The prevalence and features of the Delphian lymph nodes' involvement in patients with papillary thyroid carcinoma

doi:10.21203/rs.3.rs-3408406/v1

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The prevalence and features of the Delphian lymph nodes' involvement in patients with papillary thyroid carcinoma

https://doi.org/10.21203/rs.3.rs-3408406/v1

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There is ongoing debate on the extent of dissection in patients with papillary thyroid cancer. Evaluating Delphian lymph nodes (DLNs) at the time of the procedure could be helpful in determining the extent of dissection. The objective of this study was to evaluate the frequency and features of DLN in patients with papillary thyroid carcinoma.

Methods

This cross-sectional study included patients who underwent PTC surgery for papillary thyroid carcinoma. The patients were classified according to whether their DLNs were involved. Age, sex, mass location, lymphatic involvement, tumor size, tumor features, pathology report, and parts of the surgical note were compared between the two groups. The final pathology slides of the patients were evaluated for DLN features.

Results

Among the 61 patients (mean age:38.2 ± 12.0), 45 (73.8%) were female. Of the 13 patients (21.3%), one patient's interaction with DLNs was documented. Other lymph nodes on the same side (P = 0.001), opposite side (P = 0.041), and central lymph nodes (P = 0.001) were significantly associated with DLN involvement. Furthermore, vascular invasion was significantly higher in patients with DLN involvement (P = 0.012).

Conclusion

As DLN involvement is strongly linked to significant nodal involvement, it is suggested that DLNs be evaluated during surgery to determine the correct level of dissection.

Delphinan lymph nodes (DLNs) are among the level VI nodes of the neck. Because these nodes are located in front of the cricothyroid membrane, the surgeon first identifies them during complete thyroidectomy [1]. For a very long time, it was thought to be associated with a decreased chance of survival or an increased risk of relapse in head and neck cancers [2, 3, 4]. The DLNs are directed into the lateral neck by the superior thyroid artery, whereas the pretracheal lymph nodes are situated in front of the isthmus and discharge into the mediastinum. The exact mechanism underlying lymph node (LN) metastasis remains unknown [4, 5, 6]. Research has shown that the presence of DLNs in laryngeal and hypopharyngeal cancers is a poor prognostic factor [7, 8, 9]. Papillary thyroid cancer (PTC), the most common endocrine malignancy, is the most prevalent type of thyroid cancer. Regarding the role of DLNs and their predictive significance, different findings have been reported [10], especially when level IV central LN dissection was considered. [*]

The pretracheal lymph nodes are in front of the isthmus and drain into the mediastinum. In contrast, the other hand, drain into the lateral neck by following the superior thyroid artery. However, the exact path of lymph node metastasis is still unknown [15, 16, 17]. DLN metastasis is known to be a predictor of broad LN metastases, a high frequency of recurrence, and an increased death rate, particularly in laryngeal cancer. Current guidelines suggest assessing the degree of lymph node involvement in PTC using ultrasonography before surgery [11]. However, it is important to know that ultrasonography canno't always determine if the central lymph nodes are involved because the thyroid gland is in front of them and the bones cast a shadow on them [12, 13]. The results of ultrasonography were significantly influenced by physician competency. Furthermore, it has been demonstrated that PTC patients had notably high rates of involvement of the central and lateral lymph nodes, ranging from 3.1–65.4% and 12–81%, respectively [14, 15]. Therefore, it i's critical to identify potential predictors of lymph node metastases, such as DLN involvement, to act as a marker for severe nodal involvement [13].

Several researchers have claimed that DLN involvement is not suggestive of broad involvement because it can be diagnosed irrespective of the involvement of other nodes [16]. However, many studies have shown that DLNs are useful in making predictions because they can show severe nodal and vascular involvement [3, 4, 17]. Notably, the degree of dissection, course of treatment, and prognosis of the patient depend on the involvement of the DLN [18]. In the current study, we aimed to evaluate the prevalence and characterize the features of DLN in patients with PTC.

We conducted a cross-sectional study in a tertiary care center in Zagazig University Hospital between 2019 and 2021.

There were 160 cases of papillary thyroid carcinomas every year, with a confidence interval of 95%, d = 0.05, and z = 1.96. Based on previous research and the assumption that 20% of papillary thyroid carcinomas involve DLN, a sample size of 122 was considered sufficient.

The central LN, prelarynx, trachea, and paratracheal were cut open by an endocrinologist during total thyroidectomy for patients with PTC [19]. DLNs are located in the fascia above the thyroid isthmus, between the thyroid and cricoid cartilages. They are also known as prelaryngeal or cricothyroid nodes. After the pyramidal lobe was freed, the lymph tissues in this area were removed while preserving the cricothyroid membrane and were sent for final pathology.

Each patient whose medical file contained a pathological proof of PTC within the allotted period was examined. Two board-certified pathologists validated the final pathological diagnosis. All patients received standard care in accordance with the existing recommendations. Patients who underwent surgery between the ages of 20 and 70 years and were definitively pathologically proven to have PTC were eligible for inclusion, provided that they had sufficient medical records and data from DLN evaluations.

Statestics

The experiment was closed to patients with diagnoses other than PTC, or those with incomplete medical records.

A pre-designed Excel (Microsoft, Redmond, WA, U.S.) sheet was filled in with information on the patients' age, sex, location of the mass, lymphatic involvement, tumor size, tumor features, pathology report, and parts of the operation note. Patients were divided based on their DLN involvement status. Using SPSS version 21 software, the data were examined using the T-test, Chi-square, and Fischer exact tests. Statistical significance was set at p < 0.05.

Of the 400 PTC cases examined in this study, only 122 had accessible DLN sections and permanent pathology slides. The mean age of the patients was 38.2 (SD:12.0; range:20–69), and 73.8% of them were female. In addition, the tumor's average size was 2.1 (SD:1.6; range:0.2–7.9) cm. Of the patients, 26 (21.3%) had DLNs, while 56 (78.7%) did not. On the right side, PTCs account for 58% of the total. The lymphatic involvement rate was 6.6% on one side of the mass and 14.8% on the other. Follicular-type thyroid cancers occurred second, at 14.8%, with classical papillary thyroid tumors accounting for 78.7% of all diseases. Table 1 presents the clinical features of the patients involved in the study.

Table 1

The clinical features of patients with papillary tumors
Variable		Total; N = 122	Delphian lymph node involvement		P-value*
Variable		Total; N = 122	Positive; n = 26	Negative; n = 56	P-value*
Age (years); mean ± SD		38.2 ± 12.0	39.2 ± 13.2	37.9 ± 11.7	0.743
Age group; n (%)	≤ 30	44 (36.1)	10 (38.5)	34 (35.4)	0.803
	31–40	36 (29.5)	6 (23.1)	30 (31.3)
	41–50	20 (16.4)	6 (23.1)	14 (14.6)
	51–60	16 (13.1)	2 (7.7)	14 (14.6)
	> 60	6 (4.9)	2 (7.7)	4 (4.2)
Gender; n (%)	Male	32 (26.2)	8 (30.8)	24 (25.0)	0.728
Gender; n (%)	Female	90 (73.8)	26 (69.2)	72 (75.0)	0.728
Location of mass; n (%)	Right	62 (50.8)	16 (61.5)	46 (47.9)	0.240
	Left	42 (34.4)	2 (7.7)	40 (41.7)
	Bilateral	18 (14.8)	8 (30.8)	10 (10.4)
Lymphatic involvement; n (%)	Same side of mass	18 (14.8)	16 (61.5)	2 (2.1)	< 0.001
	The opposite side of mass	8 (6.6)	6 (23.1)	2 (2.1)	0.041
	Central lymph node	30 (26.3)	18 (69.2)	12 (12.5)	< 0.001
Tumor size (centimeter); mean ± SD		2.1 ± 1.6 (0.2–7.9)	2.4 ± 1.3	2.0 ± 1.7	0.428
Tumor size group; n (%)	≤ 1 cm	34 (29.8)	6 (27.3)	28 (30.4)	1.000
Tumor size group; n (%)	> 1 cm	80 (70.2)	16 (72.7)	64 (69.6)	1.000
Tumor characteristics; n (%)	Multifocal	30 (24.6)	12 (46.2)	18 (18.8)	0.067
	Vascular invasion	46 (37.7)	18 (69.2)	28 (29.2)	0.012
	Capsule invasion	60 (49.2)	12 (46.2)	48 (50.0)	0.806
	Perineural invasion	10 (8.2)	2 (7.7)	8 (8.3)	1.000
Pathology; n (%)	Classical	56 (78.7)	24 (92.3)	72 (75.0)	0.875
	Follicular	18 (14.8)	2 (7.7)	14 (16.7)
	Medullary/papillary microcarcinoma	2 (1.6)	0 (0)	2 (2.1)
	Tall cell	2 (1.6)	0 (0)	2 (2.1)
	Tall cell and follicular	2 (1.6)	0 (0)	2 (2.1)

SD standard deviation; bold text indicates strong association.

* Independent sample t-test, chi-square test, or Fisher's exact test

Table 2 shows lymphatic involvements in the mass itself, the mass on the other side, the central lymph nodes, and vascular invasion. For each, we can also see the PPV, NPV, sensitivity, and specificity.

Table 2

The Delphian lymph node involvements* prognostic power for other locations
	Same side of mass	Opposite side of mass	Central lymph node	Vascular invasion
PPV	17/26; 61.5%	6/26; 23.1%	18/26; 69.2%	18/26; 69.2%
NPV	94/96; 97.9%	94/96; 97.9%	84/96; 87.5%	68/96; 70.8%
Sensitivity	16/18; 88.9%	6/8; 75.0%	18/30; 60.0%	18/46; 39.1%
Specificity	94/104; 90.4%	94/114, 82.5%	42/46; 91.3%	68/76; 89.5%

Both positive and negative predictive values (NPV and PPV, respectively) were calculated for the significant findings.

There was no statistically significant difference in the incidence of DLN between men and women (P = 0.728). The incidence of DLN involvement was statistically significant (P = 0.024) and was greater in the right masses. Moreover, substantial statistical correlations were found between DLN involvement and involvement of other lymph nodes on the same side (P < 0.001), opposite side (P = 0.041), and central lymph nodes (P < 0.001). Furthermore, vascular invasion was significantly higher in patients with DLN involvement (P = 0.012).

The overall age of patients with DLN involvement was 39.2 ± 13.2 years, and their average mass size was 1.3 ± 2.4 cm. The independent t-test revealed no statistically significant relationship between age, mass size, and DLN participation (P = 0.428 and 0.743, respectively).

None of the participants in our study experienced any problems, such as nerve or blood vessel damage. None of our patients showed evidence of clinical or symptomatic hypocalcemia. Furthermore, individuals who underwent laboratory testing for transient hypocalcemia had calcium levels greater than 7.5 mg/dL. These patients were discharged with oral calcium supplements, and they underwent laboratory calcium assessments every 48 h, during which time their prescriptions were adjusted or continued.

In the current study on patients with PTC, we found a substantial link between lymphatic involvement on the opposite side of the mass, central lymph nodes, and DLNs. Additionally, a significant correlation between vascular invasion and participation of DLNs was discovered. The incidence of DLN metastasis in PTC patients ranged from 8.2 to 24.8%, according to a meta-analysis by Wang et al. [20]. In line with previous research, DLN were involved in 23.1% of the patients in our study.

Previous studies have investigated whether DLN involvement could be a predictor of extensive nodal involvement in PTC, with the goal of assisting the surgeon in determining how much dissection is required. Since almost all thyroid gland regions provide lymphatic output to DLNs [6], DLN are a good indicator of extensive nodal involvement. A meta-analysis conducted by Huang et al. [21] revealed that patients with positive DLNs were much more likely to experience metastases to the central and lateral lymph nodes than those with negative DLNs. Although they were aware of their limitations and the fact that the studies they looked at were not all the same, they suggested that DLNs should be checked using frozen sections during surgery. If the nodes were positive, they suggested that the primary lymph node be cut open, and the lateral lymph nodes were carefully checked. These results are similar to those of our study, which found a strong link between lymphatic involvement on the other side, involvement of central lymph nodes, and involvement of the mass in the DLN.

Moreover, contrary to other studies [18, 20, 22, 23], we did not detect any significant correlation between DLN involvement and poor prognostic factors such as male sex, older age, larger tumor size, and mass location. More recent studies have demonstrated a relationship between PTC location and DLN characteristics. According to a study by Zaho et al. [24], 14.9% of 1305 patients with isthmus PTC exhibited positive lymph nodes. According to a different study by Liu et al. [25], metastasis was observed in 25.2% of the DLNs in 522 patients with unilateral PTC. Both investigations reinforce our findings that there is a significant correlation between central and lateral lymph node metastases and DLN positivity. As such, frozen sections of the DLNs should be obtained during surgery to determine the extent of dissection. However, these findings should be interpreted with caution, as additional long-term studies are required to support these findings.

The DLN is one of the first locations examined during full thyroidectomy, and because of its drainage properties, it can help estimate the extent of dissection required in PTC patients [26]. We may use this checkpoint as a prediction metric for our process, preventing additional investigations that could cause damage to the arteries and nerves. Although DLN involvement could be concerning, its rarity might make it difficult to detect during surgery, leading to incorrect diagnoses and treatment of individuals who have undergone full thyroidectomies.

Researchers have questioned the routine use of frozen sections in thyroid surgery because of their low sensitivity and high risk of false-negative results [27]. Real-time diagnosis of DLN status can be easily guided by intraoperative frozen section evaluation [28]. Additionally, studies have indicated that central compartment neck dissection should be performed if the results of the intraoperative frozen section evaluation indicate that the DLN is positive. It is important to thoroughly assess the ipsilateral lateral LN of Levels II, III, and IV [28]. Nevertheless, a more accurate and thorough individual LN evaluation that integrates clinicopathological features at every sublateral level is required [29, 30]. According to Iyer et al., thyroid tumors with DLN metastases are associated with metastases to the central and lateral neck lymph nodes. Following surgery, frozen-section biopsy and total LN excision are required [31]. Because the DLN is located near the region of the thyroid cartilage or cricoid, a central neck dissection should be performed if the frozen section of the DLN is positive and if one is not previously scheduled [26]. Kim et al. reported that, depending on the results of a frozen section biopsy performed after surgery, treating PTC patients may only require ipsilateral central neck LN dissection and thyroid lobectomy, with contralateral central neck LN dissection reserved for specific circumstances [1].

When evaluating the extent of invasion, it i's critical to acknowledge the limits of frozen segment's. Hence, it was recommended that permanent pathology be used, as we did in our investigation, as a marker of extra- or capsular invasion; however, tissues that should be sent for permanent pathology may deteriorate in frozen slice [27]. For patients with dubious microneedle aspirations for malignancy, the frozen portion is believed to be helpful prior to surgery [32, 33]. Given the higher risk of post-operative complications associated with central lymph node dissection during thyroidectomy, previous studies have recommended pre- or intraoperative molecular techniques to determine the extent of surgery or only perform dissection for high-risk groups [27, 34, 35, 36]. Although DLNs can serve as a surrogate for significant nodal and vascular invasion, in our study, the pre-laryngeal region's lymph tissues were removed and sent for final pathological examination to produce more accurate and reliable results. During surgery, lymph tissues in this area may be sent for frozen sections as an alternative method. Subsequently, depending on whether the DLNs are implicated, a decision on further lymph dissection, which can require finishing a central lymphadenectomy, might be made. Consequently, future studies should employ several intraoperative diagnostic methods to determine the DLN involvement. Because of the anatomical location of DLNs, we believe that this operation has an advantage over others in that extensive dissection may not always be required, and there is less risk of injuring arteries and nerves during dissection and resection of lymphatic tissues in this area.

Previous studies have found a strong link between DLN and the invasion of lymphovascular or arterial structures, which is similar to what we found [1, 20].

This study did not have any flaws. Since PTC is more common in girls, the study's proportion of females over males is warranted. Second, the small sample size and the fact that this was a single-center study restrict the amount of data we can provide despite our best efforts to provide a sufficiently large sample of our patients. Third, the study's cross-sectional design precluded the estimation of patients' survival or recurrence rates.

More prospective studies should look at the connection between certain tumor locations, major node involvement, survival rate, recurrence, and prognosis of patients with and without DLN involvement to obtain a fuller picture of this subject.

Significant vascular and nodal involvement may coexist with DLN metastases in PTC patients. As a result, it makes sense to thoroughly evaluate DLNs during the process and determine the level of dissection by examining the positive and negative aspects of DLNs.

DLN:

Delphian lymph node

PTC:

Papillary thyroid cancer

SD:

Standard deviation

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Research Ethics Committee of the Zagazig University Faculty of Medicine. Permission to carry out the study and access patient records was sought from the respective university administrators. The study was conducted in compliance with the relevant guidelines and regulations and the Declaration of Helsinki and was approved by the ethics committee of the university. Written informed consent for participation was obtained from all the patients.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request and with permission from the Research Ethics Committee of the Zagazig University Faculty of Medicine.

Competing interests

The authors declare that they have no competing interests or financial

disclosures.

Funding

No specific funds were received for this study

Authors Affilatiion

Hassan A. Saad¹,

Azza Baz²,

Mohamed Riad¹,

Mohamed E Eraky¹,

Ahmed El-Taher¹,

Mohamed I Farid¹,

Khaled Sharaf¹

Huda E. M. Said³

¹Surgical Department, Faculty of Medicine, Zagazig University, Zagazig City, Egypt.

²Surgical Department, Alahrar Teaching Hospital, Zagazig University, Zagazig City, Egypt

Three Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig City, Egypt

Corresponding author: Hassan A. Saad, Telephone: (+20) 01221025689, ORCID:0000-0002-6242-7823. E-mail: [email protected]

Author contributions

HAS, ME: contributed to the conception and design of

MR. AKE organised the database and

performed the statistical analysis.

HAS,KS: wrote sections of the manuscript

and prepared tables.

MIF, AB,HEM: contributed to the manuscript.

revision and investigation.

All authors read, approved, and equally shared the submitted version

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No competing interests reported.

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The prevalence and features of the Delphian lymph nodes' involvement in patients with papillary thyroid carcinoma

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Abstract

INTRODUCTION

METHODS

Statestics

RESULTS

DISCUSSION

CONCLUSION

Abbreviations

Declarations

Ethics declarations

Ethics approval and consent to participate

Consent for publication

Availability of data and materials

References

Additional Declarations

Status:

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