Isolated Perifacial Lymph Node Metastasis in Oral Squamous Cell Carcinoma With Clinically Node-Negative Neck

The Laryngoscope VC 2016 The American Laryngological, Rhinological and Otological Society, Inc. Isolated Perifacial Lymph Node Metastasis in Oral Squamous Cell Carcinoma With Clinically Node-Negative Neck Sangeet Kumar Agarwal, DNB; Sowrabh Kumar Arora, DNB; Gopal Kumar, MS; Deepak Sarin, MS Objectives/Hypothesis: The incidence of occult perifacial nodal disease in oral cavity squamous cell carcinoma is not well reported. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. The study will shed light on current controversies and will provide valuable clinical and pathological information in the practice of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. Study Design: Prospective analysis. Methods: This study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of the metastatic rate to different lymph node levels in 231 patients of oral squamous cell cancer with a clinically node-negative neck. Results: The current study demonstrated that 19 (8.22%) out of 231 patients showed ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial nodes did not differ significantly between the oral tongue (7.14%) and buccal mucosa (7.75%). Incidence was statistically significant in cases with lower age group (<45 years), advanced T stage, and higher depth of tumor invasion. Conclusions: Isolated perifacial node metastasis is high in oral squamous cell carcinoma with a clinically node-negative neck. The incidence of isolated perifacial involvement is high in cases of buccal mucosal and tongue cancers. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. Key Words: Perifacial nodes, selective neck dissection, node-negative neck, oral squamous cell carcinoma. Level of Evidence: 4 Laryngoscope, 126:2252 2256, 2016 From the Department of Head and Neck Oncosurgery, Medanta Cancer Institute, Medanta The Medicity, Gurgaon, India. Editor s Note: This Manuscript was accepted for publication February 8, 2016. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Sangeet Kumar Agarwal, DNB, 100/10, Third Floor, Gautam Nagar, New Delhi, India 110049. E-mail: drsangeetagarwal@gmail.com DOI: 10.1002/lary.25954 2252 INTRODUCTION Squamous cell carcinoma is the most common malignancy of the oral cavity. The incidence varies worldwide, with India and Southeast Asia showing the highest rates. The global incidence is estimated to be 275,000 new cases per year. 1 The most significant prognostic factor in the treatment of patients with oral squamous cell carcinoma is cervical lymph node status. 2 Even a single lymph node metastasis may diminish survival by approximately 50%. 3,4 Lymph node positivity significantly changes the decision of adjuvant therapy. Therefore, meticulous clearance of cervical lymph nodes is a crucial part of treatment in these patients. It has been proven that elective neck dissection has better results than therapeutic neck dissection in the clinically node-negative neck. 5 Selective neck dissection, whether supraomohyoid (level I III) or extended supraomohyoid (level I IV), is the surgery of choice to address the clinically node-negative neck in oral squamous cell carcinomas. 6 Selective neck dissections are also associated with some morbidity. One of them is postoperative facial nerve dysfunction, which may result in ipsilateral lower lip weakness, and it may be due to handling of the marginal mandibular nerve during the complete removal of perifacial nodal pads near the anterior facial vein. The perifacial or perivascular lymph node is one of the subunits of the submandibular lymph node (level IB). These lymph nodes are composed of five groups: preglandular, prevascular, retrovascular, retroglandular, and intracapsular submandibular lymph nodes as described by Rouviere and Tobies. 7 The prevascular node is defined in relation to the anterior facial vein, and is usually singular and lies anterior to the anterior facial vein on top of the facial artery. Retrovascular nodes are posterior to the anterior facial vein. Of these nodal groups, the prevascular and retrovascular are known as the perifacial lymph node group. These perifacial lymph nodes may be the major metastatic reservoir in oral squamous cell carcinoma. 8 Incidence of isolated perifacial nodes in clinically node-negative necks is largely undocumented. Most of the surgeons routinely remove these nodal pads, but postoperative facial nerve dysfunction may occur as a result of ischemic injury to the nerve or even gross preservation of it during dissection. One of the issues not clearly settled in the literature is whether meticulous clearance of these nodes is needed for cancer of all the subsites of the oral cavity.

Isolated positivity of this group of nodal pads in clinically node-negative necks is still a contentious issue, and unfortunately there is no significant study in this area. Therefore, there is urgent need for further study to resolve this important issue in node-negative patients with oral squamous cell carcinoma. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. This study will boost the current concepts and provide useful information regarding the necessity of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. MATERIALS AND METHODS This prospective study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of metastatic rate to different lymph node levels in patients of oral squamous cell carcinoma and a clinically node-negative neck. The medical records of 231 patients who had undergone the surgery (excision of primary tumor with selective neck dissection and reconstruction) from August 2011 to July 2015, in the Department of Head and Neck Oncology Surgery, Medanta Hospital, were analyzed. The key eligibility criteria were patients between the ages of 22 and 82 years (mean age, 62.4 years), with histopathologically proven oral squamous cell carcinoma and a clinically and radiologically node-negative neck (N0), who were scheduled for surgery as the primary treatment. All of the patients underwent selective neck dissection simultaneously with the excision of the primary tumor. Preoperative clinical staging of the primary tumor and neck staging was done by complete clinical and radiological examination, which included physical examination, pan endoscopic examination, and radiological examination by contrastenhanced computed tomography, magnetic resonance imaging, or positron emission tomography scan. Ultrasound was only used when one of the above investigations was contraindicated. All patients were staged according to latest (7th edition) American Joint Committee on Cancer classification. We excluded patients with recurrent tumors, those having received neoadjuvant therapy, and patients with a prior history of any neck surgery. Fig. 1. Intraoperative neck dissection, with the longest arrow showing perifacial nodal pads, the midlength arrow showing the ligated anterior facial vein, and the shortest arrow showing the marginal mandibular nerve. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.] fashion from level IA to level IV. After completing the neck dissection, we routinely separated the levels from the main neck specimen along with the clipped perifacial nodal pads and sent them to the histopathology department for analysis. After final pathological reporting, we analyzed the report and entered the data into an Excel spreadsheet (Microsoft Corp., Redmond, WA). Surgical Technique and Lymph Node Sampling Neck dissection was done along general principles for the operation. In level IB, the flap was elevated in the subplatysmal plane. The fascia over the submandibular gland was not elevated with the skin flap nor was the facial vein ligated during the process of flap elevation. The marginal mandibular nerve was then identified, and its branches were skeletonized and then elevated off the level IB contents. This was done to prevent any fatcontaining nodes getting accidently elevated along with skin flaps or the nerve. All of the fat was then separated from the inferior border of the mandible and dropped down. The facial vessels were ligated over the mandible after elevation off a deeper branch of the facial nerve running on their surface. This allowed the entire fat pad lying between the submandibular gland and the mandible to be included in the level IB dissection. We clipped the area anterior and posterior to the gland for identification as perifacial nodal pads (anatomical landmarks taken for perifacial nodes was according to Rouvier and Tobies 7 classification) (Fig. 1). After completion of the neck dissection, the clipped area that was identified as the perifacial nodal pad was separated from level IB contents. Then, routine neck dissection was done in the standard Statistical Analysis The data collected were analyzed using SPSS version 14.0 (IBM Corp., Armonk, NY) for the quantitative variables where mean and standard deviation were calculated. The Student t test was used to test the statistical significance. P value <.05 was considered significant. RESULTS This prospective study included a total of 231 patients with oral squamous cell carcinoma and a clinically nodenegative neck. All of the patients underwent an elective selective neck dissection. We performed an extended supraomohyoid neck dissection (from level I IV) in each case. Out of 231 patients, 190 (82.25%) were male and 41 (17.74%) were female, whose ages ranged from 22 to 82 years, with a mean age of 62.4 years. The distribution of primary cancer subsites is shown in Table I. Notably, the majority of the patients had primary tumors in the buccal mucosa (50.21%) and oral tongue (36.36%). 2253

TABLE I. Isolated Perifacial Node Involvement Versus Neck Node Involvement Ratio According to Various Subsites. No. Subsite No. of Cases PF Node Metastasis Cases With Overall Lymph Node Metastasis P Value 1 Upper lip 1 0 (0%) 0 (0%) 2 Lower lip 2 1 (50%) 1 (50%).317 3 Upper alveolus 12 1 (8.33%) 3 (25.5%).855 4 Lower alveolus 15 2 (13.33%) 5 (33.33%).627 5 Oral tongue 84 6 (7.14%) 29 (34.52%).436 6 Floor of mouth 1 0 (0%) 0 (0%) 7 Buccal mucosa 116 9 (7.75%) 32 (27.58%).898 Total 231 19 (8.22%) 70 (30.30%) Not significant, P >.05. PF 5 perifacial node. Isolated Perifacial Lymph Node Involvement and Primary Subsites Histopathological analysis revealed 19 (8.22%) out of 231 patients with ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial node did not differ significantly between the two most common subsites, the oral tongue (7.14%) and buccal mucosa (7.75%). Distribution of primary cancer subsites and incidence rate of isolated perifacial nodes with primary cancer subsites is given in Table I. Relationship Between Perifacial Lymph Node Involvement and Various Clinicopathological Factors The incidence of isolated perifacial lymph node metastasis was statistically significant in cases with advance TABLE II. Relationship Between the Isolated Perifacial Lymph Node Involvement and Several Various Clinicopathological Factors. No. Variables No. of Cases PF Node Metastasis % P Value 1 Age, yr 0.031 (significant)* <45 61 9 14.75 >45 170 10 5.88 2 Sex Male 190 16 8.42 1.000 Female 41 3 7.31 NS 3 Pathologic T stage T1 106 6 5.66 T1 vs. T2 5.539 T2 89 7 7.86 T1 vs. T3 and T4 5.040* T3 and T4 36 6 16.66 T2 vs. T3 and T4 5.144 4 Pathologic N stage N1 vs. N2A 5.289 N0 161 0 0 N1 59 18 30.50 N2A 8 1 12.5 N2B 3 0 0 5 Histological grade WDSCC 1 MDSCC 226 18 7.96.333 PDSCC 5 1 20 NS 6 Perineural invasion Positive 101 12 11.88.075 Negative 130 7 5.38 NS 7 Tumor depth <.001 (highly significant) <5 mm 151 4 2.64 >5 mm 80 15 18.75 MDSCC 5 moderately differentiated squamous cell carcinoma; NS 5 not significant; PDSCC 5 poorly differentiated squamous cell carcinoma; PF 5 perifacial node; WDSCC 5 well-differentiated squamous cell carcinoma. 2254

TABLE III. Comparison Between the Incidences of Isolated Perifacial Node Involvement Versus Overall Neck Node Involvement According to Various Clinicopathological Factors. No. Variables No. of Cases PF Node Metastasis Cases With Overall Lymph Node Metastasis P Value 1 Age, yr <45 61 9 (14.75%) 19 (31.14%).092 >45 170 10 (5.88%) 51 (30%) NS 2 Sex Male 190 16 (8.42%) 56 (29.47%) 1.000 Female 41 3 (7.31%) 14 (34.14%) NS 3 Pathologic T stage T1 106 6 (5.66%) 20 (18.86%).798 T2 89 7 (7.86%) 32 (35.95%).489 T3 and T4 36 6 (16.66%) 18 (50%).609 4 Pathologic N stage NS N0 0 (0%) 161 (69.69%) N1 231 18 (7.7%) 59 (25.54%) N2A 1 (0.4%) 8 (3.46%) N2B 0 (0%) 3 (1.29%) 5 Perineural invasion Positive 101 12 (11.88%) 40 (39.60%).637 Negative 130 7 (5.38%) 30 (23.07%) NS 6 Tumor depth <5 mm 151 4 (2.64%) 25 (16.55%).279 >5 mm 80 15 (18.75%) 45 (56.25%) NS Not significant, P >.05. NS 5 not significant; PF 5 perifacial node. T stage (T3 and T4), patients with a higher depth of tumor invasion, and patients in a lower age group (<45 years). The relationship between the isolated perifacial lymph node involvement and several various clinicopathological factors are shown in Table II. Isolated Perifacial Node Involvement Versus Neck Node Involvement Ratio Correlation between the incidence of isolated perifacial lymph node and overall nodal positivity was found to be statistically insignificant; however, overall incidence of isolated perifacial nodal positivity (8.22%) is very high, as summarized in Tables I and III. Analysis of Overall Lymph Node Metastases Seventy (30.30%) out of 231 cases had microscopic metastatic lymphadenopathy. Lymph node metastases from oral cancers were seen predominantly at lymph node levels including perifacial, IB, and IIA. The patterns of lymph nodes from different subsites within the oral cavity are shown in Table IV. DISCUSSION It is now well established that for oral squamous cell carcinoma with a clinically node-negative neck, elective neck dissection is an integral part of surgical treatment. 5 An elective neck dissection accurately stages the neck, provides important prognostic information, and has therapeutic impact and guides adjuvant therapy. Selective neck dissections are also associated with some distressing complications. One of them is weakness or complete paralysis of the ipsilateral lower lip due to accidental injury to the marginal mandibular nerve. Even gross preservation of the marginal mandibular nerve can lead to some degree of postoperative facial nerve dysfunction. Retraction during the clearance of perifacial lymph nodes may sever the nerve and/or cause ischemia, although the marginal mandibular nerve is only minimally dissected. Seppalainen et al. 9 showed that in patients undergoing neck dissection, who were considered to have no gross surgical damage, 23% of patients were found to have damage as demonstrated by electromyography. Forty percent of patients with a possible distension of the marginal mandibular nerve experienced a slight loss of motor units. Because of this risk, surgeons prefer not to dissect extensively in this region when they judge the risk of nodal metastasis to the perifacial nodes to be low. Unfortunately, there are very few studies on this topic, 8,10,11 but all of these studies had less sample size, and none of them looked into isolated perifacial lymph node metastasis in oral squamous cell carcinoma in node-negative necks. Lim et al., in 2006, revealed that the incidence rate of metastasis to the perifacial lymph node was 35% in oral cavity squamous cell carcinoma and 8% in oropharyngeal squamous cell carcinoma, but this study included clinically node-positive necks and cases with oropharyngeal squamous cell carcinoma. Another study by Di Nardo et al., 8 in 2255

TABLE IV. Patterns of Overall Lymph Node Metastases Incidence of Metastasis in Lymph Node Levels No. Subsite No. of Cases IA IB IIA IIB III IV PF 1 Upper lip 1 (0.43%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 2 Lower lip 2 (0.86%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (50%) 3 Upper alveolus 11 (4.70%) 0 (0%) 1 (9.09%) 1 (9.09%) 0 (0%) 0 (0%) 0 (0%) 2 (18.18%) 4 Lower alveolus 16 (6.92%) 0 (0%) 2 (12.50%) 2 (12.50%) 0 (0%) 0 (0%) 0 (0%) 3 (18.75%) 5 Oral tongue 84 (36.36%) 0 (0%) 16 (19.04%) 9 (10.71%) 0 (0%) 1 (1.10%) 0 (0%) 11 (13.09%) 6 Floor of mouth 1 (0.43%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 7 Buccal mucosa 116 (50.21%) 0 (0%) 17 (14.65%) 15 (12.93%) 2 (1.72%) 2 (1.72%) 0 (0%) 15 (12.93%) Total 231 0 (0%) 36 (15.58%) 27 (11.68%) 2 (0.86%) 3 (1.29%) 0 (0%) 32 (13.85%) The level IB column excludes perifacial nodes, which shows the importance of the perifacial nodal group. PF 5 perifacial node. 1998, evaluated the rate of metastasis to perifacial lymph node in patients with floor of mouth squamous cell carcinoma. In this study, 29% of patients manifested pathologic perifacial node involvement. However, it is unclear whether the study population was node positive or node negative. Lim et al., 11 in 2004, conducted a study on patients with tongue and floor of mouth squamous cell carcinoma with a node-negative neck, and concluded that four out of 72 cases with tongue carcinoma and two out of 27 cases with floor of mouth carcinoma had perifacial lymph node positivity. Our study significantly differs, as we analyzed all subsites of oral squamous cell carcinoma including the oral tongue, buccal mucosa, alveolus, and floor of mouth with nodenegative neck to see the isolated perifacial nodal positivity in each subsite. We found 19 out of 231 (8.22%) cases with isolated perifacial nodal metastasis (distribution according to subsites shown in Table I). Furthermore, we correlated the isolated perifacial node positivity with clinicopathologic factors, and found a significant association of perineural invasion, advanced T stage, and depth of tumor invasion with isolated perifacial node positivity in node-negative necks (correlation between various clinicopathological factors and isolated perifacial nodal metastasis shown in Table II). Isolated Perifacial Node Involvement Versus Neck Node Involvement Ratio In general, this ratio eliminates the factors that increase the chances of nodal positivity. It reflects more accurately the importance of addressing this station when the neck is being electively treated for suspected microscopic disease. We found this to be high for primaries located in the buccal mucosa (7.75%) and interestingly high in primaries of the tongue as well (7.14%), a fact previously not stressed in the literature or based upon anatomical knowledge regarding neck management in oral tongue cancer. Drawbacks of the Study Our current study did not contain a large number of patients from subsites other than buccal mucosa and tongue to draw meaningful conclusions about isolated perifacial nodal involvement. We did not document the incidence of marginal mandibular nerve paralysis in this study. For some surgeons this may be the deciding factor in a risk-benefit analysis when deciding on clearing the perifacial nodes. However, we feel that the absolute incidence in tongue and buccal mucosa cancers is high enough to justify clearing this area. CONCLUSION Isolated perifacial node metastasis is high in oral squamous cell carcinoma, significantly in the buccal mucosa and tongue subsites with a clinically node-negative neck. The nodal involvement is higher in patients in a lower age group, advanced T stage, and greater depth of tumor invasion. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. BIBLIOGRAPHY 1. 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