperative clinical findings, along with frozen section, if necessary, for the lymph node metastasis as to whether the surgeon should consider completion thyroidectomy to facilitate RAI treatment. Every patient consented for lobectomy should be informed that they may need total thyroidectomy based on individual clinical findings and surgeon judgement.

The authors’ series represents 1,500 patients, which is a large number based on which they have developed a nomogram that is quite helpful. A study by Thompson et al. from Australia developed a preoperative nomogram for prediction of ipsilateral central compartment lymph node metastasis (9). They defined age, sex, tumor size, tumor site, and multifocality as important prognostic factors. Based on these data, they developed a nomogram that was validated using an external cohort.

The authors of this manuscript ought to be congratulated for distinguishing between low-volume central compartment disease and high-volume central compartment metastasis. This distinction is clearly very important for making critical intraoperative decisions; however, what remains unclear is the role of contralateral central compartment dissection and postoperative RAI ablation, which would necessitate a total thyroidectomy. We have been shifting more toward thyroid lobectomy and unilateral central compartment dissection without RAI. The contralateral central compartment is evaluated clinically, and if there are any suspicious lymph nodes, we would consider resecting those nodes. The complications related to temporary or permanent nerve injury and temporary or permanent hyperparathyroidism are clearly high, and of major concern for bilateral central compartment dissection. It is interesting that almost 40–50% of patients have microscopic lateral nodal disease, which remains quiescent in the lifetime of the patient, and only a small percentage of patients develop clinically apparent disease that requires subsequent surgical procedures.

Even though nodal metastasis in thyroid cancer is considered to have minimal to no impact on the prognosis, certain risk factors in nodal metastasis are of concern. These include low or high-volume nodal disease, number of lymph node metastases, extranodal extension, aggressiveness of histology, BRAF positivity, and lymph node ratio or lymph node density. The location of the nodal metastasis is also important, such as deep superior mediastinal nodes, parapharyngeal or retropharyngeal nodes.

It appears that nodal metastasis may have some prognostic implications, especially for further recurrence, and the requirement for additional surgeries.

The nomogram described by the authors discusses their extensive clinical experience and is clearly an important addition to the literature for predicting high-volume central compartment lymph node metastasis.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0400/coif). A.R.S. serves as an unpaid editorial board member of Gland Surgery from August 2024 to December 2026. The author has no other conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

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