1 Volume 22 2023 e237798 Original Article Braz J Oral Sci. 2023;22:e237798http://dx.doi.org/10.20396/bjos.v22i00.8667798 1 Nitte (Deemed to be University), AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Department of Oral Medicine and Radiology, Mangalore, India. Corresponding author: Dr Renita Lorina Castelino Nitte (Deemed to be University), AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Department of Oral Medicine and Radiology, Mangalore, India. Contact info-9880143370 Email: renita.castelino@yahoo.com Editor: Dr. Altair A. Del Bel Cury Received: December 6, 2021 Accepted: May 6, 2022 Prevalence of soft tissue calcifications in the maxillofacial region – a radiographic study Deepthi Darwin1 , Renita Lorina Castelino1,* , Gogineni Subhas Babu , Mohamed Faizal Asan1 Aim: To evaluate the prevalence of soft tissue calcifications in orofacial region and their panoramic radiographic characteristics using digital panoramic radiographs among patients reporting to a tertiary dental hospital. Methods: 1,578 digital panoramic radiographs were retrieved from the archives and scrutinized for the presence of calcifications. Soft tissue calcifications were recorded according to age, gender, site (left or right). Data were analysed using Chi-square and Fisher’s exact test using SPSS software and a p < 0.05 was considered statistically significant. Results: Among the total number of radiographs, calcified carotid artery (34.3%), calcified stylohyoid ligament (21%), tonsillolith (10.3%), phlebolith (17.6%), antrolith (6.3%), sialolith (5.9%), rhinolith (2.5%) and calcified lymph nodes (1.9%) were identified. The most commonly observed calcifications were calcification of carotid artery and stylohyoid ligament and the least commonly observed calcifications were rhinolith and calcified lymph node. A statistically significant association of the presence of calcifications of carotid artery and stylohyoid ligament on the left and right side was observed in females and tonsillolith on the right side in males (p-value < 0.05). Considering the gender and age group, the occurrence of antrolith among males and rhinolith among females of young-adult population, tonsillolith among the males, calcified carotid artery and stylohyoid ligament among the females of middle-aged population was found to be significant. Conclusion: Soft tissue calcifications are often encountered in dental panoramic radiographs. Our study revealed that the soft tissue calcifications in orofacial region were more common in women and were found to be increased above 40 years of age. Keywords: Radiography, panoramic. Calcinosis. Plaque, atherosclerotic. Eagle syndrome. Diagnostic imaging. https://orcid.org/0000-0003-2440-1012 https://orcid.org/0000-0002-8696-549X https://orcid.org/0000-0001-9383-7886 https://orcid.org/0000-0001-9747-1914 2 Darwin et al. Braz J Oral Sci. 2023;22:e237798 Introduction Calcium is a micronutrient that is required for a variety of physiological functions such as cellular activities, neuronal activity, tooth and bone formation, etc.1. Deposition of calcium salts in the tissues can be manifested in various physiological and patholog- ical conditions2. Calcium salts, primarily calcium phosphate gets accumulated in the soft tissues in an unstructured manner resulting in pathological calcifications which is also referred to as heterotopic calcification3. Pathologic calcifications can be either dystrophic which occurs in degenerating and necrotic tissues or metastatic which occurs due to the precipitation of excess calcium and phosphate in the normal tis- sues4. Occasionally, such calcifications may occur bilaterally and symmetrically sec- ondary to the skeletal deposits from a malignancy5,6. Extra-skeletal calcifications such as calciphylaxis, calcifications within the brain such as primary familial brain calcification, calcifications of tumour, arthritic bone spurs, gall and kidney stones are some of the typical sites of soft tissue calcifi- cations6,7. Soft tissue calcifications in the orofacial region are commonly detected as incidental findings during routine radiographic examinations with orthopanto- mograms (OPGs)4,8. Evaluation of such calcification should be carried out in a sys- tematic manner considering the anatomical location, distribution, shape, size and number of calcifications to arrive at an appropriate diagnosis9. Digital panoramic imaging is a routinely employed modality for diagnosing pathologies of the jaw- bones. It is considered as an initial imaging modality that allows appropriate dis- cernibility of the structures of the maxillofacial region10. There are various pieces of evidence available in the literature that delineates the detection of soft tissue calci- fications in OPG, but the prevalence of such calcinosis differs widely among various studies and the population studied5. The calcifications that can be encountered in panoramic radiographs include rhinolith, antrolith, tonsillolith, phlebolith, sialolith, carotid artery calcifications, calcified lymph nodes and stylohyoid ligament11. With the increased utilization of digital panoramic imaging in routine dental practices, understanding of the soft tissue calcifications and their characteristics is necessary for formulating a diagnosis and establishing an appropriate referral strategy12,13. Hence, considering the wide span of pathologies and the paucity of research, we undertook this retrospective study with the aim of evalu- ating the prevalence of soft tissue calcifications using digital panoramic radiographs among patients reporting to a tertiary dental hospital. Materials and methods Selection of patients The present retrospective study was carried out after the approval of the Institu- tional Ethical Committee (ETHICS/ABSMIDS/149/2021). Panoramic radiographs of individuals who had visited the Department of Maxillofacial Radiology from January 2020 to December 2020 were retrieved from the archives and screened based on our inclusion criteria. The panoramic radiographs of all age groups and gender with 3 Darwin et al. Braz J Oral Sci. 2023;22:e237798 good diagnostic quality were included in the study. We obtained a total of 1693 radio- graphs which were scrutinized for the presence of soft tissue calcifications. However, 115 radiographs were excluded due to the presence of radiographic artifacts, facial deforming pathologies, obscure images with superimposition of structures and lack of diagnostic quality.  Image acquisition The radiographic images were procured with an orthopantomogram unit, Plan- meca ProMax S2-2D (Helsinki, Finland, 2008) using Planmeca Romexis software (Version 2.4.2) and viewed on a full-screen monitor. The panoramic radiographs were taken by a trained radiographer with the exposure parameters of 64-70 kV; 7-14 mA and an average exposure time of 16 seconds. All the images were evaluated by two independent Oral and Maxillofacial Radiologists with a minimum of ten years of clin- ical experience. The evaluation of the radiographs was done based on parameters such as age, gender, site and type of calcification. Image analysis Soft tissue calcifications were classified according to their number, location, shape, distribution (side of involvement) and appearance. For the ease of identification of soft tissue calcifications, the panoramic radiographs were divided into eight equal quadrants by sketching one horizontal and three vertical lines following the method described by Rajkumar et al.1. A horizontal line was drawn across the occlusal plane. Vertical lines were drawn across the midline passing through the nasal septum and along the anterior aspect of the mandibular ramus on either side and numbered from 1-8 as shown in figure-1. The soft tissue calcifications were documented based on their anatomical location and the quadrant in which they were present. Table-1 enu- merates the calcifications in the maxillofacial region based on their characteristic radiographic appearance as found in our study. The description of the characteristic radiographic features based on the location of the soft tissue calcifications is cited from the previous literature1,5,9,14-16. Figure 1. Division of OPG divided into 8 boxes arbitrarily. 1 5 6 7 2 3 4 8 L 4 Darwin et al. Braz J Oral Sci. 2023;22:e237798 Statistical Analysis Statistical analysis was performed with SPSS statistics program (IBM, Armonk, NY, USA) Version 22 for Windows. Numerical data were represented as mean and stan- dard deviation values. The categorical data were represented as frequencies and per- centages and analysed with the help of Fisher’s exact test and Chi-squared tests. A p-value of 0.05 was considered to assess the level of significance.  Results The demographic data of the study subjects are enlisted in Table-2. Our study included a total of 1578 panoramic radiographs which comprised of 644 males and 934 females, and the age of subjects ranged from 7 to 82 years with a mean age of 45.60 ± 15.9 years. Out of 1578 radiographs, only 204 (12.9%) had visible soft tissue calcifications of which 78 (38.2%) were males and 126 (61.8%) were females. Table 1. Characteristics of calcifications located in the maxillofacial region S.No Type of Calcification Number Radiographic Appearance Location 1 Antrolith 2nd or 3rd quadrant • Commonly appears as a solitary radiopacity which is well-defined, round to ovoid, irregular or smooth in outline. • Seen in the antrum of maxillary sinus. 2 Rhinolith Medial aspect of 2nd or 3rd quadrant • These are heterogenous or homogenous radiopacities with a laminar appearance. • Seen in the nasal fossa. 3 Phlebolith 5th or 8th quadrant • Seen as small, multiple circular or oval layers of concentric radiolucent and radiopaque rings. • Often, these calcified bodies have the characteristic radiopaque “bulls eye” or “target” appearance. Common sites are: • Posterior region of body of mandible. • Internal aspect of inferior alveolar canal. 4 Tonsillolith 1st or 4th quadrant • Appears as unilateral ill-defined radiopacities in clusters. • Seen superimposed over the mid-portion of ramus along the Oro-pharyngeal air space. 5 Sialolith 1st or 4th quadrant • Single or multiple, irregularly shaped calcified structures with a smooth outline. • Submandibular gland sialolith (83-94%) – Along the ramus or angle of the mandible. • Parotid gland sialolith (4-10%) – Along the upper-third of mandibular ramus (within parotid space). 6 Calcified lymph nodes 5th, 8th or lateral aspect of 6th or 7th quadrant • Calcified structures with “cauliflower-like” lobulated appearance and an irregular periphery. • Commonly located at the inferior border of mandible near the angle. 7 Atherosclerosis (Carotid artery calcifications) 5th or 8th quadrant • Irregular, heterogenous vertico-linear radiopacities with a characteristic “pipe-line” or “Tram-track” appearance. • Seen at the level of intervertebral space between C3 and C4. 8 Calcified stylohyoid ligament From 1st to 6th quadrant or 4th to 7th quadrant • Ossified radiopaque ligaments which can be slender, segmented, tapering and often longer than 30 mm. • Extends from mastoid region to the hyoid bone, crossing the posterior-inferior aspect of mandibular ramus. 5 Darwin et al. Braz J Oral Sci. 2023;22:e237798 The study samples were categorized based on the age group classification given by World Health Organization as subjects, between 3 to 39 years as young adults; sub- jects between 40 to 59 years as middle age and subjects between 60 to 99 years as old age. The majority of soft tissues calcifications observed in our study were more common in the middle-aged (44.1%) population followed by the young adult popu- lation (40.7%). Among the 204 calcifications, calcifications of carotid artery (34.3%) were the most predominantly observed calcification followed by calcified stylohyoid ligament (21%), phlebolith (17.6%), tonsillolith (10.2%), antrolith (6.4%) and sialolith (5.9%). The presence of calcification in the nasal cavity (2.4%) and lymph nodes (1.9%) were the least encountered calcifications (Figures-2,3,4 and 5). Subjects identified with soft tissue calcifications comprised of 33% and 35.7% of carotid artery calcifica- tions, 19.8% and 22.4% of calcified stylohyoid complex, 17.9% and 16% of phleboliths, 11.3% and 8.5% of tonsilloliths, 7.5% and 5.1% of antroliths, 6.6% and 5.1% of sialo- liths, 2.8% and 2% of rhinoliths, 0.9% and 3% of calcified lymph nodes on left and right sides of the radiographs respectively. Analysis of Soft tissue calcifications based on various age groups and Gender: In the present study, the occurrence of antrolith, rhinolith, tonsillolith, calcifications of the carotid artery and stylohyoid ligament (p > 0.05) was significant. We found a Table 2. Demographic data of the study sample. Total no. of panoramic radiographs Collected and screened 1693 No. of panoramic radiographs excluded 115 No. of panoramic radiographs included 1578 CHARACTERISTICS OF THE INCLUDED RADIOGRAPHS GENDER n % Males 644 40.8 Females 934 59.2 AGE GROUP n % 03-39 (Young Adults) 498 31.5 40-59 (Middle aged) 516 32.7 60-99 (Old aged) 564 35.7 CHARACTERISTICS OF THE RADIOGRAPHS WITH CALCIFICATIONS No. of panoramic radiographs with soft tissue calcifications 204 GENDER n % Males 78 38.2 Females 126 61.8 AGE GROUP n % 03-39 (Young Adults) 83 40.7 40-59 (Middle aged) 90 44.1 60-99 (Old aged) 31 15.1 6 Darwin et al. Braz J Oral Sci. 2023;22:e237798 Figure 2. (A) The arrow on the panoramic radiograph showing a radiopaque mass in the right maxillary sinus suggestive of antrolith. (B) The arrows on the panoramic radiograph showing well-defined elongated radiopacity at the level of third cervical vertebrae suggestive of carotid artery calcification. L L A B Figure 3. (A) The arrows on the panoramic radiograph showing well-defined circular radiopacities in the internal aspect of inferior alveolar canal bilaterally suggestive of phleboliths. (B) The arrow on the panoramic radiograph showing a radiopacity near the angle of mandible on right side suggestive of sialolith. L L A B 7 Darwin et al. Braz J Oral Sci. 2023;22:e237798 Figure 4. (A) The arrow on the panoramic radiograph showing a well-defined radiopacity with a “cauliflower appearance” near the mandibular angle suggestive of calcified lymph node. (B) The arrow on the panoramic radiograph showing a well-defined radiopacity close to the nasal fossa on left side suggestive of rhinolith (The contrast of the radiograph is altered for better visualisation of the calcification). L L A B Figure 5. (A) The arrows on the panoramic radiograph depicting calcified stylohyoid ligament bilaterally. (B) The arrow on the panoramic radiograph showing multiple radiopaque masses superimposed on the right mid-ramus region suggestive of tonsilloliths (The contrast of the radiograph is altered for better visualisation of the calcification). L L A B 8 Darwin et al. Braz J Oral Sci. 2023;22:e237798 statistically significant association of the occurrence of antrolith (p=0.018) among the males and rhinolith (p=0.025) among the females and it was predominantly seen in the young-adult population. We also observed a significant prevalence in the occur- rence of tonsillolith (p=0.007) among the males, carotid artery calcifications (p=0.001) and calcified styloid ligament (p=0.022) among the females and was predominantly seen among the middle-aged population respectively (Table-3). Analysis of Soft tissue calcifications based on Site and Gender: Our results revealed that most of the calcifications occurred on the left side and the prevalence of calcifications on the left and right sides comprised 51.9% and 48% respectively. There was a statistically significant association of occurrence of Tonsil- lolith in the right side of males (p=0.011). In addition, the occurrence of carotid artery calcification in the left (p=0.011); right (p=0.029) sides and calcified stylohyoid liga- ment in the left (p=0.041); right (p=0.009) sides in females were found to be statisti- cally significant (Table 4). However, there was no significant difference in the occur- rence of antrolith, rhinolith, phlebolith, sialolith, calcified lymph nodes among males and females (p-value > 0.05). Table 3. Distribution of various soft tissue calcifications based on age group and gender TYPE OF CALCIFICATION AGE p-value03-39 (YOUNG ADULTS) 40-59 (MIDDLE AGED) 60-99 (OLD AGED) Antrolith M 6 (100%) 0 0 0.018 F 4 (57.1%) 3 (42.6%) 0 Rhinolith M 0 1 (20%) 0 0.025 F 4 (80%) 0 0 Phlebolith M 11 (50%) 5 (22.7%) 6 (27.3%) 0.111 F 4 (28.6%) 8 (57.1%) 2 (14.3%) Tonsillolith M 3 (17.7%) 10 (58.8%) 4 (23.5%) 0.007 F 4 (100%) 0 0 Sialolith M 3 (33.3%) 4 (44.4%) 2 (22.2%) 0.513 F 2 (66.7%) 1 (33.3%) 0 Calcified Lymph Node M 1 (100%) 0 0 0.248 F 1 (33.3%) 0 2 (66.6%) Carotid artery calcifications M 12 (80%) 3 (20%) 0 0.001 F 8 (14.5%) 35 (63.6%) 12 (21.8%) Calcified styloid ligament M 4 (57.1%) 1 (14.3%) 2 (28.6%) 0.022 F 16 (44.4%) 19 (52.8%) 1 (2.8%) 9 Darwin et al. Braz J Oral Sci. 2023;22:e237798 Discussion Panoramic radiography (OPG) is an imaging modality that can aid in simultaneous preliminary radiographic examination of both maxillary and mandibular jaws. Despite being a two-dimensional radiograph, OPG is one of the frequent radiographic inves- tigations employed in maxillofacial radiology due to its low cost and reduced patient radiation exposure17. Thereby, given its popularity, dental clinicians should be familiar with the typical patterns and characteristic radiographic features of various soft-tis- sue calcifications that are encountered in the maxillofacial region. These calcifica- tions are often asymptomatic and detected as incidental findings4. According to the recommendations of the American Academy of Oral and Maxillofacial Radiology, the use of a three-dimensional imaging modality like CBCT, which has the advantage of providing high-quality diagnostic images, cannot be justified in the initial evaluation of soft tissue calcifications unless the patient is symptomatic18,19. In our study, we observed soft tissue calcifications in 12.9% of the total radiographs, which is comparatively higher than the reports of previous studies which revealed a prevalence rate varying between 2.6% and 19.7%3,5,10,20. This difference in the preva- lence can be attributed to several factors such as racial, age, geographical and ethnic variations. Apart from this, the possibility to alter the image density and contrast in the radiographic images can also attribute to the variations as reported by Monsour et al.20. We found that the majority of calcifications within the soft tissues were more common in middle-aged (44.1%) population followed by young adults (40.7%). These Table 4. Frequency of various soft tissue calcifications based on gender TYPE OF CALCIFICATION GENDER p-value MALE FEMALE Antrolith L 4 (30.8%) 4 (30.8%) 0.717 R 2 (15.4%) 3 (23%) 0.401 Rhinolith L 1 (20%) 2 (40%) 0.668 R 0 2 (40%) 0.167 Phlebolith L 12(33.3%) 7 (19.4%) 0.806 R 10 (27.8%) 7 (19.4%) 1.0 Tonsillolith L 8 (38%) 4 (19%) 0.762 R 9 (42.9%) 0 0.011 Sialolith L 5 (41.7%) 2 (16.7%) 0.701 R 4 (33.3%) 1 (8.3%) 0.649 Calcified Lymph Node L 0 1 (25%) 0.410 R 1 (25%) 2 (50%) 0.668 Carotid artery calcifications L 7 (10%) 28 (40%) 0.011 R 8 (11.4%) 27 (38.6%) 0.029 Calcified styloid ligament L 4 (9.3%) 17 (39.5%) 0.041 R 3 (6.9%) 19 (44.2%) 0.009 10 Darwin et al. Braz J Oral Sci. 2023;22:e237798 findings were consistent with the results of Icoz et al. and Ribeiro et al. who also sug- gested that the prevalence of calcifications increased above 40 years4,10. The process of calcinosis begins at an early age and progresses as the patient ages thus becom- ing radiographically identifiable. The most commonly observed soft tissue calcification in the present study was calcification of the carotid artery constituting 4.4% of all included radiographs. The results were statistically significant and were consistent with the findings of Bayer et al., Saati et al. and Garay et al. who reported a higher prevalence of calci- fications of carotid artery in the middle-aged female population3,17,21. Women were more typically affected in the post-menopausal period (>50 years) owing to the diminished oestrogen levels. The role of oestrogen in the metabolism of lipopro- teins is well established in the literature, and it is known to inhibit the formation of atheromatous plaques4,22. The link between the risk of ischemic stroke and the occurrence of carotid artery calcifications has been a source of debate. Significant narrowing of an arterial lumen with a lucent defect is indicated by a massive cal- cification. According to the literature, the calcium levels in cervical carotid arteries serves as an independent marker for the detection of ischemic symptoms23. Liter- ature evidences have accounted stroke to be the second-leading cause of death globally (11.6%). Risk of stroke in the presence of atherosclerosis of the carotid artery is 8%. Hence, active observation of the asymptomatic patients with the aid of panoramic radiographs can potentially reduce the occurrence of any life-threatening consequences such as stroke and myocardial infarction5,10,17,24. Out of the total radiographs evaluated, our study reported an overall prevalence of 2.7% of calcified stylohyoid ligament. Previous studies have reported varied prevalence rates ranging from 7.9% to 38.57%5,14,25. We observed the occurrence of calcified stylohyoid process to be significantly higher in women and predomi- nantly on the right side compared to the left. We also observed an increasing trend in the calcification of the stylohyoid ligament in the middle-aged population which was statistically significant. Our findings are in accordance with the study by Guimarães et al. and Oztas et al., which reported patients above 40 years of age to have higher prevalence of calcification of the stylohyoid complex26,27. This could be attributed to the anatomical variations, variability in the muscle stress owing to occlusal interferences and racial differences of the population studied. The stylohy- oid ligament was considered to be calcified if the length of the stylohyoid complex exceeded more than 30mm extending from the inferior border of the external acous- tic meatus10. Till date, there is an absence of a consensus regarding the standard size of this medially angulated ligament14,17. OPG is a preferred choice for the evaluation and visualization of the calcified stylo- hyoid complex which is one of the major etiological factors for Eagle’s syndrome10. This syndrome which was initially described by Wett Eagle in 1937 is characterized by persistent dull pain in the facial and oropharyngeal region. The affected individuals may present with dysphagia and subjective sensation of a foreign body in the throat accompanied by unexplained headache and increased salivation28. In our study, tonsilloliths constituted 1.3% of the total included radiographs. Our find- ings can be matched with the reports by Garay et al. and Ribeiro et al. who reported 11 Darwin et al. Braz J Oral Sci. 2023;22:e237798 prevalence rates of 1.4% and 0.9% respectively3,10. Occurrence of tonsilloliths in the right side were significant in males which is consistent with the findings reported by Saati et al.17. In addition, we observed a significant association of tonsillolith with age, as majority of these calcifications were seen in individuals above the age of 40. Garay et al.3 in their study have also reported similar findings. Often, these small con- cretions are asymptomatic and are detected incidentally on panoramic radiographs29. However, the presence of these calcifications in a relatively larger size may cause difficulty in swallowing, reflex otalgia, odynophagia, halitosis and may predispose to peritonsillar abscess due to superinfection30. The prevalence of antrolith, observed in our study was 0.8% and most of them were found on the left side. Rhinoliths were observed in 0.3% of the total radiographs stud- ied and was more frequent on the left side. In our study, the occurrence of antroliths was more in the young-adult males and rhinoliths in the young-adult females. These results were found to be significant and was similar to the findings of Ribeiro et al.10. In most individuals, calcifications in the antrum or nasal cavity may not cause any clinical symptoms. Occasionally, such calcifications can cause facial pain, epistaxis, epiphora, perforation of the mucosa16,31. Of the total radiographs studied, 36 (2.3%) of the radiopacities represented the char- acteristic features of phleboliths, which are the calcifications of the venous sys- tem. Similar findings were reported by Saati et al. who observed a prevalence rate of 0.29% of phleboliths17. In the present study, 0.7% of sialoliths and 0.2% of calci- fied lymph nodes were observed on the radiographs. According to the findings of Ayranci et al.32, calcification of the salivary glands is known to affect one in every 10,000 to one in every 30,000 individuals. These calcifications may obstruct the duc- tal flow causing acute pain that intensifies with meals. The understanding of vari- ous calcifications occurring in the maxillofacial region is necessary to aid in their diagnosis and to predict their possible consequences, which could be beneficial for patients. The present study has certain inherent limitations of cross-sectional studies like the inability to acquire the entire medical history of the patient. There exists a lack of con- sensus in the standardization of criteria for analysing soft tissue calcifications in the panoramic radiographs. Further, better-designed multi-centric prospective studies using three-dimensional radiographic modalities focusing on long-term follow-up are necessary to define the typical radiographic appearances of specific calcifications and to describe their clinical effects on symptomatic and asymptomatic patients. Such future researches would not only provide more relevant information to an individual’s medical care but also permits an accurate referral so as to prevent any potential morbidities. In conclusion, the present study emphasizes the radiographic appearances of various soft tissue calcifications occurring in the maxillofacial region, so as to aid in a better diagnosis. We found the soft tissue calcifications to be more predominant in women with increased occurrences over 40 years of age. Optimal knowledge of the normal anatomy of the maxillofacial skeleton is inevitable to arrive at a precise radiographic diagnosis of such calcifications. 12 Darwin et al. Braz J Oral Sci. 2023;22:e237798 Acknowledgements No acknowledgements. Conflicts of interest None. Data availability Datasets related to this article will be available upon request to the corresponding author. Author Contribution Deepthi Darwin: Methodology, Investigation, Writing – original draft preparation, review and editing. Renita Lorina Castelino: Conceptualization, Methodology, Formal analysis, Validation. Gogineni Subhas Babu: Conceptualization, Resources, Validation. 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