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JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.18 - Dec./2023 DOI: https://doi.org/10.52389/ydls.v18ita.

2153

Comparison of clinicopathological features between


children and adults with differentiated thyroid carcinoma

Nguyen Van Phu Thang, Nguyen Thi Ngoc Anh, 108 Military Central Hospital
Ngo Thi Minh Hanh, Le Thi Thanh Xuan, Nguyen Du Hoang,
Le Thi Trang, Nguyen Quang Thi, Dinh Ngoc Minh Anh
Summary
Objective: To compare the clinicopathological features between children (≤ 18 years) and adults
with differentiated thyroid carcinoma (DTC). Subject and method: A descriptive study on 50 children and
158 adults with DTC at the 108 Military Central Hospital from January 2015 to March 2022. We collected
the clinicopathological features and evaluated the difference in these features between children and
adult groups. Result: The rate of DTC in children was 0.65% of all DTC patients. In both groups, female
patients accounted for the majority (66% and 84.2%, respectively). Papillary thyroid carcinoma (PTC) was
the most common subtype (92% and 97.5%). The pediatric DTC patients had higher rates of large tumor
size, extrathyroidal extension, vascular invasion, intrathyroidal spread, and lymph node metastasis
(LNM). There was no difference between the two groups regarding bilaterality, multifocality, tumor
necrosis, and chronic thyroiditis. Conclusion: DTC in the children group revealed more aggressive
patterns than DTC in the adults group, with larger tumor size, higher rate of multifocality, extrathyroidal
invasion, and LNM.
Keywords: Children, adults, differentiated thyroid carcinoma, clinicopathological.

1. Background extension, and high rates of lymph node metastasis


(LNM) and distant metastasis [8-12]. However, pediatric
Differentiated thyroid cancer (DTC) is one of the
DTC has a good prognosis with 30-year survival
most common endocrine malignancy in pediatric
ranging from 99 to 100% [4]. Because of the unique
patients, accounting for 1.8% of all thyroid cancer
characteristics of pediatric DTC, specific treatment
(TC) diagnosed, with 5.9 cases per million people
methods for children are recommended [3].
annually [1, 4]. The incidence of pediatric DTC has
been increasing [4, 8]. According to the American There have been some studies compared DTC
Thyroid Association, pediatric TC is defined as TC in between children and adults [7-12]. However, there
children aged 18 years and younger [3]. have been no studies comparing histopathological
characteristics of DTC between Vietnamese children
DTC comprises 90% to 95% of all childhood TC
and adults. Our study aims to find differences in
with similar frequency in adults. However, children tend
clinicopathological features between children and
to present more often with advanced disease than
adults with DTC at the 108 Military Central Hospital.
adults do at the time of diagnosis [7]. It has been
suggested that DTC in children often has more 2. Subject and method
aggressive features with large tumors, extrathyroidal
2.1. Subject

Received: 10 October 2023, Accepted: 02 November 2023 We collected all pediatric patients and adult
Correspondence to: Nguyen Van Phu Thang - Department of patients (with at least three times the number of
Pathology, 108 Military Central Hospital pediatric patients) who underwent thyroidectomy at
Email: phuthangk39hvqy@gmail.com the 108 Military Central Hospital from January 2015 to

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JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.18 - Dec./2023 DOI: https://doi.org/10.52389/ydls.v18ita.2153

March 2022. All of the patients were pathologically Tumor size was determined as the maximal
diagnosed with DTC. dimension of the tumor. Multifocality was defined as
The adult patients were listed in an excel file. having two or more tumors in the thyroid gland. In
One hundred and eighty patients were randomly the case of multifocal lesions, the tumor size and
selected using SPSS software. The proportions of pathological features were determined by the
gender and histopathological type were not largest tumor.
different from the original adult patient group The extrathyroidal extension (ETE) was reported
(p>0.05). when the tumor invadeed adjacent structures,
We excluded patients whose criteria were as including perithyroid tissue, strap muscle, trachea,
follows: 1) Histological type was not DTC; 2) History larynx, esophagus, recurrent laryngeal nerve,
of thyroid surgery; 3) Incomplete data. Finally, a total prevertebral fascia, or encasing carotid artery or
of 50 pediatric patients and 158 adults were enrolled mediastinal vessels.
in this study. 2.3. Statistical analysis
2.2. Method Categorical variables were presented by
A cross-sectional, descriptive study. numbers and percentages. Continuous variables
Clinicopathological features were recorded, were expressed as mean (± SD). Differences
including age, gender, tumor size, multifocality, between two groups were analyzed by Chi-square
histological types, extrathyroidal extension, or Fisher's exact tests when appropriate.
intrathyroidal spread, vascular invasion of tumor Student’s t test and Mann-Whitney test were used
and the LNM. for continuous numerical data appropriately. We
used IBM SPSS Statistics software version 26.0 for
Age, gender, tumor size, number of tumors
statistical analysis. A statistically significant
were collected through medical records and
difference was recorded when p-value less than
pathology reports.
0.05.
Histological subtypes, extrathyroidal extension,
intrathyroidal spread, vascular invasion of tumor, 3. Result
and the LNM were evaluated by experienced
From January 2015 to March 2022, we recorded
pathologists from the Department of Pathology.
7661 patients with DTC. Among them, 50 patients
Histological subtypes were classified according were children, accounting for 0.65%.
to WHO 2017.

Table 1. Clinical features of patients

Children Adults
Features p value
n % n %
Female 33 66.0 133 84.2
Gender 0.005
Male 17 34.0 25 15.8
Age (years), mean ± SD 15.22 ± 2.82 45.08 ± 11.15 <0.001

The proportion of female patients in the pediatric patient group were lower than the adult patient
group, the difference was statistically significant (p<0.05).

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JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.18 - Dec./2023 DOI: https://doi.org/10.52389/ydls.v18ita.2153

Table 2. Location, number and size of the tumor


Children Adults
Features p value
n % n %
Absent 45 90.0 143 90.5
Bilaterality 1.000
Present 5 10.0 15 9.5
Absent 40 80.0 128 81.0
Multifocality 0.874
Present 10 20.0 30 19.0
Mean ± SD 19.74 ± 10.03 11.58 ± 6.91 <0.001
Tumor size
≤ 10 11 22.0 95 60.1
(mm) <0.001
> 10 39 78.0 63 39.9

There was no difference between pediatric and adult patients in bilaterality and multifocality (p>0.05).
Children had a higher average tumor size and a higher proportion of large tumors (> 10mm) compared to
adult patients (p<0.05).
Table 3. The differences in pathological features of differentiated thyroid carcinoma between
children and adults
DTC in DTC in
Pathological features children patients adults patients p value
n % n %
PTC 46 92.0 154 97.5
Histopathological type 0.097
FC 4 8.0 4 2.5
Extrathyroidal invasion
No invasion 23 46.0 77 48.7
0.002
Fatty tissue invasion 12 24.0 64 40.5
Muscles, trachea, esophagus invasion 15 30.0 17 10.8
Absent 43 86.0 153 96.8
Vascular invasion 0.009
Present 7 14.0 5 3.2
Absent 35 70.0 147 93.0
Intrathyroidal spread <0.001
Present 15 30.0 11 7.0
Absent 49 98.0 146 92.4
Necrosis 0.197
Present 1 2.0 12 7.6
Absent 38 76.0 122 77.2
Chronic thyroiditis 0.859
Present 12 24.0 36 22.8
Number of lymph nodes removed 15.08 ± 16.98 5.15 ± 8.42 <0.001
Number of LNM 7.26 ± 8.78 1.22 ± 2.77 <0.001
N0/Nx 15 30.0 108 68.4
N1a 14 28.0 37 23.4
Lymph node metastasis <0.001
N1a+ N1b 18 36.0 11 7.0
N1b 3 6.0 2 1.3

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JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.18 - Dec./2023 DOI: https://doi.org/10.52389/ydls.v18ita.2153

In both groups, PTC accounted for the majority (92% and 97.5%).
Pediatric patients had a higher rate of follicular carcinoma than that in adult patients (8% and 2.5%).
However, the difference was not statistically significant (p>0.05).
The rate of ETE was similar in the two groups of patients (46.0% and 48.7%). However, the percentage of
muscles, trachea, and esophagus invasion was higher in children (30% and 10.8%).
Pediatric patients had higher rates of tumors with vascular invasion and intrathyroidal spread than
adults (p<0.05). There was no difference between the two groups of patients in the rate of tumor necrosis
and chronic thyroiditis.
The number of dissected and metastatic lymph nodes in the pediatric patient group was significantly
higher than in adult patients (p<0.001).
The central and lateral LNM rates were higher in children than in adult patients (p<0.001).

Papillary thyroid carcinoma Papillary thyroid carcinoma


(HE, 100X, M1835) (HE, 40X, E3792)

Extrathyroidal extension with fibrofatty tissue invasion


Extrathyroidal extension with muscle invasion
(HE, 40X, 21B8314)
(HE, 100X, 20B3412)

Vascular invasion Lymph node metastasis


(HE, 200X, 20C5154) (HE, 200X, D9311)

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JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.18 - Dec./2023 DOI: https://doi.org/10.52389/ydls.v18ita.2153

4. Discussion In our study, the most common age group for


DTC in children is 15-18, without patients under ten
We reviewed and investigated 50 pediatric DTCs
years old. The average age was 15.22 ± 2.82 years;
and compared them to 158 adult DTCs.
the youngest patient was ten years old. Compared
Clinical features of patients with adult patients, children with DTC had a higher
Age is one of the critical prognostic factors used proportion of males. However in both groups,
in staging DTC. DTC can occur at any age. According female patients had a higher proportion than male
to the American Thyroid Association guidelines, patients. Our results were similar to previous studies.
pediatric DTCs are defined as DTCs found in children The age and gender rates in the children's DTC are
aged ≤ 18 years. Most pediatric DTCs occur in female shown in the following table:
patients aged 15-18 years [3].

Table 4. Proportion of age group and gender of DTC in across studies


Authors Number of patients < 15 years ≥ 15 years Female Male
Qian et al. (2019) [13] 1806 23.4 76.6% 80.5% 19.5%
Sharma et al. (2020) [14] 2271 22.7 77.3% 81.8% 18.2%
Nguyen Thi Nhung (2018) [10] 90 47.4% 52.6% 74.4% 25.6%
Nguyen Van Loc (2021) [11] 85 30.6% 69.4% 82.4% 17.6%
Ngo Quoc Duy (2022) [9] 99 32.3% 67.7% 68.7% 31.3%
Our study 50 14% 86% 66.0% 34.0%

In adults patients, the rate of female patients were 80.2%, similar to our results in our adult group
(84.2%) [2].

Tumor size is an important prognostic factor


Location, number, and size of the tumor
determining the TNM classification's T stage. The
According to the data in Table 2, there is no average tumor size in children in this study was
difference between pediatric and adult patients in 19.74 ± 10.03mm, higher than in adults at 11.58 ±
the characteristics of bilaterality and multifocality 6.91mm. This finding can be explained by the fact
(p>0.05). Bilateral tumors were 10% in this study, that most adult patients were admitted to the
lower than the results of Ngo Quoc Duy (2022) [9]
hospital because the thyroid tumor was detected by
and Soo Young Kim (2022) [7], with the rates of
a routine health check. In contrast, most children
bilaterality being 18.2% and 21.6%, respectively,
were admitted to the hospital due to a tumor in the
maybe due to their sample sizes were larger than
anterior neck, cervical lymph nodes, or symptoms of
that in our study.
compression [9]. The pediatric DTC group has a higher
The rate of multifocality in pediatric DTC has
average tumor size and a higher proportion of tumors
been reported from 19.2% to 60% [5, 7-9]. Our data
larger than 10 mm compared to the adult group
was 20%, consistent with Ngo Quoc Duy (19.2%) [9].
(78.0% and 39.9%, respectively). Other authors also
Soo Young Kim et al. (2022) also found no difference
have similar results. Ngo Quoc Duy reported that
between children and older patients in the rate of
82.8% of patients have tumors > 10mm in size [9]. In
multifocality [8]. Multifocality is associated with poor
adult patients, microcarcinoma (≤ 10mm) accounted
prognosis in pediatric DTC with higher rates of LNM
and distant metastasis [9]. for 60.1% of cases. This result is similar to the data in

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JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.18 - Dec./2023 DOI: https://doi.org/10.52389/ydls.v18ita.2153

other studies on adult patients, with 66.2-73.6% of a high rate of LNM in children, with a range from
cases being microcarcinoma [2, 6]. 73.0% to 93.7% [5, 8, 12].
The differences in pathological features of DTC To the best of our knowledge, our research was
between children and adults the first Vietnamese study to compare DTC in children
and adults at the same hospital. We compared the
The data in Table 3 show that PTC in children two groups on several histopathological features and
and adults accounts for the majority (92% and demonstrated more aggressiveness in pediatric DTC
97.5%). Follicular thyroid carcinoma was higher in than in adults. However, our study has some
children than in adults (8% and 2.5%); however, the limitations. Firstly, our study is a retrospective, single-
difference was not statistically significant. Our center research and tends to have a selection bias.
results were consistent with the data reported in Secondly, the treatment outcomes of the patients
previous studies. Ngo Quoc Duy (2022), Nguyen Van were not included. We will conduct further studies to
Loc (2021), and Nguyen Thi Nhung (2018) also investigate the relationship between
showed a high rate of PTC (96%, 95.3%, and 91.1%, histopathological features and treatment outcomes.
respectively) [9-11]. Dinh Huu Tam (2022) reported
the rate of adult PTC patients was 95.6% [2]. 5. Conclusion
Pediatric patients had higher rates of tumors In conclusion, our data indicated that DTC in the
with ETE, vascular invasion, and intrathyroidal children group revealed more aggressive patterns
spread than adults. ETE is a poor prognostic factor in than DTC in the adults group, with larger tumor size,
DTC patients. In our study, over half of children higher rate of extrathyroidal invasion, vascular
patients presented ETE (54%), similar to published invasion, and LNM. Special attention should be
studies [9, 12]. Sang Soo Kim (2012) determined that given to treatment strategies for pediatric patients
pediatric DTC has a higher rate of ETE than older with DTC.
patients [7]. The role of vascular invasion and
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