|Year : 2017 | Volume
| Issue : 2 | Page : 75-78
Incidence of occult metastasis in clinically N0 oral tongue squamous cell carcinoma and its association with tumor staging, thickness, and differentiation
Neena Chaudhary1, Rajeev Kumar Verma1, Usha Agarwal2, Shashank Gupta1, Shweta Jaitly1
1 Department of Otorhinolaryngology, VMMC and Safdarjung Hospital, New Delhi, India
2 Department of Pathology, National Institute of Pathology Indian Council of Medical Research, New Delhi, India
|Date of Web Publication||22-Jan-2018|
Dr. Rajeev Kumar Verma
Krashi Upaz Mandi Road, Ward No. 1, Srimadhopur, Sikar, Rajasthan
Source of Support: None, Conflict of Interest: None
Introduction: Oral squamous cell carcinoma (SCC) is the most frequent head and neck cancer. The metastatic dissemination of these tumours usually occurs through the lymphatic system. The presence of occult lymph node metastasis is the most important prognostic factor. The high incidence of occult lymph nodal metastasis is a strong argument for the indication of elective neck dissection. However, there is a high percentage of patients who do not have metastasis in the pathological exam (pN0). Taking a homogenous group of patients all of whom received primary surgical treatment, at the same institution without prior radiotherapy or chemotherapy, applying stringent patient selection criteria, and standard pathological evaluation methods across the group, this study aims to establish predictors of cervical node metastasis in squamous carcinomas of the oral tongue. Result: During the study period, a total of 112 patients (98 males and 14 females; Mean age 49.7 years (range 15-70)) underwent resection of the primary tumor with SOND for N0 lymph node status of neck. A total of 1489 lymph nodes were analyzed in this study. Occult metastasis was found in 26 patients (23.2%). T-stage 4 was found to be a statistically significant predictor of occult lymph node metastasis in a cN0 neck. (95% CI, p-value 0.02). There was no correlation between gender, tumor thickness, and tumor differentiation and occurrence of occult metastasis. Discussion: Controversy exists over management of the neck in patients with cN0 oral SCC. As is evident there is no consistent statistically significant factor that can be attributed as a predictor of occult metastasis in head and neck cancer of the oral cavity. The search to identify reliable and accurate predictor(s) of occult metastases, or approaches to the management of patients with cN0 oral SCC, must continue. In absence of such predictors, keeping the high incidence of occult metastasis in mind, we recommend END in all cases of N0 OSCC.
Keywords: Carcinoma, differentiation, elective neck dissection, metastasis, occult, staging, thickness, tongue
|How to cite this article:|
Chaudhary N, Verma RK, Agarwal U, Gupta S, Jaitly S. Incidence of occult metastasis in clinically N0 oral tongue squamous cell carcinoma and its association with tumor staging, thickness, and differentiation. J Head Neck Physicians Surg 2017;5:75-8
|How to cite this URL:|
Chaudhary N, Verma RK, Agarwal U, Gupta S, Jaitly S. Incidence of occult metastasis in clinically N0 oral tongue squamous cell carcinoma and its association with tumor staging, thickness, and differentiation. J Head Neck Physicians Surg [serial online] 2017 [cited 2021 May 12];5:75-8. Available from: https://www.jhnps.org/text.asp?2017/5/2/75/223759
| Introduction|| |
Oral squamous cell carcinoma (SCC) is the most frequent head and neck cancer in the world. The metastatic dissemination of these tumors usually occurs through the lymphatic system, and most frequently involves Level I and II neck lymph nodes., Oral SCC spreads to the cervical lymph nodes in about 18% to 45% of cases, causing clinically N+ disease.
The prognosis of these tumors depends on multiple host factors, characteristics of the tumor, and type of treatment. The presence of occult lymph node metastasis is, however, the most important prognostic factor. It leads to a reduction in the probability of disease control and reduces overall survival by 30% to 50%., The incidence of occult metastasis in neck lymph nodes in patients of oral SCC ranges from 23.7% to 42%., As occult metastases are not always identified by modern techniques of diagnostic imaging, it is important to investigate the nodes in the neck.
While high incidence of occult lymph nodal metastasis presents a strong case for elective neck dissection (END), majority of patients do not have metastasis and do not need the additional cosmetic and functional morbidity associated with neck dissection. Determining whether END will be beneficial to the patient or not continues to be an important clinical dilemma. The identification of factors associated with the risk of lymph node metastasis may be useful for the proper selection of patients for END.,
Taking a homogeneous group of patients all of whom received primary surgical treatment, at the same institution without prior radiotherapy or chemotherapy, applying stringent patient selection criteria, and standard pathological evaluation methods across the group, this study aims to establish predictors of cervical node metastasis in squamous carcinomas of the oral tongue. This is in order to identify a subset of patients who are more likely to harbor subclinical node metastasis and could therefore be the right candidates for END at the time of first surgery.
| Methodology|| |
This retrospective study was carried out in the Department of Otorhinolaryngology and Head and Neck Surgery, VMMC and Safdarjung Hospital, Delhi, India, from 2011 to 2016. Patients having oral tongue squamous cell cancer [Figure 1] with clinically and radiologically (computerized tomography [CT]/magnetic resonance imaging) N0 neck and T stage T2, T3, T4, who underwent surgery as the primary mode of treatment between July 2011 to July 2015, were enrolled in this study. T1N0 cases received definitive radiotherapy.
|Figure 1: Squamous cell carcinoma involving the right lateral border of the tongue|
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All patients underwent clinical examination and contrast-enhanced CT scanning before the initial treatment.
The tumor, node, metastasis classification and clinical stage were determined according to the criteria established by the American Joint Committee on Cancer and the International Union Against Cancer.
All patients underwent wide local excision of the primary tumor along with unilateral Supraomohyoid neck dissection (Level Ib, IIa, III) [Figure 2] and [Figure 3].
In this study, demographic factors (age, gender, substance abuse), clinical factors (tumor site, stage), and pathological factors (histological grade and thickness) were analyzed.
The microscopic slides were reviewed by a single pathologist using the following criteria:
- Histological grade determined on the basis of classification proposed by the World Health Organization (well-differentiated carcinoma [Grade I], moderately differentiated [Grade II], poorly differentiated [Grade III])
- The maximum depth of invasion was measured using an ocular micrometer. The maximum depth of invasion was measured vertically from the virtual normal mucosal line to the deepest infiltrating tumor cell
- The specimen of the neck dissections were fixed in 10% neutral-buffered formalin. All lymph nodes visible or palpable were carefully dissected from fat. All nodes that were 5 mm or larger were cut in half. From each node, two to three 4 μm thick sections were obtained and stained with hematoxylin and eosin (H and E). The paraffin-embedded lymph nodes were totally sectioned in 4 μm thick sections. Every tenth section was stained with H and E and was examined by single senior pathologist.
The result of clinical examination, radiological imaging was compared with histopathological results of neck dissection specimen; the presence and absence of metastatic lymph nodes, their number, size, and level in the neck were noted. Positive nodes were correlated with the grading, thickness, and differentiation of the primary tumor.
Correlation analyses were made between occult metastasis and the variables studied by the Chi-square test.
The variables were also analyzed in Python 2.0 software (open source statistical analysis software, PSF, USA). Values of P < 0.05 were considered statistically significant.
| Results|| |
During the study period, a total of 112 patients (98 males and 14 females; median age 49 years (range: 15–70)) underwent resection of the primary tumor with SOND for N0 lymph node status of neck. [Table 1] and [Table 2] show the distribution of clinical and histological characteristics of the patients.
|Table 1: Clinical and histological characteristics of 112 patients with oral squamous cell carcinoma|
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A total of 1489 lymph nodes were analyzed in this study. Occult metastasis was found in 26 patients (23.2%). The relationship of occult metastasis with T-staging, tumor thickness, and tumor differentiation is depicted in [Table 3].
|Table 3: Occurrence of occult metastasis with T-staging, tumor thickness, and tumor differentiation|
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T-stage 4 was found to be a statistically significant predictor of occult lymph node metastasis in a cN0 neck (P = 0.02). There was no correlation between gender, tumor thickness, and tumor differentiation and occurrence of occult metastasis.
| Discussion|| |
Controversy exists over management of the neck in patients with cN0 oral SCC. Various authors have studied this dilemma and come to different conclusions regarding the approach to the cN0 neck. While Ebrahim et al. in a study of 153 patients found the incidence of occult metastasis in T1, T2 cN0 tumors to be 37%; Capote et al. in a similar study of 154 patients found the incidence to be 0%. Similar contradictions are seen from studies by Keski-Säntti et al. and Layland et al. who found occult metastasis occurring in 34% and 12% cases, respectively. Based on these findings, the authors have recommended management ranging from observation of patient to managing the disease by END.
These contrasting recommendations have stimulated the search for various predictors of occult metastases to identify those who might benefit most from END.
The incidence of occult metastasis in our study was found to be 23.12%. This is in keeping with similar studies from around the globe.,,,
We found that as the T-staging of N0 oral SCC increases, the incidence of occult metastasis also increases (from 10.5% in T2 to 32.4% in T4). Similar increase in incidence was also found with increase in depth of tumor invasion and pathological grading of the tumor.
In our study, the only statistically significant predictive indicator for occult metastasis was found to be stage T4. Other authors have studied different promising factors that may help us to predict nodal metastasis in N0 neck. Spiro et al. found tumor thickness and not T-stage to be correlated with treatment failure and survival. Fakih et al. found tumor depth >4 mm to be a significant predictor of metastasis. Bryne et al. and Odell et al. found grading of invasive tumor margins and pattern of invasion, respectively, to be the best prognostic factors in oral SCC, respectively.
It is evident that there is no consistent statistically significant factor that can be attributed as a predictor of occult metastasis in head and neck cancer of the oral cavity.
Advances in imaging technology, use of biomarkers, and the role of sentinel node biopsy require further research and validation. Therefore, the search to identify reliable and accurate predictor(s) of occult metastases or approaches to the management of patients with cN0 oral SCC must continue.
In the absence of such predictors, keeping the high incidence of occult metastasis in mind, we recommend END in all cases of N0 OSCC.
This study includes 112 patients. A larger sample size would enable better understanding of the association. Patients must continue to be managed by multidisciplinary teams until more suitable predictors or new approaches have been identified. Sentinel lymph node biopsy and advances in research into biomarkers may have an invaluable role in their future management.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Arthur K, Farr HW. Prognostic significance of histologic grade in epidermoid carcinoma of the mouth and pharynx. Am J Surg 1972;124:489-92.
Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB. Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer 1994;73:187-90.
El-Naaj IA, Leiser Y, Shveis M, Sabo E, Peled M. Incidence of oral cancer occult metastasis and survival of T1-T2N0 oral cancer patients. J Oral Maxillofac Surg 2011;69:2674-9.
Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB. Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer 1993;71:452-6.
Okamoto M, Nishimine M, Kishi M, Kirita T, Sugimura M, Nakamura M, et al.
Prediction of delayed neck metastasis inpatients with stage I/II squamous cell carcinoma of the tongue. J Oral Pathol Med 2002;31:227-33.
Khafif RA, Gelbfish GA, Tepper P, Attie JN. Elective radical neck dissection in epidermoid cancer of the head and neck. A retrospective analysis of 853 cases of mouth, pharynx, and larynx cancer. Cancer 1991;67:67-71.
Po Wing Yuen A, Lam KY, Lam LK, Ho CM, Wong A, Chow TL, et al.
Prognostic factors of clinically stage I and II oral tongue carcinoma-A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez-Gimeno score, and pathologic features. Head Neck 2002;24:513-20.
Kowalski LP. Result of salvage treatment of the neck in patients with oral cancer. Arch Otol Head Neck 2002;128:58-62.
Spiro RH, Huvos AG, Wong GY, Spiro JD, Gnecco CA, Strong EW, et al.
Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg 1986;152:345-50.
Ebrahimi A, Moncrieff MD, Clark JR, Shannon KF, Gao K, Milross CG, et al.
Predicting the pattern of regional metastases from cutaneous squamous cell carcinoma of the head and neck based on location of the primary. Head Neck 2010;32:1288-94.
Capote A, Escorial V, Muñoz-Guerra MF, Rodríguez-Campo FJ, Gamallo C, Naval L, et al.
Elective neck dissection in early-stage oral squamous cell carcinoma – Does it influence recurrence and survival? Head Neck 2007;29:3-11.
Keski-Säntti H, Atula T, Törnwall J, Koivunen P, Mäkitie A. Elective neck treatment versus observation in patients with T1/T2 N0 squamous cell carcinoma of oral tongue. Oral Oncol 2006;42:96-101.
Layland MK, Sessions DG, Lenox J. The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+. Laryngoscope 2005;115:629-39.
Pimenta Amaral TM, Da Silva Freire AR, Carvalho AL, Pinto CA, Kowalski LP. Predictive factors of occult metastasis and prognosis of clinical stages I and II squamous cell carcinoma of the tongue and floor of the mouth. Oral Oncol 2004;40:780-6.
Ganly I, Patel S, Shah J. Early stage squamous cell cancer of the oral tongue – Clinicopathologic features affecting outcome. Cancer 2012;118:101-11.
Kligerman J, Lima RA, Soares JR, Prado L, Dias FL, Freitas EQ, et al.
Supraomohyoid neck dissection in the treatment of T1/T2 squamous cell carcinoma of oral cavity. Am J Surg 1994;168:391-4.
D'Cruz AK, Siddachari RC, Walvekar RR, Pantvaidya GH, Chaukar DA, Deshpande MS, et al.
Elective neck dissection for the management of the N0 neck in early cancer of the oral tongue: Need for a randomized controlled trial. Head Neck 2009;31:618-24.
Fakih AR, Rao RS, Borges AM, Patel AR. Elective versus therapeutic neck dissection in early carcinoma of the oral tongue. Am J Surg 1989;158:309-13.
Bryne M, Koppang HS, Lilleng R, Kjaerheim A. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol 1992;166:375-81.
Odell EW, Jani P, Sherriff M, Ahluwalia SM, Hibbert J, Levison DA, et al.
The prognostic value of individual histologic grading parameters in small lingual squamous cell carcinomas. The importance of the pattern of invasion. Cancer 1994;74:789-94.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]
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