Clinicopathological Findings of 220 Pediatric,Adolescent,and Young Adult Patients with Thyroid Cancer in Fukushima Medical University Hospital

Abstract

Background:

Thyroid ultrasound examinations (TUEs), conducted as part of the Fukushima Health Management Survey (FHMS), were initiated to monitor the health status of residents after the Fukushima Daiichi Nuclear Power Plant accident owing to concerns regarding the increased incidence of thyroid cancer among children, as observed after the Chernobyl Nuclear Power Plant accident. This study reported the clinicopathological characteristics of patients with thyroid cancer diagnosed through the FHMS and treated at the Fukushima Medical University Hospital.

Methods:

Data regarding the clinicopathological characteristics of patients with thyroid cancer were collected and evaluated in this descriptive study.

Results:

Among the 263 patients diagnosed with thyroid cancer as of September 2021, 220 patients with cytologically diagnosed thyroid cancer were treated as referrals from the FHMS. The median (interquartile range) age at the time of diagnosis was 18.6 (16.2–20.3) years. The median maximum tumor diameter was 13.0 (10.4–18.0) mm. To reduce surgical invasiveness, 199 patients (90.1%) underwent unilateral lobectomy. Pathological findings were suggestive of papillary thyroid carcinomas (PTC) in 216 (98.2%) patients; among them, 205 patients had PTC of the classical type. In addition, 216 (98.2%) patients had stage I disease. Cancer cell extension in the sternothyroid muscle or perithyroidal soft tissues and microscopic lymphovascular invasion were observed in 112 (50.9%) and 123 (55.9%) patients, respectively. No differences were observed between the two age groups (<18.6 years and ≥18.6 years) in terms of the clinical or pathological characteristics of thyroid cancer: risk classification (p = 0.69) and American Thyroid Association pediatric risk level (p = 0.24). Compared with those from previous reports, few surgical complications were observed.

Conclusions:

Patients with thyroid cancer diagnosed with TUEs underwent safe and minimally invasive operations, and careful postoperative follow-up was provided. The pathological findings of the detected thyroid cancers indicated that the majority were classical papillary carcinomas, and approximately half of the patients had extrathyroidal or lymphovascular invasion. No differences were observed between the two age groups in terms of the clinical or pathological characteristics of thyroid cancer.

Introduction

The prevalence of thyroid nodules and cancers among children and adolescents has been increasing in the United States¹ and Europe.² Radiation exposure, autoimmune thyroid disease, iodine deficiency, elevated thyrotropin (TSH) levels, and genetic disorders are known risk factors for thyroid cancer.³ The histological criteria used to diagnose thyroid cancer in the pediatric population are identical to those used to diagnose adults with thyroid cancer. However, pediatric patients differ from adults in that 1) they are more likely to develop regional lymph node involvement, extrathyroidal extension, and lung metastases⁴; 2) they are less likely to die of thyroid cancer⁵; and 3) the clinical courses of these patients with thyroid cancer and lung metastases are stable after radioiodine treatment.^6,7 Nevertheless, a widely accepted optimal surgical treatment strategy remains to be established for children with thyroid cancer, given the scarcity of evidence from prospective trials on surgical treatment.

The Fukushima Health Management Survey (FHMS) was conducted to monitor the long-term health effects observed in the residents of Fukushima following the Fukushima Daiichi Nuclear Power Plant accident on March 11, 2011.⁸ Nodules and cysts were detected in approximately 380,000 children and adolescents who underwent thyroid ultrasound examinations (TUEs) as part of the FHMS.⁹ The suspected cancer lesions were diagnosed cytologically according to the guidelines of the Japan Association of Breast and Thyroid Sonology.^10,11 Five rounds of thyroid examinations and surveys for those 25 years of age were conducted between October 9, 2011, and June 30, 2021. As a result, 263 individuals were cytologically diagnosed with malignancy or suspected malignancy.⁹ Among the 220 patients who underwent surgical treatment at the Department of Thyroid and Endocrinology, Fukushima Medical University Hospital (FMUH), 199 (90.5%) underwent unilateral lobectomy (UL) to preserve thyroid function. The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) reported that the exposure dose detected among the residents of Fukushima was substantially lower than that detected among the individuals affected by the Chernobyl accident¹²; nevertheless, careful monitoring of the residents of Fukushima continues.

The present study reported the clinical and pathological characteristics of patients with thyroid cancer who were diagnosed through the FHMS and treated at FMUH.

Methods

Study participants

This descriptive study was conducted as part of a retrospective cohort study. As described in the study by Shimura et al.,⁹ TUEs revealed the presence of ≥1 nodule measuring ≥5.1 mm and/or cyst of ≥20.1 mm diameter in 7775 participants. Among them, 263 participants received a cytological diagnosis of malignancy or suspected malignancy. Following the exclusion of patients treated at other hospitals and those who did not give informed consent, 220 patients with a cytological diagnosis of thyroid cancer who were treated at the Department of Thyroid and Endocrinology, FMUH, between June 2012 and September 2021, were included in this study. Notably, 219 of the enrolled patients had postoperative findings suggestive of papillary thyroid carcinoma (PTC). The remaining patients had benign nodules (Supplementary Fig. S1). A diagnosis of thyroid cancer was made preoperatively based on the results of the cytological and ultrasound examinations. Treatment modalities, including surgical procedures, were selected by at least three endocrine surgeons in accordance with the guidelines of the Japan Association of Endocrine Surgery (JAES),¹³ which included children and young adults as participants. Ultrasound examinations were performed to evaluate contralateral lymph node metastases and multiple nodular lesions in the thyroid gland. UL was selected as the treatment of choice in the absence of contralateral lymph node metastasis, intrathyroidal dissemination, or metastasis to other organs. All patients underwent central lymph node dissection. Ultrasound-guided fine-needle aspiration cytology (FNAC) was performed on suspicious lymph nodes on the lateral side to determine whether lateral dissection was required. Patients with contralateral lymph node metastasis, bilateral dissemination, or metastasis underwent total thyroidectomy (TT). TNM staging was performed in accordance with the eighth edition of the Cancer/Tumor–Node–Metastasis Staging System proposed by the American Joint Committee.¹⁴

Ethics

This study was approved by the Ethics Committee of the Fukushima Medical University (approval no. 29195). Written informed consent was obtained from the patients or their guardians if the patient was <18 years of age, in accordance with the Declaration of Helsinki. All patients were managed by a team of endocrine surgeons and continued to receive standard care during the follow-up period.^10,15,16

Ultrasound and pathological diagnosis

Details of the ultrasonography method and selection of cases for FNAC in FHMS have been reported previously.^10,15

–18 Surgical specimens collected during surgery were processed at the Department of Pathology of FMUH to prepare pathological specimens. The final histopathological diagnosis was made at a pathology consensus meeting with four or more licensed pathologists from other institutions specializing in thyroid pathology. A licensed pathologist at the FMU explained the pathological findings to each patient, and all attending licensed pathologists specializing in thyroid tumor pathology discussed the findings. A consensus on each case was reached consequently.

Blood test findings

Electrochemiluminescence immunoassay was performed using Atellica (Siemens Healthineers, Bayern, Germany) or Cobas (Roche Diagnostics GmbH, Mannheim, Germany) to determine the serum FT₃, FT₄, and TSH concentrations. Titer levels of >28.0 IU/mL and >9.0 IU/mL indicated positivity for antithyroglobulin autoantibody (Tg-Ab) and antithyroperoxidase autoantibody (TPO-Ab), respectively. The reference range for thyroglobulin (Tg) levels was 0–33.7 IU/mL (Roche Diagnostics GmbH).

Risk classification

According to the JAES guidelines, the PTC risk classification¹⁹ categorized T1a–N0–M0 as “very low-risk” and T1b–N0–M0 as “low-risk.” “High-risk” PTC presents with at least one of the following features: 1) tumor size >4 cm, 2) extrathyroidal extension to adjacent structures except for the sternothyroid muscle or extranodal extension to structures adjacent to the metastatic lymph node, 3) clinical node metastasis >3 cm, and 4) distant metastasis. Tumors that did not belong to the very low-, low-, or high-risk groups were categorized as “intermediate-risk tumors.” Patients with “very low-risk” and “low-risk” cases underwent UL; patients with “intermediate-risk” cases underwent UL or TT; and patients with “high-risk” cases underwent TT.

Primary outcomes

The primary outcome measures of this study were postoperative pathological, and other findings, including TNM stage classification, American Thyroid Association (ATA) risk level, minimal extrathyroidal extension, lymphovascular invasion, and extranodal extension. The association among these outcomes, participant characteristics, and clinical variables were explored.

Statistical analyses

Nonparametric Mann–Whitney U test (continuous variables) and the χ² test (categorical variables) were used to perform intergroup comparisons. Preoperative baseline characteristics and postoperative complications were descriptively reported according to the age and surgical procedure groups. The median age (18.6 years) was used to create two age groups: <18.6 and ≥18.6 years. The median age (18.6 years) was used to ensure that the sample sizes of the younger and older age groups were identical while analyzing the effect of age on the findings because of the small size of the study cohort. The age group classification was not planned. The postoperative pathological findings and TNM stage were classified according to the age and surgical procedure groups. All statistical analyses were performed using STATA (version 14.2) and STATA MP (version 18.0) (Stata Corp., College Station, TX, USA).

Results

Table 1 presents the clinical findings of the 220 patients at the time of preoperative diagnosis. The median (interquartile range) age at diagnosis was 18.6 (16.2–20.3) years. Sensitivity analyses conducted in the two groups (age <18.6 years and ≥18.6 years) produced similar results. Four patients (1.8%), who had undergone angiography and whole-body radiation before hematopoietic stem cell transplantation, had a history of medical radiation exposure. The thyroid hormone and TSH levels were generally within the reference range. Functional goiter was not suspected in any case. Tg-Abs and TPO-Abs were detected in 54 (24.5%) and 103 patients (46.8%), respectively. Ultrasound examination revealed that the median maximum tumor diameter was 13.0 mm, with 25th and 75th percentiles of 10.4 mm and 18.0 mm, respectively. Multifocal nodules were detected in the thyroid gland of 18 (8.2%) patients. No statistically significant differences were observed between the two age groups in terms of sex, medical radiation history, thyroid hormone levels, TSH levels, anti-Tg/TPO antibody positivity, maximum tumor diameter, or nodule multifocality.

Table 1.

Baseline Characteristics of Young Patients with Thyroid Cancer by Age Group (n [%]; N = 220)

	Age <18.6 (n = 110)	Age ≥18.6 (n = 110)	Total (N = 220)	p value
Sex, male	41 (37.3)	48 (43.6)	85 (38.6)	0.68
Age at the accident (year, median [IQR])	11.1 (8.3, 13.3)	16.6 (13.8, 17.3)	13.3 (10.1, 16.6)	<0.001
Interval after the accident (year, median [IQR])	4.8 (3.3, 7.3)	4.5 (3.2, 8.2)	4.5 (3.2, 7.9)	0.87
Age at diagnosis (year, median [IQR])	16.2 (14.4, 17.5)	20.3 (19.42, 21.7)	18.6 (16.2, 20.3)	N/A
Medical radiation exposure	3 (2.7)	1 (0.90)	4 (1.8)	0.31
Blood test results
TSH (µIU/mL, median [IQR])	1.95 (1.16, 2.54)	1.8 (1.43, 2.56)	1.89 (1.29, 2.55)	0.62
FT₃ (pg/mL, median [IQR])	3.53 (3.19, 3.90)	3.47 (3.15, 3.83)	3.54 (3.17, 3.89)	0.46
FT₄ (ng/dL, median [IQR])	1.28 (1.18, 1.45)	1.33 (1.22, 1.43)	1.3 (1.20, 1.45)	0.15
Tg (ng/mL, median [IQR])	19.8 (9.48, 42.3)	17.1 (9.9, 43.1)	18.9 (9.6, 43.0)	0.94
Tg-Ab (positive)	28 (25.5)	26 (23.6)	54 (24.5)	0.75
TPO-Ab (positive)	21 (19.1)	25 (22.7)	46 (20.9)	0.51
Calcitonin (pg/mL, median [IQR])^a	19 (0.76–31)	20.5 (1.18–30)	20 (0.95–30)	0.71
Ultrasound findings
Maximal tumor diameter (mm, median [IQR])	13.1 (10.4, 17.9)	13 (10.2, 18.0)	13 (10.4, 18.0)	0.87
Multifocality	7 (6.4)	11 (10.0)	18 (8.2)	0.33
Risk classification^b				0.69
Very low	20 (18.2)	23 (20.9)	43 (19.5)
Low	62 (56.4)	59 (53.6)	121 (55.0)
Intermediate	22 (20.0)	25 (22.7)	47 (20.5)
High	6 (5.5)	3 (2.7)	9 (4.1)
Neck dissection				0.172
Unilateral lateral neck dissection	15 (13.6)	12 (10.9)	27 (12.3)
Bilateral lateral neck dissection	3 (2.7)	0 (0)	3 (1.4)
Postoperative radioactive iodine use^c	4 (3.6)	0 (0)	4 (1.8)

A total of 27 participants did not have data on calcitonin; <0.5 pg/mL was calculated as 0.5.

Risk classification was suggested by the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery.

Postoperative radioactive iodine use within 1 year from surgery.

IQR, interquartile range; N/A, not available.

Forty-three (20.0%) and 121 (55.5%) patients were categorized as T1a–N0–M0 (very low-risk) and T1b–N0–M0 (low-risk), respectively, in the preoperative evaluation. Forty-seven and nine patients were categorized as intermediate- and high-risk, respectively. No statistically significant differences were observed between the two age groups in terms of these risk categories (p = 0.69).

Twenty-one (9.5%) and 199 (90.5%) patients underwent UL and TT, respectively (Table 2). No differences were observed between the UL and TT groups in terms of sex or age. The maximum tumor diameter of the patients who underwent UL was smaller compared with those who underwent TT (12.8 mm vs. 22.5 mm, respectively; p < 0.001). Eight (44.4%) of 18 patients with multifocal thyroid nodes underwent UL as cytological examinations revealed no malignant lesions in the opposite lobe. According to the JAES risk classification, all 43 very low-risk patients (100.0%) and 121 low-risk patients (100.0%) underwent UL. Thirty-four (72.3%) and 13 (27.7%) patients in the intermediate-risk group underwent UL and TT, respectively. Eight of the nine high-risk patients underwent TT. A high-risk patient with tumors localized to one lobe and only tumor diameter as a risk factor underwent UL. Individualized assessments of the environment and treatment setting were conducted, along with follow-up assessments.

Table 2.

Baseline Characteristics and Postoperative Complications of Young Patients with Thyroid Cancer by Surgical Procedure Group (n [%]; N = 220)

	Unilateral lobectomy(n = 199)	Total thyroidectomy(n = 21)
Sex, male	76 (38.2)	9 (42.9)
Age at diagnosis (year, median [IQR])	18.5 (16.2, 20.3)	18.8 (15.5, 20.3)
Ultrasound findings
Maximal tumor diameter (mm, median [IQR])	12.8 (10.2, 17.2)	22.5 (14.7, 30.8)
Multifocality	8 (4.0)	10 (47.6)
Risk classification^a
Very low	43 (21.6)	0 (0)
Low	121 (60.8)	0 (0)
Intermediate	34 (17.1)	13 (61.9)
High	1 (0.5)	8 (38.1)
Postoperative complications^b
Bleeding	1 (0.5)	0 (0)
Temporary recurrent nerve injury	6 (3.0)	1 (4.7)
Hoarseness	0 (0)	0 (0)
Hypoparathyroidism (within 90 days from operation)	0 (0)	8 (38.1)
Hypoparathyroidism (over 90 days from operation)	0 (0)	2 (9.5)

Risk classification was suggested by the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery.

The χ² test was not performed for postoperative complications because of the small sample size.

IQR, interquartile range.

Histopathological examinations revealed that 212 patients (96.3%) had PTC; among them, 205 patients (Table 3) had the classical type. The PTC subtypes detected were as follows: follicular (n = 3), solid subtype (n = 2), and diffuse sclerosing subtype (n = 2). One, one, and four patients were diagnosed with follicular thyroid carcinoma, poorly differentiated carcinoma, and carcinoma, respectively. Papillary carcinoma was suspected in two patients based on the cytological findings; histological examination revealed the presence of chromophobe cells in the surgically resected tissues. These cases were categorized as “others.” The diffuse sclerosing subtype of PTC is more aggressive.^20,21 Nevertheless, no statistically significant differences were observed between the two age groups in terms of the histopathological classification of thyroid cancer (PTC classical: p = 0.42).

Table 3.

Pathological Findings by Age Group (n [%]; N = 220)

	Age < 18.6 (n = 110)	Age ≥ 18.6 (n = 110)
Pathology classifications
Classical PTC	104 (94.5)	101 (91.8)
FS-PTC	1 (0.9)	2 (1.8)
SS-PTC	0 (0)	2 (1.8)
DSS-PTC	2 (1.8)	0 (0)
CMTC	1 (0.9)	3 (2.7)
FTC	0 (0)	1 (0.9)
PDTC	1 (0.9)	0 (0)
Others	1 (0.9)	1 (0.9)

PTC, papillary thyroid carcinoma; FS, follicular subtype; SS, solid subtype; DSS, diffuse sclerosing subtype; CMTC, cribriform-morular thyroid carcinoma; FTC, follicular thyroid carcinoma; PDTC, poorly differentiated thyroid carcinoma.

Table 4 presents the postoperative TNM staging results. No statistically significant differences were observed between the two age groups in terms of the frequency of tumor stage (p = 0.82). Forty-six patients (21.0%) were categorized as T2 or higher. Nineteen, 15, 7, 5, and 0 cases were classified as pT2, pT3a, pT3b, and pT4a, respectively. No cases of pT4b were detected. No statistically significant differences were observed between the two age groups in terms of the postoperative classification of thyroid cancer (p = 0.24). Lymph node metastasis was observed in 174 patients (79.5%): pN1a, 144 (65.8%) and pN1b, 30 (13.7%). The prevalence of pN1b among patients <18.6 years of age was higher than that among those ≥18.6 years of age (18.4% vs. 9.1%; p = 0.10). Microscopic pathological vascular invasion, lymphatic inversion, and extranodal extension were observed in 108 (49.55%), 47 (21.7%), and 33 (15.1%) patients, respectively; nevertheless, no statistically significant differences were observed between the two age groups regarding these aspects (p = 0.89, p = 0.11, and p = 0.55). Metastases to the lungs were observed in four patients (1.8%). Cases in which cancer cell extension was observed in the sternothyroid muscle or perithyroidal soft tissues (n = 112 patients, 51.1%) were defined as having minimal extrathyroidal extension²²; no statistically significant differences were observed between the age groups (p = 0.25). The TNM stage classification (tumor, p = 0.001; node, p < 0.001; metastasis, p < 0.001) and ATA pediatric risk level (p < 0.001) differed significantly among the patients who underwent UL and those who underwent TT; however, no statistically significant differences were observed between the groups in terms of minimal extrathyroidal extension (p = 0.13), vascular invasion (p = 0.055), lymphatic invasion (p = 0.34), and extranodal extension (p = 0.24).

Table 4.

Disease Stage Classification by Age and Surgical Procedure Group (n [%]; N = 219)

	Age < 18.6(n = 109)	Age ≥ 18.6(n = 110)	p value	Unilateral lobectomy(n = 198)	Total thyroidectomy(n = 21)	p value	Total (N = 219)
Tumor			0.82			0.001
pT1a	22 (20.2)	25 (22.7)		46 (23.2)	1 (4.8)		47 (21.5)
pT1b	63 (57.8)	63 (57.3)		118 (59.6)	8 (38.1)		126 (57.6)
pT2	8 (7.3)	11 (10.0)		14 (7.1)	5 (23.8)		19 (8.7)
pT3a	8 (7.3)	7 (6.4)		10 (5.1)	5 (23.8)		15 (6.9)
pT3b	5 (4.6)	2 (1.8)		6 (3.0)	1 (4.8)		7 (3.2)
pT4a	3 (2.8)	2 (1.8)		4 (2.0)	1 (4.8)		5 (2.3)
Node			0.10			<0.001
pN0	19 (17.4)	26 (23.6)		41 (20.7)	4 (19.1)		45 (20.6)
pN1a	70 (64.2)	74 (67.3)		139 (70.2)	5 (23.8)		144 (65.8)
pN1b	20 (18.4)	10 (9.1)		18 (9.1)	12 (57.1)		30 (13.7)
Metastasis; M1	2 (1.8)	2 (1.8)	0.99	0 (0)	4 (19.1)	<0.001	4 (1.8)
ATA Pediatric Risk Level^a			0.24			<0.001
Low	29 (26.4)	39 (35.5)		65 (32.7)	3 (14.3)		68 (30.9)
Intermediate	68 (61.8)	63 (57.3)		125 (62.8)	6 (28.6)		131 (59.6)
High	13 (11.8)	8 (7.3)		9 (4.5)	12 (57.1)		21 (9.6)
Minimal extrathyroidal extension	60 (55.1)	52 (47.3)	0.25	98 (49.5)	14 (66.7)	0.13	112 (51.1)
Vascular invasion	54 (50.0)	54 (49.1)	0.89	94 (47.5)	14 (70.0)	0.055	108 (49.5)
Lymphatic invasion	28 (26.2)	19 (17.3)	0.11	41 (20.8)	6 (30.0)	0.34	47 (21.7)
Extranodal extension	18 (16.5)	15 (13.6)	0.55	28 (14.1)	5 (23.8)	0.24	33 (15.1)

We included patients with minimal extrathyroidal extension in the intermediate risk level group (ATA pediatric risk level).

ATA, American Thyroid Association.

Discussion

TUEs were initiated as a part of the FHMS after the Fukushima Daiichi Nuclear Power Plant accident owing to concerns about an increase in the incidence of thyroid cancer among children, as observed after the Chernobyl Nuclear Power Plant accident. Approximately 380,000 individuals <18 years of age living in Fukushima Prefecture at the time of the nuclear power plant accident and those born the following year underwent discretionary TUEs in this study. The fifth round of surveys performed as of June 30, 2021, revealed malignant or suspected malignant lesions in 263 examinees based on pathological cytology.^8,17,23 A total of 220 patients underwent surgical treatment at the Department of Thyroid and Endocrine Surgery at FMUH as of September 2022. This study reported the clinical characteristics and pathological diagnoses of these patients.

In 2020/2021, UNSCEAR reported that the cases of thyroid cancers detected in Fukushima Prefecture were not related to the nuclear power plant accident based on the following evidence: the radiation exposure levels of the residents of Fukushima, the short latency period after the accident, the lack of cases involving individuals exposed at a very young age (<5 years), and the small number of cases diagnosed with the solid subtypes of PTCs previously associated with ¹³¹I exposure from the Chernobyl accident.¹² Previous studies conducted in Fukushima Prefecture revealed no regional differences in terms of the incidence of thyroid cancer based on the external radiation doses.^9,24 Similarly, no differences were observed across consecutive surveys in terms of the incidence of thyroid cancer.²⁵ Furthermore, the findings of the present study were consistent with those of several previous studies that compared the characteristics of the cases of thyroid cancer reported in Fukushima and Chernobyl.^25,26 Thus, it was hypothesized that the etiology of PTC in Fukushima Prefecture was nonradiogenic. The findings of this study revealed the clinical characteristics of children and adolescents unaffected by radiation exposure. BRAF^V600E mutation, rather than RET/PTC3 rearrangements, were detected in patients with thyroid cancer in Fukushima in our previous study. This finding also supports the hypothesis.²⁷ Compared with previous analyses of the prevalence of thyroid cancer among children and adolescents,²⁸ the present study of 220 patients was characterized by a higher median age (18.6 years) and a high prevalence of classical type PTC (90.1%). The cases of thyroid cancer were detected during TUEs performed as a part of the FHMS conducted after a nuclear power plant accident in the present study. TUEs are unique in that they adopt a diagnostic flow based on the FNAC implementation criteria, according to the evaluation of ultrasound findings. However, this diagnostic strategy may have resulted in a lower rate of detection of follicular thyroid carcinoma, which often presents with benign ultrasound findings.^3,28 In addition, the exclusion of calcitonin and carcinoembryonic antigen tests may have contributed to the low incidence of thyroid medullary carcinoma observed.

Analyses of the clinical and pathological characteristics of thyroid cancer according to the age group (<18.6 years and ≥18.6 years) revealed no differences in terms of the risk classification of PTC advocated by the JAES based on the degree of tumor invasion¹⁹ (Table 1). Thus, thyroid cancers diagnosed at a younger age during TUEs conducted as a part of the FHMS might precede cancers detected in adulthood or later. Our previous study²⁷ revealed that BRAF point mutations without genetic rearrangements account for most thyroid cancers detected during the TUEs conducted as a part of the FHMS, which is a characteristic of thyroid cancers detected in adulthood. This finding also supported this hypothesis.²⁹

Notably, 98.2% and 78.7% of the cases were classified as stages 1 and T1, respectively. The prevalence of pN1b was higher among younger patients. However, no statistically significant differences were observed between the two age groups in terms of pathological microscopic vascular invasion, lymphatic invasion, or extranodal extension. Furthermore, no differences were observed in terms of extrathyroidal extension, indicating no significant age-related differences with respect to thyroid cancer progression or malignancy.

Cancer progression was carefully evaluated preoperatively, and minimally invasive UL was selected as the treatment strategy for 199 patients (90.5%) based on the JAES risk classification. The proportion of patients with pN1 and minimal extrathyroidal extension was high, consistent with the findings of previous studies.³⁰ A lower rate of postoperative complications was observed in patients with thyroid cancer in the Chernobyl region.²⁹ Furthermore, the incidence of permanent hypoparathyroidism after TT was 5.5–25% in previous population-based studies^31

–34; thus, the incidence in the present study (9.5%) was not remarkable. Moreover, the management criteria used herein matched those of the European and British guidelines.^35,36 Careful postoperative management was implemented, and few instances of permanent hypoparathyroidism, hemorrhage, or recurrent nerve palsy associated with surgery were reported.

The main strengths of this study are as follows: six pathologists objectively confirmed the pathological diagnosis; surgical treatment was performed at a single hospital; and uniform treatment methods. Nevertheless, this study has certain limitations. First, the confirmation of medical radiation exposure was based on interviews, and detailed information was unavailable. Second, the sample size was small. Third, the survey was conducted at a single facility. Fourth, 18.6 years was selected as the cutoff age to ensure a uniform sample size for each group; however, the rationale for this choice was not clinically justified. Fifth, the long-term outcomes of thyroid cancer could not be assessed owing to the insufficient observation time.

In conclusion, the clinicopathological findings of 220 patients with thyroid cancer diagnosed through the FHMS were reviewed in the present study. Most pathological findings were of the classical type of PTC, and only a few cases of anterior cervical muscle infiltration or strap muscle invasion were observed despite the relatively small tumor size (median diameter, 13.0 mm). However, extraglandular extension of the thyroid cancer, including perithyroidal soft tissues surrounding the thyroid gland, was observed in half of these cases. Further research is warranted to follow up on the long-term outcomes, including recurrence time, according to risk classification.

Footnotes

Acknowledgments

The authors thank the staff of Fukushima Medical University, Toshihiko Fukushima, Keiichi Nakano, Chiyo Ookouchi, Hiroshi Mizunuma, Izumi Nakamura, and Manabu Iwadate, and the participants who joined the FHMS.

Authors’ Contributions

Y.M.: conceptualization (lead); methodology (lead); writing—original draft (lead); and writing—review, editing, and revising (lead). Y.K.: writing—review, editing, and revising (equal). Y.Y.: methodology (lead); revising (lead); formal analysis; and interpretation of the data (lead). M.S.: methodology (lead); revising (lead); formal analysis; and interpretation of the data (lead). E.S.: methodology (equal); formal analysis; and interpretation of the data (equal). K.S.: review and editing (equal). A.O.: review and editing (equal). Satoshi Suzuki: review and editing (equal). Satoru Suzuki: review and editing (equal). H.S.: review and editing (equal). S.Y.: review and editing (equal). Y.H.: review and editing (equal). T.O.: review and editing (equal). F.F.: review and editing (equal) and conceptualization (equal). Shinichi Suzuki: review and editing (equal) and management of surgery and postoperative follow-up. All authors have reviewed, revised, and approved the final version of the article for submission.

Author Disclosure Statement

The authors declare no conflicts of interest.

Funding Information

No funding was received for this article.

Supplementary Material

Supplementary Figure S1

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