Comparison of the clinicopathologic features and prognosis of bilateral versus unilateral multifocal papillary thyroid cancer: An updated study with more than 2000 consecutive patients.
BACKGROUND
Bilaterality is common in papillary thyroid cancer (PTC), but its clinical and prognostic implications are still controversial, and it remains unclear whether its behavior is more aggressive than multifocality.


METHODS
The clinicopathologic features of 2211 consecutive patients with PTC who underwent surgical treatment at the authors' institute between 1997 and 2011 were reviewed. Among these surgical patients, 425 (19.2%) had bilateral PTCs, and 1786 had unilateral PTCs. The patients who had unilateral PTCs were subdivided into a group with unilateral-multifocal PTCs (210 patients) and a group with solitary PTCs (1576 patients). The 10-year disease-free survival (DFS) rates were calculated to compare the prognosis between groups. B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation status was examined by direct DNA sequencing.


RESULTS
Patients who had bilateral PTCs were likely to have larger tumors, higher rates of extrathyroid extension and lymph node metastasis, and more advanced tumor stage than those who had unilateral-multifocal PTCs. Multivariate analysis identified only lymph node metastasis as an independent risk factor for PTC recurrence (P < .001). The 10-year DFS rate for patients with bilateral PTCs was much lower than that for those with unilateral-multifocal and solitary PTCs (78.8% vs 85.7% and 89.3%, respectively; P = .005). It is noteworthy that patients who had bilateral PTCs with lymph node metastasis had the worst prognosis in terms of DFS. Incidence of the BRAF V600E mutation (valine to glutamic acid mutation at position 600) was higher in the bilateral PTC group than that in the unilateral and unilateral-multifocal PTC groups.


CONCLUSIONS
The current results provide initial evidence that bilateral PTCs are more aggressive than unilateral-multifocal PTCs, and patients who have bilateral disease have more advanced stage and shorter DFS. The poorer outcome of patients with bilateral PTCs may be caused in part by their high incidence of lymph node metastasis. Cancer 2016;122:198-206. © 2015 American Cancer Society.
Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York.
Weibin
W
Wang
Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xingyun
X
Su
Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Kuifeng
K
He
Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yanli
Y
Wang
Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Haiyong
H
Wang
Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Haohao
H
Wang
Department of Ophthalmology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yinu
Y
Zhao
Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Wenhe
W
Zhao
Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York.
Rasa
R
Zarnegar
Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York.
Thomas J
TJ
Fahey
Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xiaodong
X
Teng
Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Lisong
L
Teng
D000328:Adult; D000704:Analysis of Variance; D001707:Biopsy, Needle; D002277:Carcinoma / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D002291:Carcinoma, Papillary; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy / Q000379:methods
BRAFV600E mutation; bilaterality; lymph node metastasis; multifocality; papillary thyroid cancer