Clinical anatomy of coronoid foramina of mandible and review of its implications in maxillofacial surgery

A foramen in the coronoid process of the human mandible is a recently identified anatomic variant. The authors in this script aim at presenting a detailed assessment of the coronoid foramen terming it as ‘’'foramen of Nyer' (FN) based on the person first identifying it. Mandibular cone beam computed tomography scans from a total of 2168 patients were evaluated on a prospective and retrospective scale for confirmation of the coronoid foramen after first identification over a panoramic radiograph. The coronoid foramen was found and confirmed in 96 (4.4%) patients. This script identifying the coronoid foramina of mandible becomes requisite research as a foundation for further analysis due to the scarcity of literature on this recent find. This anatomical–radiological study aims to explore the variant foramina using cone beam computed tomography while determining its prevalence and evaluating its variability in terms of unilateral, bilateral, or gender predilection and propose the significance of this unique anatomic finding. The lack of information about the presence of such variant foramina may lead to emergence of clinical morbidities such as increased risk of intra osseous hemorrhage and tumor spread due to presence of accessory blood vessels.


Introduction
An integral part of anatomical science is constituted by the variant anatomy which is related to the abnormalities within the human body morphology. For a long time, variations of the normal human anatomy were well-illustrious and oftentimes were cases of gross abnormalities, such as a hand with six digits [2]. With the advent of radiographs, it became clear the spectrum of variations from the standard anatomy was far broader than had been appreciated. The cognizance of variants in anatomy has to be considered an integral part of anatomy schooling [6,24]; knowledge of common variants reflects the ability to recognize the diverse clinical reality of anatomy. One such variation in the structural morphology of the coronoid process of mandible was recently identified by Nyer Firdoose and has been elaborated as coronoid foramen ( Fig. 1) in the oro-facial region [11].
There was no literature on the presence of coronoid foramen in the mandible of living humans until the mention of the same in the case reported with a stereolithographic 3D reconstructed model by Firdoose [11]. Clinicians need to be aware of the prevalence of anatomic variants so patients could be prevented from being (mis)treated for pseudo pathology based upon a misunderstanding of a normal anatomical variation as a pathological finding [8,27]. Real anatomy exists in three dimensions and cone beam computed tomography (CBCT) imaging with its high spatial resolution provides superior image quality and allows accurate threedimensional visualization of anatomic variations such as mandibular accessory foramina (MAF) and minute nutrient canals in comparison with the panoramic radiography [26,30].
Owing to the scarcity of literature, the authors in this script aim at presenting a detailed assessment of the coronoid foramen terming it as 'foramen of Nyer' (FN) based on the person first identifying it [11]; in a clinical series to determine its prevalence using CBCT while evaluating its variability in terms of unilateral, bilateral or gender predilection and propose the significance of such an anatomic variation in clinical practice.

Inclusion criteria
All panoramic radiographs with corresponding mandibular CBCT scans with adequate field of view size were included in this study.

Exclusion criteria
• Duplicate radiographs/scans • Lack of corresponding mandibular CBCT scans/isolated maxillary CBCT scans • Insufficient quality, low field of view size, image artifacts • Pathologies or fracture in posterior mandible • Normal structural variations such as medial sigmoid depression A total of 19,979 panoramic radiographs were evaluated from August 2015 till Dec 2021 of which 7768 were excluded for being duplicate radiographs taken as part of follow-up, further 9573 radiographs were excluded as lack of CBCT co-relation/maxillary scans. Finally, 2638 patients having undergone CBCT assessment of the mandibular region for various reasons involving bone evaluation for implant placement and pathologic lesion exclusion were excluded because of insufficient quality, a low field of view size, normal structural variations like Medial sigmoid depression (MSD), images with artifacts, fracture, or pathologies in the posterior region of the mandible. Each author did the screening independently to reach a final consensus. All measurements were made on scale integrated in the CBCT software. Two maxillofacial radiologists performed all the measurements with near perfect agreement.
All procedures followed were per the protocol of the work center and ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. This study was approved by the ethical board with vide approval number 20-242E.

Cone beam computed tomography parameters
The basic mandible reconstruction was performed based on volumetric methods of scanning using 3D CBCT by Orthopantomograph OP300 scanner with technical parameters: image volume size 80 × 150 mm, tube current 15 mA, tube voltage 80 kV, scan time 16 s, exposure time 12 s pulsed X-ray was used for all images.
The software used was DICOM OnDemand3D from Cybermed, USA, for the reconstruction of sagittal, axial, coronal, and three-dimensional images. Image acquisition and scans were reported and consulted by three specialists with at least two-decade experience in their respective fields of Maxillofacial radio diagnosis, medical imaging, and Head & Neck imaging to rule out the MSD, other possible pathologies and to rule out the occurrence of pseudo foramina or a pseudocyst as a post-acquisition or manipulation error in doubtful cases. All evaluations were performed on a 15.6inch monitor with a resolution of 1366 × 768.

Statistical analysis
The data obtained were analyzed using Statistical software SPSS 2.2.0 and R environment 3.2.2. Descriptive and inferential analysis was done. Based on the available data the following assumptions were considered: dependent variables should be normally distributed, Scans drawn from the patients were random and cases of the scans being independent. The recorded variables were the patient's gender, age, distribution pattern, and surface localization of the foramina. The dependent variables were assessed to see if they were normally distributed using a Shapiro-Wilk test.
Chi-Square/Fisher Exact test was used to find the significance of study parameters on a categorical scale between two or more groups & a non-parametric setting for qualitative data analysis was done. The Fisher Exact test was used when cell samples were small while investigating the normal distribution of the variables. On the interpretation of the results, the level of significance was set at 0.05; in the case of p < 0.05, there was a significant association between variables, whereas in the case of p > 0.05 there was no significant association with the variables on a categorical scale.
Kappa test for interobserver variability was done and K = 0.81 which was near perfect agreement.

Results
In the present research, descriptive statistics such as number, gender, age, and surface localization for the variables are represented in Tables 1, 2, 3, and 4. Mandibular scans from a total of 2168 patients were evaluated of which 1480 (68%) were females and 688 (32%) males, age range is between 8 and 80 years with a mean age of 41.5 years whereas the median age was 45 years. Analysis for FN revealed its presence in 96 (4.4%) patients, among which 32 (1.5%) patients had FN unilaterally, the bilateral presence of FN was found in 59 (2.7%) patients, and bilateral FN with accessory foramina were found in 5 (0.2%) patients. From the unilateral type 13 (0.6%) were left-sided while 19 (0.9%) were right-sided respectively ( Table 1).
The association of variant type with gender revealed the presence of FN unilaterally in 21 (21.87%) females and 11 (11.4%) males, the bilateral variant type was seen in 39 (40.62%) females and 20 (20.83%) males, whereas the bilateral variant with accessory foramina was seen in 4 (4.16%) females and 1 (1.04%) male, respectively. This showed no statistically significant difference in the presence of FN with regards to gender, p = 0.831 (p > 0.05) ( Table 2).
The FN based on surface localization was found to be more prevalent over the medial aspect 129 (74.6%) as compared to 44 (25.4%) over the lateral aspect (Table 3).
However, the association of the variant type with age showed a statistically significant relationship, p = 0.0058 (p < 0.05). Much of the bilateral variant type about 31 (68.9%) were found between the 41-50 years group followed by 11 (64.7%) in the 51-60 years group. Likewise, the unilateral left-sided variant 10 (22.2%) were mostly found in the 41-50 years age group, whereas the unilateral right-sided variant 9 (69.2%) were identified in the 21-30 years group followed by 4 (8.9%) in the 41-50 years group. The bilateral with accessory foramina variant 3 (25%) was identified to be more prevalent in the 31-40 years group (Table 4).
The coronoid process when considered as a triangular structure showed a significant distribution pattern of the foramina (Fig. 3), from the 173 foramina identified majority were located towards the base up to 111 (64.2%) followed by the central aspect accounting for 28 (16.2%), the postero-superior aspect towards the sigmoid notch added up to 21 (12.1%) and the least being the antero-inferior surface accounting for only 13 (7.5%) ( Table 5).
In the present study, the gender distribution pattern based on age revealed a greater number of females compared to males in all age groups (Fig. 4) and the gender distribution based on variant type revealed the prevalence of FN more in females compared to the males in the ratio of 1:2 both unilaterally and bilaterally (Fig. 5).
The diameter of the FN was measured. When the measurement was less than 0.25 mm it was measured as absent. The mean diameter of the FN was 1.89 mm and 2.32 mm ± 0.22 mm (range 0. 26-4.28) whereas the median diameter of the FN was 1.81 mm and 2.31 mm respectively.

Discussion
Unearthing the confines of normality in anatomical studies was and will never be easy. The exceptional work way back in 1542, which referred to anatomical variations 'De Humani Corporis Fabrica' merits Vesalius, for being the father of modern anatomy after Galen [14,17,29,31]. Many several decades later Bergman et al., published a compendium of human anatomical variations which forms the most recent compilation of such observations in anatomical variants with scope for improvising additions with the newest editions [2]. The anatomy of organisms is not the same within each species is an established certainty by now, and this applies inter alia to humans [1,17,22,29]. The anatomical variations consequently cannot be limited to variants or anomalies; it also encompasses "normal" variation among individuals [6,23,25]. The number of MAF vary from mandible to mandible, knowing where such variant foramina are located can also help explain how a tumor spreads. Their significance is based on the fact that such distinctive MAF potentially act as direct pathways for tumor cells to migrate from the lateral surfaces to the medullary surfaces of the mandible. It has been found that the foramina that directly connect    with cancellous areas serve as the most efficient means of tumor propagation thereby impacting the ability to predict the tumor progression [9]. In the present study, we determined the FN as a normal anatomical variation in the coronoid process in human mandibles analyzed radiographically amongst the patients of Saudi origin. A systematic review identified only five studies that reported the prevalence of FN in live humans [11-13, 15, 16]. Most of the foramina and canals continue towards progressive obliteration from birth to the first year of life [1]. Any persistence of foramina into adulthood is considered as anatomic variation [17,18,23]. The first description of FN in a live human was associated with the presence of lateral accessory foramina and canal on the mandibular ramus attributing itself to a phylogenetic hypothesis which implied that FN was not observed in humans except for fossilized mammals [11,12]. It was Ferretti and Debruyne [10] mentioning in their article 'Elephas Maximus' as having a foramen and a canal merging with the alveolus at the distal-most erupting molar [3,10]. This canal emerging as the coronoid canal was elaborated as a synapomorphic feature of paenungulates by Tassy and Shoshani [32]. Continuous studies of human morphology are warranted to understand better this anatomic variation. The youngest patient to date was a 7-yearold boy and the oldest patient was a 75-year-old lady to have the confirmed variation in their mandible, the only other published study of similar variation at such a young age was by Ghousia et al. [15]. The study by Gunduz et al. was in association with the accessory mandibular foramina in a Turkish population reporting a mere 2% presence of FN in a sample size of 979 radiographs scanned retrospectively [16]. The deficiency in their results can be attributed to the difference in sample size, interpretation methods, and other variables in comparison to our study. The present script is the only isolated study of the FN carried out meticulously to detail out its occurrence in both genders' along with its prevalence of occurrence on the left or right Furthermore, it is the obligation of the radiologist evaluating a head and neck scan to carefully peruse the topographic anatomy in search of variants and to document on them [5,19], specifically when surgery is under consideration. It is undeniable that diagnostic to a prognostic evaluation of such patients needs to be studied further for a better understanding of the outcome.

Clinical implication
MAF is an opening apart from alveolar sockets, mandibular and mental foramina, and constant structure in the mandible [6,7,26]. MAF is commonly observed in the posterior mandible and symphysis region. Moreover, MAF is more frequently found on the medial surface of the mandible than on the lateral surface [20,21,23]. Bilateral symmetry is frequent, but variations are observed in size, number, and shape [28,32]. Undoubtedly, FN falls well under this category of a well-established normal variant of the mandibular accessory foramen.
For obvious reasons, these variants such as MAF and the FN have been reported to cause implications in clinical practice and may lead to complications if not previously determined. These variant foramina are almost always occupied by the neurovascular bundle [7,20], leading to failure of local anesthesia over adjacent structures and or difficulties in controlling intraosseous hemorrhage due to the presence of accessory blood vessels [8,21]. Understanding variations in the coronoid process of the mandible is particularly important for dental implants and several surgical operations such as orthognathic surgeries, use of coronoid process as autogenous graft for reconstruction of maxillofacial defects or corrective mandibular surgeries involving diagnostic techniques and therapeutic interventions [6,21,22,24,33]. Also, it has been reported that accessory foramina in the mandible provide an easy way for tumor spread following radiotherapy [7,9,28]. If FN is present, the clinicians must be informed and careful while planning for radiotherapy. Clear information and understanding of anatomic and morphologic variations of landmarks will help the surgeon thwart complications. For this reason, extensive and detailed preoperative radiologic assessment using proper imaging modalities should be performed. Moreover, adequate information on the anatomy will help surgeons achieve superior planning and surgical outcomes while preventing wrong interpretation and misdiagnosis [8,19,24,27]. Therefore pertinent diagnostic and pre-surgical assessment of the region will not only help to assess any anatomical variants present but also influences the outcome of surgical procedures related to that particular region along with preventing any sort of iatrogenic injuries to these variant structures postoperatively.

Limitations
1. Unequal gender distribution in different age groups. 2. The study is confined to Saudi population, requires analyses on larger geographic and demographic regions. 3. Lack of knowledge on the co-occurrence and or association with additional anatomic variant(s) other than orofacial region.

Conclusion
The presence of anatomic variants generally does not interfere with the function of the mandible and never typically manifests as pathological units and can be an unpleasant surprise for the operating specialist when revealed during a diagnostic or therapeutic intervention. Moreover, under certain circumstances, these variants can worsen existing pathological conditions or even evoke new ones. A sub-optimal anatomical knowledge regarding the existence or possibility of anatomical variants and the ignorance of the same has more often than not been attributed to an increase in medicolegal claims making it believe as malpractice [4,8]. For such reasons, it gets paramount to consider variant anatomy an unmissable aspect of the body which may potentially defeat a clinician from achieving successful treatment outcomes.
To the best of our knowledge, this is the exclusive FN series report. Additional studies with higher investigation modalities such as magnetic resonance imaging are necessary to clearly understand and discuss the contents of FN and we hope this series will be a foundation for future investigations.
Ethical approval All procedures followed were per the protocol of the work centre and ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. This study was approved by the ethical board with vide approval number 20-242E.