Current Opinion in Otolaryngology & Head & Neck Surgery:
HEAD AND NECK ONCOLOGY: Edited by Piero Nicolai and Cesare Piazza
Is it time to incorporate ‘depth of infiltration’ in the T staging of oral tongue and floor of mouth cancer?
Piazza, Cesare; Montalto, Nausica; Paderno, Alberto; Taglietti, Valentina; Nicolai, Piero
Department of Otorhinolaryngology, Head and Neck Surgery, University of Brescia, Brescia, Italy
Correspondence to Cesare Piazza, MD, Department of Otorhinolaryngology, Head and Neck Surgery, University of Brescia, Piazza Spedali Civili 1, 25123 Brescia, Italy. Tel: +39 30 3995319; e-mail: email@example.com
Purpose of review: To summarize recent acquisitions in three-dimensional tongue and floor of mouth anatomy that can help in better evaluation of the pathways of cancer progression within these oral subsites, thus giving some hints for refining of the current TNM staging system.
Recent findings: The Visual Human Project is an initiative aimed at establishing a three-dimensional dataset of anatomy of two cadavers made available free to the scientific community. Visual human data have been analyzed by specific software thus improving our three-dimensional understanding of the tongue myostructure. It is already known that there is limited prognostic utility in using the two-dimensional surface diameter alone as criterion for T1–T3 definition. Recently, also the T4a categorization for the infiltration of ‘deep’ or extrinsic tongue muscles has been criticized. This is largely because the descriptor ‘deep’ does not take into account the fact that considerable portions of these muscles lie in a very superficial plane. Different prognosticators have been proposed for inclusion into the TNM staging system of oral cancer but ‘depth of tumor infiltration’ seems to be the most robust, universally recognized, and reproducible in the preoperative, intraoperative, and postoperative settings.
Summary: Oral tongue and floor of mouth cancer needs to be classified according to a revised TNM staging system in which ‘depth of infiltration’ should be taken into account. An ‘ideal cut off’ for distinguishing ‘low’ (T1–T2) from ‘high-risk’ (T3–T4) categories has been proposed based on the literature review, but needs retrospective as well as large prospective trials before its validation.
Five-year overall survival for squamous cell carcinoma (SCC) of the mobile tongue and floor of mouth, which are the most commonly involved oral subsites in the Western countries, ranges between 50 and 60% and has not changed substantially over the last three decades in spite of the most aggressive modern multimodality treatments [1–6]. This may be in part due to our suboptimal understanding of the complex three-dimensional muscular anatomy of the tongue and patterns of tumor progression within intrinsic, extrinsic muscles, and other paths of least resistance, leading to a less than radical surgical approach to a subset of tongue and floor of mouth SCC. In fact, persistent/recurrent locoregional disease is still the most common cause of treatment failure in such a clinical scenario [7–12].
The TNM classification of oral SCC , which is the most frequently and universally used staging system , has been criticized by several authors [15–18]. Classification of patients affected by cancer remains a major element of discussion for the scientific community, as it forms the basis for selecting a specific treatment, is one of the main prognosticators, and allows fruitful comparisons between different centers using various treatment strategies. The most important limitations of the current anatomic approach to stage tongue and floor of mouth SCC are the limited prognostic value of using the two-dimensional surface diameter alone as criterion to define T1–T3 lesions [8,9,11,19] and the ambiguity within the T4a category of the definition ‘invasion into deep (extrinsic) muscles of tongue’, where the descriptor ‘deep’ does not take into account the fact that considerable portions of extrinsic muscles lie in a very superficial plane [20▪▪,21▪▪]. In addition, a number of different prognosticators ranging from depth of infiltration and tumor volume evaluated by imaging [20▪▪,21▪▪,22–24], to multiparameter histopathologic risk score [10,25], perineural spread [26,27], lymphovascular infiltration , and tumor-induced modification of myofibroblasts [29–32] have been proposed for inclusion into the TNM staging system of the oral cavity. Clearly, some of these can be of easy and reproducible application in every multidisciplinary head and neck team, while others are more difficult to standardize and use routinely. Moreover, the issue of whether SCC of the oral tongue and floor of mouth should be considered distinct from the other ‘oral cancers’ for its well known higher biologic aggressiveness, propensity for regional and distant spreading, and overall worse oncologic outcomes has been raised.
The aim of this review is to summarize some of the most recent acquisitions in the evaluation of the three-dimensional anatomical arrangement of the tongue and floor of mouth that can help to better understand pathways of growth of neoplastic disease within these oral subsites, thus providing some hints for future refinements of the current staging system.
The myostructure of the human tongue is one of the less understood anatomical issues of the body. Its complex three-dimensional muscular arrangement has been described in some landmark articles [33–36] that still form the basis of our knowledge. However, their iconographic material is out of date and fails to convey the complex relationships of the muscles and their distribution in the volume of the tongue. In this respect, the most relevant acquisition for deeper insight into this subject comes from the Visual Human (Visual Human) Project, an initiative of the National Library of Medicine that started in 1986 and is still ongoing . The aim of the project was to establish a database of a normal 37-year-old male and 59-year-old female anatomy through high-resolution computed tomography (CT) and MRI with a slice thickness of 0.33 mm of cadavers prior to their embedment in ice, serial sectioning (with a slice thickness of 1 mm for the male and 0.33 mm for the female), and photography. A three-dimensional dataset of the complete human anatomy was thus made available free to the entire scientific community. The visual human female is the more comprehensive of the datasets , providing unrivalled anatomical details of the lingual myostructure without the distortion effects of disease processes and shrinkage of fixed tissues. Moreover, some computer science departments have developed specific software to reconstruct the visual human data in various forms. Using these platforms, our three-dimensional understanding of the tongue muscular anatomy has been greatly improved, as demonstrated by the most recent publications on this topic [20▪▪,21▪▪,39▪▪].
The tongue may be grossly divided into three parts: base (oropharynx), body, and blade or tip (oral cavity). Its average length (including all the three parts) is 9 cm, whereas its mean width is 5, 6.4, and 2.9 cm, respectively . The tongue is, like the octopus’ tentacles and the elephant's trunk, a muscular hydrostat, that is, a structure with a highly aqueous content, formed by muscles whose biomechanical characteristics are more similar to those of a hydraulic system than to those of other skeletal muscles . The connective tissue, in the absence of bones inside the organ, keeps its volume constant during muscle contractions. In fact, every muscular hydrostat has the ability to both create and supply the structural support for motion, deforming itself isovolemically . The tongue, as any other muscular hydrostat, is composed of a number of muscle groups (distinguished in intrinsic and extrinsic) arrayed across a large spectrum of angles and exhibiting the capacity for multidirectional contraction. This renders study by gross dissection or standard histological methods particularly difficult. Moreover, all the named tongue muscles can be identified as discrete entities only in some regions of the organ, whereas in other parts they separate into smaller fascicles interweaving with those of other muscles.
The intrinsic muscles originate and insert within the tongue and have no bony attachments. They are the superior and inferior longitudinal, the vertical, and the transverse muscles (the latter two being more commonly indicated as a single unit as they are too closely intertwined to be outlined separately by any imaging or standard histological section) [39▪▪]. For the purpose of this article, their anatomic descriptions will not be treated in detail. In contrast, the extrinsic muscles have one attachment to a bone (mandible, hyoid, or styloid process), whereas the other end inserts within the tongue. These are the genioglossus, hyoglossus, styloglossus, palatoglossus, and glossopharyngeus muscles. As their involvement in tongue and floor of mouth SCC is specifically addressed by the TNM staging system currently in use , a brief description of their most important anatomic features is herein included.
The genioglossus are the largest muscles of the tongue. They originate from the superior mental spine of the mandibular symphysis, immediately cranial to the point of origin of the geniohyoid muscles, and fan out in a 90° arc. The genioglossus muscle fascicles, after passing between those of the transverse and vertical unit, terminate in the connective tissue of the lingual dorsum. They can be divided into three main components: vertical, oblique, and horizontal. The vertical portion is the most anterior one. It is usually thin and its most anterior fascicles are very superficial, just below the mucosa of the anterior floor of the mouth and ventral surface of the mobile tongue where they form the lingual frenulum, an important landmark defining the border between the tip (or blade) and the tongue body [39▪▪] (Fig. 1). Each genioglossus is in strict relationship with the ipsilateral sublingual space laterally. The genioglossus is absent from the most anterior part of the tongue, composed only by intrinsic muscles. At more posterior levels, within the tongue body, the entire genioglossus muscle as well as its fascicles become wider and change their orientation from vertical to oblique. These fascicles, after fanning out from their origin on the mandible, pass between the transverse and superior longitudinal muscles and then insert throughout most of the length of the tongue. The two genioglossus muscles are separated from each other by the fibrofatty median raphe, inserted on the anterior arch (a cap-like thickening of the lamina propria) at the level of the tongue blade. The genioglossus on their side are surrounded by the thin but distinct fibrofatty paramedian septum, which separates the genioglossus from the hyoglossus, the styloglossus, and the inferior longitudinal muscle. The importance of such a connective tissue framework, going from the lateral aspect of the median raphe to the hyoglossal membrane posteriorly, was recognized in 1938 in the landmark paper of Abd-El-Malek , who accurately described that lingual artery, its venae comitantes, and a part of the hypoglossal nerve are contained within it (Fig. 2). Moreover, at this level, Rouvière  also described the presence of lingual lymph nodes located on the lateral aspect of the genioglossus and on the hyoglossus muscles, along the course of the lingual artery and veins. The third component of the genioglossus is the most posterior one, or horizontal, originating from the mandible and coursing backward to insert directly onto the hyoid bone or the connective tissue above it.
The hyoglossus originates from the body and greater cornu of the hyoid bone. The chondroglossus, arising from the medial aspect of the hyoid lesser cornu, is herein considered a part of the hyoglossus, from which it is however separated by a thin, lateral fascicle of the genioglossus passing to the side of the pharynx. The hyoglossus, at its origin, is a thin, planar muscle, rhomboid in shape, which separates cranially into three distinct components that fan out superolaterally and insert along the length of the tongue. The most anterior part is composed of fascicles coursing anteriorly along the lateral edge of the tongue and intermingling with the inferior longitudinal, genioglossus, and styloglossus muscles (all forming the so-called combined longitudinal unit) [39▪▪]. The hyoglossus middle component courses in an oblique and superior direction, inserting on the lateral edge of the tongue body. The most posterior component goes superiorly and medially across the posterior surface of the tongue base, merging with some fascicles of the superior longitudinal muscle. The hyoglossus is bordered by the genioglossus and inferior longitudinal muscles medially and the styloglossus laterally. It represents a fundamental surgical and radiological landmark as it divides the sublingual space at the level of the floor of mouth into two compartments: the medial one contains the lingual artery and vein (and corresponds to the lower part of the paramedian septum), whereas the lateral is filled by the hypoglossal and lingual nerves, sublingual gland, the cranial part of the submandibular gland and its duct. Boland et al.[20▪▪] measured the distance relative to the lingual mucosal surface, defined as the length of a line drawn perpendicular to the mucosal surface to the most superficial fibers of hyoglossus, using the dataset of the visual human female. The mean distances were 2.9 mm on the right and 4.3 mm on the left in the axial plane, and 1.8 and 1.6 mm, respectively, on the coronal plane (Fig. 3).
The styloglossus takes origin from the anteromedial surface of the styloid process and the stylomandibular ligament, and is the most lateral of the tongue muscles. It is thin, comparatively small, and often difficult to distinguish from the adjacent hyoglossus fascicles. It is formed by two components: a larger anterior one, coursing along the lateral aspect of the organ and merging with the inferior longitudinal, the hyoglossus, and the genioglossus muscles to form the combined longitudinal complex, and a smaller posterior component passing through the lateral surface of the hyoglossus at the tongue base and merging with it. The mean distance of the styloglossus from the mucosal surface according to Boland et al.[20▪▪] is 1.3 mm on the right and 2.9 mm on the left in the axial plane, and 0.8 and 2.3 mm, respectively, in the coronal plane (Fig. 2). The very superficial course of styloglossus from lateral base of tongue to the apex has also been confirmed by diffusion tensor imaging with tractography . Both the hyoglossus and styloglossus are separated from the more medially located inferior longitudinal muscle by another fibrofatty structure called the lateral septum, inserted on the paramedian septum medially, in which the trunk of lingual artery with its dorsal branches, the glossopharyngeal nerve, branches of the hypoglossus with venae comitantes, and the lingual nerve are located  (Fig. 4). It therefore, corresponds, at least in its inferior portion, to the lateral part of the sublingual space as described above.
The palatoglossus, the smallest of all extrinsic muscles, arises from the anterior surface of the soft palate, at the level of its aponeurosis, courses inferiorly to form the palatoglossal arch, and inserts on the lateral margin of the tongue, just medial to the styloglossus. The glossopharyngeus muscle is another very subtle muscle, usually considered the most inferior part of the superior pharyngeal constrictor muscle, which inserts on the lateral border of the tongue, medial to the palatoglossus.
In 2001, Takemoto  proposed a three-dimensional model of the arrangement of intrinsic and extrinsic tongue musculature of outstanding interest for the present purposes. By systematic microdissection of four hemitongues, he was able to clearly distinguish and explain the laminar structure of this organ. In particular, he identified the subsequent regions: the ‘stem’ composed exclusively by fibers of genioglossus; the ‘core’ (which is the most part of the mass of the organ) composed by fibers of genioglossus, transverse, and vertical muscles; the ‘cover’ composed by longitudinal fibers of intrinsic muscles, hyoglossus, styloglossus, and palatoglossus, the latter three projecting outward and backward from the posterior substance of the tongue forming the so called ‘fringes’; and an external mucous membrane (Fig. 5). The ‘stem’ and ‘core’ were also grouped as inner musculature, whereas the ‘cover’ and ‘fringes’ were termed outer musculature. Even though Takemoto  did not specifically address the problem of thickness of the single layers, from the data he reported on the number of sections performed in each specimen block, it is possible to quantify the thickness of the ‘cover’ with the overlying mucous membrane, which is around 10 mm at the level of the mobile tongue and 13 mm at the tongue base.
SEARCHING FOR AN ‘IDEAL CUT OFF’ FOR TUMOR DEPTH OF INFILTRATION
The most frequent sites of occurrence of mobile tongue SCC are its lateral aspect and ventral surface, at the junction between this organ and the floor of mouth, with the dorsal portion of the tongue being the least involved area . For this reason, we will herein frequently refer to mobile tongue and floor of mouth SCCs as a whole.
Different authors [17,18] have proposed the inclusion of various ‘nonanatomic’ prognosticators (such as histopathologic features, molecular biologic factors, patient-related, and environment-related variables) in the TNM staging system. However, as surgery is still considered the mainstay in the management of oral tongue and floor of mouth SCC, it is advisable to include also ‘anatomic’ prognosticators of the T category in the staging system. As the purely bi-dimensional surface extension of these tumors does not seem to appropriately stratify different T categories in relation to their oncologic outcomes, the inclusion of the third dimension could increase the prognostic power of the current staging system. The idea of applying the depth of neoplastic infiltration as a prognosticator in the TNM staging system is not new as its routine use in cutaneous melanoma, colorectal, gastric, uterine, and bladder cancers has been widely accepted by the scientific community for many years. As multivariate modeling has shown that, in solid cancers, tumor volume is a dominant covariate that overwhelms both T-N categories and stage in predicting oncologic outcomes, the current use of the single-dimensional measurement as a surrogate for tongue tumor burden seems no longer justified, specially because preoperative accurate estimations of the depth of infiltration and tumor volume are currently available using several imaging tools (intraoral ultrasonography, CT, and MRI).
The consistent adverse effect on lymph nodes metastases, local recurrence, and survival rates of oral tumor thickness (or, more precisely, tumor depth of infiltration defined as ‘the deepest invasion of tumor in the tissue from the mucosal surface or from a theoretical reconstructed normal mucosal line’) [45,46] is well known for decades. However, direct comparisons of data in the literature have been traditionally difficult because of the different definition that some authors have given to the ‘invasion depth’ concept. Even though in the present review we will follow the most adopted definition of Moore , others, more recently, have proposed less practical measurements of the depth of tumor invasion from the basement membrane, stating that this dimension (even though difficult to obtain in the preoperative setting) would better reflect the propensity of a lesion to precociously involve lymphatic and blood vessels of the tongue muscles [47,48].
The valuable meta-analysis by Huang et al. set the optimal cut-off point for cervical lymph nodes occult involvement at 4 mm of tumor invasion depth. Interestingly, Bier-Laning et al. found that tumor thickness more than 3.75 mm is also an independent risk factor for the development of contralateral neck nodes metastases (with a 5% increase for every 1-mm increase in tumor depth of infiltration). Preda et al., assessing the ability of MRI to predict tongue tumor thickness and volume, tentatively concluded that the depth of infiltration by imaging more than 5 and 20 mm were indications to ipsilateral and bilateral elective neck dissections, respectively. Recently, Ganly et al. confirmed these assumptions noting that, in low-risk T1–T2 tongue SCCs treated by partial glossectomy with ipsilateral neck dissection and no postoperative radiotherapy, 40% of recurrent patients failed in the undissected contralateral neck. Most were affected by lesions with a thickness of 4 mm or more.
Similarly, a number of authors [45,53–56] have suggested the inclusion of tumor depth of infiltration within the TNM staging system to obtain a modified and more adequate cT and pT classification. The combined application of these two prognosticators, that is, tumor diameter and depth of infiltration, would not render the TNM staging system more complex than it is at present and would not translate into a loss of clinical viability. On the contrary, it would increase the prognostic value of T categories. Once this assumption is accepted, the main problem lies in the identification of ‘ideal cut off’ values of tumor depth of infiltration for ‘low-risk’ (T1–T2) vs. ‘high-risk categories’ (T3–T4).
The first attempt to define T categories on the base of tumor depth of infiltration was made by Moore et al. in 151 patients affected by SCC of the upper aerodigestive tract, mainly located in the oral and oropharyngeal cavities. They proposed to define lesions with a thickness between 13 and 18 mm as T3, and those thicker than 18 mm as T4. Interestingly, the authors found their proposal for a new TNM staging system specially useful for the lesions of the floor of mouth, tongue, buccal mucosa, gum, and soft palate, but not for larynx and pharynx localizations.
Howaldt et al. went a step further by evaluating the impact of their re-classification on 1439 oral cancer patients prospectively treated at 23 institutions in Germany, Austria, and Switzerland (the DOSAK cooperative group) between 1987 and 1991. For the T3 category, the authors proposed to use a thickness more than 20 mm (if the greatest superficial diameter is 2 cm), a thickness between 5 and 20 mm (if the superficial diameter is between 2 and 4 cm), and a thickness between 5 and 10 mm (if the tumor surface is larger than 4 cm). Likewise, for the T4 category they proposed a tumor depth of infiltration of 20 mm (for lesions with a maximum superficial diameter of more than 2 cm), and a depth of 10 mm (for tumors with a surface measure of more than 4 cm). Using such a system, definitively less intuitive than the standard TNM staging system and acknowledged as rather cumbersome by the authors themselves, Howaldt et al., however, found a more even distribution of the entire group of patients within the different T categories, with better graduation and discrimination of survival probabilities.
Yuen et al. found that tumor thickness was the only statistically significant independent risk factor at multivariate analysis, when compared to tumor area, width, and perineural infiltration. In particular, tumor thickness showed significant impact on nodal metastasis, local recurrence, and survival. For this reason, the authors proposed to re-classify oral tongue SCCs according to the following thickness cut off: T1 for tumors less than 3 mm of depth, T2 for thickness between 3 and 9 mm, and T3 for lesions more than 9 mm. The latter group showed a 65% rate of nodal metastasis, 26% of local recurrence, and 60% of 5-year actuarial disease-free survival. These data were confirmed in a second article from the same authors 2 years later . Ling et al. used similar cut off criteria, distinguishing patients with tumors less than 4 mm deep (5-year disease specific survival of 75%), between 4 and 9 mm (56%), and more than 9 mm (17%). Süslü et al. also confirmed these findings using a single cut off of 8 mm (as did Jung et al. with a value of 9 mm, and Jerjes et al. with values of 7.6, 8.6, and 9.5 mm for recurrence-free, locoregional, and distant spreads, respectively), thus distinguishing tumors with good vs. those with poor prognosis in terms of overall, disease-specific, and relapse-free survivals.
Recently, Chen et al. retrospectively evaluated a cohort of 58 patients affected by T4a tongue SCC on the basis of preoperative MRI and oncologic outcomes. They found a mean tumor thickness of 22 mm for the entire T4a category; this is interestingly in agreement with those already reported by Moore et al. and Howaldt et al.[53,54]. Moreover, the authors arbitrarily stratified these patients in three different risk groups according to the MRI-derived tumor depth of infiltration as follows: ‘short’ group (less than 20 mm; mean, 16 mm), ‘middle’ group (between 20 and 26 mm; mean, 23 mm), and ‘long’ group (more than 26 mm; mean, 33 mm). Not surprisingly, they found a strict correlation between the depth of invasion group and the 2-year disease-specific survival rates, which were 72, 62, and 27%, respectively.
Therefore, the main limits of the current TNM staging system of the oral tongue cancer seems to be, on one hand, the extreme paucity of tumors to be grouped in the T3 category and, and on the other hand, the inclusion in the T4a category of a group of extremely heterogeneous lesions that may range from tumors with a limited thickness of few millimeters (sufficient however to reach the styloglossus, palatoglossus, hyoglossus, and genioglossus muscles below the mucosal surface as pointed out by Boland et al.) [20▪▪,21▪▪] to very deeply infiltrating lesions reaching the midline raphe of the tongue. The current understanding of the three-dimensional tongue extrinsic and intrinsic muscular arrangement, together with the somewhat outdated but unsurpassed description by Abdel-El-Malek  of the connective barriers and vascular distribution within this organ, allow us to redefine the critical depth of infiltration for the definition of T3–T4 tumors. Even though, to the best of our knowledge, no ‘in-vivo’ measurement has been performed on the mean distances of the septa from the mucosal surface of the oral tongue and floor of mouth, a tumor depth of invasion between 10 and 20 mm certainly allows the lesion to transgress the external ‘cover’ and ‘fringes’ layers described by Takemoto , to reach the organ's ‘core’, and to infiltrate such neurovascular pathways of spread. This translates in an increased incidence of perineural diffusion, lymph nodes, and distant metastases, with an ensuing worse locoregional control and disease-specific survival. In fact, an interesting report from Okura et al. correlated the incidence of lymph nodes metastases not only with oral tongue tumor thickness, but also with the distance of the deepest portion of the lesion from what they called the ‘paralingual space’, defined as a thin, high-intensity area in coronal plane of T1-weighted MRI, extending from the medial border of the sublingual space to the lingual artery along the lateral border of the genioglossus. This structure clearly corresponds to the paramedian septum described 75 years ago by Abdel-El-Malek . The authors found that a tumor with a ‘paralingual space’ distance less than 5.2 mm was statistically more prone to lymph nodes metastases. Moreover, all their patients with tumors of the lateral border of the tongue reaching the ‘paralingual space’ (mean thickness of 17.8 mm) had lymph nodes metastases and poor oncologic outcomes. Quite similar findings were already published by Steinhart and Kleinsasser  for SCC of the floor of mouth; the authors found that the most frequent pathways of spreading of such lesions were through the sublingual space and between the genioglossus and intrinsic muscles between the floor of mouth and ventral surface of the tongue (the paramedian septum of Abdel-El-Malek, even though it was not specifically named in their article). In this respect, comparison of critical thickness for oral tongue and floor of mouth SCC has been only rarely reported, because of the frequent overlapping of lesions of the ventral surface of the tongue with those primarily arising in the floor itself and subsequently extending to the tongue. However, it is worth noting the observation of Woolgar  that the critical tumor thickness in relation to lymph nodes metastases is less for tumors of the floor of mouth/ventral surface of the tongue (mean, 12 mm; range, 8–17 for those with metastases vs. mean, 5.9 mm; range, 2–11 for those without) than for cancers originating from the lateral border of the tongue (mean, 17.1; range 9–30 vs. mean, 9.2; range, 3–20, respectively). Also these findings are indirect confirmations of the easiest involvement of the paramedian septum from tumors originating at the level of the ventral surface of the organ in comparison to those growing from its lateral border.
By combining all this information, a modified TNM staging system of oral tongue and floor of mouth SCC can be proposed as follows: T1, lesions less than 2 cm in superficial diameter and depth of infiltration inferior to 10 mm; T2, lesions between 2 and 4 cm and depth inferior to 10 mm (both ‘early’ or ‘low-risk’ categories limited to the ‘cover’ and ‘fringes’ layers); T3, lesions with every superficial diameter and depth more than 10 and less than 20 mm (’intermediate-advanced’ category involving the ‘core’ and the paramedian septum); T4, lesions with every superficial diameter and depth more than 20 mm (’advanced’ category transgressing the paramedian septum, involving the ‘stem’ and approximating the midline raphe). Clearly, large cohorts of patients must be retrospectively and prospectively assessed with the proposed staging system to confirm its ability to achieve a better prognostic stratification of T categories.
Although there is increasing body evidence that the depth of tumor infiltration has vital implications as an independent prognosticator in oral tongue and floor of mouth SCC, up to now it has not been included in the TNM staging system. Moreover, in spite of the existence of different studies on this topic, the optimal cut off for tumor thickness to define ‘high-risk’ categories (T3 and T4) has not been definitively identified. The most recent advances in understanding the complex three-dimensional muscular anatomy of the tongue together with the accuracy of current morphologic imaging techniques in depicting anatomic details may stimulate prospective studies by stratifying patients according to the proposed, modified TNM staging system.
Conflicts of interest
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anatomy; depth of infiltration; floor of mouth; oral cancer; oral tongue; TNM; tumor thickness
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