Abstract
(1) To study layer of invasion as predictor of cervical lymph node metastasis. (2) To decide a cut off depth according to layer of invasion for neck dissection. It is a prospective study with sample size of 220 patients at tertiary care hospital with previously untreated operable buccal mucosa carcinoma over period of 21 months. The factors considered under the study were Tumor layer of invasion, lymph node metastasis, Ultrasonography doppler neck, CT scan and gender. Wide excision of the lesion and reconstruction was done. Histopathological analysis of resected specimen were recorded as part of data collection for all the cases. Quantitative data represented using Mean ± SD (Standard Deviation) and median and interquartile range compared using Chi square test. Standard principles of univariate analysis was used according to statistical methods. Depth when measured according to layer of invasion, was significantly associated with lymph node metastasis with 89% of the muscle as layer of invasion being Lymph node positive (p = 0.009). There is 1.39 times chances of lymph nodal metastasis in patients with muscle invasion as compared to submucosal invasion. Tumour layer of invasion plays important role in predicting chances of nodal metastasis in clinically N0 neck in buccal mucosa cancer. According to the study, we should electively proceed with ipsilateral lymph node dissection once the layer of tumour invasion is muscle. This study is limited by sample size and short duration of one year and nine months.
Keywords: Buccal mucosa, Depth of invasion, Layer of invasion, Lymph nodes
Introduction
Oral cancer is the most frequent head and neck malignancy worldwide. According to the World Health Organization (WHO), oral cancer rates are expected to increase from 10 million cases in 2000 to 15 million cases in 2020 [1]. There is global and regional variation in the incidence of oral cancers due to local geographical, biological, dietary and environmental factors. Needless to say, the majority of these cancers are squamous cell carcinomas. Among the subsites of the oral cavity, the buccal mucosa is one of the most common areas involved, accounting for 50% of all oral cavity tumours. Buccal mucosa involvement is due to people's frequent consumption of pan, betel nut, and tobacco [2].
Squamous cell carcinoma of the buccal mucosa is an aggressive malignancy, with a greater propensity for invasion into the surrounding tissues and metastasis to the cervical lymph nodes [3]. The involvement of the cervical lymph nodes greatly impacts the treatment protocol and the prognosis of squamous cell carcinoma of the buccal mucosa [4].
Advanced stage tumours with clinical or radiological evidence of neck nodes warrant a definitive neck dissection [5]. It is the early stage tumors without any clinical or radiological evidence whose management remains controversial [6–8]. They may harbor disease (36–42%), as reported in the literature [9–11]; however, at the same time, performing an unnecessary neck dissection can lead to avoidable complications.
Certain parameters can help in identifying high-risk patients, for whom an elective neck dissection is justifiable [12–15].
In the present study, the experience in using tumor depth of invasion and layer of invasion as predictor for identifying occult neck nodal metastases in clinically and radiologically negative necks in squamous cell carcinoma of the buccal mucosa is described.
It is a study intended to find the impact of depth of invasion (according to layer of invasion) in buccal mucosa carcinoma (Figs. 1 and 2) on lymph node involvement. The objective is to determine the relationship of the tumor depth with the neck node metastasis in carcinoma of the buccal mucosa. In this study, the depth according to layer the tumour has involved (submucosa and muscle layer and beyond) has been assessed.
Fig. 1.
Anatomy of buccal mucosa
Fig. 2.
SMAS: Superficial Muscular Aponeurotic System. The layers of buccal mucosa from inside to outside are mucosa, submucosa, muscle, SMAS, subcutaneous fat and skin. Layers of invasion in buccal mucosa
The depth according to layer of invasion viz. non-muscle invasive (mucosa and submucosa) and muscle invasive has also been included in the present study. The muscle, subcutaneous fat and skin are all included as one as Muscle invasive.
The aim of this study is to determine the relationship and prognostic impact of the tumour depth according to plane of invasion with the neck node metastasis in carcinoma of the buccal mucosa.
Materials and Methods
Study site: In patients Department (IPD), Surgical Oncology, Prince Aly Khan Hospital, Mumbai.
Study population: All patients coming to Prince Aly khan Hospital Mumbai with previously untreated operable buccal mucosa carcinoma.
Study Duration: June 2018 to March 2020.
Sample Size: Calculated using proportion of relative precision.
Z2 P(1 − P)/€P2
Z2: 1.96 with 95% confidence interval
P: 76%
€: 10%
3.84 × 76 × 24/(0.10 × 76)2 = 121
Estimated sample size would be 121 patients.
-
5.
Inclusion Criteria: Patients with previously untreated operable carcinoma of buccal mucosa. Preoperatively, the neck was N0 in all cases clinically and radiologically.
The following factors were considered under the study:
- Clinical Factor:
- Tumour site
- Histopathological Factors:
- Tumor layer of invasion
- Radiological investigation:
- Ultrasonography doppler neck
- CT head and neck.
- Exclusion Criteria:
- Patients with inoperable stage IV disease, which includes stage IV B tumours.
- Patients with previous history of head and neck cancers, recurrent or distant disease, preoperative chemotherapy, radiation therapy or surgery.
- Patients with multifocal disease involving other sites.
Methodology
It was a prospective study in which detailed assessment was done using case proforma. Detailed clinical history and examination of head and neck, metastatic work up was done. Wide excision of the lesion with and reconstruction was done for all cases. After surgery, histopathological analysis of resected specimen were recorded as part of data collection for all the cases.
-
8.Statistical Methods
- Quantitative data represented using Mean ± SD (Standard Deviation) and median and interquartile range compared using Chi square test.
- Standard principles of univariate and multivariate were used according to statistical methods.
Results
Out of total 220 patients in this study, 90.45% were males and 9.55% were females (Table 1, Fig. 3).
Table 1.
Gender
| Total | Male | Female |
|---|---|---|
| 220 | 199 (90.45%) | 21 (9.55%) |
Fig. 3.
Gender and Incidence of buccal mucosa carcinoma
As apparent from Table 2 and Fig. 4, 143 patients were node negative with 25.17% non muscle invasive (DOI is submucosa) and 74.83% muscle invasive tumours. Out of 77 node positive patients, 10.39% had submucosal disease and 89.61% had muscle invasive disease.
Table 2.
Nodal status and layer of invasion
| Nodal status | Submucosa | Muscle |
|---|---|---|
| Negative (143) (65%) | 36 (25.17%) | 107 (74.83%) |
| Positive (77) (35%) | 08 (10.39%) | 69 (89.61%) |
| Total (220) | 44 | 176 |
Fig. 4.
Bar charts representing depth according to layer of invasion and LN status
Out of 220 cases 44 patients (20%) have submucosal layer of invasion of which 82% were node negative and 18% were node positive. 176 patients (80%) have muscle layer of invasion, of which 61% were node negative and 39% were node positive. The ratio of node negative: positive is 4.5:1 in submucosal subgroup whereas the ratio of node negative: positive is 1.5:1 in muscle subgroup. So from above ratios, it is evident that node negativity decreases with layer of invasion.
As shown in Table 3, the data were analysed on total 220 patients, out of which 143 were negative for lymph node metastasis and 77 were positive. Depth when measured according to layer of invasion, was significantly associated with lymph node metastasis with 89% of the muscle as layer of invasion being LN positive (p = 0.009).
Table 3.
Statistics and association of layer of invasion using chi-square test for association
| LN | Total (220) | p value | ||
|---|---|---|---|---|
| Negative (n = 143) | Positive (n = 77) | |||
| Depth of invasion (layer) | ||||
| Sub mucosa | 36 (25.17%) | 8 (10.39%) | 44 (20%) | 0.009 |
| Muscle | 107 (74.83%) | 69 (89.61%) | 176 (80%) | |
Here all percentages in brackets are with reference to lymph nodes
As is evident from Table 4, in univariate logistic regression, the Depth of invasion (Layer) were found to be statistically significant predictors of LN metastasis.
Table 4.
Univariate logistic regression
| Univariate logistic regression | ||||
|---|---|---|---|---|
| OR | 95% CI for OR | Significance | ||
| Lower | Upper | |||
| Depth of invasion (layer) | ||||
| Muscle | 2.78 | 1.23 | 6.26 | 0.0139 |
| Submucosa (Ref.) | ||||
Discussion
The median age of studied patients was 56 years (range 28–75 years), which is similar to age distribution reported by other studies from India [16, 17]. This validates the fact that prolonged contact of the quid with the mucosal site is suggested as an important etiological factor in terms of high incidence at specific sites. In addition, the data indicates that prolonged use and high frequency of quid uptake seen in older individuals increased oral cancer [16, 18]. Out of the 220 patients, only about 10% were females and 90% were males. This discrepancy in sex seems to reflect the fact that the prevalence of betel quid chewing, which is known to have cause-effect relationship with oral cavity cancer, is much higher among men than women in India [19, 20]. Majority of patients in the present study presented with early operable/locally advanced cancer. The high percentage (60–80) of advanced stage at diagnosis in India has been documented by a number of studies [21] and has been largely attributed to lack of screening and early detection programs in India [22].
The aim is to analyse the layer of invasion of the tumour as predictors of cervical lymph node metastasis.
Analogous to the finding as asserted by Kane SV, Gupta M, Kakade AC, A D' Cruz [23] studied many factors to know chances of lymph node metastasis.
Of all the parameters studied, microscopic tumour depth and thickness were the only significant factors (P value = 0.026 and 0.046, respectively) which correlated with cervical node metastasis on univariate analysis. Tumour depth emerged as a single most significant predictor on multivariate analysis. Majority of the patients with node metastasis had a tumour depth of more than or equal to 5 mm. Depth is the most significant predictor of cervical node metastasis in early squamous carcinomas of the oral cavity.
Further, the depth according to layer of invasion viz. submucosa and muscle (including subcutaneous fat and overlying skin) have been sub-divided. It was found that Depth when measured according to layer of invasion, was significantly associated with lymph node metastasis with 89% of the muscle as layer of invasion being Lymph node positive (p = 0.009). The patients with muscle as depth of invasion were 1.39 times more likely to have lymph node metastasis positivity as compared to patients with submucosal layer. Thus, in case of muscle involvement, it is always safer to electively proceed with neck dissection.
There are certain limitations of the present study which need to be acknowledged. The study has been conducted at a single institution, is of retrospective nature, and relies on data not primarily meant for research. Therefore, this study might be limited by bias, such as lack of random assignment and incomplete data acquisition, particularly, in case of co morbidities, as only those conditions that were recorded in the medical case sheets were taken into consideration. A prospectively collected data will identify more detailed prognostic factors that can better account for the outcomes. Second, the single institutional nature of dataset may again be interpreted as a limitation, as demographic characteristics of the study cohort may be unique and may not be relevant in risk prediction of other patient populations. However, the study cohort being from a single institution had the advantage of having a uniform treatment policy, including postsurgical adjuvant therapy.
To conclude the study depth of invasion according to layer predicts the chance of metastasis in lymph nodes in clinically N0 neck in buccal mucosa cancer.
Budget: There is no budget need for this study as it is a prospective study and all the investigations were being done as needed for surgery.
Footnotes
Publisher's Note
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