Assessment of depth of invasion in oral squamous cell carcinoma of the tongue: a study protocol

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 6^th leading cause of death.¹ The mortality and rate of OSCC are higher in developing nations.² Worldwide statistics for OSCC show these malignancies are predominant wherever the utilization of tobacco and alcohol found to be high.³

OSCC is seen at various sites in the oral cavity e.g. buccal mucosa, labial mucosa, gingivobuccal sulcus, floor of mouth, retromolar trigone and tongue. The OSCC of tongue is associated with higher mortality than OSCC in other sites.⁴ This could be due to increased risk of cervical nodal metastasis when contrasted with other sub-site which more likely because of rich lymphatics of tongue and floor of the mouth. About 25% patients with OSCC of tongue exist with occult metastasis at initial presentation.¹ In spite of recent advances in diagnosis and treatment of oral malignancy in past several years, the long-term prognosis with five-year survival rates with advanced OSCC of the tongue is poor.⁵

The utilization of TNM staging of OSCC to assess the clinical response to treatment and survival result is for many years. Prognosis of malignancy also depends on the histopathological grading of the OSCC. 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.⁶

Earlier, staging was elicited by superficial evaluation of tumor extension, however, current American Joint Committee on Cancer (AJCC), Cancer Staging Manual, 8^th 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. It has been shown a significant factor in rethinking about the staging, which is evolving in progression dependent on depth of invasion cut off that is 5 mm and 10 mm.¹

Furthermore, current research speculates that, DOI with histomorphological 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 tongue.

Hence, in the current study, we aimed to assess the significance of DOI in the prognosis and clinicopathological features and survival of OSCC lesions.

Methods

The present study will be 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 tongue from year 2009 to 2015 in this institute will be retrieved from the archival of the department.

This study will be a retrospective analysis for which the required protocol was approved by the Institutional Ethical Committee of Datta Meghe Institute of Medical Sciences, deemed to be University (DMIMS (DU)IEC/2020-21/136 dated 05-02-2021). Thirty clinically and histopathologically diagnosed, surgically operated cases of OSCC Tongue will be included in the study. Patients having previous history of oral cancer, recurrence and/or distant disease and pre-operative chemotherapy, radiotherapy, or surgery excluded from the study. Demographic data pertaining to age, gender, detailed history of relevant habit with its dose and duration, site of the lesion of all the study population retrieved. The clinical staging of patients (Tumour Node Metastasis) was done in line with the American Joint Committee of Cancer staging system. Hematoxylin and eosin-stained tissue sections were obtained from archives of department for histopathological analysis. Three oral pathologists performed histopathological examination and gave grading of all oral cancer cases using Broder’s grading system in a blinded manner independently. Extent of lymph node metastasis was evaluated by histopathological examination of lymph nodes from surgically excised specimens. A pilot study was carried out to appraise inter and intra-observer reliability for scoring of the histopathological parameters. Follow-up information for disease free survival of five years was documented in the records.

To determine the DOI, tissue section stained with H & E was inspected using light microscope (Leica) at 100× magnification.

Discussion

One author studied the possibility of cervical lymph nodal metastasis and the recurrence with respect to depth in OSCC of tongue. They evaluated 179 patients and divided them according to 8^th edition AJCC. In group A=1-5 mm; B= 6-10 mm; C>10 mm. They found that the risk of local recurrence and metastasis was higher in group C. So, they concluded that depth more than 10 mm is of increased risk for recurrence and metastasis.¹

A study reviewed the importance of depth of invasion in prognosis of oral squamous cell carcinoma. They also reviewed its determination in carcinoma. They said that histological parameter such as DOI might be used as prognostic factor in carcinoma. DOI is ruled out by detecting the invasion, which is deepest in the underlying tissue. After being histologically examined the treatment of patient may be changed. So, DOI measurement should be part of routine histological examination.⁶

Another study evaluated the clinicopathological factor with the cervical metastasis in oral squamous cell carcinoma of tongue. They reviewed 44 patients of OSCC of tongue, who were treated with only Partial glossectomy. Within five years, cervical metastasis was developed in 21 patients. Some factors were associated with the development of metastasis they are, nuclear polymorphism, and invasive growth, border of tumor, thickness and depth of invasion. They concluded that stage II or I carcinoma having more than 4mm thickness of tumor is at higher risks for metastasis.⁷

Some author compared the tumor thickness with the depth of invasion for their effect to determine the eighth edition of American Joint Committee on Cancer T category on survival of OSCC. 927 patients of OSCC were included on this cohort study. Result showed six percent patients had diverse AJCC-8 T category if they use thickness rather than depth. fifteen patients were staged (T₂) from (T₁) and ten patients (T₃) from (T₂), whereas there was the same stratification of overall survival found for T category based on DOI and TT.⁸

Another author evaluated the literature and impact of depth of invasion in OSCC and its role in predicting mystical cervical lymph node metastasis. There was unambiguous management implication in the review which explains role for elective neck dissection based on DOI. There are large number of studies giving new strategies to treat early stage of OSCC. These altering disease-free survival of OSCC.⁹

There is a study which characterised same histopathological findings which complicates in the measurement of depth of invasion in squamous cell carcinoma of tongue like lacking of residual biopsy after biopsy, deep positive margins, extratumoral invasion, lymphatic invasion.¹⁰ The squamous cell carcinoma of tongue having less than 4 cm and negative cervical lymph node were taken for study. They concluded that measurement of DOI for OSCC of tongue requires re-examination of biopsy in around 20% of cases because of absence of residual carcinoma in specimens of glossectomy.^11–13