|Year : 2023 | Volume
| Issue : 3 | Page : 364-368
Assessment of depth of invasion in oral squamous cell carcinoma of the tongue
Shelley Rajendra Durge, Alka Harish Hande, Madhuri Nitin Gawande, Swati Krishnakant Patil, Archana Madhukar Sonone, Aayushi Prakash Pakhale
Department of Oral and Maxillofacial Pathology and Microbiology, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, Maharashtra, India
|Date of Submission||11-Aug-2022|
|Date of Decision||07-Nov-2022|
|Date of Acceptance||10-Nov-2022|
|Date of Web Publication||29-Aug-2023|
Dr. Alka Harish Hande
Department of Oral and Maxillofacial Pathology and Microbiology, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignancy of oral cavity. It remains a leading cause of mortality and morbidity around the world. The mortality rate of OSCC is higher in developing nations. OSCC is predominant in region where the consumption of tobacco and alcohol is high. The mortality of OSCC of tongue is higher as compared to other sites. American Joint Committee on Cancer (AJCC) 8th edition has incorporated depth of invasion (DOI) into T staging. Histopathological assessment by measuring DOI enables us the insight about the extent of invasion by neoplastic cells. Aim and Objectives: To assess the significance of DOI in the prognosis by corelating with the clinicopathological features of OSCC of tongue. Materials and Methods: Surgically operated cases of OSCC of tongue from year 2009 to 2015 in this institute was retrieved from the archival of the department. The patient cohort was categorized into two, DOI ≤ 4mm and with >4mm. Results: We observed statistically significant correlation between clinical TNM stage and DOI > 4mm (P = 0.0015); histopatholgical grading and DOI > 4mm (P = 0.002); metastasis by cervical lymph node (LNM) and DOI > 4mm (P = 0.041). Conclusion: We observed statistically significant correlation of DOI with TNM staging, histopathological grading and LNM. This prognostic factor will help the clinician for treatment management protocol.
Keywords: Depth of invasion, disease-specific survival rate, oral squamous cell carcinoma, tumor thickness
|How to cite this article:|
Durge SR, Hande AH, Gawande MN, Patil SK, Sonone AM, Pakhale AP. Assessment of depth of invasion in oral squamous cell carcinoma of the tongue. J Datta Meghe Inst Med Sci Univ 2023;18:364-8
| Introduction|| |
Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity. It remains a leading cause of mortality and morbidity around the world. Overall OSCC represents more than 550,000 cases throughout the world yearly and the 6th leading cause of death. The mortality rate of OSCC is higher in developing nations. OSCC is predominant in region where the consumption of tobacco and alcohol is high.
Buccal mucosa, labial mucosa, gingivobuccal sulcus, floor of mouth, retromolar trigone, and tongue are the common site in oral cavity for OSCC. The mortality of OSCC of the tongue is higher as compared to other sites. This could be due to increased risk of cervical nodal metastasis which is because of rich lymphatics of the tongue and floor of the mouth as compared to other subsites. About 25% of patients with OSCC of the tongue exist with occult metastasis at initial presentation. In spite of recent advances in diagnosis and treatment in past several years, the prognosis with 5-year survival rates with advanced OSCC of the tongue is poor.
Prognosis of OSCC is related to its tumor node metastasis (TNM) staging and histopathological grading. Although the tumor stage has consistently been an important contributor to the prognosis of the malignancy, tumor grade is additionally a significant factor to prognostication and type of management. Subsequently, the prognosis and management of OSCC rely upon stage and grade of the tumor.
Earlier, staging was elicited by superficial evaluation of tumor extension; however, the current American Joint Committee on Cancer (AJCC), cancer staging manual, 8th edition has incorporated depth of invasion (DOI) into T staging, which by definition is the distance from the reconstructed mucosal surface to deepest Level of invasion [Figure 1].
|Figure 1: A line drawn from basement membrane (A) to invasive front of tumor (B). Line A to B is Depth of invasion (DOI)|
Click here to view
Tumor thickness and DOI are two different concepts that cannot be used interchangeably. In exophytic tumors, tumor thickness can be higher than DOI, but in endophytic/ulcerated development patterns, tumor thickness can be lower than DOI. Lymph node metastasis (LNM) risk has been proven to be less correlated with tumor thickness (LNM). The DOI cutoff for doing an elective neck dissection (END) is not universally acknowledged (END). In the literature, values between 1.5 mm and 10 mm are noted. Furthermore, the current researches speculated that DOI with histopathological parameters should be included as prognosticating factor in OSCC patients.
Histopathological assessment by measuring DOI enables us the insight about the extent of invasion by neoplastic cells. This observation will further be helpful for treatment management protocol, particularly in OSCC of the tongue. Hence, in the current study, we aimed to assess the significance of DOI in the prognosis by correlating with the clinicopathological features of OSCC of the tongue.
| Materials and Methods|| |
This retrospective cohort study was carried out at the “Department of Oral and Maxillofacial Pathology and Microbiology,” “Sharad Pawar Dental College and Hospital,” “Datta Meghe Institute of Medical Sciences,” (Deemed to be University), Sawangi (Meghe), Wardha, Maharashtra, India. Surgically operated cases of OSCC of the tongue from 2009 to 2015 in this institute were retrieved from the archival of the department, and informed consent was obtained from the patients.
The Institutional Ethical Committee (DMIMS (DU) IEC/2020–21/136 dated February 05, 2021) accepted the study's necessary protocol. The study comprised 30 surgically operated instances with OSCC tongue with clinical and histological diagnoses. Patients who had previously undergone preoperative chemotherapy, radiation, or surgery for oral cancer and/or had the illness relapse or spread to distant sites were excluded from the trial. Age, gender, a thorough history of each relevant habit with its dosage and duration, and the location of the lesion for the entire study sample were all obtained. The American Joint Committee of Cancer staging system 9 was used for the clinical staging of patients (TNM). For histological analysis, tissue slices stained with hematoxylin and eosin were retrieved from the department's archives. In accordance with Broder's grading system, three oral pathologists independently and blindly carried out histopathological examinations. Histopathological analysis of lymph nodes from surgically removed specimens allowed for the evaluation of the lymph node metastases' extent. To evaluate inter- and intraobserver reliability for the histopathological assessment, a pilot research was conducted. The DOI was measured as per the AJCC 8th edition criteria. The basement membrane of adjacent normal mucosa was considered a baseline for the measurement of DOI. A vertical line was drawn with a transparent ruler overlaid on slide from the plane to the deepest point of tumor cell infiltration. The patient cohort was categorized into two, DOI ≤4 mm and with >4 mm.
Chi-square test was utilized for the statistical analysis, which was conducted using descriptive and inferential statistics. SPSS 27.0 (SPSS Inc., Chicago, IL) and GraphPad Prism 7.0 versions of software were employed, and a significance threshold of P = 0.05 was chosen.
| Results|| |
There were 30 cases of tongue OSCC with a mean age with standard deviation of 52.13 ± 13.36 (23–75 years). On evaluation of the gender, majority of the cases were male, 25 (83.33%).
On evaluation of clinical TNM staging, most of the cases were in stage III, 13 (43.33%), followed by stage IV, 11 (36.67%). Only 6 cases were in stage II (20%). Further, we correlated TNM staging with DOI and we observed a statistically significant correlation between clinical TNM stage and DOI >4 mm (P = 0.0015) [Table 1].
|Table 1: Correlation between tumor node metastasis staging and depth of invasion|
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On evaluation of histopathological grading, majority of cases were Moderately differentiated squamous cell carcinoma (MDSCC), 24 (80%) followed by Well differentiated squamous cell carcinoma (WDSCC), 4 (13.33%), and only 2 (6.67%) cases were in PDSCC. On correlation of histopathological grading with DOI, we observed a statistically significant correlation with DOI >4 mm (P = 0.002) [Table 2].
On evaluation of metastasis by cervical lymph node, we observed that 17 (85%) cases were positive for metastasis with >4 mm DOI and shows a positive correlation with DOI (P = 0.041) [Table 3].
|Table 3: Correlation between lymph node metastasis and depth of invasion|
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On evaluation of perineural and muscle invasion, we observed 6 cases were positive for muscle invasion, whereas no cases showed perineural invasion.
On evaluation of muscle invasion, we observed that 5 (83.33%) cases were positive with DOI >4 mm.
| Discussion|| |
OSCC of the tongue has shown higher risk of cervical nodal metastasis as compared to other subsites. Probably, this may be as a result of abundant lymphatics of the tongue and floor of the mouth.
Prognostic classification of patients with early-stage tongue OSCC is still lacking despite advancements in oral cancer therapy. The biggest histological indicators for recurrence and death from early-stage tongue OSCC are DOI and worst pastern of invasion.
With the use of END to enhance locoregional control and DOI-based criteria, early-stage OSCC continues to show improvements in survival results. However, the DOI is supported by the literature data to help with case selection for END, although the DOI cutoff value is still up for debate. Others consider 3 mm to be the ideal cutoff for END situations, instead of the DOI guides' 4 mm cutoff. By predicting the status of the regional lymph nodes, the addition of DOI in the pT category for OSCC may enhance the prognostic performance of AJCC staging.,
The TNM approach of cancer staging evaluates the primary tumor size (T), the involvement of local lymph nodes (N), and distant metastases to determine the amount of tumor progression throughout the body (M). This classification is crucial for therapy selection, calculating recurrence risk, and gauging overall survival.
We correlated the TNM staging with the DOI and found a significant correlation with increasing tumor grade with increasing DOI (P = 0.001, S) [Table 1]. In stage I, 0 (0%) cases showed >4 mm DOI, in stage II - 1 (16.67%), in stage III - 10 (76.92%), and in stage IV - 22 (73.33%) [Table 1]. However, no studies have been reported in the literature regarding the correlation of TNM staging and DOI. As per our knowledge, this is the first attempt to find out the correlation between TNM staging and DOI.
Based on variations in tumor differentiation, Broders originally developed histopathological grading for squamous cell carcinoma of the lip. Later, Jakobsson et al., Anneroth et al., and Bryne et al. proposed more intricate grading systems.,,, We further correlated histopathological grading with DOI. In WDSCC, we observed 0% cases showing DOI >4 mm; in MDSCC, 83.33%; and in PDSCC, 100% cases. Our results are in accordance with Arora et al. They observed a correlation with the DOI and as an independent prognostic factor (P = 0.003) [Table 1].,
Morphological and cellular alteration in dysplastic cells is noticeable in histological examination of tissue. With reference to histological grading of OSCC, the DOI found increased in MDSCC as compared to WDSCC. There is more cellular activity seen in MDSCC as compared to WDSCC. So isolated undifferentiated neoplastic cells invasion increases with increase DOI.
LNM is an important prognostic factor for patients with OSCC. In our study, we measured DOI according to the AJCC 8th edition and cases were categorized into two, with DOI ≤4 mm and DOI >4 mm. We have observed that patients having DOI >4 mm showed higher rate of LNM 17 (85%) than that of DOI ≤4 mm 3 (15%).
Our result is in accordance with Faisal et al. and Mohit-Tabatabai et al. They studied possibility of cervical lymph nodal metastasis and the recurrence with respect to depth in OSCC of the tongue and reviewed patients, who were treated with only partial glossectomy. They observed that the risk of local recurrence and metastasis was higher in patients with DOI >4 mm. Within 5 years, cervical metastasis was developed in some patients. Thus, the DOI more than 4 mm is of increased risk for recurrence and metastasis., In OSCC of tongue, LNM positive cases were reported in 20-30 % whereas in buccal mucosa 15.4% cases and in floor of mouth 41.7% cases were positive for LNM. These discrepancies can be attributed to the varying distances between tumors and lymphatic vessels as well as the various vessel sizes found at the various subsites.
The proximity to blood arteries and lymphatic channels may be determined by the DOI and the microvascular proliferation brought on by neoplastic development, which would facilitate the metastatic process. The ability to categorize patients into low-risk and high-risk groups using DOI has been demonstrated to be useful. The DOI is a reliable and independent predictor of neck LNM. Treatment planning is a multifaceted process, and numerous variables and criteria with varying impacts should be taken into account when making decisions about how to manage OSCC. Regarding OSCC, Bur et al. included tumor grade to predict LNM in early-stage tumors. Kim et al. employed tumor stage for prognostication in a manner similar to this that may improve prediction of survival following treatment for OSCC. Alabi et al. estimated the likelihood of recurrence in early oral tongue cancer using stage and grade.,,,
Literature evaluated the impact of DOI in OSCC and its role in predicting cervical LNM. There was unambiguous management implication in the review which explains role for END based on DOI. There are large number of studies giving strategies to treat early stage of OSCC. These strategies are altering the disease-free survival of OSCC.,,,,,,,,,,
| Conclusion|| |
The extent of tumor invasion into deeper tissue can be assessed histopathologically by measuring DOI which can be utilized as a prognostic factor. We analyzed 30 cases of carcinoma of the tongue by histopathological assessment of DOI. Further, we observed a statistically significant correlation of DOI with TNM staging, histopathological grading, and LNM. Hence, measurement of the DOI should be included as part of routine histopathological reporting. This prognostic factor will help the clinician for treatment management protocol.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]