In this study, the association between macroscopic ENE and lung metastasis in PTC was investigated. Macroscopic ENE was found in 10.4% of PTC patients, and lung metastasis was found in 2.3% of patients. Macroscopic ENE and lung metastasis rates were similar to the published literature[9–11, 4]. After multivariate logistic regression analysis, macroscopic ENE, macroscopic ETE and number of positive nodes showed association with lung metastasis, which indicated the independent predictive value. Patients with macroscopic ENE positive nodes were seven-fold greater to have lung metastasis than patients with macroscopic ENE-negative nodes. This further supports a role for macroscopic ENE not just in regional lymph node metastasis, but also in distant metastasis.
Lymph node metastasis is common in PTC patients. The clinical significance of lymph node metastasis had been widely studied. These studies focused on different aspects of metastatic nodes, including, but not limited to, anatomical location[12], number[13, 3], maximum size[14, 15, 13], and ratio of positive nodes[16, 17].
ENE has become an understudied aspect of lymph node metastasis in PTC. The clinical significance of ENE in PTC patients remains to be explored. The utility of ENE to clinicians still continues to be debated. Previous studies have suggested a significant correlation between ENE in PTC and higher risk of recurrence[18, 10, 11, 19–21, 8]. ENE was also associated with compromised survival in PTC patients[10, 22, 23], and was an independent risk factor for nonexcellent response to initial therapy[24, 25]. ENE was proposed as an prognostic value to upstage the TNM staging for ENE-positive PTC patients[26].
Some advanced PTC patients may have distant metastasis. Lung is the most common site of distant metastasis. Lung metastasis predicts shorter disease-specific survival of PTC patients[27, 28]. Some clinicopathological factors were found to be correlated with lung metastasis, such as number of metastatic nodes[3], bilateral lateral cervical lymph node metastasis[4, 5], and ETE[6]. In our series, number of positive nodes and macroscopic ETE were also found to be independent prognostic risk factors of lung metastasis.
The association between ENE and lung metastasis was rarely reported. In our study, we show that macroscopic ENE is associated with increased likelihood of lung metastasis on multivariate analysis. Therefore, macroscopic ENE is an independent predictor of lung metastasis, indicating a role for ENE in PTC dissemination. Our results reinforce findings of other studies. In Lee’s study, ENE and age 45 years or older were risk factors for distant metastasis[29]. In Jeon’s study, ENE and aggressive pathologic subtype of metastatic nodes could help to assess the risk of distant metastasis in patients with papillary thyroid microcarcinoma[30].
Our study has some limitations. First, this is a retrospective study from a single institution. The results need to be validated in prospective studies. Second, though macroscopic ENE is associated with lung metastasis in our series, the association between macroscopic ENE and tumor prognosis needs to be investigated further. Third, there are no long-term follow-up data in our series, so metachronous lung metastasis was not included. Four, lung metastases in this study were only clinically evaluated, and there was a lack of surgical and pathological evaluations.
In conclusion, our data suggest that macroscopic ENE, macroscopic ETE, and number of positive nodes are independent risk factors of lung metastasis in PTC. Macroscopic ENE may be used as a stratification tool to assess the risk of distant metastasis in PTC patients. Further investigations are needed to figure out the clinical utility of ENE.