Summary of Fukushima thyroid cancer cases as of November 27, 2014

Number of cases suspected or confirmed of thyroid cancer = 104
Cases that had surgery = 58
Cases confirmed of thyroid cancer = 57 (1 of 58 turned out to be benign nodules)
55 of 58 cases were operated on at Fukushima Medical University (FMU)
 1 case turned out to be benign nodules
 52 cases of papillary thyroid cancer
 2 cases of poorly differentiated thyroid cancer
Pre-operative diagnosis:
42 cases (78%) had pre-surgical tumor diameter > 10 mm
12 cases (22%) had pre-surgical tumor diameter ≤ 10 mm
 3 cases were suspected to have distant metastasis.
 7 cases with proximity to trachea or recurrent laryngeal nerve, or
extrathyroidal extension
 2 cases of voluntary surgery despite recommendation of non-surgical followup
Overall, 17 cases (31%) had lymph node metastasis and 2 cases (4%) had
distant metastasis to the lungs
Operative methods:
5 cases (8%) had total thyroidectomy
49 cases (91%) had hemithyroidectomy
All 54 cases had lymph node dissection
Post-operative pathological diagnosis:
15 cases (28%) had tumor diameter ≤ 10 mm, and 3 (6%) of them had no lymph
node metastasis or distant metastasis (pT1a pN0 M0)
37% (?20 cases?) had extrathyroidal extension
74% (?40 cases?) were positive for lymph node metastasis
No post-operative complications (post-surgical hemorrhage, permanent paralysis
of recurrent laryngeal nerve, hypoparathyroidism, or hypothyroidism after
hemithyoidectomy) observed.
Note: 2 cases of lung metastasis were from papillary thyroid cancer cases.

*****
Information that was released by Shinichi Suzuki at the Thyroid Examination
Evaluation Subcommittee meeting held on November 11, 2014
https://www.pref.fukushima.lg.jp/uploaded/attachment/90997.pdf
Regarding Surgically Indicated Cases
Three years have passed since the disaster struck. Of 1,848 subjects that
underwent secondary examination up to June 30, 2014, 485 had cytological
examinations. Suspicious or malignant cases totaled 104, and 58 of them already
have been operated on.
Surgeries on 55 of 58 cases were conducted at the Division of Thyroid and
Endocrine Surgery, Fukushima Medical University. 3 cases were operated on at
other facilities. As 1 of 55 cases turned out to be benign nodules post-operatively,
only the 54 thyroid cancer cases were considered there.
According to the pathological evaluation, 52 cases were papillary cancer, and 2
were poorly differentiated thyroid cancer.
In pre-operative diagnosis, 42 cases (78%) had tumor diameter > 10 mm. and 12
(22%) were ≤ 10 mm in diameter. Also, of the 12 cases with tumor diameter of
≤10 mm, 3 (5%) were suspected to have lymph node metastasis and/or distant
metastasis. 9 (17%) cases were not suspected to have lymph node or distant
mestasis (cT1a cN0 cM0).
Of these 9 cases, 7 were suspected to be close to the trachea or the recurrent
laryngeal nerve, or have extrathyroidal extension. The remaining 2 cases were
operated on based on patients’ wishes, despite the recommendation of nonsurgical follow-up.
Furthermore, 17 cases (31%) were positive for lymph node metastasis, and 2
cases (4%) were suspected of multiple lung metastasis.
Surgical methods included total thyroidectomy in 5 cases (9%), and
hemithyroidectomy in 49 cases (91%). Lymph node dissection was conducted in
all cases, with 67% limited to the central compartment and 33% including lateral
compartment. As much as possible, small-size incisions of 3 cm were used.
Post-surgical pathological diagnosis revealed 15 cases (28%) with tumor
diameter ≤ 10 mm, and 3 (6%) of them had no lymph node or distant metastasis
(pT1a pN0 M0). Extrathyroidal extension, pEX1, was seen in 37%, and 74% was
positive for lymph node metastasis. No post-operative complications (postsurgical hemorrhage, permanent paralysis of recurrent laryngeal nerve,
hypoparathyroidism, or hypothyroidism after hemithyoidectomy) were observed.

The 57th Annual Meeting of the Japan Thyroid Association
November 14, 2014
Identification of gene clusters related to initiation of thyroid cancer and
elucidation of pathogenesis in children and yound adults
Shinichi Suzuki 1, Toshihiko Fukushima 1, Michiko Matsuse 3, Yudai Hirata 1,
Hirokazu Okayama 1, Chiyo Okouchi 1, Toshiyuki Monma 2, Hiroshi Mizunuma 1,
Satoshi Suzuki 1, Norisato Mitsutake 3, Shunichi Yamashita 3

Department of Thyroid and Endocrinology, School of Medicine, Fukushima
Medical University, 2 Department of Organ Regulatory Surgery, Fukushima
Medical University, 3 Department of Radiation Medical Sciences, Atomic Bomb
Disease Institute, Nagasaki University
There has been an increase in the number of pediatric and young adult patitents
dianosed with thyroid cancer due to the advance in diagnostic ultrasound
technology and implementation of pediatric thyroid ultrasound screening.
However, pathogenesis relating to initiation and development of these cancers is
yet to be fully understood. As it is anticipated the number of cases will increase
in the future, we will identify gene clusters related to cancer initiation and
elucidate the mechanism of pathogenesis in order to reveal biological features of
these cancers. In this study, we investigated the gene clusters known to be
related to thyroid cancer initiation.
Study subjects: 24 surgical cases (male:female = 1:2, average age 17.9 years (922 years)) in children and young adults. 23 cases were papillary thyroid cancer
and 1 was follicular cancer (Note: The follicular cancer may be a misprint as
Suzuki referred to poorly-differentiated cancer during the presentation).
Method: DNA and RNA were extracted from excised tumor tissues and analyzed
with direct sequencing and PT-PCR. Mutation in BRAF, K-, N-, and H-RAS and
rearrangement in RET/PTC1 and RET/PTC3 were investigated.
Results: 67% was positive for BRAF mutation. Also, 12.5 % had rearrangement
of RET/PTC1, but no mutation was found in RET/PTC3, K-, N-, and H-RAS.
Information from the transcript of the presentation by Shinichi Suzuki
23 cases were papillary thyroid cancer (19 cases of classical type, 1 case of
follicular variant, and 3 cases of cribriform-morular variant or CMVPTC), and 1
case was poorly-differentiated thyroid cancer.
23 patients were from the Fukushima Health Management Survey Thyroid
Examination, and 1 case of a 22-year-old female was unrelated to the survey.

Genetic analysis results:
RET/PTC1: positive in 3 cases or 12.5%(average age 17.8 years)
ETV6/NTRK3: positive in 1 case or 4.2% (16-year-old female)
BRAF (known to be common in adults): positive in 18 cases or 67%(average
age 18 years)
No RET/PTC3, K-, N-, H-RAS, or TRK detected.
5 cases (all females, average age 16.7 years) were negative for RET/PTC1,
BRAF, or ETV6/NTRK3.
The patient unrelated to Fukushima Health Management Survey, a 21-year-old
female, was RET/PTC1 positive.
BRAF, RET/PTC1 and ETV6/NTRK3 cases were all classical type papillary
thyroid cancer.
Five all-negative cases included 1 case of follicular variant papillary thyroid
cancer, 1 case of poorly-differentiated cancer, and 3 cases of cribriform-morular
variant. CMVPTC cases are under investigation for APC genetic mutations which
are known to be causative. All 3 CMVPTC cases have family history.
Five all-negative cases had slightly larger tumor diameter than others. These 5
cases were the only cases undergoing total thyroidectomy.
BRAF positive cases are said to be aggressive. RET/PTC1 is tends to be seen in
older children and associated with cases unrelated to radiation exposure.
RET/PTC3 is seen in younger children, and seen frequently in Chernobyl,
although it is not considered to be the definitive oncogene for radiation-induced
PTC. It is commonly thought gene rearrangements are more frequently seen in
children, whereas point mutations are seen more in adults.
As a conclusion, BRAF, the genetic mutation detected most frequently, is what is
usually seen in typical adult PTC. It is highly possible that cases which may not
have been detected if it weren’t for the thyroid ultrasound screening are being
discovered in children and young adults as a result of the screening.
Note: Suzuki’s presentation of these details outside the Thyroid Examination
Evaluation Subcommittee, especially before the information was shared with the
Subcommittee and the public, created controversy as to the handling of data.
Suzuki claims the study was accepted by the ethics committee at Fukushima
Medical University, but the thyroid examination itself is conducted with the money
provided by the central government to Fukushima Prefecture, and the data
belongs to the prefecture and the residents. Suzuki has a track record of not
revealing the data to the Thyroid Examination Evaluation Subcommittee or the
Prefectural Oversight Committee for Fukushima Health Management Survey
before presenting it at an academic meeting in August 2014, as described below.

*****
The 52nd Annual Meeting of Japan Society of Clinical Oncology
August 28-30, 2014
Organ Specific Symposium 03, August 28, 2014 10:00-12:00
OS3-5 “Treatment of pediatric thyroid cancer in Fukshima”
Shinichi Suzuki
Division of Thyroid and Endocrinology, School of Medicine, Fukushima Medical
University
Pediatric thyroid cancer has been considered rare, consisting approximately 12% of all thyroid cancer. They might appear to be advanced at first sight, with
lung metastasis or widespread lymph node metastasis discovered at the time of
diagnosis, but long-term survive is known to be extremely good.
After the Fukushima Daiichi nuclear power plant accident following the Great
East Japan earthquake and tsunami on March 11, 2011, Fukushima Prefecture
was burdened with the prospect of faces long-term radiation health effects.
Fukushima Health Management Survey was launched in Fukushima Prefecture,
with one of the surveys being thyroid ultrasound examination of residents who
were children at the time of the accident. Initial Screening has already completed,
and thyroid cancer cases have been discovered. We report our experience in
treating these aymptomatic pediatric thyroid cancers detected through ultrasound
screening, unlike the usual symptomatic thyroid cancer.
Study subjects are 269,354 children (participation rate 80.8%) who underwent
primary examination from October 2011 to December 31, 2013. Of these, 1796
required secondary examination, and 75 of them were diagnosed with malignant
or suspicious tumor as a result of fine-needle aspirational biopsy. 34 already had
surgery, and 33 were confirmed to have thyroid cancer. We are reporting here on
the 31 cases operated on in our department.
Average age at the time of surgery is 16.4 (9-20) years, the male to female ratio
is 14:17, and 9 cases were from Fiscal Year 2011 (from 13 municipalities
designated by the government to be evacuation zone), and 22 cases were from
Fiscal Year 2012.
Average tumor diameter at the time of surgery was 14.9 mm (6-13 mm). Preoperative diagnosis revealed 22 cases of T1 (7 cases of T1a and 15 cases of
T1b1), 7 cases of T2, and 2 cases of T3. 19 cases were N0, 12 cases were N1 (4
cases of N1a and 8 cases of N1b), 29 cases of M0 and 2 cases of M1 (lungs).
Surgical method was 28 cases of hemithyroidectomy and 3 cases of total
thyroidectomy, and lymph node dissection included 19 cases of central
compartment dissection, and 12 cases of lateral compartment dissection. Postoperative diagnosis revealed 24 cases of papillary thyroid cancer (conventional
variant), 3 cases of follicular-type papillary thyroid cancer, 3 cases of diffuse
sclerosing papillary thyroid cancer, and 1 case was suspicious of poorly

differentiated thyroid cancer. 21 cases of pT1 (9 cases of pT1a, 12 cases of
pT1b), 3 cases of pT2, 7 cases of pT3 (EX1), 7 cases of pN0, and 24 cases of
pN1 (12 pN1a and 12 pN1b). Two cases with pre-operative suspicion of M1
(lungs), which had the Tg level in the blood dropping below detection range after
total thyroidectomy, will be scheduled for either CT scan of lungs or I131
scintigraphy.
In all cases, intraoperative monitoring of the recurrent laryngeal nerve was
conducted using NIM. Surgical incision for neck dissection was limited to small
skin incisions of 3 cm in the central compartment dissection and 3-5 cm in the
lateral compartment dissection. No paralysis of the recurrent laryngeal nerve or
hypoparathyroidism was observed.