Intra-parotid lymph node metastasis in primary parotid gland cancer: a narrative review of its significance, anatomic distribution, and therapeutic implications

Introduction

The incidence of salivary gland cancer is estimated at 0.5–3.0 per 100,000 annually, accounting for approximately 5% of head and neck cancers (1,2), and 64–80% of primary salivary gland tumors occur in the parotid gland (3). In primary parotid gland cancer (PGC), the presence or occurrence of cervical lymph node (LN) metastasis (LNM) is a well-known prognostic factor for recurrence, treatment outcomes, survival, and prognosis (4-6). Recent studies have increasingly reported evidence that metastasis into the LN within the parotid gland (intra-parotid LNM) from PGC also has a significant impact on disease recurrence and patient prognosis (7).

However, anatomic information or the details of distribution of intra-parotid LNM within the parotid glands are lacking, having rarely been included in previous studies. To decide where to treat or not to treat, this kind of knowledge about the target site and a potential risk of disease involvement or recurrence is critical for improving treatment outcomes. In this narrative review, we sought to go beyond the presence or absence of intra-parotid LNM in PGC and to also tackle the anatomical distribution of intra-parotid LNM to provide clinically relevant information for managing these diseases.

Therefore, the following key questions were assumed in this study:

• What is the sub-site distribution in the parotid gland if intra-parotid LNM occurs in PGC?
• To target the potential intra-parotid LNM, what is the adequate extent of surgery (parotidectomy)—for example, total parotidectomy versus more limited parotidectomy (superficial or subtotal parotidectomy?
• How can tumor pathology or grade influence the occurrence or distribution of intra-parotid LNM?
• To gain anatomical information about intra-parotid LNM, how do we incorporate sub-site information into the intra-parotid LNM report following pathology examination?

Because of the lack of the relevant articles on this topic, we tried to answer these clinical questions only through conducting a narrative review, and we suggest a future study by generating a study hypothesis. We present this article in accordance with the Narrative Review reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2024-575/rc).

Methods

A database search using the online databases Web of Science (https://webofknowledge.com/) and PubMed (https://pubmed.ncbi.nlm.nih.gov/) was conducted in August 19, 2023 (Table 1). The following keywords were used in the search: “parotid gland”, “parotid neoplasm”, “lymph node”, “lymphatic metastasis”, “intraparotid”. Articles in English published between January 1980 and July 2023 were searched. Then, the authors reviewed the retrieved articles (abstract or text) and excluded not related to the topic of discussion, case reports, non-English article, inaccessible full texts. As a result, we found 28 key references including 1 systematic review and meta-analysis article.

Discussion

Prognostic significance of intra-parotid LNM in PGC

Intra-parotid LNM has been proven to be an independent predictor of worse prognosis in patients with primary PGC in multiple studies (8-17). In a recent meta-analysis, the average hazard ratio for tumor recurrence in PGC patients with intra-parotid LNM, as compared to those without LNM, was 2.67, with a standard deviation of 0.58 (range, 2.22–3.64) (7). Meanwhile, the average hazard ratio for the risk of death was 2.14 [standard deviation, 0.55 (range, 1.85–2.97)] in PGC patients with intra-parotid LNM (7). Several retrospective studies have also suggested that the location and number of intra-parotid LNMs are also significant determinants of prognosis (9,13,15).

Shang et al. indicated that intra-parotid LNM markedly decreases recurrence-free survival, particularly when considering LNMs involved in the deep lobe of the parotid gland (13). The risk of recurrence may be further increased if more than two LNs are involved, with the reported 5-year recurrence-free survival rate dropping to 11–22% in PGC with intra-parotid LNM (7,9). Another study reported that the presence of intra-parotid LNMs could increase the risk of distant metastasis in PGC patients, with the impact mainly depending on the number of intra-parotid LNMs (15). Although multiple studies have suggested the prognostic significance of intra-parotid LNMs in primary PGC, the current tumor-node-metastasis (TNM) staging system (from the American Joint Committee on Cancer TNM staging manual, eighth edition) does not yet incorporate the status of intra-parotid LNM under nodal staging (N classification) (18).

Incidence of intra-parotid LNM in PGC

In primary PGC, the rate of intra-parotid LNM varies significantly across reports. This inconsistency is likely due to the retrospective nature of most studies and notable differences in patient clinicopathologic factors among different cohorts. In a recent meta-analysis of 19 studies published between 1992 and 2020, the pooled prevalence of intra-parotid LNM rates in adult PGC patients was reported to be 24.1% (95% confidence interval: 18.0–30.3%) (7). Here, we examined research from the systematic review and additional studies published after 2020 to assess the rate of intra-parotid LNM (6,8,10,12,15,16,19-22); our findings, summarized in Table 2, indicate a range of 11.1–46.7%. In particular, Lombardi and colleagues previously reported results from the largest multicenter study in Europe, revealing that intra-parotid LNM occurred in 22.1% of their 298 patients (21). In contrast, a different study focusing exclusively on high-grade tumors found a metastasis rate of 46.7% (20).

In our analysis of 423 patients, we observed a relatively low intra-parotid LNM rate of 11.1%, which may be attributed to the inclusion of a greater percentage of patients with histologically low-grade tumors (19). When the tumors were stratified into low-grade and high-grade histologic types, the rates of intra-parotid LNM were shown to be 8.0% and 45.4%, respectively (19). In summary, the rate of intra-parotid LNM appears to be significant (>40%) in high-grade PGC. Meanwhile, intra-parotid LNM seems to occur rarely, especially in low-grade PGC. To better understand the prevalence of intra-parotid LNM, future research should include prospective multicenter studies with detailed histopathological examinations.

LN distribution in the normal parotid gland

The parotid gland is a single-compartment secretory gland; however, as the facial nerve (FN) passes through it, it is arbitrarily divided into two parts: the superficial and deep lobes. This distinction is clinically significant for determining the appropriate surgical approach as well as facilitating FN identification and dissection around the parotid tumor. Therefore, earlier studies were conducted to determine the distribution of LNs to the FN plane by performing a thin-cut pathological analysis of cadaver parotid glands (without disease). McKean and colleagues meticulously dissected 20 parotid glands and reported that the average number of LNs was 8.8 (range, 2–22) in the superficial lobe and 0.8 (range, 0–4) in the deep lobe, respectively (23). Of the total 193 LNs, only 16 (<10%) were observed in the deep lobe, with no LNs found in half of the deep lobes.

Another recent study investigating 84 parotid glands showed similar results, with 87.7% of the LNs located in the superficial lobe and no LNs found in 58 of 84 (69%) deep lobes (24). The number of parotid LNs has been reported to change with age. According to a study analyzing 60 parotid glands from 30 patients [16 men and 14 women; mean age, 54±25.3 years (range, 11–89 years)], LNs with reactive germinal centers decreased with age in both parotid lobes (25). Meanwhile, in this study, LNs were detected in 75% of the deep lobes, and the number of nodes varied between 0 and 9 (mean, 2.3). Another cadaver study by Marks revealed that there is about one LN in the deep lobe, suggesting that, in cases of superficial parotidectomy, there is a possibility of leaving about one LN on average (26). Collectively, it is thought that the majority (>80%) of LNs in the parotid glands are located in the superficial lobe, while the deep lobe contains on average one LN (Table 3). However, this trend varies between studies, and individual differences should be taken into consideration.

Surgical pathology in PGC and intra-parotid LNM

To address the detailed distribution of LNs and the pattern of metastasis, it is necessary to specify the precise location of intra-parotid LNM when reporting surgical pathology. There is a need to establish an objective framework for dividing anatomical sub-sites of the parotid glands. Recently, the European Salivary Gland Society (ESGS) proposed a classification system to standardize surgical reporting and facilitate scientific communication (27) that suggests dividing the parotid gland into five levels—I (lateral superior), II (lateral inferior), III (deep inferior), IV (deep superior), and V (accessory)—according to the plane of the FN and the location of the FN main trunk (Figure 1). This classification system is simple and practical for defining the extent of surgery in parotid resection and can be applied to reporting the intra-parotid LNM.

Figure 1 Schematic diagram showing the ESGS level classification of the parotid gland, with the relative volume of the gland (indicated by blue color) and the incidence of parotid LN metastasis per level (indicated by red color). ESGS, European Salivary Gland Society; LN, lymph node; LNM, lymph node metastasis.

Researchers further evaluated the gland volume and weight of each level, as well as the number and distribution of intra-parotid LNs, through cadaveric studies (28,29). Obtained results showed that the relative weight of each parotid level was greatest in level II (lateral and inferior) (40–47%). Levels I and III had similar relative weights, ranging from 20–25% each. Meanwhile, level IV (deep superior) only accounted for 8–10% of the total. Finally, level V (accessory lobe) was confirmed in about half of the parotid glands dissected and represented less than 5% of the total parotid weight when present. Regarding the distribution of intra-parotid LNs, 86.1% were located in the superficial lobe and 13.9% were found in the deep lobe, consistent with previous reports (24). Notably, while the greatest concentration of LNs were found in level II, only 5% of intra-parotid LNs were located in level IV (superior deep lobe). These objective criteria are expected to contribute to further data accumulation on the distribution and patterns of intra-parotid LNM in each PGC pathology type and to help guide the extent of resection.

Sub-sites (or locations) vulnerable to intra-parotid LNM in PGC

Aside from the LN distribution in normal parotid glands, the sub-site distribution of intra-parotid LNM in PGC remains unclear. In head and neck cancer, particularly squamous cell carcinoma, the LN levels of occult metastasis have been extensively investigated (30-32). The extent of prophylactic LN dissection (or radiation) is determined by the potential risk of LNM depending on the risk of cervical LN involvement and the primary sites (33-35), not by the normal distribution of LNs. One thing to note in PGC, unlike in head and neck squamous cell carcinoma, is the wide variety of tumor pathology, revealing different potentials of regional LNM. Unfortunately, only a few studies to date have reported the sub-sites of intra-parotid LNM in PGC according to the tumor pathology or tumor grade.

In their study, Shang et al. reported that, among patients with high-grade mucoepidermoid carcinoma, 15.6% (19/122) had metastasis in the deep lobe LNs, which accounted for 32.2% of all intra-parotid LNMs, and indicated that intra-parotid LNM in the deep lobe could be not an uncommon occurrence (13). Similarly, a German multicenter study analyzed 75 patients with high-grade PGC and found that 49.3% had intra-parotid LNM, with 22.7% (17/75) showing metastasis to the deep lobe LNs (20). These findings suggest that total parotidectomy, including the deep lobe LNs, is advisable in cases of high-grade PGC. However, not enough is known about the exact sub-locations of intra-parotid LNM in PGC.

Our group recently performed detailed pathological evaluations to report the topography of intra-parotid LNM in PGC (19). According to the results, most intra-parotid LNMs were observed in the superficial gland (90.6%) and peri-tumoral areas (in contact with the tumor) (31.3%), while metastasis to the deep parotid LNs was low, at 9.4% (Figure 1). Additionally, when dividing the parotid gland based on the FN, the intra-glandular superficial (lateral) and inferior (below the FN trunk) LNs were the most common site (62.5%) of intra-parotid LNM, followed by the superficial (lateral) and superior LNs (28.1%). These results suggest that, considering surgeons generally proceed with LN dissection when there is a greater than 15–20% risk of LNM (36,37), surgical removal of the total parotid gland (both superficial and deep lobes) may not be necessary to completely eradicate or prevent potential recurrence of intra-parotid LNM. However, only 32 cases (68.1% of the total cases) were available for our sub-site analysis of intra-parotid LNM; thus, the distribution of intra-parotid LNM sub-sites should be confirmed in a larger cohort.

LNs around parotid glands can also be involved from primary PGC and metastatic tumors. These nodes are pre-auricular, post-auricular, sub-occipital, or infra-parotid LNs, and the metastasis to these nodes from PGC may depend on the location, size, and tumor grade of the primary PGC. However, the incidence or clinical significance of peri-parotid LNM from PGC has not been studied thoroughly compared with intra-parotid LNM. Most of the reports about the peri-parotid LNM have come from investigating metastatic tumors in these LN groups. These topics should also be studied in the future.

Extra-nodal extension (ENE) of intra-parotid or cervical LNM

The prognostic role of ENE in primary parotid cancer is still a debatable area, whereas ENE is a well-established prognostic factor in squamous cell carcinomas of other head and neck subsites. Overall, a growing body of research indicates that ENE may not play a significant role as a prognostic factor in salivary gland cancer (21,38-42). Cheraghlou and colleagues analyzed data from the U.S. National Cancer Database, which includes a relatively large number of patients diagnosed with salivary gland cancer, and concluded that positive ENE was associated with worse survival in cases of squamous cell carcinoma of the salivary glands, but not in cases of non-squamous salivary cancers (39). Another study relying on the U.S. National Cancer Database suggested that the presence of ENE appeared to have no impact on survival when accounting for the number of metastatic LNs (38). Its authors concluded that quantitative LN burden, rather than the presence of ENE, is an important determinant of survival in patients with salivary gland cancer (38).

In contrast, some papers have reported that ENE of LNM could be an important prognostic factor in PGC from multivariable analyses of risk factors (41,42). In this kind of analysis, it is essential to consider whether ENE is independent of or dependent on LNM burden in PGC. As for squamous cell carcinomas of the head and neck, the ENE seems to depend on the LNM burden (43). However, this correlation has not been proven clearly in PGC; therefore, it should be pre-checked in any multivariable analyses of risk or prognostic factors in PGC. Therefore, we have yet come to conclusions that the presence of ENE in PGC LNM plays an independent role in risk stratification of PGC because of a lack of adequate evidence. Instead, it may be simply a surrogate marker of LNM burden (the size, number, or extent of LNM) in PGC.

Therapeutic implications

Detailed anatomical and pathological mapping of intra-parotid LNM based on tumor pathology and primary tumor site in PGC is crucial for optimizing treatment strategies. The majority of intra-parotid LNMs in PGC occur in the superficial lobe, with less than 10–20% involving the deep lobe. Developmentally, deep parotid LNs are located along the course of retromandibular vein, which lies deeper than the FN plane, and predominantly in the parotid tail (23,44-48). Therefore, most parotid LNs along the retromandibular vein are included in the level III (deep, inferior LN groups, ESGS classification). If we target the superficial (levels I–II) and deep inferior (level III) parotid glands for some selected PGC (sub-total parotidectomy), we can remove vulnerable LN groups for intra-parotid LNM safely (including retromandibular LN groups), instead of total parotidectomy (levels I–IV). However, the risk of intra-parotid LNM sub-sites and decision of parotidectomy extent should be assessed in individual patients, considering the size, location and tumor grade of the primary. Such approaches will require further prognostic studies to validate oncological safety.

Furthermore, the specific location of intra-parotid LNM may be influenced by the site of the primary tumor in PGC. For instance, primary tumors located in the inferior portion of the parotid gland are less likely to metastasize to the superior deep parotid LNs, potentially due to distinct lymphatic drainage pathways. However, this hypothesis lacks robust anatomical and prognostic validation and warrants further investigation. Although this study primarily focuses on intra-parotid LNs, it is also important to consider selective approaches to cervical LNM. For instance, in PGC, cervical LNM predominantly occurs in level II, making it the primary target for elective neck dissection. In contrast, level I involvement varies: metastasis to level Ia (submental) LNs is infrequently observed, whereas level Ib (submandibular) LNM is more commonly associated with post-vascular or post-glandular LNs (19).

Collectively, by accumulating detailed information on the specific locations of LNMs in PGC, select therapeutic approaches could be implemented for both prophylactic intra-parotid and cervical LN dissection, as well as radiation therapy planning. Furthermore, this knowledge would enable focused surveillance of high-risk areas prone to recurrence or metastasis during post-treatment follow-up.

It could be suggested that the preoperative detection of intra-parotid LNs may enhance diagnostic accuracy and aid in treatment planning. Unfortunately, the imaging accuracy or diagnostic predictability for intra-parotid LNM in PGC has not been clearly established with computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT (46,49). The preoperative diagnosis of intra-parotid LNM in PGC with various imaging modalities appears to be beyond the scope of this review and warrants a future, separate study. Therefore, it is reasonable that targeting intra-parotid LNM (extent of parotidectomy) relies on clinical (surgical) findings and tumor characteristics (location, size, and tumor grade) of the primary PGC.

Conclusions

In summary, we found that the rate of intra-parotid LNM in the parotid deep lobe may not be high enough to justify total parotidectomy in all PGC cases. For high-grade PGC, total or subtotal parotidectomy (skipping level IV) should be considered due to the increased risk of intra-parotid metastasis, which may impact oncologic outcomes. In contrast, the extent of parotidectomy for low-grade PGC should be tailored based on tumor size and location within the parotid gland. Some PGC cases, adopting a more selective approach preserving a portion of the deep parotid gland with a low risk of intra-parotid LNM might be an alternative to total parotidectomy. A limitation of this study is that most of the included studies were retrospective, resulting in a lower level of evidence. Additionally, there is a possibility that some relevant studies were missed during the literature search and selection process. Thus, our suggestion should be validated through future prospective clinical studies with large cohorts to determine the optimal surgical approach based on tumor characteristics and metastatic risk.

Acknowledgments

The authors appreciate Woohyun Cho (Ajou University School of Medicine, Medical Information & Media Center) for the medical illustration of Figure 1.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2024-575/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2024-575/prf

Funding: This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (Ministry of Science and ICT) (Nos. 2023R1A2C1003096 and 2022R1A2C1091133). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2024-575/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Pinkston JA, Cole P. Incidence rates of salivary gland tumors: results from a population-based study. Otolaryngol Head Neck Surg 1999;120:834-40. [Crossref] [PubMed]
2. Stenner M, Klussmann JP. Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved. Eur Arch Otorhinolaryngol 2009;266:333-41. [Crossref] [PubMed]
3. Ellis GL, Auclair PL, Gnepp DR. Surgical Pathology of the Salivary Glands. 2nd ed. Philadelphia: W.B. Saunders; 1991.
4. Ettl T, Gosau M, Brockhoff G, et al. Predictors of cervical lymph node metastasis in salivary gland cancer. Head Neck 2014;36:517-23. [Crossref] [PubMed]
5. Stodulski D, Mikaszewski B, Majewska H, et al. Probability and pattern of occult cervical lymph node metastases in primary parotid carcinoma. Eur Arch Otorhinolaryngol 2017;274:1659-64. [Crossref] [PubMed]
6. Klussmann JP, Ponert T, Mueller RP, et al. Patterns of lymph node spread and its influence on outcome in resectable parotid cancer. Eur J Surg Oncol 2008;34:932-7. [Crossref] [PubMed]
7. Guntinas-Lichius O, Thielker J, Robbins KT, et al. Prognostic role of intraparotid lymph node metastasis in primary parotid cancer: Systematic review. Head Neck 2021;43:997-1008. [Crossref] [PubMed]
8. Lim CM, Gilbert MR, Johnson JT, et al. Clinical significance of intraparotid lymph node metastasis in primary parotid cancer. Head Neck 2014;36:1634-7. [Crossref] [PubMed]
9. Feng Y, Liu F, Cheng G, et al. Significance of intraparotid node metastasis in predicting local control in primary parotid cancer. Laryngoscope 2019;129:2309-12. [Crossref] [PubMed]
10. Nisa L, Salmina C, Dettmer MS, et al. Implications of intraglandular lymph node metastases in primary carcinomas of the parotid gland. Laryngoscope 2015;125:2099-106. [Crossref] [PubMed]
11. Niu X, Fang Q, Liu F. Role of intraparotid node metastasis in mucoepidermoid carcinoma of the parotid gland. BMC Cancer 2019;19:417. [Crossref] [PubMed]
12. Schneider S, Kotowski U, Kadletz L, et al. Intraparotid and cervical lymph nodes metastasis in primary parotid gland carcinoma-impact on clinical outcome. Oral Surg Oral Med Oral Pathol Oral Radiol 2020;129:570-4. [Crossref] [PubMed]
13. Shang X, Fang Q, Liu F, et al. Deep Parotid Lymph Node Metastasis Is Associated With Recurrence in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland. J Oral Maxillofac Surg 2019;77:1505-9. [Crossref] [PubMed]
14. Song Y, He Y, Li H, et al. Intraparotid node metastasis affects the long-term survival of patients with resectable recurrent parotid gland carcinoma. Eur Arch Otorhinolaryngol 2023;280:5547-55. [Crossref] [PubMed]
15. Han X, Wang J, Li Y, et al. Intraparotid lymph node metastasis affects distant metastasis in parotid adenoid cystic carcinoma. Sci Rep 2023;13:11185. [Crossref] [PubMed]
16. Kouka M, Koehler B, Buentzel J, et al. Role of Intraparotid and Neck Lymph Node Metastasis in Primary Parotid Cancer Surgery: A Population-Based Analysis. Cancers (Basel) 2022;14:2822. [Crossref] [PubMed]
17. Seng D, Fang Q, Liu F, et al. Intraparotid Lymph Node Metastasis Decreases Survival in Pediatric Patients With Parotid Cancer. J Oral Maxillofac Surg 2020;78:852.e1-6. [Crossref] [PubMed]
18. Edge SB, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.
19. Choi N, Kang YJ, Cho J, et al. Topography and probability diagram of cervical and intra-parotid lymph node metastasis in parotid gland cancer. Clin Exp Metastasis 2024;41:33-43. [Crossref] [PubMed]
20. Karp EE, Garcia JJ, Chan SA, et al. The role of total parotidectomy in high-grade parotid malignancy: A multisurgeon retrospective review. Am J Otolaryngol 2022;43:103194. [Crossref] [PubMed]
21. Lombardi D, Tomasoni M, Paderno A, et al. The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification. Oral Oncol 2021;112:105076. [Crossref] [PubMed]
22. Li W, Yu W, Cao H, et al. Number of positive lymph nodes is superior to neck stage of the 8th AJCC in predicting prognosis in parotid mucoepidermoid carcinoma. Head Neck 2023;45:2613-8. [Crossref] [PubMed]
23. McKean ME, Lee K, McGregor IA. The distribution of lymph nodes in and around the parotid gland: an anatomical study. Br J Plast Surg 1985;38:1-5. [Crossref] [PubMed]
24. Sönmez Ergün S, Gayretli O, Büyükpınarbaşılı N, et al. Determining the number of intraparotid lymph nodes: postmortem examination. J Craniomaxillofac Surg 2014;42:657-60. [Crossref] [PubMed]
25. Garatea-Crelgo J, Gay-Escoda C, Bermejo B, et al. Morphological study of the parotid lymph nodes. J Craniomaxillofac Surg 1993;21:207-9. [Crossref] [PubMed]
26. Marks NJ. The anatomy of the lymph nodes of the parotid gland. Clin Otolaryngol Allied Sci 1984;9:271-5. [Crossref] [PubMed]
27. Quer M, Guntinas-Lichius O, Marchal F, et al. Classification of parotidectomies: a proposal of the European Salivary Gland Society. Eur Arch Otorhinolaryngol 2016;273:3307-12. [Crossref] [PubMed]
28. Pujol-Olmo A, Mirapeix RM, Sañudo-Tejero JR, et al. Description and relationships of the parotid gland levels proposed by the European Salivary Gland Society staging system: an anatomical study. Surg Radiol Anat 2020;42:1101-7. [Crossref] [PubMed]
29. Sönmez S, Orhan KS, Kara E, et al. Determining the number and distribution of intraparotid lymph nodes according to parotidectomy classification of European Salivary Gland Society: Cadaveric study. Head Neck 2020;42:3685-92. [Crossref] [PubMed]
30. Mücke T, Mitchell DA, Wagenpfeil S, et al. Incidence and outcome for patients with occult lymph node involvement in T1 and T2 oral squamous cell carcinoma: a prospective study. BMC Cancer 2014;14:346. [Crossref] [PubMed]
31. Sanabria A, Shah JP, Medina JE, et al. Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review. Cancers (Basel) 2020;12:1059. [Crossref] [PubMed]
32. Zhang Y, Su X, Qiao Y, et al. Occult lymph node metastasis in the contralateral neck of oropharyngeal squamous cell carcinoma: a meta-analysis and literature review. Eur Arch Otorhinolaryngol 2022;279:2157-66. [Crossref] [PubMed]
33. Finegersh A, Moss WJ, Saddawi-Konefka R, et al. Meta-analysis of risk of occult lymph node metastasis in the irradiated, clinically N0 neck. Head Neck 2020;42:2355-63. [Crossref] [PubMed]
34. Kaya S, Yilmaz T, Gürsel B, et al. The value of elective neck dissection in treatment of cancer of the tongue. Am J Otolaryngol 2001;22:59-64. [Crossref] [PubMed]
35. Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg 1994;120:699-702. [Crossref] [PubMed]
36. D'Cruz AK, Vaish R, Kapre N, et al. Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer. N Engl J Med 2015;373:521-9. [Crossref] [PubMed]
37. Chen TM, Terng SD, Lee LY, et al. Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system? Cancer Med 2024;13:e6894.
38. Aro K, Ho AS, Luu M, et al. Development of a novel salivary gland cancer lymph node staging system. Cancer 2018;124:3171-80. [Crossref] [PubMed]
39. Cheraghlou S, Yu PK, Otremba MD, et al. Extracapsular extension is not a significant prognostic indicator in non-squamous cancers of the major salivary glands. Cancers Head Neck 2018;3:5. [Crossref] [PubMed]
40. Hsieh CE, Hung CY, Lin CY, et al. High metastatic node number, not extranodal extension, as a node-related prognosticator in surgically treated patients with nodal metastatic salivary gland carcinoma. Head Neck 2019;41:1572-82. [Crossref] [PubMed]
41. Lee H, Roh JL, Cho KJ, et al. Positive lymph node number and extranodal extension for predicting recurrence and survival in patients with salivary gland cancer. Head Neck 2020;42:1994-2001. [Crossref] [PubMed]
42. Wang L, Shi W. Metastatic lymph node burden impacts overall survival in submandibular gland cancer. Front Oncol 2023;13:1229493. [Crossref] [PubMed]
43. Kang YJ, Park G, Park SY, et al. Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis. Cancers (Basel) 2024;16:659. [Crossref] [PubMed]
44. Guo CB, Feng Z, Zhang JG, et al. Supraomohyoid neck dissection and modified radical neck dissection for clinically node-negative oral squamous cell carcinoma: a prospective study of prognosis, complications and quality of life. J Craniomaxillofac Surg 2014;42:1885-90. [Crossref] [PubMed]
45. Lee YY, Wong KT, King AD, et al. Imaging of salivary gland tumours. Eur J Radiol 2008;66:419-36. [Crossref] [PubMed]
46. Kashiwagi N, Murakami T, Toguchi M, et al. Metastases to the parotid nodes: CT and MR imaging findings. Dentomaxillofac Radiol 2016;45:20160201. [Crossref] [PubMed]
47. Batsakis JG. Pathology consultation. Parotid gland and its lymph nodes as metastatic sites. Ann Otol Rhinol Laryngol 1983;92:209-10. [Crossref] [PubMed]
48. Last JM. The measurement of medical care in general practice. Med J Aust 1965;1:280-3. [Crossref] [PubMed]
49. Horii A, Yoshida J, Honjo Y, et al. Pre-operative assessment of metastatic parotid tumors. Auris Nasus Larynx 1998;25:277-83. [Crossref] [PubMed]