Over 90% of newly diagnosed differentiated thyroid cancers are papillary thyroid cancers (PTC) (1). Lymph node metastasis is common in PTC. While macroscopic lymph node metastases are detected in approximately 35% of adult patients, this rate rises to 80% microscopically (2,3). The impact of lymph node metastasis on mortality is debatable.
Some studies report that lymph node metastasis does not affect prognosis (4). However, recent studies suggest that lymph node metastasis, especially in patients over 45 years of age, is associated with increased mortality (5). Unlike mortality, lymph node metastasis is reported as a risk factor for local recurrence and distant metastasis (6). Long disease-specific survival can be achieved after initial treatment for PTC. Depending on the initial treatment and tumor stage, recurrence occurs in 20-30% of cases over a few decades, with two-thirds of these recurrences occurring within the first decade after treatment (1).
In the Ohio State series, the overall recurrence rate was 23.5% during a median follow-up of 16.6 years, with 74% of the 17.8% local recurrences being lymph node recurrences (7). Therefore, the frequent occurrence of lymph node metastasis is a significant factor in monitoring patients for recurrence. Additionally, prophylactic central dissection in PTC remains a controversial topic (3). Not all patients develop clinical lymph node metastasis. Understanding the factors associated with lymph node metastasis development can aid in evaluating prophylactic central neck dissection in high-risk patients and monitoring for recurrence. This study aims to assess clinicopathological features influencing the development of lymph node metastasis.
MATERIALS AND METHODS
Patients diagnosed with PTC between March 2012 and December 2013, who underwent total thyroidectomy along with central and, when necessary, therapeutic lateral neck dissection, were retrospectively analyzed. Patients suspected of PTC or confirmed by preoperative fine-needle aspiration biopsy (FNAB) were evaluated for lymph node metastasis using preoperative ultrasound (US). FNAB of suspicious lateral lymph nodes on US was used to pathologically confirm metastasis.
Patients with suspected PTC on FNAB underwent intraoperative frozen section analysis to confirm the diagnosis. Total thyroidectomy was performed in all patients. Central neck dissection was performed for patients with tumor sizes below 2 cm who showed no clinical or ultrasonographic evidence of extrathyroidal extension, but with suspicious lymph nodes identified intraoperatively. Bilateral or unilateral central neck dissection (UCND) was performed based on the presence or absence of metastasis in frozen section analysis. Prophylactic UCND was performed in tumors larger than 2 cm or those with extrathyroidal extension. Therapeutic lateral neck dissection (LND) was conducted for patients with confirmed lateral lymph node metastasis. TNM staging was used to assess tumor size, with age categorized as below or above 45 years.
Tumor stages were classified as T1 (0-2 cm), T2 (2.1-4 cm), and T3 (>4 cm). Extrathyroidal extension and lymph node metastasis were analyzed for their relationship with age, gender, tumor stage, multifocality, and lymphovascular invasion. Lateral metastasis was also analyzed for its association with central metastasis, the number of metastatic central lymph nodes, and extracapsular spread. Statistical analyses were performed using "Mann-Whitney U," "Chi-square," and "Fisher's Exact Test." A p-value of <0.05 was considered significant.
RESULTS
A total of 32 patients treated during this period, with a mean age of 45.7±15.4 years, were included. Of these, 24 (75%) were female, and 8 (25%) were male. Patient characteristics are summarized in Table 1. Total thyroidectomy with unilateral UCND was performed in 12 patients, and total thyroidectomy with bilateral UCND in 20 patients. Additionally, therapeutic unilateral LND was performed in 12 patients.
Tumor stages were T1 in 23 patients, T2 in 6, and T3 in 3 patients. Lymphovascular invasion was observed in 62.5% (20 patients), multifocality in 68.75% (22 patients), and extrathyroidal extension in 50% (16 patients). Central metastasis occurred in 59.4% (19 patients), and lateral metastasis in 28.1% (9 patients). Central metastasis was significantly associated with extrathyroidal extension (p<0.05), multifocality (p<0.01), and lymphovascular invasion (p<0.01) (Table 2). Lateral metastasis was significantly associated with central metastasis (p<0.01) (Table 3).
DISCUSSION
Depending on whether dissection is prophylactic or therapeutic, and its extent, central metastasis rates in thyroid cancer are reported to be 60-75%, and lateral metastasis rates 25-75% (9-11). In our series, central metastasis occurred in 59.4% and lateral metastasis in 28.1% of cases. The high central metastasis rate could be related to prophylactic central neck dissection performed for tumors larger than 2 cm or those with extrathyroidal extension.
Prophylactic lateral dissection was not performed, and the lateral metastasis rate aligns with clinical series. Rarely, skip metastasis occurs directly to the lateral region without central involvement (12). Risk factors for central and/or lateral lymph node involvement have been evaluated in the literature (13-19). Patients younger than 45 years have a higher risk of lymph node metastasis compared to older patients (14).
Our study found that central metastasis risk increases with extrathyroidal extension and lymphovascular invasion. Multifocality was another significant factor for central metastasis. Local invasive tumors and elevated thyroglobulin levels have been reported as potential risk factors for lymph node metastasis (23). Postoperative recurrence is more likely in patients with both central and lateral metastasis, necessitating careful follow-up.
Our study’s limitations include its retrospective nature and the small sample size. Larger studies are needed to better understand lymph node metastasis in PTC. Careful preoperative imaging is essential for evaluating extrathyroidal extension and lymph node involvement to guide surgical planning and reduce recurrence risks.
