Skip to main content

Role of intraparotid node metastasis in mucoepidermoid carcinoma of the parotid gland



Prognostic factors for parotid mucoepidermoid carcinoma (MEC) usually include disease grade, tumor stage, node stage, perineural invasion, and lymphovascular invasion. But the role of intraparotid nodes (IPNs) remains unclear, therefore, the study aimed to analyze the significance of IPNs in predicting recurrence in parotid MEC.


One hundred and ninety patients were included for analysis finally. Data regarding demography, pathological characteristics, IPN metastasis, TNM stage, follow up was collected and evaluated. The recurrence-free survival (RFS) was the main study endpoint.


A total of 47 (24.7%) patients had IPN metastasis, and the IPN metastasis was significantly related to tumor stage, pathologic N stage, lymph-vascular invasion, perineural invasion, and disease grade. Recurrence occurred in 34 (17.9%) patients. For patients without IPN metastasis, the 10-year RFS rate was 88%, for patients with IPN metastasis, the 10-year RFS rate was 54%, the difference was significant (p < 0.001). Further Cox model analysis confirmed the independence of IPN metastasis in predicting the prognosis.


The IPN metastasis is relatively common in parotid MEC, it is significantly related to tumor stage and disease grade, IPN metastasis means worse recurrence-free survival.

Peer Review reports


Parotid gland cancer is an uncommon neoplasm [1], but according to their architectural and cytological features, there were 24 types of malignant tumors classified by The World Health Organization [2, 3], mucoepidermoid carcinoma (MEC) is the most common pathologic subtype, some clinic-pathologic variables, including histologic grade, lymphovascular and perineural invasion as well as tumor stage, have been well described to be associated with the prognosis in parotid MEC [4,5,6].

Because of the exceptional growth process, there are intraparotid nodes (IPNs) in the parotid gland [7], its prognostic value remains unclear [8,9,10,11]. The IPNs are classified into superficial and deep lobe nodes [12], therefore the IPNs are significantly affected by different surgical procedures, compared to total parotidectomy, lateral or superficial parotidectomy has a lower probability to find all relevant IPNs, but in the above-mentioned researches [8,9,10,11], a certain number of procedures of lateral or superficial parotidectomy are included, therefore the exact IPN metastasis rate as well as its survival impact in patients with MEC remains unclear.

Therefore, the current study aimed to evaluate the IPN metastasis rate and the significance of IPN metastasis in predicting recurrence in parotid MEC.


Our study was approved by the Zhengzhou University institutional research committee, and an informed consent agreement for medical research before initial treatment was achieved for all participants, and all experiments were performed in accordance with the Declaration of Helsinki.

Patients undergoing surgical treatment for primary parotid MEC during January 2001 and December 2017 were retrospectively tracked. Data regarding demography, pathological characteristics, TNM stage, IPN metastasis, and follow-up information was collected and assessed. The tumor stage and tumor grade were formulated based on the AJCC8th classification and the WHO 2017 classification, respectively. Ultrasound and CT or MRI examination was conducted for every patient, and total parotidectomy was conducted when malignant epithelial disease was supported by frozen section of the primary tumor.

The relationship between the clinical-pathologic variables and the IPN metastasis was assessed by the Chi-square test. The main study endpoint was the recurrence-free survival (RFS), and it was calculated by the Kaplan-Meier method (Log-rank test), the Cox proportional hazards method was used to analyze the factors which were significant in the univariable analysis to determine the independent risk factors for the RFS. All statistical analyses were performed by SPSS 20.0, and a p < 0.05 was considered to be significant.


One hundred and ninety patients (101 female and 89 male) were included for analysis, the mean age was 48.7 years with a range from 18 to 85. Pathologic tumor stages of T1, T2, T3, and T4 presented in 27, 95, 45, and 23 cases, respectively. Neck metastatic node disease was found in 41 cases of the 62 patients undergoing a neck dissection. Negative (R0) and positive margin (R1/2) was achieved in 181 and 9 patients, respectively. Perineural and lymphovascular invasion was noted in 23 and 22 patients, respectively. Low grade MEC reported in 104 cases, intermediate grade in 62 cases, and high grade in 24 cases, .

A total of 47 (24.7%) patients had IPN metastasis. As described in Table 1, pathologic N stage, tumor stage, perineural invasion, lymph-vascular invasion, and disease grade were significantly related to the IPN metastasis (all p < 0.05).

Table 1 Association between intraparotid node metastasis and clinical-pathologic variables

After a mean time of 71.1 months follow-up, adjuvant radiotherapy was performed in 65 patients, and recurrence occurred in 34 patients: 17 patients had local recurrence, 10 patients had neck recurrence, and 7 patients had both local and regional recurrence. The overall 10-year RFS rate was 79%. In univariable analysis, tumor stage, IPN metastasis, perineural invasion, and lymphovascular invasion as well as disease grade were significantly associated with the recurrence (Table 2, all p < 0.05). The 10-year RFS rate was 54% for patients with IPN metastasis, and 88% for patients without IPN metastasis, the difference was significant (p < 0.001) (Fig. 1). In Cox model analysis, IPN metastasis, lymphovascular invasion, and disease grade were independent prognostic factors for the RFS (Table 3, all p < 0.05).

Table 2 Univariate analysis for recurrence in patients with primary parotid cancer
Fig. 1
figure 1

Recurrence-free survival rate in patients with or without intraparotid node metastasis (p < 0.001)

Table 3 Cox model for recurrence in patients with primary parotid cancers


Literature regarding the prognostic value of IPN metastasis was very few [8,9,10,11, 13,14,15,16]. Previous authors had reported the IPN metastasis rate ranged from 15 to 38%, and the IPN metastasis was significantly related to TNM stage and disease grade [8,9,10,11, 13,14,15,16,17,18], the finding was consistent with ours.

The IPN metastasis might affect the prognosis by two aspects. Firstly, lymph nodes existed in both lobes of the parotid gland, undiagnosed metastatic IPNs might be caused by non-total parotidectomy, and then recurrent disease might be expected owing to the residual disease. Therefore, total parotidectomy was suggested for all parotid cancer patients by previous authors [15]. The high 10-year RFS rate in current study came into our attention, it was better than previous researches [8, 11], the favorable outcome might be partially explained by our routine total parotidectomy. Another potential explanation was that high grade disease only accounted for less than 15% in our sample, and previous authors had described the disease grade was an important prognostic factor in parotid cancers [17].

Secondly, owing to the lymphatic system in head and neck area, the IPN might acted as sentinel role for finding early neck metastasis. Although Klussmann et al. [8] described pathologic neck metastasis was detected in only 33.3% of the patients with positive IPNs, both Lim et al. [12] and Nisa et al. [13] reported there was relatively high reliability of IPN metastasis in predicting neck metastasis. The viewpoint was also supported by our finding.

Risk factors for recurrence in parotid cancers had been frequently analyzed. Reported predictors included higher TNM stage, perineural invasion, lymphovascular invasion, high disease grade [13,14,15,16,17,18,19,20,21,22]. But the value of IPN metastasis remained unclear. Lim et al. [10] reported locoregional recurrence was more likely to occur in patients with cN0 neck but IPN metastasis than patients without IPN metastasis. Klussmann et al. [8] presented there was additional risk associated with the IPN involvement for tumor recurrence. Nisa et al. [11] described patients with IPN metastasis had poorer disease control. However, the three studies were limited to small sample size, and also a considerable number of patients had not undergone total parotidectomy, there might be undiagnosed IPNs. In current study, all patients underwent an total parotidectomy, it made our result more accurate, our results presented IPN metastasis was related to worse disease control, all the findings revealed that IPN metastasis carried higher risk of recurrence [23].

Association between adjuvant radiotherapy and survival benefit had been widely evaluated. In a large National Cancer Database study, Safdieh et al. [24] reported adjuvant radiotherapy improved overall survival in 4068 patients with salivary gland cancer. Similar finding was also described by Lee et al. [25]. But in current study, we failed to note there is positive relationship between radiotherapy and improved RFS. In another paper by Erovic et al. [26], the authors also presented that adjuvant radiotherapy did not significantly increase disease control in parotid cancers. More studies were required to assess the role of radiotherapy on predicting the survival in parotid cancers.


In summary, the overall IPN metastasis rate in parotid MEC was 24.7%, it was significantly affected by tumor stage and disease grade. Moreover, the IPN metastasis was independently related to two-fold risk for recurrence, more adjuvant intervention was needed if there was IPN metastasis.



intraparotid node


mucoepidermoid carcinoma


recurrence-free survival


  1. Terhaard CH, Lubsen H, Van der Tweel I. Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group. Head Neck. 2004;26:681–92.

    Article  PubMed  Google Scholar 

  2. Barnes LEJRP, Sidransky D. World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. IARC. IARC: Lyon; 2005.

    Google Scholar 

  3. Barnes LEJ, Reichart P, Sidransky D. World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. IARC. IARC: Lyon; 2005.

    Google Scholar 

  4. Szewczyk M, Golusiński P, Pazdrowski J, Pieńkowski P, Marszałek S, Sygut J, Golusiński W. Patterns of treatment failure in salivary gland cancers. Rep Pract Oncol Radiother. 2018;23:260–5.

    Article  PubMed  Google Scholar 

  5. Nisa L, Borner U, Dür C, Arnold A, Giger R. Recurrent parotid gland carcinoma: how effective is salvage surgery? Eur Arch Otorhinolaryngol. 2018;275:507–13。.

    Article  PubMed  Google Scholar 

  6. Scherl C, Kato MG, Erkul E, Graboyes EM, Nguyen SA, Chi AC, Morgan PF, Day TA. Outcomes and prognostic factors for parotid acinic cell carcinoma: a National Cancer Database study of 2362 cases. Oral Oncol. 2018;82:53–60.

    Article  PubMed  Google Scholar 

  7. Pisani P, Ramponi A, Pia F. The deep parotid lymph nodes: an anatomical and oncological study. J Laryngol Otol. 1996;110:148–50.

    Article  CAS  PubMed  Google Scholar 

  8. Klussmann JP, Ponert T, Mueller RP, Dienes HP, Guntinas-Lichius O. Patterns of lymph node spread and its influence on outcome in resectable parotid cancer. Eur J Surg Oncol. 2008;34:932–7.

    Article  CAS  PubMed  Google Scholar 

  9. Lau VH, Aouad R, Farwell DG, Donald PJ, Chen AM. Patterns of nodal involvement for clinically N0 salivary gland carcinoma: refining the role of elective neck irradiation. Head Neck. 2014;36:1435–9.

    Article  PubMed  Google Scholar 

  10. Lim CM, Gilbert MR, Johnson JT, Kim S. Clinical significance of intraparotid lymph node metastasis in primary parotid cancer. Head Neck. 2014;36:1634–7.

    Article  PubMed  Google Scholar 

  11. Nisa L, Salmina C, Dettmer MS, Arnold A, Aebersold DM, Borner U, Giger R. Implications of intraglandular lymph node metastases in primary carcinomas of the parotid gland. Laryngoscope. 2015;125:2099–106.

    Article  PubMed  Google Scholar 

  12. Sönmez Ergün S, Gayretli O, Büyükpınarbaşılı N, Yıldız K, Gürses IA, Avşar A, Cavlak M. Determining the number of intraparotid lymph nodes: postmortem examination. J Craniomaxillofac Surg. 2014;42:657–60.

    Article  PubMed  Google Scholar 

  13. Lima RA, Tavares MR, Dias FL, Kligerman J, Nascimento MF, Barbosa MM, Cernea CR, Soares JR, Santos IC, Salviano S. Clinical prognostic factors in malignant parotid gland tumors. Otolaryngol Head Neck Surg. 2005;133:702–8.

    Article  PubMed  Google Scholar 

  14. Shinomiya H, Otsuki N, Yamashita D, Nibu K. Patterns of lymph node metastasis of parotid cancer. Auris Nasus Larynx. 2016;43:446–50.

    Article  PubMed  Google Scholar 

  15. Stenner M, Molls C, Luers JC, Beutner D, Klussmann JP, Huettenbrink KB. Occurrence of lymph node metastasis in early-stage parotid gland cancer. Eur Arch Otorhinolaryngol. 2012;269:643–8.

    Article  PubMed  Google Scholar 

  16. Stodulski D, Mikaszewski B, Majewska H, Wiśniewski P, Stankiewicz C. Probability and pattern of occult cervical lymph node metastases in primary parotid carcinoma. Eur Arch Otorhinolaryngol. 2017;274:1659–64.

    Article  PubMed  Google Scholar 

  17. Rajasekaran K, Stubbs V, Chen J, Yalamanchi P, Cannady S, Brant J, Newman J. Mucoepidermoid carcinoma of the parotid gland: a National Cancer Database study. Am J Otolaryngol. 2018;39:321–6.

    Article  PubMed  Google Scholar 

  18. Armstrong JG, Harrison LB, Thaler HT. The indications for elective treatment of the neck in cancer of the major salivary glands. Cancer. 1992;69:615–9.

    Article  CAS  PubMed  Google Scholar 

  19. Shi S, Fang Q, Liu F, Zhong M, Sun C. Prognostic factors and survival rates for parotid duct carcinoma patients. J Craniomaxillofac Surg. 2014;42:1929–31.

    Article  PubMed  Google Scholar 

  20. Zbären P, Schüpbach J, Nuyens M, Stauffer E, Greiner R, Häusler R. Carcinoma of the parotid gland. Am J Surg. 2003;186:57–62.

    Article  PubMed  Google Scholar 

  21. Niu X. Sarcomatoid carcinoma in the parotid gland: a review of 30 years of experience. Laryngoscope. 2018 [Epub ahead of print.

    Article  PubMed  Google Scholar 

  22. Fang Q, Liu F, Seng D. Oncologic outcome of parotid mucoepidermoid carcinoma in pediatric patients. Cancer Manag Res. 2019;11:1081–5.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Feng Y, Liu F, Cheng G, Fang Q, Niu X, He W. Significance of intraparotid node metastasis in predicting local control in primary parotid cancer. Laryngoscope. 2018.

  24. Safdieh J, Givi B, Osborn V, Lederman A, Schwartz D, Schreiber D. Impact of adjuvant radiotherapy for malignant salivary gland tumors. Otolaryngol Head Neck Surg. 2017;157:988–94.

    Article  PubMed  Google Scholar 

  25. Lee A, Givi B, Osborn VW, Schwartz D, Schreiber D. Patterns of care and survival of adjuvant radiation for major salivary adenoid cystic carcinoma. Laryngoscope. 2017;127:2057–62.

    Article  CAS  PubMed  Google Scholar 

  26. Erovic BM, Shah MD, Bruch G, Johnston M, Kim J, O'Sullivan B, Perez-Ordonez B, Weinreb I, Atenafu EG, de Almeida JR, Gullane PJ, Brown D, Gilbert RW, Irish JC, Goldstein DP. Outcome analysis of 215 patients with parotid gland tumors: a retrospective cohort analysis. J Otolaryngol Head Neck Surg. 2015;44:55.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


None declared.


This study was not funded by any outside source.

Availability of data and materials

All data generated or analyzed during this study are included in this published article. And the primary data could be achieved from the corresponding author.

Author information

Authors and Affiliations



Study design and manuscript writing: N-XY. Studies selecting and data analysis: N-XY, LF and F-QG. Study quality evaluating: N-XY and F-QG. Manuscript revising: N-XY. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Xingyu Niu.

Ethics declarations

Ethics approval and consent to participate

Our study was approved by the Zhengzhou University institutional research committee, and an informed consent agreement for medical research before initial treatment was achieved for all participants, and all experiments were performed in accordance with the Declaration of Helsinki.

Consent for publication

All the material came from our cancer center, and the publish consent have been obtained from all the patients.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Niu, X., Fang, Q. & Liu, F. Role of intraparotid node metastasis in mucoepidermoid carcinoma of the parotid gland. BMC Cancer 19, 417 (2019).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: