Paediatric follicular thyroid carcinoma – indolent cancer with
low prevalence of RAS mutations and absence of
PAX8–PPARG fusion in a Japanese population
Huy Gia Vuong,
1
Tetsuo Kondo,
1
Naoki Oishi,
1
Tadao Nakazawa,
1
Kunio Mochizuki,
1
Akira Miyauchi,
2
Mitsuyoshi Hirokawa
3
& Ryohei Katoh
1
1
Department of Pathology, University of Yamanashi, Yamanashi,
2
Department of Surgery, Kuma Hospital, Kobe, and
3
Department of Pathology, Kuma Hospital, Kobe, Japan
Date of submission 31 March 2017
Accepted for publication 12 June 2017
Published online Article Accepted 16 June 2017
Vuong H G, Kondo T, Oishi N, Nakazawa T, Mochizuki K, Miyauchi A, Hirokawa M & Katoh R
(2017) Histopathology 71, 760–768. https://doi.org/10.1111/his.13285
Paediatric follicular thyroid carcinoma – indolent cancer with low prevalence of RAS
mutations and absence of PAX8–PPARG fusion in a Japanese population
Aims: Paediatric follicular thyroid carcinomas are
uncommon, and their clinicopathological features
and molecular profiles are still unknown. In the pre-
sent study, we aimed to investigate the clinicopatho-
logical aspects of a large series of follicular thyroid
carcinomas (FTCs) in paediatric patients and to anal-
yse the point mutations in codons 12, 13 and 61 of
NRAS, HRAS and KRAS genes and the rearrange-
ments of PAX8–PPARG.
Methods and results: A total of 41 paediatric FTCs
less than 21 years of age were enrolled into the pre-
sent study. We used direct sequencing and reverse
transcription–polymerase chain reaction (RT–PCR) to
detect RAS mutations and PAX8–PPARG fusions,
respectively. The paediatric FTCs were 6:1 in a female
to male ratio, with a mean tumour size of 52.7 mm.
Distant metastasis was found in one case at the time
of presentation. During a median follow-up time of
69 months, two cases had lung metastasis and all
patients were alive. Histologically, all cases were min-
imally invasive FTCs and varied in growth patterns:
microfollicular (39%), follicular (14.6%), solid/trabec-
ular (6%), oncocytic (4.9%) and mixed patterns
(26.8%). The mean Ki67 index was 5.7% and it was
not statistically different among the growth patterns.
NRAS mutations were found in five cases (12.2%)
and associated significantly with small tumour size
(P = 0.014). PAX8–PPARG fusion was not detected
in our series.
Conclusion: Paediatric FTCs are indolent in clinical
course in spite of their large tumour size and have a
distinct genetic background. RAS mutations and
PAX8–PPARG fusions may not play major roles in
the tumorigenesis of paediatric FTCs.
Keywords: adolescent, cancer, childhood, follicular thyroid carcinoma, paediatric, RAS mutation
Introduction
Thyroid cancer in paediatric patients is uncommon,
accounting for only 5% of all thyroid cancers.
1
Most
studies on paediatric thyroid cancer have focused
mainly on its most common histological type,
papillary thyroid carcinoma (PTC). In paediatric thy-
roid cancer, PTCs account for 80–85% and follicular
thyroid carcinomas (FTCs) comprise only of 10–15%
of cases.
2,3
Interestingly, paediatric PTCs were
reported to manifest different clinicopathological fea-
tures compared with adult PTCs, which tend to have
solid growth in histology, more aggressive clinical
behaviour but a favourable outcome and different
genetic profiles.
1,4,5
In contrast, little is known about
the clinicopathological features of FTC in paediatric
Address for correspondence: R Katoh, Department of Pathology,
University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi
409-3898, Japan. e-mail: rkatoh@yamanashi.ac.jp
© 2017 John Wiley & Sons Ltd.
Histopathology 2017, 71, 760–768. DOI: 10.1111/his.13285