Clinicopathologic Features in Minimally Invasive Follicular Thyroid Cancer Patients with Distant Metastasis

Young Wook Ju; Su-jin Kim; Young Jun Chai; Jin Wook Yi; Chan-Yong Seong; Jong-Kyu Kim; Hyeong Won Yu; June Young Choi; Kyu Eun Lee

doi:10.16956/kjes.2016.16.4.100

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Ju, Kim, Chai, Yi, Seong, Kim, Yu, Choi, and Lee: Clinicopathologic Features in Minimally Invasive Follicular Thyroid Cancer Patients with Distant Metastasis

Original Article

Korean Journal of Endocrine Surgery 2016; 16(4): 100-106.

Published online: 23 December 2016

DOI: https://doi.org/10.16956/kjes.2016.16.4.100

Clinicopathologic Features in Minimally Invasive Follicular Thyroid Cancer Patients with Distant Metastasis

Young Wook Ju¹, Su-jin Kim^1,^2,³, Young Jun Chai^2,⁴

, Jin Wook Yi^1,^2,³, Chan-Yong Seong^1,^2,³, Jong-Kyu Kim^1,^2,³, Hyeong Won Yu^2,⁵, June Young Choi^2,⁵, Kyu Eun Lee^1,^2,³

¹Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

²Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

³Division of Surgery, Thyroid Center, Seoul National University Cancer Hospital, Seoul, Korea.

⁴Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.

⁵Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Correspondence: Su-jin Kim. Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Tel: +82-2-2072-7208, Fax: +82-2-766-3975, su.jin.kim.md@gmail.com

Received 25 September 2016 Revised 4 October 2016 Accepted 14 October 2016

(open-access):

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Although minimally invasive follicular thyroid carcinoma (MIFTC) is considered a thyroid tumor with low malignant potential, some MIFTC can spread, metastasize, and eventually lead to death. This study investigates the risk factors for distant metastasis in MIFTC patients.

Methods

Between 1981 and 2014, the records of 365 consecutive patients who underwent thyroidectomy for MIFTC at Seoul National University Hospital were reviewed. Univariate and multivariate analyses were performed to identify risk factors associated with distant metastasis.

Results

Of 351 patients, 10 (2.9%) presented with distant metastasis. Of these, two (0.6%) were found at the time of thyroidectomy, while eight (2.3%) were detected at later exams, over a median of 7.3 years (range, 0.2~30.8). In univariate analysis, lymph node metastasis (P<0.001) was significantly associated with distant metastasis. In multivariate analysis, lymph node metastasis (P<0.001) and locoregional recurrence (P=0.008) were significantly associated with distant metastasis.

Conclusion

Distant metastasis in MIFTC patients were associated with high-risk clinicopathologic features and more aggressive clinical courses. Further study will be needed to ascertain these results with long-term surveillance.

Keywords: Minimally invasive follicular thyroid cancer, Distant metastasis, Clinicopathologic features

Figures and Tables

Table 1

Clinicopathologic characteristics of the study population (n=351)

Characteristics	Number (%)
Age at diagnosis (y)
Mean	45.4
Range	15∼79
＜45 y	158 (45.0)
≥45 y	193 (55.0)
Gender
Male	67 (19.1)
Female	284 (80.9)
Size of tumor
≤4 cm	275 (78.3)
>4 cm	76 (21.7)
Multifocality	37 (10.5)
Capsular invasion	344 (98.0)
Lymphatic invasion	9 (2.6)
Vascular invasion	33 (9.4)
Lymph node metastasis	6 (1.7)
Central node metastasis	1 (0.3)
Lateral node metastasis	1 (0.3)
Central & lateral node metastasis	3 (0.9)
Unknown	1 (0.3)
Locoregional recurrence	2 (0.6)
Distant metastasis	10 (2.9)
- At presentation	2 (0.6)
- During follow-up	8 (2.3)
Site of distant metastasis
- Lung	4 (1.1)
- Bone	1 (0.3)
- Lung & bone	4 (1.1)
- Lung & mediastinum	1 (0.3)
TNM stage
I	212 (60.4)
II	89 (25.4)
III	44 (12.5)
IV	6 (1.7)
Final extent of thyroidectomy
- Less than total thyroidectomy	245 (69.8)
- Total thyroidectomy	106 (30.2)
Radioactive iodine therapy	146 (41.6)
External radiotherapy	1 (0.3)

TNM = Tumor-node-metastasis staging system.

Table 2

Characteristics of the 10 patients who had distant metastasis

Case	Age^*/Sex	Operation date	Follow-up (month)	Extent of thyroidectomy	pTNM	Size^† (cm)	LN^‡	RAI^§ (mCi)	EBRT	Location^∥	Time of diagnosis of distant metastasis	Status
1	32/F	1981-08-18	2.3	TT	T3N1M1	6.0	Yes	150	No	Lung	1981-10-27	Unavailabe
2	31/F	1989-02-09	331.2	TT	T3N0M1	6.1	No	30	No	Bone	2014-03-28	Alive/PD
3	64/M	1992-08-17	288.5	Lobectomy & subtotal	T2N0M1	3.5	No	1,560	No	Lung	2002-05-24	Alive/NED
4	22/F	2001-10-12	168.4	TT & MRND, Rt.	T1N1M1	1.0	Yes	840	No	Lung	2005-02-05	Alive/NED
5	67/M	2003-05-23	156.9	TT	T1N0M1	1.2	No	550	No	Lung, bone	2012-06-25	Alive/NED
6	44/F	2004-01-15	147.4	TT	T2N0M1	2.2	No	910	No	Lung, mediastinum	2005-03-04	Alive/PD
7	46/F	2006-01-05	116.8	Lobectomy & subtotal	T1N0M1	1.3	No	60	No	Lung	2006-06-10	Alive/NED
8	64/F	2006-04-27	123.6	TT	T3N0M1	4.2	No	1,290	No	Lung, bone	2008-10-31 (lung)	Alive/PD
8	64/F	2006-04-27	123.6	TT	T3N0M1	4.2	No	1,290	No	Lung, bone	2009-11-02 (bone)	Alive/PD
9	40/F	2007-09-04	105.8	TT	T2N0M1	3.6	No	1,210	No	Lung, bone	2007-08-30 (at diagnosis)	Alive/PD
9	40/F	2007-09-04	105.8	TT	T2N0M1	3.6	No	1,210	No	Lung, bone	2011-06-17 (bone)	Alive/PD
10	58/M	2008-12-16	58.8	TT	T2N1M1	3.2	Yes	1,000	Yes	Lung, bone	2008-10-22 (at diagnosis)	Alive/PD

pTNM = Pathological tumor-node-metastasis staging system; EBRT = External beam radiotherapy; TT = Total thyroidectomy; MRND = Modified radical neck dissection; PD = Progressive disease; NED = No evidence of disease.

^*Age: Age at diagnosis; ^†Size: Tumor size; ^‡LN: Lymph node metastasis; ^§RAI: Total accumulative dose of radioactive I-131 ablation; ^∥Location: Location of distant metastasis.

Table 3

Association between distant metastasis and clinicopathologic features in 351 patients with MIFTC

Risk factors	Patients (n)	Distant metastasis n (%)	No distant metastasis n (%)	Fisher's exact test (P value)
Age at diagnosis (y)				0.759
<45 y	158	5 (50.0)	153 (44.9)
≥45 y	193	5 (50.0)	188 (55.1)
Gender				0.410
Male	67	3 (30.0)	64 (18.8)
Female	284	7 (70.0)	277 (81.2)
Size of tumor				0.456
≤4 cm	275	7 (70.0)	268 (78.6)
>4 cm	76	3 (30.0)	73 (21.4)
Multifocality				0.285
Unifocal	314	8 (80.0)	306 (89.7)
Multifocal	37	2 (20.0)	35 (10.3)
Capsular invasion	344	10 (100)	334 (95.2)	1.000
Lymphatic invasion	9	1 (10.0)	8 (2.3)	0.231
Vascular invasion	33	1 (10.0)	32 (9.4)	1.000
Positive resection margins	3	0 (0)	3 (0.9)	1.000
Lymph node metastasis	6	3 (30.0)	3 (0.9)	<0.001
Central node	1	0	1 (0.3)
Lateral node	1	1 (10.0)	0
Central & lateral node	3	1 (10.0)	2 (0.3)
Unknown	1	1 (10.0)	0
Locoregional recurrence	2	1 (10.0)	1 (0.3)	0.056

MIFTC = Minimally invasive follicular thyroid carcinoma.

Table 4

Univariate and multivariate analysis for distant metastasis in 351 patients with MIFTC

Risk factors	Univariate		Multivariate^*
Risk factors	Hazard ratio (95% CI)	P	Hazard ratio (95% CI)	P
Age at diagnosis (y)
<45 y	Ref.
≥45 y	0.81 (0.23~2.86)	0.759
Gender
Male	Ref.
Female	0.54 (0.14~2.14)	0.410
Size of tumor
≤4 cm	Ref.	0.456
>4 cm	1.57 (0.40~6.24)
Multifocality
Unifocal	Ref.
Multifocal	2.19 (0.45~10.70)	0.285
Capsular invasion	0.98 (0.97~1.00)	1.000
Lymphatic invasion	4.63 (0.52~41.0)	0.231
Vascular invasion	1.07 (0.13~8.74)	1.000
Positive resection margins	0.99 (0.98~1.00)	1.000
Lymph node metastasis	48.29 (8.25~282.54)	＜0.001	51.32 (8.29~317.57)	＜0.001
Locoregional recurrence	37.79	0.056	57.42 (2.87~1149.92)	0.008

MIFTC = Minimally invasive follicular thyroid carcinoma; CI = Confidence interval.

^*Multivariate: adjusted for age at diagnosis (y), gender.

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ORCID iDs: Young Jun Chai
https://orcid.org/http://orcid.org/0000-0001-8830-3433
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