Risk Factors For Central Or Lateral Lymph Node Metastasis In Conventional Papillary Thyroid Microcarcinoma

BackgroundThyroid cancer is the most widespread tumor of endocrine system,and papillary thyroid carcinoma(PTC),including papillary thyroid microcarcinoma(PTMC),have been the most common thyroid cancer.Despite the increasing incidence of PTMC,the prognosis is usually favorable,with a 10-year survival rate of>99%.Optimal management for PTMC remains controversial.The purpose of this study was to explore clinicopathologic factors predictive of cervical lymph node metastasis in conventional PTMC and to improve perioperative decision-making for those harboring cervical lymph node metastases.MethodsWe retrospectively reviewed the cases of 2,404 conventional PTMC patients who were undergone surgery and had been confirmed by pathology,and analyzed the relationship between the clinicopathologic factors of the patients and cervical lymph node metastasis in central or lateral,including gender,age,tumor size,extrathyroidal extension(ETE),intrathyroidal spreading,multifocality,lymphovascular invasion,chronic lymphocytic thyroiditis,nodular goiter,BRAF V600E mutation,etc.ResultsIn 2404 cases of conventional papillary thyroid microcarcinoma,central lymph node(CLN)metastases and lateral lymph node(LLN)metastases were observed in 915(38.1%)and 184(7.7%)cases,respectively.Multivariate regression analysis found that male(adjusted odds ratio[OR]=1.974,P<0.001),age less than 45(adjusted OR=1.601,P<0.001),tumor size greater than 5mm(adjusted OR=1.935,P<0.001),extrathyroidal extension(ETE)(adjusted OR=1.647,P<0.001),multifocality(adjusted OR=1.416,P<0.001),and intrathyroidal spreading(adjusted OR=3.355,P<0.001)were independent predictors for CLN metastasis.In particular,younger age(adjusted OR=1.57,P<0.05),multifocality(adjusted OR=1.98,P<0.01),and intrathyroidal spreading(adjusted OR=4.43,P<0.001)were significantly associated with a high number of CLN metastases(n≥5).Chronic lymphocytic thyroiditis(CLT)was significantly associated with less CLN metastases(adjusted OR=0.731,P<0.01).In subgroup analysis of patients that underwent lateral neck dissection(n=248),the presence of CLN metastasis was strongly associated with LLN metastasis(adjusted OR=5.426,P<0.001),but other clinicopathologic factors(gender,age,tumor size,ETE,intrathyroidal spreading,multifocality,lymphovascular invasion,CLT,nodular goiter,BRAF V600E)were not associated with LLN metastasis.Molecular analyses in a subset of PTMC patients(n=644)suggested that ETE was significantly associated with BRAF V600E mutation(adjusted OR=2.312,P<0.001),but no correlation was found between the BRAF V600E mutation and cervical lymph node metastasis.ConclusionIn the conventional PTMC patients undergoing surgery,male,younger age,tumor size,ETE,multifocality,and intrathyroidal spreading were found to be predictive of CLN metastasis,while coexisting CLT was associated with less CLN metastasis.Further,younger age,multifocality,and intrathyroidal spreading were associated with a high volume of positive CLN metastases(n≥5).In patients presenting with a suspicious lateral lymphadenopathy in pre-operative imaging,the presence of CLN metastasis was strongly associated with LLN metastasis.BRAF V600E mutation can’t estimate the cervical lymph node metastasis in PTMC.