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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 28  |  Issue : 1  |  Page : 29-32

Effect of depth of invasion on lymph node metastasis in early stage


Department of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey

Date of Submission23-Jan-2019
Date of Acceptance19-Feb-2019
Date of Web Publication31-Dec-2019

Correspondence Address:
Dr. Burak Kaya
Department of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Ankara University, 06590, Dikimevi, Ankara
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjps.tjps_8_19

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  Abstract 


Introduction: Lip cancer is the most common type of cancer in the oral cavity. It occurs in the lower lip at a rate of 90%–95%, and among lower lip tumors, squamous cell carcinoma (SCC) is the most common type. Objective: In this study, we investigated the influence of the depth of invasion on the decision for an elective lymph node dissection in cases with early-stage (T1–T2 N0 M0) SCC of the lower lip. Methods: Thirty-two patients that were surgically treated were retrospectively reviewed. Results: Three patients had metastatic lymph node, and their mean depth of invasion was 10.60 mm. Lymph node metastasis significantly increased in tumors with a depth of invasion larger than 5 mm (P = 0.033). Conclusion: The rate of cervical lymph node metastasis increases as the depth of invasion increases.

Keywords: Elective lymph node dissection, lip cancer, lymph node metastasis, squamous cell carcinoma


How to cite this article:
Ozden NS, Aydinli Y, Babayev N, Ozdemir A, Kaya B. Effect of depth of invasion on lymph node metastasis in early stage. Turk J Plast Surg 2020;28:29-32

How to cite this URL:
Ozden NS, Aydinli Y, Babayev N, Ozdemir A, Kaya B. Effect of depth of invasion on lymph node metastasis in early stage. Turk J Plast Surg [serial online] 2020 [cited 2020 Jul 12];28:29-32. Available from: http://www.turkjplastsurg.org/text.asp?2020/28/1/29/274444




  Introduction Top


Lip cancers are more frequently seen in males than females (ratio, 6:1), and their incidence rate increases cumulatively in the 50+ years' age group.[1] Squamous cell carcinoma (SCC) is the most common type of lower lip tumor, while adenocarcinoma and melanoma are the rare types. As in other types of malignant tumors exposure to ultraviolet light, smoking and alcohol consumption, history of radiotherapy, immunosuppression, repeated traumas, and genetic factors are the main causes.[2]

Prognostic factors include lymph node metastasis, tumor size, and the extent of the margins of surgical excision. Immunohistochemically, p53, Ki67, CD44, vascular endothelial growth factor, and epidermal growth factor receptor expression are poor prognostic factors.[3] Recent studies have demonstrated the prognostic value of the depth of invasion in the oropharyngeal and laryngeal types of the head and neck cancers.[4]

Preoperative detection of tumors carrying a high risk of occult metastasis has been shown to eliminate both unnecessary treatment and the occurrence of late metastases, hence increase survival rates.[5]

In the last update to the tumor node metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), tumors of the lower lip were redefined as T2 if the diameter is larger than 2 cm and the depth of invasion is more than 5 mm; and as T3 if larger than 4 cm and more than 10 mm, respectively [Table 1].[6]
Table 1: Updated T category criteria defined in the American Joint Committee on Cancer TNM staging system (revisions are given in red print)

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Following the latest TNM update, in this study, we investigated the influence of the depth of invasion on the decision for an elective lymph node dissection in cases with SCC of the lower lip.


  Methods Top


The study was conducted at the Plastic Reconstructive and Aesthetic Surgery Department of Ankara University School of Medicine. The hospital database and the patient files were retrospectively screened for patients who were admitted to the department between January 2010 and July 2018 with a mass in the lower lip and were diagnosed with SCC as a result of incisional biopsy. Sociodemographic characteristics (age and gender), pathology reports, and surgical results of patients were evaluated. The SPSS version 23 software (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp) was used for statistical analysis. The analysis was performed with frequency and applicable statistical tests, namely, the Chi-square test for categorical variables, and the Mann–Whitney U-test for continuous variables. Statistical significance was accepted at the level of P < 0.05.


  Results Top


Of the 32 patients evaluated in the study, 26 (81%) were male with a mean age of 64 years (range: 35–87). Following mass excision, three patients were treated with a free radial forearm flap, two patients with a Nakajima flap, and five patients with a Karapandzic flap, while primary reconstruction was used in the remaining 22 patients. Ultrasound (US), computed tomography (CT), and magnetic resonance imaging were performed in the preoperative period in all patients to assess tumor and lymph node dissemination and to determine the staging.

Supraomohyoid neck dissection was performed on six patients who had a clinically palpable lymph node and showed a pathological lymph node in US imaging of the neck. Lymph node metastases were also histopathologically confirmed in three patients. The mean depth of invasion was 10.60 mm (standard deviation [SD] = 2.24) in cases with and 4.41 mm (SD = 1.68) in those without cervical metastasis. The differences among the tumor thicknesses of both groups were statistically significant (P < 0.05). According to the latest TNM staging system, 25 patients were classified as pT1N0, 4 patients as pT2N0, 1 patient as pT1N1, 1 patient as pT2N1, and 1 patient as pT3N1. The mean postoperative follow-up was 2 years. In this period, patients were monitored for lymph node metastasis through physical examination and US imaging of the neck at 6-month intervals. Lymph node metastasis was not identified in any of the patients, clinically or radiologically, in the 2 years after the surgery.

Metastasis rate increased as the depth of invasion increased, and the result was statistically significant (P = 0.031). When the correlation between the depth of invasion and lymphatic metastasis was analyzed with a cutoff value of 4 mm, the result was statistically insignificant (P = 0.197); this correlation, however, was found statistically significant with a cutoff value of 5 mm or more (P = 0.033). No statistically significant differences were found between the age and gender variables and the involvement of lymph nodes (P = 0.35) [Table 2].
Table 2: Statistical assessment of lymph node metastasis rates based on gender and depth of invasion cutoff value

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  Discussion Top


The most important prognostic factor in lower lip cancers is occult cervical lymph node metastasis.[7] While elective lymph node dissection is recommended prophylactically in T3–T4 N0 tumors, its necessity in early-stage T1–T2 N0 tumors is controversial.[8] In our study, we investigated the necessity of prophylactic lymph node dissection based on the updated AJCC tumor staging criteria.

Uncontrolled recurrence of the disease in the neck is the major cause of mortality in the lower lip SCC patient group. The rate of occult lymph node metastasis in T1 lower lip cancers is reported as 0%–15%. Therefore, even if elective lymph node dissection is not necessary in patients with T1 N0 lower lip cancer, these patients must be closely monitored. In our study, we did not identify any occult lymph node metastasis in the T1 lower lip cancer cases. This rate, on the other hand, is 11%–35% in T2 tumors. In our study, the rate of occult lymph node metastasis among T2 tumors was 33%. Although elective lymph node dissection in T2 tumors is a controversial topic, if elective lymph node dissection is not performed and lymph node metastasis occurs in the neck afterward, the possibility of a surgical treatment decreases and prognosis worsens.[9],[10],[11] Many studies reported in the literature[9],[10],[12] indicate the depth of invasion, perineural invasion, and angiolymphatic invasion as the major risk factors for occult lymph node metastasis. In our clinic, we consider the tumor's depth of invasion to be the most important factor in the decision of an elective lymph node dissection.

In our study, clinical and pathological examination identified differences in the N stages of the three patients. This difference was thought to be perhaps due to the reactive hyperplasia in the lymph nodes caused by poor oral hygiene.[8]

There are different cutoff values reported in the literature for the tumor depth that was taken as reference for a lymphatic metastasis risk. Frierson and Cooper[13] report that the number of cervical lymph node metastases significantly increased in tumors with a depth of invasion of more than 6 mm. Kligerman et al.[14] report that the number of lymph node metastases increased in tumors with a depth of invasion of more than 4 mm and that elective lymph node dissection should be performed when the depth of invasion exceeds this value. Onercl et al.,[15] in their study of 27 patients, established that the rate of occult cervical lymph node metastases significantly increased when the depth of invasion was 5 mm or larger. In our study, no occult cervical lymph node metastases were identified in tumors that were smaller than 3 mm. Nevertheless, the rate of occult cervical lymph node metastasis in this study was 4.2% based on a cutoff value of 4 mm, and 33.3% based on a cutoff value of 5 mm. Given that this is a statistically significant difference, the probability of an occult lymph node metastasis in the neck should be considered, and additional intervention should be performed in tumors larger than 5 mm.

Vanderlei et al.[16] report the rate of cervical lymph node metastases as 9% in T2a cases with tumors smaller than 3 cm, and 43.9% in T2b cases with tumors larger than 3 cm. The authors suggest that elective lymph node dissection should be performed in primary cases when the tumor is 3 cm or larger. In our clinic, we perform a lymph node dissection in lesions with tumors larger than 2 cm regardless of the depth of invasion.

US imaging or CT scan is often used to preoperatively identify cervical lymph node metastases.[17] These methods, however, fail to detect lymph nodes of 5 mm or less.[18] In our study, whereas pathological examination identified metastases in Level 1 lymph nodes in two of the three cases that underwent lymph node dissection, no metastases had been revealed on the preoperative US images of these cases. Given the shortcomings of US imaging and the invasive nature of elective lymph node dissection, less invasive methods such as sentinel lymph node biopsy (SLNB) and positron emission tomography (PET)-CT scanning are being investigated in increasingly more studies[19],[20],[21] for the purposes of detecting occult lymph node metastasis in N0 tumors. Since the follow-up periods are not long enough in studies investigating PET-CT scanning, the effects of PET-bilgisayarlı tomografi scanning on survival or morbidity have not yet been evaluated, and more studies are needed in this area.[9],[21] Since the first radiological examination method in our clinic is US imaging, PET-CT, or SLNB was not used in any of the patients.

In their study on the SLNB technique for identifying occult cervical lymph node metastases, Melkane et al.[20] report to have identified micrometastatic foci in only 14 (33%) of the 42 positive sentinel lymph nodes. When examined by means of classical pathological methods, the sensitivity of intraoperative SLNB in detecting micrometastases was found 60%, and because SLNB requires a second surgical procedure, this led to increases in morbidity and mortality as well as delays in additional therapies. The evaluation of these information shows that the SLNB technique falls short in detecting cervical metastases.

Contrary to SLNB, elective lymph node dissection in cervical cancers is deemed to make a significant contribution to the prognosis of the disease. Jones et al.[22] propound that elective lymph node dissection made a small contribution to the longevity of patients, but indicate that supraomohyoid dissection caused minimal morbidity and only slightly extended the surgery time. Kligerman et al.,[14] in their study, investigating the effectiveness of elective supraomohyoid lymph node dissection in T1 and T2 tumors, determined a 3.5-year disease-free survival rate as 49% in patients who underwent an excision alone, and as 72% in those who underwent an elective lymph node dissection together with excision. These results suggest that elective lymph node dissection should be the preferred treatment method in cervical cancers.

Another key aspect is the assessment of metastatic lymph nodes. Adjuvant radiotherapy or chemotherapy can be applied if extracapsular and/or perivascular spread is detected in the lymph nodes by pathological examination after an elective lymph node dissection. In their study, Johnson et al.[23] identified extracapsular spread in 56% of their patients who had N1 lymph node metastasis and started adjuvant radiotherapy. Disease-free lifespan was seen to have significantly increased in the group that received adjuvant radiotherapy versus the group that did not. In our study, the extracapsular spread was identified in one patient who was referred to the Radiation Oncology Department.

With the inclusion of the depth of invasion as a criterion together with tumor size in the definition of T2 in the latest update of the TNM staging system of AJCC, elective lymph node dissection should be performed in addition to excision in patients with T2 N0 SCC of the lower lip in consideration of a possible occult cervical lymph node metastasis. Based on the studies of Daǧlı, Weiss and Kane elective lymph node dissection is necessary in lesions with a diameter ≥2 cm and a depth ≥5 mm since the rate of cervical lymph node metastases is as high as 20%.[18],[24],[25] Given this high rate of occult cervical lymph node metastasis in T2 N0 tumors and the benefits mentioned in this report, in our clinic, we perform elective cervical dissection in addition to excision in early-stage tumors with a depth of invasion ≥5 mm.


  Conclusion Top


The presented study is the first dedicated to examine how the updates made to the TNM staging system affect the treatment and has shown, in line with the literature that the rate of cervical lymph node metastasis increased together with the increase in the depth of invasion of the tumor. The depth of invasion is a predictor of cervical metastases, as well as a parameter and prognostic factor in determining the necessity of an elective lymph node dissection.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Agostini T, Spinelli G, Arcuri F, Perello R. Metastatic squamous cell carcinoma of the lower lip: Analysis of the 5-year survival rate. Arch Craniofac Surg 2017;18:105-11.  Back to cited text no. 8
    
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Onercl M, Yilmaz T, Gedikoǧlu G. Tumor thickness as a predictor of cervical lymph node metastasis in squamous cell carcinoma of the lower lip. Otolaryngol Head Neck Surg 2000;122:139-42.  Back to cited text no. 15
    
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Vanderlei JP, Pereira-Filho FJ, da Cruz FA, de Mello FL, Kruschewsky Lde S, de Freitas LC, et al. Management of neck metastases in T2N0 lip squamous cell carcinoma. Am J Otolaryngol 2013;34:103-6.  Back to cited text no. 16
    
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Daǧlı M, Araç M, İnal E, Köybaşıoǧlu A, İleri F. Comparison with clinical examination and CT and US in selecting practical screening method in staging cervical lymph nodes in head and neck cancer patients. Kulak Burun Boǧaz Baş Boyun Cerrahisi Derg 1999;2:123-8.  Back to cited text no. 18
    
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