THE EFFECT OF DEPTH

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Oral cavity squamous cell carcinomas (OCSCC) are relatively common among the head ... perineural perivascular invasion, growth pattern and epidemiological ...
Editorial Manager(tm) for Ear, Nose & Throat Journal Manuscript Draft Manuscript Number: 09392R2 Title: THE EFFECT OF DEPTH OF INVASION, DEGREE OF DIFFERENTIATION AND TUMOR SIZE IN ORAL CAVITY CARCINOMAS Article Type: Clinical Studies Section/Category: Head and Neck Clinic Keywords: Oral cavity carcinoma; depth of invasion; differentiation; cervical lymph node metastasis; TNM staging Corresponding Author: Dr. Hasan Mete Inancli, M.D. Corresponding Author's Institution: Ankara Oncology Training and Research Hospital First Author: Mehmet Haksever, MD Order of Authors: Mehmet Haksever, MD; Hasan Mete Inancli, M.D.; Umit Tuncel, Ass. Prof.; Sefik S Kurkcuoglu, MD; Melek Uyar, MD; Omer Genc, MD; Cigdem Irkkan, MD Abstract: Objectives: Cervical lymph node metastatasis is the only most important prognostic factor in head and neck carcinomas. Many factors affecting the neck nodal involvement has been previously studied. TNM staging system is widely used in patient evaluation and treament policy decisions for the oral cavity squamous cell carcinomas. In this study we analysed the effect of three different variables (depth of invasion, degree of differentiation and tumor size) on neck nodal metastasis. Study Design: Retrospective study. Subjects and Method:, Patients who were primarily treated for oral cavity squamous cell carcinomas by surgery, between 2006 and 2008, were included in this study. Primary tumor depth and other pathological features were determined from the pathological specimens and their correlation between the cervical lymph node metastasis was investigated. Fishers's exact test was used for statistical analysis. Results: Thirty-six of these 50 patients were clinically N0 preoperatively. Occult lymph node metastases were calculated as 36.1% (13 of 36). Neck lymph node metastasis in T1-2 and T3-4 categories was 51.5% and 58.8% respectively. The relation between depth of invasion and degree of differentiation with neck nodal metastasis were found to be statistically significant but there was no statistically significant difference between tumor size and neck nodal metastasis. Conclusion: The rate of neck lymph node metatasis in oral cavity squamous cell carcinomas is increased as the tumor depth increases and the tumor differentiation decreases as shown in previous studies. But interestingly tumor size (T) which is the major parameter in TNM system was not significantly correlated with neck lymph node involvement.

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THE EFFECT OF DEPTH OF INVASION, DEGREE OF DIFFERENTIATION AND TUMOR SIZE IN ORAL CAVITY CARCINOMAS

Running title: EFFECT OF DEPTH OF INVASION IN CARCINOMA OF THE ORAL CAVITY

Mehmet Haksever 1, Hasan Mete Inancli1, Umit Tuncel2, Sefik Sinan Kurkcuoglu1, Melek Uyar1, Ömer Genç1 and Cigdem Irkkan3

1. MD, resident in Ankara Oncology Training and Research Hospital, Department of Otorhinolaryngology, Ankara, Turkey. 2. Ass. Prof, chief of the Department of Otorhinolaryngology in Ankara Oncology Training and Research Hospital, Ankara, Turkey. 2. MD, resident in Ankara Oncology Training and Research Hospital, Department of Pathology, Ankara, Turkey.

Corresponding Author: Hasan Mete Inancli, MD Address: Bilkent Camlik Sitesi D3 Blok, Daire 1, Bilkent, 06800, Ankara, Turkey Phone

: +905058392202

Fax

: +902123439040

e-mail

: [email protected]

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Inancli HM Absract: Objectives: Cervical lymph node metastatasis is the only most important prognostic factor in head and neck carcinomas. Many factors affecting the neck nodal involvement has been previously studied. TNM staging system is widely used in patient evaluation and treament policy decisions for the oral cavity squamous cell carcinomas. In this study we analysed the effect of three different variables (depth of invasion, degree of differentiation and tumor size) on neck nodal metastasis. Study Design: Retrospective study. Subjects and Method:, Patients who were primarily treated for oral cavity squamous cell carcinomas by surgery, between 2006 and 2008, were included in this study. Primary tumor depth and other pathological features were determined from the pathological specimens and their correlation between the cervical lymph node metastasis was investigated. Fishers’s exact test was used for statistical analysis. Results: Thirty-six of these 50 patients were clinically N0 preoperatively. Occult lymph node metastases were calculated as 36.1% (13 of 36). Neck lymph node metastasis in T1-2 and T3-4 categories was 51.5% and 58.8% respectively. The relation between depth of invasion and degree of differentiation with neck nodal metastasis were found to be statistically significant but there was no statistically significant difference between tumor size and neck nodal metastasis. Conclusion: The rate of neck lymph node metatasis in oral cavity squamous cell carcinomas is increased as the tumor depth increases and the tumor differentiation decreases as shown in previous studies. But interestingly tumor size (T) which is the major parameter in TNM system was not significantly correlated with neck lymph node involvement.

Keywords: Oral cavity carcinoma, depth of invasion, differentiation, cervical lymph node metastasis, TNM staging

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Inancli HM Introduction: Oral cavity squamous cell carcinomas (OCSCC) are relatively common among the head and neck cancers. As they grow, they invade the surrounding tissue and metastasize to cervical lymph nodes. This is thougth to be due to the filtering effect of the rich lymphatic system on the drainage way of these cancers. This rich lymphatic system captures the cancer cells and prevents their spread to the other organs. Cervical lymph node metastatasis is the single most important prognostic factor in head and neck carcinomas (HNC).1, 2 Therefore, appropriate management of the neck is important. With reference to the TNM staging system, when dealing with the large lesions (T3 and T4) or preoperative N-positive neck disease, there is an agrement on the treatment necessity of the neck lymph nodes. However, there are still many doubts concerning the best way to approach to the neck in case of early stage-disease.3 It is generally known that overall survival of patients with clinically negative lymph nodes is high, nodal recurrence as a result of undetectable subclinical nodal metastasis is, however, the main problem in the managment of early stage I and II cancers.4 Despite the recent advances in the imaging techniques for the detection of lymph node metastasis, 20-50% of lymph node negative patients with occult node metastasis are unidentified. These patients develop a clinically evident cervical metastasis, usually within 2 years of followup.5,

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Although Kamer et al shown that local failures are the most important parameter affecting the final

outcome usually the outcome of the patients with neck failure is poor.7 Elective neck dissection provides pathological confirmation of the metastatic status of the neck lymph nodes, helps to determine the need for additional therapy, and can also remove undetectable cancer cells in the lymph nodes. But many patients migth not need such treatment as this treatment may cause additional morbidity and may remove or destroy a natural barrier of cancer spread.8 During the preoperative evaluation of the patients, TNM staging is used, as it is an objevtive, internationally accepted system. On the other hand several studies have shown that many paramaters which TNM staging system does not include, histologic parameters; tumor thickness, depth of invasion, degree of differentiation, perineural perivascular invasion, growth pattern and epidemiological parameters; age, sex, race, alcohol and tabocco use, also have affects on the prognosis of disease.3,

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Since there are correlations between these

parameters and prognosis, it is logic to think that there migth be also a correlation between these parameters and cervical lymph node involvment which is the most important prognostic factor for the oral cavity carcinomas.

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Inancli HM In this study we aimed to show the correlation between three parameters (tumor thickness, degree of differentiation and tumor size) and cervical lymph node involvement.

Materials and methods: Patients Patients, who admitted to Ankara Abdurrahman Yurtaslan Oncology Training and Research Hospital, between 2006 and 2008, were included in to our study. All patients had T1 to T4 oral cavity cancer and were primarily treated with surgery. Patients who were previously treated with radiotherapy or chemotherapy were excluded. The stage of the oral cancers was determined by TNM staging system according to the recommendation of the 2002 American Joint Committee on Cancer criteria. Preoperative assesment of the neck lymph node metastasis included a physical examination. In some patient charts, the lymph node metastases were supplemented by imaging techniques either with ultrasonography, computed tomograpy or magnetic resonans imaging. The evaluation of distant metastasis was assessed by chest X-ray and further imaging techniques if needed. When a proven or suspected distant metastasis was detected, the patients were excluded from the study. The term cTNM and pTNM indicate clinical (pre-operative) and pathological (post-operative) tumor staging, respectively. All patients had undergone primary surgical excision and neck dissection (bilateral or unilateral depending on the tumor location and status of the neck) at the same time. Histopatological examinations The surgical specimens were oriented and labeled by surgeons and fixated in 10% buffered formalin. The specimens were processed and examined under microscopical vision by pathologist. Parafin processing was applied, one day after the fixation of the specimen. Tumor size and depth of invasion, degree of differentiation, cervical lymph node metastases status was obtained from the pathological reports. The depth of invasion was calculated as the distance between the bazal membrane and the deepest point of the invaded stromal tissue. Statistical analysis Data retrieved for analysis included pre-operative TNM, depth of tumor invasion, and degree of tumor differentiation. The significance of lymph node metastasis with different variables was investigated by means of ‘Fisher’s Exact Test’. A p value less than 0.05 was considered to be statistically significant.

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Inancli HM Results: Patient characteristics Fifty patients with histologically proven oral cavity squamous cell carcinoma were analysed retrospectively from their records and pathological specimen reports. The age of the patients ranged from 27 to 77 years with an average age of 55 years. There were 36 male and 14 females. All patients were primarly treated surgically by wide exsision of tumor and neck dissection followed by radiotherapy and/or chemotherapy if necessary. Distribution of tumor locations were; 24 in the tongue, 12 in the oral floor, 7 in the gingiva, 4 in the retromolar trigon, 2 in the buccal mucosa and one in the hard palate. Lip cancers are not included in this study (Table I). Examination findings According to 2002 American Joint Committee on Cancer Criteria, TNM staging of all patients preoperatively was; 15 patients were cT1 (30%), 18 patients were cT2 (36%), 10 patients were cT3 (20%) and 7 patients were cT4 (14 %). Preoperative N distribution was; 36 patients were cN0 (72%) and 14 patients were cN+ (28%). The detailed cT and cN distributions are shown in Table II. Pathological specimen findings Pathological specimen reports were analiysed regarding to the neck lymph metastasis, tumor differentiation and depth of tumor invasion. One or more lymph node metastasis was accepted as pN+. Twenty seven of 50 (54%) patients were pN+. When cN0 patients were analysed 13 of 36 patients (36.1%) was pN+, meaning that occult neck metastasis rate was 36.1 %( Table III). Tumors were well differentiated in 21 cases, moderate differentiated in 14 cases and poor differantiated in 5 cases. Differention of 10 cases were undetermined. We excluded these 10 cases which didn’t have any differentiation determination from the statistical assessments of differentiation. Ten cases (20%) had depth of invasion equal or less than 5 mm, 15 cases (30%) had depth of invasion between 5-10 mm, and 25 cases (50%) had depth of invasion more than 10 mm. Correlation between different variables and neck nodal metastasis All the variables were statistically analyzed to find any significant correlations with neck nodal metastasis. Regarding the tumor size, cases were grouped as T1+T2 (early stage) and T3+T4 (late stage). The neck metastases (pN+) in T1+T2 and T3+T4 groups were 51.5% and 58.8% respectively.

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Inancli HM Regarding the differantiantion, the neck nodal metastatis was present in 8 of 21 cases, 8 of 14 cases and 4 of 5 cases in well, modaretly and poorly differantiated groups respectively. When we evaluate the cN0 patients with differentiation and neck nodal metastasis, the nodal involvement rates were 3 of 14 cases in well differentiated, 4 of 10 cases in moderately differentiated and 3 of 4 cases in poorly differentiated groups. The nodal metastases rate in the group with depth of invasion equal or less than 5 mm was 40%, in the group with depth of invasion between 5.1-10 mm was also 40%, in the group with depth of invasion more than 10 mm was 68%. When we evaluate the depth of invasion in only cN0 cases, the neck nodal metastasis rates would be 22.2%, 35.7%, and 46.1% respectively. The incidence of lymph node metastasis is significantly higher when the depth of invasion is increased (p=0.011). Similarly, as the differentiation of tumor decreases, the rate of nodal involvement increases significantly. (p=0.027). The correlation of nodal metastasis with the depth of invasion and differentiation in the cN0 group were statistically significant, p=0.05, p=0.023 respectively (TableIV).

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Inancli HM Discussion: The presence of neck lymph node metastasis is the most important prognostic factor in HNC patients. 9, 10 Neck treatments are always perfomed when there is obvious clinically detectable lymph nodes in patients with OCSCC. But the treatment of neck remains controversial in clinically neck negative or early stage oral cavity carcinomas (T1-2, N0). Here there are two options for the treatment of the neck. One is elective neck dissection policy and the other is wait-see policy. Elective neck dissection provides accurate neck staging, removes possible neck metastasis and determines additional needs for radioterapy. But it causes additional morbidity, may destroy natural tumor barrier. Considering the high rate of occult metastasis reported by various authors there are many proponents of an elective neck dissection.5, 11 In our study the rate of occult metastasis in OCSCC was calculated as 36.1%. This rate is about average result of cases with upper aerodigestive squamous cell carcinoma (SCC). This means that by wait-see policy one in 3 patients would live in high risk of recurrence in the neck during follow-up. On the other hand one can find a literature supporting that wait and see group had better survival than elective neck dissection group.12, 13 Since early oral cavity carcinomas can be excised by per oral route, elective neck dissection puts the patient through a second surgey. Despite the advantages and disadvantages of both policies most of the cancer centers and also our department, prefer elective treatment of neck especially when tumor is located on the tongue and on oral floor. It has been found that the surface tumor size, and hence TNM stage does not correlate with occurence of metastasis in oral squamous cell carcinoma.5, 14, 15 So when deciding the treatment modalities of cases regarding only TNM system, it may not be enough. There are different variables related with neck metastasis discussed in the litreture. One of the most important one is depth of invasion of tumor and tumor thickness.16 These two terms are not the same but sometimes they are misused synonymously. Depth of invasion is defined as extension of tumor beneath the epitelial surface; where epitelium is destroyed. Tumor thickness is the measurement of vertical bulk of tumor and includes exophytic as well as endophytic portion of the tumor.4 Many studies demostrate that depth of invasion is an appropriate factor to predict cervical metastasis of oral squamous cell carcinoma.4, 11, 17, 18 Other studies show that there is a statistically significant correlation between the depth of invasion and the neck nodal metastasisis in all patient groups including clinically N0 group. We think this correlation is more important in patients with cN0, because in such cases the treatment necesity of the neck is still controversial.

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Inancli HM It has been reported that patients with a tumor depth of greater than 9 mm did significantly better than those with a tumor depth of grater than 9 mm (p3 mm to 9 mm was associated with a 50% nodal metastasis rate, wheares Hosal et al19 found that thickness of > 9mm was only variable that predicts occult lymph node metastasis in carcinoma of oral tongue. Yuen et al20 and Fukano et al11 recommended elective neck treatment of patients with a tumor depth of invasion 3 mm to 5 mm respectively. Although there is a consenscus about the importance of tumor depth or thickness on the nodal involvement of the neck, the most valid cut off value is not decided yet.21 These differences in cut off value may be attributable to many factors, such as definition of tumor depth or thickness, and oblique section in processing surgical specimens. In future multicentered studies with high number of cases and standardised measurement of depth of invason will lead us to decide ideal cutoff value. But here there are two issues. One is; depth of invasion is mostly measured postoperatively with the report of pathological specimen. During surgical treatment, operation begins with the neck dissection, followed by tumor exsicion and if possible en-block resection of tumor and neck specimen alltogether. So most of the time we do not know the depth of invasion preoperatively and decision on neck treatment regarding depth of invasion is not possible. In the future we hope; by imaging techniques like magnetic resonance imaging, preoperative tumor depth can be determined with high correlation with pathological result of tumor depth so that we can re-evaluate the neck, especially in N0 cases before surgery. Another way of determining the depth of invasion might be studing frozen sections during operation which can help to decide on neck treatment. But the problem is, most of the time neck dissection is applied before tumor excision.

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Inancli HM Another clinical parameter used was the histologic differentiation of tumor. Our study showed that as the differentiation of tumor is decreased the rate of nodal neck involvement is significantly increased. Some of other basic studies on oral cavity squamous cell carsinomas verified this clinical behaviour. Chen et al17 designed a study on tongue cancer and they found that poor and modarate differentiated tumors had higher rate of neck nodal involvement than well differantiated ones. A study showed that differentiation of tumor is not only correlated with neck nodal involvement but also it is correlated with the regional recurrence.22 Despite many studies supporting the significant correlation between differentiation and nodal neck involvement there is a study by Fukano et al11 showing that no significant correlation between pN0 and pN+ regarding differentiation. In the literature, most of the studies concerning differentiation also evalute some other histopathological factors such as perineural invasion, lymphovascular permeation, muscle invasion. These studies showed a significant correlation between nodal neck involvement and histopathological factors.11, 17 The largest dimension of tumor surface is used to indicate the tumor size (T) as a characteristic of tumor staging. In our study the cases were sub-grouped as T1-2 and T3-4. We found the neck nodal metastasis in T1-2 and T3-4 patients as 51.5% and 58.8% respectively. But this difference is not statistically significant; meaning that as the tumor size increases the rate of nodal metastasis does not significantly increase. Similar results were also found in the studies of Chen et al17. On the other hand it has been shown that T stage tends to be more advanced in N+ groups. These controversies may be attributable to many histopatological factors such as depth of invasion, degree of differantiation, exophytic or endophytic growth pattern.

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Inancli HM Conclusion: As mentioned earlier, two (depth of invasion, degree of differentiation) of 3 variable factors analysed in our study were significantly correlated with the neck nodal metastasis. However regarding the tumor size (T) the correlation was not statistically significant. Here we want to focus on TNM staging system used to evalute patients preoperatively. Since it is a widely used system, it does not evalute many variables (especially depth of invasion) affecting neck nodal metastasis and on prognosis, but it evalutes the effect of tumor size on neck involvement and prognosis which can still be discussed. This controversy may be due to diffuculty in determination of these variables preoperatively. In the future we hope that determination of depth of invasion of the tumor preoperatively by imaging techniques or intraoperatively by frozen section provides us a more accurate staging.

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Inancli HM References: 1.

De Zinis LO, Bolzoni A, Piazza C. Prevalence and localization of nodal metastases in squamous cell carcinoma of the oral cavity: role and extension of neck dissection, Eur Arch Otorhinolaryngol. 2006;263(12):1131-5.

2.

Ferlito A, Rinaldo A, Devaney KO, Nakashiro K, Hamakawa H.Detection of lymph node micrometastases in patients with squamous carcinoma of the head and neck : Eur Arch Otorhinolaryngol. 2008;265(10):1147-53

3.

Pentenero M, Gandolfo S, Carrozzo M. Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature. Head Neck. 2005;27(12):1080-91.

4.

Kane SV, Gupta M, Kakade AC, D' Cruz A. Depth of invasion is the most significant histological predictor of subclinical cervical lymph node metastasis in early squamous carcinomas of the oral cavity. Eur J Surg Oncol. 2006;32(7):795-803.

5.

Hiratsuka H, Miyakawa A, Nakamori K, Kido Y, Sunakawa H, Kohama G. Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity. Cancer. 1997;80(3):351-6.

6.

Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, Genden E, Urken ML, Wang BY. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol. 2005;29(2):167-78.

7.

Kamer S, Esassolak M, Demirci S, Akyildiz S, Sengul A, Yavuzer A. Relapse patterns and related prognostic factors in patients with mobile tongue cancer treated with postoperative radiotherapy. J BUON. 2009 Jan-Mar;14(1):51-6.)

8.

Onerci M, Yilmaz T, Gedikoğlu 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(1):139-42.

9.

Le Tourneau C, Velten M, Jung GM, Bronner G, Flesch H, Borel C. Prognostic indicators for survival in head and neck squamous cell carcinomas: analysis of a series of 621 cases. Head Neck. 2005;27(9):801-8.

10. Sessions DG, Spector GJ, Lenox J, Haughey B, Chao C, Marks J. Analysis of treatment results for oral tongue cancer. Laryngoscope. 2002;112(4):616-25.

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Inancli HM 11. Fukano H, Matsuura H, Hasegawa Y, Nakamura S. Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. Head Neck. 1997;19(3):205-10. 12. Vandenbrouck C, Sancho-Garnier H, Chassagne D, Saravane D, Cachin Y, Micheau C. Elective versus therapeutic radical neck dissection in epidermoid carcinoma of the oral cavity: results of a randomized clinical trial. Cancer. 1980;46(2):386-90. 13. Nieuwenhuis EJ, Castelijns JA, Pijpers R, van den Brekel MW, Brakenhoff RH, van der Waal I, Snow GB, Leemans CR. Wait-and-see policy for the N0 neck in early-stage oral and oropharyngeal squamous cell carcinoma using ultrasonography-guided cytology: is there a role for identification of the sentinel node? Head Neck. 2002;24(3):282-9. 14. Ambrosch P, Kron M, Fischer G, Brinck U. Micrometastases in carcinoma of the upper aerodigestive tract: detection, risk of metastasizing, and prognostic value of depth of invasion. Head Neck. 1995;17(6):473-9. 15. Moore C, Kuhns JG, Greenberg RA. Thickness as prognostic aid in upper aerodigestive tract cancer. Arch Surg. 1986;121(12):1410-4. 16. Pentenero M, Gandolfo S, Carrozzo M. Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature. Head Neck. 2005 Dec; 27(12):1080-91. 17. Chen YW, Yu EH, Wu TH, Lo WL, Li WY, Kao SY. Histopathological factors affecting nodal metastasis in tongue cancer: analysis of 94 patients in Taiwan. Int J Oral Maxillofac Surg. 2008;37(10):912-6 18. Lim SC, Zhang S, Ishii G, Endoh Y, Kodama K, Miyamoto S, Hayashi R, Ebihara S, Cho JS, Ochiai A. Predictive markers for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral tongue. Clin Cancer Res. 2004;10(1 Pt 1):166-72. 19. Hoşal AS, Unal OF, Ayhan A. Possible prognostic value of histopathologic parameters in patients with carcinoma of the oral tongue. Eur Arch Otorhinolaryngol. 1998;255(4):216-9. 20. Yuen AP, Lam KY, Wei WI, Lam KY, Ho CM, Chow TL, Yuen WF. A comparison of the prognostic significance of tumor diameter, length, width, thickness, area, volume, and clinicopathological features of oral tongue carcinoma. Am J Surg. 2000;180(2):139-43.

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Inancli HM 21. Po Wing Yuen A, Lam KY, Lam LK, 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(6):513-20. 22. An SY, Jung EJ, Lee M et al. Factors related to regional recurrence in early stage squamous cell carcinoma of the oral tongue. Clin Exp Otorhinolaryngol. 2008;1(3):166-70.

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Inancli HM

Table Legends: Table I:

Characteristics, TNM stage and features of 50 oral squamous carcinomas.

Table II: Stages of cases. Table III: Clinical and pathological neck evaluatin of cases. Table IV: Univariate analysis of the clinical and pathological indicators for neck nodal metastasis.

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Inancli HM

Table I. Characteristics, TNM stages and features of 50 oral squamous carcinomas. Covariate Age (years) Gender Tumor Size Tumor Localization

Description (number of patients and percentage of total) 71 (4, 8%) Male (36, 72%); Female (14, 28%) T1(15, 30%); T2 (18, 36%); T4 (10, 20%); T4 (7, 14%) Tongue (24, 48%); Oral Floor (12, 24%); Gingiva (7, 14%), Retromolar Trigon (4, 8%), Buccal Mucosa (2, 4%); Hard Palate (1, 2%)

Neck Nodal Metastasis cN0 (36, 72%); cN+ (14, 28%) and pN0 (23, 46%), pN+ (27, 54%) Tumor Stage I (14, 28%); II (12, 24%); III (10, 20%); IV (12, 24%) Tumor Differentiation* Well (21, 52%); Moderate (14, 35%), Poor (5, 8%), Undetermined 10 cases Depth of Invasion 10.1mm (25, 50%) * The cases with known differentiation are included in percentage, the undetermined cases are excluded from the statistical analyses.

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Inancli HM

Table II. Stages of cases. cT1

cT2

cT3

cT4

Total

cN0

11

12

5

5

36

cN1

2

1

2

2

7

cN2A

-

2

-

-

2

cN2B

-

1

1

-

2

cN2C

-

1

-

-

1

cN3

1

-

1

-

2

Total

15

18

10

7

50

cT and cN refer to clinically (preoperative) evaluation of tumor and neck respectively. cN0 refers clinically no lypmph nodes on neck. cN+ refers clinically lypmph node or nodes by palpation on neck. pN0 refers histologcically no metastasis on neck dissection specimens. pN+ refers histologically metastasis on neck dissection specimens.

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Inancli HM

Table III. Clinical and pathological neck evaluation of cases.

cN0 cN+ Total

pN0 23 0 23

pN+ 13 14 27

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Total 36 14 50

Inancli HM

Table IV. Univariate analysis of the clinical and pathological indicators for neck nodal metastasis. Feature pN0 pN+ P value Tumor Size T1+T2 16 17 T3+T4 7 10 NS* Differentiation Well 13 8 Modarate 8 6 Poor 1 4 0.027 Depth of invasion 10 mm 8 17 *No Statistical Significance.

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