Clinicopathological features of recurrent papillary thyroid cancer

PTC is the most common but least aggressive histological subtype of thyroid cancer.
Most patients with PTC have excellent prognosis. However, recent studies have demonstrated
increasing incidence of recurrent PTC 2], 3]. Many factors can affect thyroid cancer recurrence, but final conclusions have not
been reached. The results of some studies show that the pathological type, staging,
degree of extrathyroid invasion, lymph node metastatic rate, age, and initial surgery
approach are related to thyroid cancer recurrence 4], 5]. Our research showed that tumor size, extrathyroid invasion, initial surgery approach,
lymph node metastasis, and pathological subtype demonstrate statistically significant
differences between the recurrent and non-recurrent groups. By contrast, factors such
as age, gender, complication with HT, and number of lesions are not correlated with
tumor recurrence. Multivariate analysis results further revealed that initial surgery
approach and pathological subtype are main factors related to PTC recurrence.

The dissection methods of primary lesions of PTC include (1) hemithyroidectomy with
or without isthmectomy, (2) total/near-total thyroidectomy, and (3) extension of surgical
scope. In case of severe extrathyroid invasion, such as invasion of the esophagus,
trachea, and nerves, extending the scope of surgery is required. The methods of neck
dissection are as follows: (1) central compartment node dissection (unilateral or
bilateral), (2) selective neck dissection, (3) functional compartmental en-bloc neck
dissection, (4) modified neck dissection, and (5) radical neck dissection 6]. Mazzaferri et al. 7] found that the recurrence rate after partial thyroidectomy is nearly twice that of
total and near-total thyroidectomy. By contrast, Cunningham et al. 8] revealed that the recurrence rates had no significant difference between hemithyroidectomy
and total/near-total thyroidectomy groups. Monacelli et al. 9] suggested that total thyroidectomy combined with central node dissection must be
performed even in the absence of risk factors and without clinically evident nodes.
However, some researchers do not advocate prophylactic central neck lymphadenectomy
10]. Univariate analysis in this research showed that initial surgery approach exerts
a great impact on the prognosis. For example, while 47.1 % (16/34) of the recurrent
PTC patients received the first type of surgery as initial surgery, only 22.1 % (62/281)
of the non-recurrent PTC patients received the first type of surgery. About 52.9 %
(18/34) of the recurrent PTC patients received the second and third types of surgery.
In comparison, 77.9 % (219/281) of the non-recurrent PTC patients received the second
and third types of surgery as the initial surgery. Multivariate analysis revealed
that initial surgery approach is the main factor related to PTC recurrence (P??0.001); specifically, initial surgery approach demonstrated a negative correlation
with PTC recurrence (??=??0.320, OR?=?0.726).

The recurrence rate decreased with increasing surgical scope. Non-standardized surgical
approaches with inappropriately small surgical scopes could lead to tumor residue.
Moreover, lesions of lymph node metastasis may be missed, thereby increasing the risk
of recurrence. Possible reasons behind the inconsistency of results are as follows:
(1) Differences among recruited patients. Patients receiving neck dissection showed
significant metastases, whereas no cervical lymph node metastasis was discovered before
the operation in patients who did not receive neck dissection. (2) Insufficient number
of recruited patients. (3) Difference in surgical techniques among surgeons. Considering
these factors, blindly extending or narrowing the surgical scope is irrational.

The World Health Organization (WHO) histological classification of tumors has redefined
the subtypes of non-conventional PTC 11]: follicular variant, oncocytic variant, diffuse sclerosing variant, tall cell variant,
columnar cell variant, solid variant, PTC with nodular fasciitis-like stroma, clear
cell variant, and diffuse follicular variant. PTC patients of different histological
subtypes may exhibit diverse clinical and biological behaviors. Subtypes including
the tall cell, columnar cell, diffuse sclerosing, and oncocytic variants have higher
invasiveness and may promote higher risks of recurrence and metastases 12]–14]. The prognosis of patients with the follicular and clear cell variants is similar
to that of patients with conventional papillary carcinoma 15]. Thyroid microcarcinoma is a type of papillary carcinoma that is less than 1 cm in
diameter with relatively low invasiveness and good prognosis 16]. This research classified histological variants according to the WHO histological
classification of tumors. Patients with the tall cell, columnar cell, diffuse sclerosing,
and oncocytic variants were classified into Group 1; patients with the follicular,
clear cell, and conventional PTC variants were classified into Group 2; and patients
with papillary microcarcinomas were classified into Group 3. The research conducted
by Boone et al. 17] showed that the recurrence rate of patients with differentiated thyroid carcinoma
is lower than that of patients with other types of thyroid carcinoma. Among the differentiated
thyroid carcinomas, the recurrence rate of PTC is lower than that of the follicular
variant. However, 30 % of the PTC patients continue to suffer from recurrence, metastasis,
and even death 18]. Univariate analysis demonstrated that pathological subtype is obviously correlated
with PTC recurrence (P??0.01). Multivariate analysis also indicated that pathological subtype is closely
related to PTC recurrence (??=?0.923, OR?=?2.517). The recurrence rate of PTC increased as the invasiveness of
the tumor increased. Thus, close follow-up must be carried out in patients with the
tall cell, columnar cell, diffuse sclerosing, and oncocytic variants. Effective treatment
measures must be taken once recurrence is discovered.

Various results are reported in the literature regarding the effect of lymph node
metastases on PTC recurrence. Some studies indicate that lymph node metastases do
not affect PTC recurrence 19]. However, some researchers have found that the number of lymph node metastases is
associated with postoperative recurrence or re-metastasis. Thus, lymph node metastasis
has become an important factor affecting the prognosis and recurrence of thyroid carcinoma
20]. The results of this research revealed statistically significant differences in lymph
node metastases between the recurrent and non-recurrent groups. Patients with lymph
node metastases at the time of initial surgery are more likely to suffer recurrence
than those without metastases. The correlation of cervical lymph node metastases with
recurrence needs to be confirmed through large-sample and long-term studies.

Of the 34 recurrent PTC patients in the group, postoperative recurrence intervals
ranged from five months to 18 years, with a median time of 46 months. Recurrence was
observed to occur within a short period of time. The majority of PTC patients, for
example, showed recurrence within two to five years from surgery. Furthermore, recurrence
may also occur more than once. Therefore, PTC patients must have regular reexamination
with frequent follow-ups within five years after the first treatment. Ultrasound examination
must be performed at least once a year within five years after the first treatment
for timely discovery of tumor recurrence.