TC is now among the most frequently diagnosed cancers in the adolescent and young adult
population, spanning ages 15 to 39 years. Since 1990, in the United States, the incidence of TC
among young adults has been rising significantly affecting both females and males. This trend
in TC suggests that it has now surpassed breast cancer as the most prevalent cancer among
females in this age group[6]. The incidence rates reported in the literature are 17.6, 43.3, and
63.0 per million inhabitants, respectively, for the age groups 15–19, 20–24, and 25–29 years old,
accounting for 8–11% of all TC cases across all age groups[7][8]. This was also
demonstrated in our study, where TC in young patients under 40 years old was found in 7.4%
of all diagnosed TC cases during the same timeframe. TC in patients under 40 years old exhibits
distinct clinical characteristics compared to older patients[9]. Understanding these specificities
is crucial for early diagnosis, appropriate management, and a more accurate prognosis for this
population. In our series, the analytical study revealed a trend towards better DFS in younger
patients. While this association did not reach statistical significance (p = 0.09), the p-value
approached significance. In patients with thyroid cancer (TC), an age below 45 years is
associated with a good prognosis and a ten-year DFS exceeding 99%[10]. The age threshold at
diagnosis was raised from 45 to 55 years in the eighth edition of the AJCC prognostic staging
system. Therefore, patients under 55 years old, even with distant metastases, are classified as
stage two, with a ten-year DFS estimated at 85–95%[11].
Our study showed a clear female predominance (35 cases, 87.5%). The male-to-female sex
ratio was 0.14. This finding is also observed in the majority of series that have addressed this
topic[12][13]. The analytical study demonstrated better survival among women with a p-value
close to significance (p = 0.08).
Roughly 30 to 50% of patients under 40 years old exhibit clinical symptoms such as a
palpable nodule in the neck region, an enlargement of the thyroid gland, neck pain, or
cervical lymphadenopathy[14]. However, a significant proportion of young patients may be
asymptomatic, and thyroid cancer can be incidentally discovered during a cervical ultrasound
performed for other reasons. This was the case in our series in six cases (15%).
Cervical ultrasound was performed in all cases, and the tumors were predominantly classified
as EU-TIRADS 5 (47.5%), indicating a high suspicion of malignancy, highlighting the crucial
role of ultrasound in characterizing thyroid nodules. The average tumor size (20.9 mm) in our
study is similar to the data reported in the literature, where TC can vary
considerably in size, ranging from a few millimeters to several centimeters[15]. Additionally,
Tran B et al have highlighted that tumors in young patients tend to have a smaller average size
compared to older patients[14]. It is important to note that these histopathological
characteristics may have implications for tumor classification and treatment choice.
In our series, we observed a high rate of bilaterality (30%) and multifocality (50%), which is
consistent with data from the literature. It is well-documented that thyroid cancers often exhibit
bilaterality and multifocality, especially in younger patients [16]. We did not find any impact
of multifocality on DFS (p = 0.24). Instead, these characteristics serve as markers defining the
extent of thyroid cancer at the time of diagnosis but are not independent prognostic factors for
long-term outcomes [16]. Additionally, a systematic review concluded that multifocality in
TC was not an independent risk factor for contralateral central lymph node metastases [17].
In our study, twenty-three cases (57.5%) were encapsulated, with 14 cases (35%) showing
capsular invasion and nine cases (22.5%) having an uninvaded capsule. Capsular invasion was
more frequently observed in classical PTC than in encapsulated variant of papillary thyroid
carcinoma (CPVEI). This observation is also supported by literature, where authors have
described a higher prevalence of capsular invasion in classical PTC compared to CPVEI. This
study also concluded that only complete invasion and complete destruction of the capsule had
a prognostic impact [18].
Data from our series revealed papillary architecture was present in 82.5% of cases. Although
this architecture is helpful for diagnosis, its presence is not mandatory. It can also be vesicular,
with or without papillary architecture [19]. Akslen LA et al conducted a study involving 228
patients with PTC revealing that 55% of these cases were of the classic type, characterized by
papillae varying considerably in structure and size. Typical nuclear atypia seen in PTCs was
observed in these classic tumors [20]. According to the WHO, papillary nuclear atypia
represents a set of characteristics that must be considered, and no single feature is
pathognomonic, hence the WHO score ranging from 1 to 3 based on the pronounced
appearance of these atypia. These atypies do not influence disease progression (p = 1.86).
The results regarding this parameter are controversial. Some authors confirm it as a prognostic factor, while others conclude that no prognostic effect is described [18]. In our series, two histological types were observed: classical PTC carcinoma (CPTC) (including one case of tall cell variant) (90%) and encapsulated variant of PTC (CPVEI) (10%). This type was identified based on its molecular characteristics, specifically presenting RAS-like mutations. However, no difference in terms of disease progression could be validated (p = 5.41). Mitotic index has recently been introduced in the assessment of papillary thyroid carcinomas (PTCs) to refine tumor classification, identify risk subgroups, and assist in therapeutic decision-making. The threshold for the number of mitoses was set at 5 mitoses per 10 high-power fields (HPFs) in the 2022 WHO classification, based on various studies on prognosis that advocate high-grade tumors exhibiting lower overall survival and DFS rates compared to low-grade tumors [21]. In our series, the majority of cases (85%) exhibited a low mitotic index (< 5 mitoses/10HPFs), while 15% showed a high mitotic count (≥ 5 mitoses/10 HPFs). A high mitotic count coexisted with necrosis in two cases.
According to some authors, tumor necrosis was an important factor, identified in 42% of
patients, with 81.5% not having tumor necrosis (p = 0.01) [2], contrary to our study, which did
not show a statistically significant relationship between DFS and the presence of tumor necrosis
(p = 0.59). This could be a characteristic of young age in PTC, but it needs to be confirmed by
larger studies. In our study, 70% of cases were low-grade, while 30% were high-grade. High
grade is defined by the presence of one of these three criteria: a mitotic count ≥ 5 mitoses /10
HPFs, tumor necrosis, or a Ki67% > 5%.
Among the high-grade PTCs in our series, some exclusively exhibited tumor necrosis (15%),
while others showed a high mitotic count (15%), and in two cases, both characteristics were
simultaneously observed (5%). Among the 12 cases of PTC classified as high-grade, three
presented with metastases. However, no significant association was found with DFS. This
could be explained by the small sample size or the fact that the threshold of 5 mitoses alone
may not confirm high grade. Indeed, changing grade based on a single mitosis, going from low
grade with 4 mitoses/10HPFs to high grade at 5 mitoses/10 HPFs, raises questions about the
validity of this grading system. In our series, angioinvasion was noted in eight cases (20%).
The number of vessels invaded ranged from one to seven, with six cases showing invasion of
more than four vessels. However, in our study, angioinvasion was associated with more
aggressive tumors but did not significantly affect DFS (p = 1.125). Several authors have
explored the prognostic significance of angioinvasion, suggesting that patients at higher risk of
developing angioinvasion are typically elderly, have larger tumor sizes, and present with both
lymph node and distant metastases. This highlights the prognostic value of assessing
angioinvasion in TC[22]. In this setting, we noted lymph node metastases in 23 cases
(57.5%), but the analytical study did not show a statistically significant relationship between
the presence of lymph node metastases and DFS (p = 1.8).
Several studies have explored the prognostic value of lymph node metastases, concluding that
despite their high frequency, they do not have a significant impact on the recurrence rate of
PTC, which remains low [23]. However, there is an assumption that not all lymph node
metastases in PTC have the same prognostic significance in terms of recurrence and mortality
[24]. One study reported that the presence of lymph node metastases in patients under 45 years
old was associated with a higher risk of local recurrence and distant disease, particularly when
there are capsular ruptures[25].. In our series, we observed 14 cases of lymph node metastases
with capsular rupture.
Nineteen patients from our series were classified as pT1 (9 cases pT1a, 10 cases pT1b), 14 patients were classified as T2, three patients pT3a, one patient pT3b, and three patients pT4; 17 cases were classified as N0, with only one case presenting distant metastases at the time of diagnosis. This is in line with the literature, which emphasizes that the classic form of PTC is often associated with an early stage of TNM classification, especially in young subjects [20].. The authors concluded that although staging is important for assessing the prognosis of PTC patients, it is necessary to take into account the specific characteristics of each patient, such as age, disease stage, and molecular factors, for a more accurate evaluation of individual prognosis.
The therapeutic data from our study reveal a standardized approach to treating the studied PTC
cases
Total thyroidectomy was performed in 37 cases (92.5%): upfront in 16 cases (40%) and
as a complementary procedure in 21 cases (52.5%), with a non-significant difference (p = 0.71).
It is noteworthy that in the majority of cases (85%), the resection margins were clear (85%)
compared to 15% with tumor-involved margins, with a non-significant difference (p = 0.80),
which is concordant with the literature where total thyroidectomy or thyroid lobectomy with
isthmectomy is the treatment of choice for PTC in young patients [26], and the decision for
surgical procedure depends on the size and extent of the tumor, as well as the specific
anatomical characteristics of each case [27].
Surgery remains the preferred treatment for PTC with nodal metastases, with a lateral cervical approach. Thorough preoperative evaluation is crucial to minimize complications by preserving nerves, vessels, and parathyroid glands.
As for adjuvant treatments, 85% of patients underwent iodotherapy (IRA therapy) as described
in the literature, given the role of radioactive iodine in treating microscopic deposits of thyroid
cancer. Adjuvant treatment with radioactive iodine is determined based on the risk of
recurrence, always within the framework of a dedicated multidisciplinary discussion. Patients
with a high risk of recurrence always require high-dose I131 treatment (approximately 100
mCi), usually after discontinuation of thyroid hormone therapy. Despite this treatment, 56 to
72% of patients have residual disease. For intermediate-risk thyroid cancer patients,
considering the estimated risk of recurrence between 5% and 30%, adjuvant treatment with
radioactive iodine is always considered, with treatment modalities ranging from low dose
(approximately 30 mCi) to high dose (approximately 100 mCi) depending on tumor
characteristics. For low-risk thyroid cancer patients, radiotherapy should be considered on a
case-by-case basis and depending on other prognostic factors (age, vascular invasion, etc.) [27].
In our series, radiotherapy was initiated in 57.5% of patients, with no significant difference
(p = 1.39) among those who had lymph node metastases at the time of diagnosis. These results
suggest a multidisciplinary approach to PTC treatment, as described in the literature. Indeed,
in some cases, adjuvant radiotherapy may be recommended to reduce the risk of recurrence,
especially for large tumors or those with extrathyroidal invasion [28].
Data from our series revealed postoperative outcomes were uncomplicated in 30 cases and complicated in five cases (three cases of hypocalcemia and two cases of dysphonia), resulting in a morbidity rate of 14%. Postoperative surveillance data were not mentioned in the medical records of five patients. In our series, the average relapse-free survival was 342.7 days with a confidence interval between 141.48 and 544.09. No cases of death were recorded in our series.
Overall, PTC in patients under 40 years of age has a better prognosis than in older patients [9]. A retrospective study revealed that patients under 45 years of age had an overall survival rate of 98.4% after ten years of follow-up [29].