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Magnetic resonance imaging: a useful tool to distinguish between keratocystic odontogenic tumours and odontogenic cysts
Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery 53 (2015) 217–222
Magnetic resonance imaging: a useful tool to distinguish between keratocystic odontogenic tumours and odontogenic cysts F.A. Probst a,∗ , M. Probst c , Ch. Pautke b , E. Kaltsi a , S. Otto a , S. Schiel a , M. Troeltzsch a , M. Ehrenfeld a , C.P. Cornelius a , U.G. Müller-Lisse d a
Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-Universität München, Munich, Germany Clinic for Oral and Maxillofacial and Plastic Surgery, Lenbachplatz 2a, 80333 Munich, Germany c Department of Neuroradiology, Technische Universität München, Munich, Germany d Institute of Clinical Radiology, Ludwig-Maximilians-Universität München, Munich, Germany b
Accepted 22 October 2014 Available online 30 December 2014
Abstract In contrast to odontogenic cysts, keratocystic odontogenic tumours often recur and require more aggressive surgical treatment, so we tried to find features that distinguished between them on magnetic resonance imaging (MRI). Without knowing the diagnosis, two radiologists reviewed intensity (low, intermediate, or high) and homogeneity (homogeneous or heterogeneous) of signals in short-tau-inversion-recovery (STIR), T1- and T2-weighted, and fat-suppressed, contrast-enhanced MRI in 20 consecutive patients with oval, radiolucent lesions of the mandible on panoramic radiography, and who were subsequently confirmed histopathologically to have either an odontogenic cyst or a keratocystic odontogenic tumour (n = 10 in each group). Fisher’s exact test was statistically significant at p < 0.05. Delineation of a contrast-enhanced wall of a cyst with high signal intensity distinguished odontogenic cysts (9/10 and 8/10, respectively) from keratocystic odontogenic tumours (3/10, p = 0.02, and 1/10, p = 0.01, respectively). One radiologist found odontogenic cysts were more likely to be homogeneous on unenhanced T1-weighted images (odontogenic cysts 9/10, keratocystic odontogenic tumours 3/10, p = 0.02) and one on contrast-enhanced MRI, when the cyst wall was enhanced (odontogenic cysts 7/9, keratocystic odontogenic tumours 0/3, p = 0.01). There were no other significant distinguishing features on MRI. In conclusion, the signal intensity of the enhanced wall seems to be a feature on contrast-enhanced MRI that differentiates odontogenic cysts from keratocystic odontogenic tumours. © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Maxillofacial Surgery; Cystic lesions of the jaw; Keratocystic odontogenic tumour; Odontogenic cyst; Contrast-enhanced MRI
Introduction Cyst-like lesions of the jaw, often detected incidentally on panoramic radiographs, are common in maxillofacial surgery. ∗ Corresponding author at: Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-Universität München, Lindwurmstr. 2a, 80337 Munich, Germany. Tel.: +49 89 51602901. E-mail addresses: [email protected], [email protected] (F.A. Probst).
Depending on the lesion’s dimension and topography in relation to features like locularity, involvement or resorption of teeth, or characteristics of the lesion’s border, various diagnoses may be considered. Key differential diagnoses are odontogenic cysts, keratocystic odontogenic tumours, and ameloblastomas, non-odontogenic cysts, other odontogenic neoplasms, or simple bone cysts.1,2 Preoperative assessment is important for planning treatment and management, but hardly possible if solely based on conventional radiographs and computed tomography (CT).1–4 An additional imaging
http://dx.doi.org/10.1016/j.bjoms.2014.10.014 0266-4356/© 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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technique that is becoming increasingly important in oral and maxillofacial surgery is magnetic resonance imaging (MRI), which has already been evaluated for differentiating between ameloblastomas and keratocystic odontogenic tumours.5–8 While dynamic, contrast-enhanced MRI has the potential to show the density of microvessels as a marker of proliferative or inflammatory activity in tissue, it has also been shown to contribute little to the differential diagnosis of odontogenic tumours, except for odontogenic fibromas and myxomas.7 Diffusion-weighted MRI may help to characterise the contents of odontogenic cysts and tumours, as pure cystic liquids would restrict free Brownian motion of water molecules to a lesser degree than matrix structures within a solid or partly solid tumour.8 Other studies on MRI have included a larger variety of cystic lesions such as radicular cysts, dentigerous cysts, pseudocysts, dermoid cysts, nasopalatine cysts, and nasolabial cysts.9–11 Differentiation between ameloblastomas and keratocystic odontogenic tumours seems to be promising,5–8 but there is to our knowledge little evidence so far about whether it is possible to discriminate between keratocystic odontogenic tumours and odontogenic cysts. Because of the possible value of preoperative discrimination between them, we tried to establish specific features of MRI that would distinguish between them. The development of odontogenic cysts in different sites follows the same pathogenetic principles of epithelial proliferation, inflammatory reaction, and development of a gradually expanding cystic cavity, so odontogenic cysts have similar walls on histopathology, with differences only in the respective degree of epithelial proliferation and inflammatory reaction.12 We therefore expected that MRI would delineate the active cyst wall from its liquid contents with potentially strong contrast enhancement, whether it was caused by proliferation of tissue or an inflammatory reaction. In turn odontogenic tumours, if solid or partly solid and partly cystic, would be expected to be less homogeneous, with little or no delineation of an active cyst wall. We have therefore attempted to disprove the hypothesis that MRI would be unable to distinguish between odontogenic cysts and keratocystic odontogenic tumours.
Patients, material, and methods Selection of patients We retrospectively studied 20 patients who had had contrastenhanced MRI between May 2009 and November 2011 for further diagnosis of oval radiolucent lesions of the mandible. After MRI, resection and histopathological examination confirmed the diagnoses of keratocystic odontogenic tumours and odontogenic cysts (n = 10 in each group). The institutional ethics committee approved the study protocol, and all data were anonymised.
MRI imaging protocol MRI examinations were made on a 1.0-T clinical unit (Magnetom Harmony; Siemens, Erlangen, Germany), a 1.5-T clinical unit (Magnetom Vision; Siemens, Erlangen, Germany), or a 3.0-T clinical unit (Philips Achieva 3.0T; Philips medical systems, Hamburg, Germany). Axial T1- and T2-weighted images, and axial and coronal fat-suppressed short-tau-inversion-recovery (STIR) images, were obtained for all patients with optimal variables. After intravenous injection of a standard dose of gadolinium-DTPA (Magnevist; Bayer Schering, Berlin, Germany), frequencyselective fat-suppressed T1-weighted images were acquired in the axial and coronal planes. The thickness of sections was 4 mm.
Analysis of images Two radiologists (UGML (investigator 1) and MP (investigator 2)), who were unaware of the definitive histopathological results, evaluated the MRI independently. As regarding the signal intensity, a signal from the connective tissue on unenhanced T1-weighted and T2-weighted images was interpreted as low, a signal from the musculature on unenhanced T1-weighted images as intermediate, and one from the cerebrospinal fluid on T2-weighted images as high. Both signal intensity and homogeneity were assessed on STIR images, T1-weighted images, T2-weighted images, and contrastenhanced T1-weighted images of the lesions’ walls and their centres. Additionally, the raters had to assess locularity and the diameter of the wall, and then decide if the contents of a lesion were of cystic, solid, or mixed character. Walls less than 1 mm thick were defined as thin. Outcome variables (Tables 1–3) were rated as being present (1) or absent (0) on a standard form.
Statistical analysis The significance of differences in the outcome variables between keratocystic odontogenic tumours and odontogenic cysts was assessed using a two-tailed Fisher’s exact test either in 2 × 2 or 3 × 2 contingency tables.13 Lesions with a predominantly high signal intensity were distinguished from those with low or intermediate intensities because this distinction would be the one most likely to be used in clinical practice. Inter-rater reliability was calculated using Cohen’s kappa coefficient and Spearman’s rank correlation coefficient with the help of IBM SPSS for Windows (Version 20.0, IBM Corp, Armonk, NY). To assess the inter-rater reliability by rank correlation, an ordinal scale was established based on the signal intensity (low = 1, intermediate = 2, high = 3). Probabilities of less than 0.05 were accepted as significant.
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Table 1 Signal intensity assessed on short tau inversion recovery (STIR) images, T1-weighted and T2-weighted images, contrast-enhanced T1-weighted images of the wall of the lesion (wall), and of the centre of the lesion (centre). KCOT = keratocystic odontogenic tumour and OC = odontogenic cyst (n = 10 in each group). Signal intensity of magnetic resonance imaging sequences
Investigator 1
Investigator 2
KCOT STIR Low/intermediate High T2-weighted image Low/intermediate High T1-weighted image Low/intermediate High Wall Low/intermediate High Centre Low/intermediate High
OC
p value
KCOT
OC
p value
1 9
1 9
0.99
2 8
3 7
0.99
0 10
0 10
0.99
4 6
4 6
0.99
6 4
8 2
0.63
7 3
9 1
0.58
7 3
1 9
0.02
9 1
2 8
0.01
6 4
8 2
0.63
7 3
8 2
0.30
Table 2 Homogeneity of the signal assessed on short tau inversion recovery (STIR) images, T1-weighted images, T2-weighted images, contrast-enhanced T1-weighted images of the wall of the lesion (wall), and of the centre of the lesion (centre). KCOT = keratocystic odontogenic tumour and OC = odontogenic cyst (n = 10 in each group). Homogeneity of magnetic resonance imaging sequences
Investigator 1
STIR Homogeneous Heterogeneous T2-weighted image Homogeneous Heterogeneous T1-weighted image: Homogeneous Heterogeneous Contrast-enhanced wall Homogeneous Heterogeneous Contrast-enhanced T1-weighted wall High signal intensity and homogeneous High signal intensity and heterogeneous Contrast-enhanced T-1 weighted centre Homogeneous Heterogeneous
Investigator 2
KCOT
OC
p value
KCOT
OC
p value
3 7
5 5
0.65
4 6
5 5
0.99
4 6
5 5
0.99
4 6
7 3
0.37
4 6
7 3
0.37
3 7
9 1
0.02
6 4
8 2
0.63
5 5
8 2
0.35
0/3 3/3
7/9 2/9
0.01
0/1 1/1
7/8 1/8
0.22
3 7
5 5
0.65
4 6
7 3
0.37
Table 3 Solid/cystic character, locularity, and diameter of wall as shown on magnetic resonance image. KCOT = keratocystic odontogenic tumour and OC = odontogenic cyst (n = 10 in each group). Investigator 1 KCOT Character of cyst Cystic Mixed Solid Locularity Unilocular Multilocular Diameter of wall Thin Thick
Investigator 2 OC
p value
KCOT
OC
p value
4 5 1
7 3 0
0.37
4 4 2
7 1 2
0.25
6 4
10 0
0.09
8 2
10 0
0.47
8 2
10 0
0.47
8 2
6 4
0.63
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Fig. 1. Odontogenic cyst (radicular cyst). Axial, fat-saturated, contrastenhanced T1-weighted image showing high and homogeneous enhancement of the wall at the left body of the mandible, which are two typical characteristics of odontogenic cysts on contrast-enhanced magnetic resonance images.
Fig. 2. Keratocystic odontogenic tumour. Axial, fat-saturated, contrastenhanced T1-weighted image showing low to intermediate and heterogeneous enhancement of the wall at the left anterior body and symphyseal region of the mandible.
Results
centre on these images looked mostly intermediate, with no significant difference between the two conditions and no significant difference in homogeneity (Tables 1 and 2). Table 3 summarises additional MRI features. In most cases, lesions presented as cystic or, more infrequently, as mixed tumours. A solid appearance of the lesions was rare and there was no significant difference between keratocystic odontogenic tumours and odontogenic cysts. The diameter of the wall was thin in most keratocystic odontogenic tumours and odontogenic tumours, and there was no significant difference between the two. All the cysts, and most of the keratocystic odontogenic tumours, were unilocular.
Tables 1–3 summarise the MRI findings for all outcome variables. Signal intensity on STIR images and T2-weighted images was high in most cases of keratocystic odontogenic tumours and odontogenic cysts, and we found no clear trend in homogeneity (Tables 1 and 2). In contrast, T1-weighted images tended to be of intermediate signal intensity. Distinction between keratocystic odontogenic tumours and odontogenic cysts on T1-weighted images was not possible (Table 1). However, T1-weighted images tended towards heterogeneity in keratocystic odontogenic tumours and homogeneity in odontogenic tumours. This difference was significant (p < 0.02), based on investigator 2’s observations (Table 2). Inter-rater agreement, based on Cohen’s kappa (0.1) was, however, poor. There was a significant trend in the signal intensity of contrast-enhanced T1-weighted images of the walls of the lesions. In most cases, odontogenic cysts (Fig. 1) presented with high signal intensity, implying strong contrast enhancement, whereas keratocystic odontogenic tumours (Fig. 2) showed low signal intensity, implying little contrast enhancement (p < 0.02 investigator 1, p < 0.01 investigator 2) (Table 1). We calculated substantial inter-rater agreement based on Cohen’s kappa (0.75). Inter-rater correspondence was also strong, based on rank correlation coefficients (Spearman correlation r = 0.91). Regarding contrast-enhanced T1-weighted images of the wall, odontogenic cysts (Fig. 1) appeared to be homogeneous in most cases, while keratocystic odontogenic tumours were homogeneous or heterogeneous to an almost equal extent (Table 2). All keratocystic odontogenic tumours with high signal intensity on contrast-enhanced T1-weighted images of the wall showed a heterogeneous picture. The signal intensity of the
Discussion Cystic lesions of the mandible typically present as ellipsoid, radiolucent, and sharply-limited shapes,1 . Clinical history and different radiographical characteristics can limit the scope of differential diagnoses. However, conventional panoramic radiographs or CT cannot reliably discriminate between odontogenic cysts, keratocystic odontogenic tumours, and ameloblastomas MRI can, however, help.9 While some studies have reported on possible differentiation between ameloblastomas and keratocystic odontogenic tumours,5–8 or between true cysts and simple bone cysts,11 we know of little if any detailed work that has focused on discrimination between keratocystic odontogenic tumours and odontogenic cysts based on MRI. Relatively few reported cases reflect this, as none of the relevant studies has included more than 10 cases of each of keratocystic odontogenic tumours and odontogenic cysts. Statistical analysis has also not been reported, so it has not been possible to assess the
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discriminant value of features between keratocystic odontogenic tumours and odontogenic cysts. Some studies are based on out-of-date MRI machines.9 It is important to outline particularly the differentiation between keratocystic odontogenic tumours and odontogenic cysts as this can have an impact on subsequent treatment. In contrast to odontogenic cysts, keratocystic odontogenic tumours are known for having high recurrence rates,14 which is why, in addition to enucleation, either peripheral ostectomy, or application of Carnoy’s solution, or even resection, is recommended in addition to enucleation.14 In an early MRI study by Minami et al. keratocystic odontogenic tumours often showed heterogeneous signals, intermediate or high T1-weighted signal intensity, and intermediate T2-weighted signal intensity. Odontogenic cysts had low-to-intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images.9 Hisatomi et al. reported that keratocystic odontogenic tumours had a tendency towards intermediate-to-high signal intensity on T1-weighted images, and heterogeneous low-to-high signal intensity on T2-weighted images. Odontogenic cysts had similar homogeneous signal intensity on both T1 and T2-weighted images.10 Konouchi et al. reported that keratocystic odontogenic tumours tended towards heterogeneous intermediate-to-high signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Odontogenic cysts showed homogeneous low signal intensity on T1-weighted images and homogeneous high signal intensity on T2-weighted images.5 Our results have shown a tendency towards a signal intensity that was intermediate on T1-weighted images and high on T2-weighted images for both keratocystic odontogenic tumours and odontogenic cysts. This tendency towards a higher signal intensity on T2- than on T1-weighted images is in agreement with other studies. However, we found that differentiation between keratocystic odontogenic tumours and odontogenic cysts is not possible by signal intensity on T1or T2-weighted images, or STIR. Consideration of homogeneity seems to be more promising, as a tendency towards heterogeneous signal intensity in keratocystic odontogenic tumours and homogenous signal intensity in odontogenic cysts was noticable. This was most distinctive on unenhanced T1, though significance was evident from the observations of only one radiologist. Keratocystic odontogenic tumours are often thought to be multilocular, but we confirm other reports that have shown that keratocystic odontogenic tumours are as likely to be unilocular as multilocular,5,9 whereas odontogenic cysts tend to be unilocular. In most cases, both seem to be cystic or have a mixed cystic and solid character, and the diameter of the wall is usually thin.9 We could find no feature that significantly discriminated between them in the cystic character, locularity, or diameter of the wall. Consequently, these variables are of minor help in differentiating between the two. However, contrast-enhanced images seem to have the greatest potential for discriminating between keratocystic
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odontogenic tumours and odontogenic cysts on MRI. A thin enhancement of the rim with no further gradation of the enhancement has been reported by Konouchi et al. and Sumi et al. for both keratocystic odontogenic tumours and odontogenic cysts.5,6 Minami et al. have classified the enhancement of the wall as weak or strong. As a result, all keratocystic odontogenic tumours, and most odontogenic cysts, showed weak enhancement.9 The results of our study confirm that keratocystic odontogenic tumours present with low signal intensity of the enhancement of the wall. However, odontogenic cysts also show a clear trend towards high signal intensities, what is in contrast to previous reports. This difference was significant according to both our observers, and therefore seems to be an important way of discriminating between the two. This result is emphasised by substantial agreement between the observers. The homogeneity of the enhancement of the wall was also recorded. Most odontogenic cysts presented with homogeneous enhancement of the wall, whereas keratocystic odontogenic tumours presented with heterogeneous or homogeneous enhancement with nearly the same incidence. Interestingly, a subgroup of keratocystic odontogenic tumours with high signal intensities in enhancement of the wall invariably presented with heterogeneous enhancement. Contrast-enhancement in the centre of the lesions was characteristically intermediate, on a range from low and high. Keratocystic odontogenic tumours tend towards heterogeneous signals, and odontogenic cysts to homogeneous signals, with no significant distinction. Some studies have outlined discriminating features on MRI between keratocystic odontogenic tumours and ameloblastomas. Keratocystic odontogenic tumours often show heterogeneous signals, intermediate or high signal intensity on the T1-weighted image, and intermediate or high signal intensity on the T2-weighted image, 5,9,10 while ameloblastomas show a signal intensity that is low on the T1-weighted image and high (unicystic ameloblastoma) or extremely high corresponding to numerous small cysts on the T2-weighted image (multicystic ameloblastomas).5,9 Keratocystic odontogenic tumours present with thin enhancement of the rim on contrast-enhanced T1-weighted images.5,6,9 In contrast, ameloblastomas characteristically have a thick enhancement of the rim, with or without papillary projections.5,9 Diffusion-weighted MRI with calculation of apparent diffusion coefficients may be used as an adjunct for differentiation between keratocystic odontogenic tumours and ameloblastomas.6,8 The strengths of our retrospective analysis include complete radiological and histopathological correlation for each individual lesion, the significance of findings despite the small sample size, and the agreement between two independent observers on the presence of the respective distinguishing features of odontogenic cysts and keratocystic odontogenic tumours on MRI. The weaknesses include the retrospective study design, with inclusion of preselected patients whose lesions had
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been confirmed by histopathological examination to be either odontogenic cysts or keratocystic odontogenic tumours, and the use of different MRI scanners with different magnetic field strengths. The retrospective design and the restriction to patients with clear histopathological proof of either condition seemed to be necessary to prove in principle whether the two entities had any distinguishing marks on MRI. In theory, T1-relaxation times are longer and their susceptibility to changes in the concentration and binding structures of hydrogen molecules are stronger at 3.0-T than at 1.0T which could degrade the quality of the image in tissues close to cortical bone. Technically, however, read-out gradients are stronger at 3.0-T which translates into higher signal intensity or higher spatial resolution, and this could improve the quality of the image, particularly in small tissue structures such as mandibular bone marrow. In our experience the differences do not alter the clinical radiological impression. In conclusion, the results of our study disprove the hypothesis that MRI would be unable to distinguish between odontogenic cysts and keratocystic odontogenic tumours. Indeed, they indicate that odontogenic cysts regularly appear with homogeneously high signal intensity of cystic walls at contrast-enhanced MRI, while keratocystic odontogenic tumours show homogeneously or heterogeneously low signal intensity after contrast enhancement. Evaluation of a cystic mandibular lesion by MRI can have an appreciable impact on diagnosis and subsequent treatment. Nevertheless, the gold standard that establishes the diagnosis remains, of course, histopathological examination. Further research should be directed at improved differentiation by diffusion-weighted or dynamic, contrast-enhanced MRI.
Conflict of interest We have no conflict of interest.
Ethics statement/confirmation of patients’ permission The institutional ethics committee approved the protocol, and all data were anonymised.
Acknowledgements This manuscript includes results of current doctoral thesis work of Effrosyni Kaltsi at Faculty of Medicine, LudwigMaximilians-Universität München. References 1. Scholl RJ, Kellett HM, Neumann DP, et al. Cysts and cystic lesions of the mandible: clinical and radiologic–histopathologic review. Radiographics 1999;19:1107–24. 2. Dunfee BL, Sakai O, Pistey R, et al. Radiologic and pathologic characteristics of benign and malignant lesions of the mandible. Radiographics 2006;26:1751–68. 3. de Avila ED, de Molon RS, Massucato EM, et al. Relationship between the prevalence of the dentigerous cyst and the odontogenic keratocyst tumor and the current etiologic hypothesis. J Craniofac Surg 2009;20:2036–40. 4. Schussel JL, Stramandinoli RT, Dissenha JL, et al. Retrospective study of 25 cases of keratocystic odontogenic tumor: epidemiology and treatment. J Contemp Dent Pract 2011;12:100–3. 5. Konouchi H, Asaumi J, Yanagi Y, et al. Usefulness of contrast enhanced-MRI in the diagnosis of unicystic ameloblastoma. Oral Oncol 2006;42:481–6. 6. Sumi M, Ichikawa Y, Katayama I, et al. Diffusion-weighted MR imaging of ameloblastomas and keratocystic odontogenic tumors: differentiation by apparent diffusion coefficients of cystic lesions. AJNR Am J Neuroradiol 2008;29:1897–901. 7. Fujita M, Matsuzaki H, Yanagi Y, et al. Diagnostic value of MRI for odontogenic tumours. Dentomaxillofac Radiol 2013;42:20120265. 8. Srinivasan K, Seith Bhalla A, Sharma R, et al. Diffusion-weighted imaging in the evaluation of odontogenic cysts and tumours. Br J Radiol 2012;85:e864–70. 9. Minami M, Kaneda T, Ozawa K, et al. Cystic lesions of the maxillomandibular region: MR imaging distinction of odontogenic keratocysts and ameloblastomas from other cysts. Am J Roentgenol 1996;166:943–9. 10. Hisatomi M, Asaumi J, Konouchi H, et al. MR imaging of epithelial cysts of the oral and maxillofacial region. Eur J Radiol 2003;48:178–82. 11. Yanagi Y, Asaumi J, Unetsubo T, et al. Usefulness of MRI and dynamic contrast-enhanced MRI for differential diagnosis of simple bone cysts from true cysts in the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:364–9. 12. Morgenroth K. Odontogenic cysts (in German). Pathologe 2008;29: 214–20. 13. Joosse SA. Fisher’s exact test; 2013. Available from: http://in-silico.net/ statistics/fisher exact test 14. Kaczmarzyk T, Mojsa I, Stypulkowska J. A systematic review of the recurrence rate for keratocystic odontogenic tumour in relation to treatment modalities. Int J Oral Maxillofac Surg 2012;41:756–67.
British Journal of Oral and Maxillofacial Surgery 53 (2015) 217–222
Magnetic resonance imaging: a useful tool to distinguish between keratocystic odontogenic tumours and odontogenic cysts F.A. Probst a,∗ , M. Probst c , Ch. Pautke b , E. Kaltsi a , S. Otto a , S. Schiel a , M. Troeltzsch a , M. Ehrenfeld a , C.P. Cornelius a , U.G. Müller-Lisse d a
Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-Universität München, Munich, Germany Clinic for Oral and Maxillofacial and Plastic Surgery, Lenbachplatz 2a, 80333 Munich, Germany c Department of Neuroradiology, Technische Universität München, Munich, Germany d Institute of Clinical Radiology, Ludwig-Maximilians-Universität München, Munich, Germany b
Accepted 22 October 2014 Available online 30 December 2014
Abstract In contrast to odontogenic cysts, keratocystic odontogenic tumours often recur and require more aggressive surgical treatment, so we tried to find features that distinguished between them on magnetic resonance imaging (MRI). Without knowing the diagnosis, two radiologists reviewed intensity (low, intermediate, or high) and homogeneity (homogeneous or heterogeneous) of signals in short-tau-inversion-recovery (STIR), T1- and T2-weighted, and fat-suppressed, contrast-enhanced MRI in 20 consecutive patients with oval, radiolucent lesions of the mandible on panoramic radiography, and who were subsequently confirmed histopathologically to have either an odontogenic cyst or a keratocystic odontogenic tumour (n = 10 in each group). Fisher’s exact test was statistically significant at p < 0.05. Delineation of a contrast-enhanced wall of a cyst with high signal intensity distinguished odontogenic cysts (9/10 and 8/10, respectively) from keratocystic odontogenic tumours (3/10, p = 0.02, and 1/10, p = 0.01, respectively). One radiologist found odontogenic cysts were more likely to be homogeneous on unenhanced T1-weighted images (odontogenic cysts 9/10, keratocystic odontogenic tumours 3/10, p = 0.02) and one on contrast-enhanced MRI, when the cyst wall was enhanced (odontogenic cysts 7/9, keratocystic odontogenic tumours 0/3, p = 0.01). There were no other significant distinguishing features on MRI. In conclusion, the signal intensity of the enhanced wall seems to be a feature on contrast-enhanced MRI that differentiates odontogenic cysts from keratocystic odontogenic tumours. © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Maxillofacial Surgery; Cystic lesions of the jaw; Keratocystic odontogenic tumour; Odontogenic cyst; Contrast-enhanced MRI
Introduction Cyst-like lesions of the jaw, often detected incidentally on panoramic radiographs, are common in maxillofacial surgery. ∗ Corresponding author at: Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-Universität München, Lindwurmstr. 2a, 80337 Munich, Germany. Tel.: +49 89 51602901. E-mail addresses: [email protected], [email protected] (F.A. Probst).
Depending on the lesion’s dimension and topography in relation to features like locularity, involvement or resorption of teeth, or characteristics of the lesion’s border, various diagnoses may be considered. Key differential diagnoses are odontogenic cysts, keratocystic odontogenic tumours, and ameloblastomas, non-odontogenic cysts, other odontogenic neoplasms, or simple bone cysts.1,2 Preoperative assessment is important for planning treatment and management, but hardly possible if solely based on conventional radiographs and computed tomography (CT).1–4 An additional imaging
http://dx.doi.org/10.1016/j.bjoms.2014.10.014 0266-4356/© 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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F.A. Probst et al. / British Journal of Oral and Maxillofacial Surgery 53 (2015) 217–222
technique that is becoming increasingly important in oral and maxillofacial surgery is magnetic resonance imaging (MRI), which has already been evaluated for differentiating between ameloblastomas and keratocystic odontogenic tumours.5–8 While dynamic, contrast-enhanced MRI has the potential to show the density of microvessels as a marker of proliferative or inflammatory activity in tissue, it has also been shown to contribute little to the differential diagnosis of odontogenic tumours, except for odontogenic fibromas and myxomas.7 Diffusion-weighted MRI may help to characterise the contents of odontogenic cysts and tumours, as pure cystic liquids would restrict free Brownian motion of water molecules to a lesser degree than matrix structures within a solid or partly solid tumour.8 Other studies on MRI have included a larger variety of cystic lesions such as radicular cysts, dentigerous cysts, pseudocysts, dermoid cysts, nasopalatine cysts, and nasolabial cysts.9–11 Differentiation between ameloblastomas and keratocystic odontogenic tumours seems to be promising,5–8 but there is to our knowledge little evidence so far about whether it is possible to discriminate between keratocystic odontogenic tumours and odontogenic cysts. Because of the possible value of preoperative discrimination between them, we tried to establish specific features of MRI that would distinguish between them. The development of odontogenic cysts in different sites follows the same pathogenetic principles of epithelial proliferation, inflammatory reaction, and development of a gradually expanding cystic cavity, so odontogenic cysts have similar walls on histopathology, with differences only in the respective degree of epithelial proliferation and inflammatory reaction.12 We therefore expected that MRI would delineate the active cyst wall from its liquid contents with potentially strong contrast enhancement, whether it was caused by proliferation of tissue or an inflammatory reaction. In turn odontogenic tumours, if solid or partly solid and partly cystic, would be expected to be less homogeneous, with little or no delineation of an active cyst wall. We have therefore attempted to disprove the hypothesis that MRI would be unable to distinguish between odontogenic cysts and keratocystic odontogenic tumours.
Patients, material, and methods Selection of patients We retrospectively studied 20 patients who had had contrastenhanced MRI between May 2009 and November 2011 for further diagnosis of oval radiolucent lesions of the mandible. After MRI, resection and histopathological examination confirmed the diagnoses of keratocystic odontogenic tumours and odontogenic cysts (n = 10 in each group). The institutional ethics committee approved the study protocol, and all data were anonymised.
MRI imaging protocol MRI examinations were made on a 1.0-T clinical unit (Magnetom Harmony; Siemens, Erlangen, Germany), a 1.5-T clinical unit (Magnetom Vision; Siemens, Erlangen, Germany), or a 3.0-T clinical unit (Philips Achieva 3.0T; Philips medical systems, Hamburg, Germany). Axial T1- and T2-weighted images, and axial and coronal fat-suppressed short-tau-inversion-recovery (STIR) images, were obtained for all patients with optimal variables. After intravenous injection of a standard dose of gadolinium-DTPA (Magnevist; Bayer Schering, Berlin, Germany), frequencyselective fat-suppressed T1-weighted images were acquired in the axial and coronal planes. The thickness of sections was 4 mm.
Analysis of images Two radiologists (UGML (investigator 1) and MP (investigator 2)), who were unaware of the definitive histopathological results, evaluated the MRI independently. As regarding the signal intensity, a signal from the connective tissue on unenhanced T1-weighted and T2-weighted images was interpreted as low, a signal from the musculature on unenhanced T1-weighted images as intermediate, and one from the cerebrospinal fluid on T2-weighted images as high. Both signal intensity and homogeneity were assessed on STIR images, T1-weighted images, T2-weighted images, and contrastenhanced T1-weighted images of the lesions’ walls and their centres. Additionally, the raters had to assess locularity and the diameter of the wall, and then decide if the contents of a lesion were of cystic, solid, or mixed character. Walls less than 1 mm thick were defined as thin. Outcome variables (Tables 1–3) were rated as being present (1) or absent (0) on a standard form.
Statistical analysis The significance of differences in the outcome variables between keratocystic odontogenic tumours and odontogenic cysts was assessed using a two-tailed Fisher’s exact test either in 2 × 2 or 3 × 2 contingency tables.13 Lesions with a predominantly high signal intensity were distinguished from those with low or intermediate intensities because this distinction would be the one most likely to be used in clinical practice. Inter-rater reliability was calculated using Cohen’s kappa coefficient and Spearman’s rank correlation coefficient with the help of IBM SPSS for Windows (Version 20.0, IBM Corp, Armonk, NY). To assess the inter-rater reliability by rank correlation, an ordinal scale was established based on the signal intensity (low = 1, intermediate = 2, high = 3). Probabilities of less than 0.05 were accepted as significant.
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Table 1 Signal intensity assessed on short tau inversion recovery (STIR) images, T1-weighted and T2-weighted images, contrast-enhanced T1-weighted images of the wall of the lesion (wall), and of the centre of the lesion (centre). KCOT = keratocystic odontogenic tumour and OC = odontogenic cyst (n = 10 in each group). Signal intensity of magnetic resonance imaging sequences
Investigator 1
Investigator 2
KCOT STIR Low/intermediate High T2-weighted image Low/intermediate High T1-weighted image Low/intermediate High Wall Low/intermediate High Centre Low/intermediate High
OC
p value
KCOT
OC
p value
1 9
1 9
0.99
2 8
3 7
0.99
0 10
0 10
0.99
4 6
4 6
0.99
6 4
8 2
0.63
7 3
9 1
0.58
7 3
1 9
0.02
9 1
2 8
0.01
6 4
8 2
0.63
7 3
8 2
0.30
Table 2 Homogeneity of the signal assessed on short tau inversion recovery (STIR) images, T1-weighted images, T2-weighted images, contrast-enhanced T1-weighted images of the wall of the lesion (wall), and of the centre of the lesion (centre). KCOT = keratocystic odontogenic tumour and OC = odontogenic cyst (n = 10 in each group). Homogeneity of magnetic resonance imaging sequences
Investigator 1
STIR Homogeneous Heterogeneous T2-weighted image Homogeneous Heterogeneous T1-weighted image: Homogeneous Heterogeneous Contrast-enhanced wall Homogeneous Heterogeneous Contrast-enhanced T1-weighted wall High signal intensity and homogeneous High signal intensity and heterogeneous Contrast-enhanced T-1 weighted centre Homogeneous Heterogeneous
Investigator 2
KCOT
OC
p value
KCOT
OC
p value
3 7
5 5
0.65
4 6
5 5
0.99
4 6
5 5
0.99
4 6
7 3
0.37
4 6
7 3
0.37
3 7
9 1
0.02
6 4
8 2
0.63
5 5
8 2
0.35
0/3 3/3
7/9 2/9
0.01
0/1 1/1
7/8 1/8
0.22
3 7
5 5
0.65
4 6
7 3
0.37
Table 3 Solid/cystic character, locularity, and diameter of wall as shown on magnetic resonance image. KCOT = keratocystic odontogenic tumour and OC = odontogenic cyst (n = 10 in each group). Investigator 1 KCOT Character of cyst Cystic Mixed Solid Locularity Unilocular Multilocular Diameter of wall Thin Thick
Investigator 2 OC
p value
KCOT
OC
p value
4 5 1
7 3 0
0.37
4 4 2
7 1 2
0.25
6 4
10 0
0.09
8 2
10 0
0.47
8 2
10 0
0.47
8 2
6 4
0.63
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Fig. 1. Odontogenic cyst (radicular cyst). Axial, fat-saturated, contrastenhanced T1-weighted image showing high and homogeneous enhancement of the wall at the left body of the mandible, which are two typical characteristics of odontogenic cysts on contrast-enhanced magnetic resonance images.
Fig. 2. Keratocystic odontogenic tumour. Axial, fat-saturated, contrastenhanced T1-weighted image showing low to intermediate and heterogeneous enhancement of the wall at the left anterior body and symphyseal region of the mandible.
Results
centre on these images looked mostly intermediate, with no significant difference between the two conditions and no significant difference in homogeneity (Tables 1 and 2). Table 3 summarises additional MRI features. In most cases, lesions presented as cystic or, more infrequently, as mixed tumours. A solid appearance of the lesions was rare and there was no significant difference between keratocystic odontogenic tumours and odontogenic cysts. The diameter of the wall was thin in most keratocystic odontogenic tumours and odontogenic tumours, and there was no significant difference between the two. All the cysts, and most of the keratocystic odontogenic tumours, were unilocular.
Tables 1–3 summarise the MRI findings for all outcome variables. Signal intensity on STIR images and T2-weighted images was high in most cases of keratocystic odontogenic tumours and odontogenic cysts, and we found no clear trend in homogeneity (Tables 1 and 2). In contrast, T1-weighted images tended to be of intermediate signal intensity. Distinction between keratocystic odontogenic tumours and odontogenic cysts on T1-weighted images was not possible (Table 1). However, T1-weighted images tended towards heterogeneity in keratocystic odontogenic tumours and homogeneity in odontogenic tumours. This difference was significant (p < 0.02), based on investigator 2’s observations (Table 2). Inter-rater agreement, based on Cohen’s kappa (0.1) was, however, poor. There was a significant trend in the signal intensity of contrast-enhanced T1-weighted images of the walls of the lesions. In most cases, odontogenic cysts (Fig. 1) presented with high signal intensity, implying strong contrast enhancement, whereas keratocystic odontogenic tumours (Fig. 2) showed low signal intensity, implying little contrast enhancement (p < 0.02 investigator 1, p < 0.01 investigator 2) (Table 1). We calculated substantial inter-rater agreement based on Cohen’s kappa (0.75). Inter-rater correspondence was also strong, based on rank correlation coefficients (Spearman correlation r = 0.91). Regarding contrast-enhanced T1-weighted images of the wall, odontogenic cysts (Fig. 1) appeared to be homogeneous in most cases, while keratocystic odontogenic tumours were homogeneous or heterogeneous to an almost equal extent (Table 2). All keratocystic odontogenic tumours with high signal intensity on contrast-enhanced T1-weighted images of the wall showed a heterogeneous picture. The signal intensity of the
Discussion Cystic lesions of the mandible typically present as ellipsoid, radiolucent, and sharply-limited shapes,1 . Clinical history and different radiographical characteristics can limit the scope of differential diagnoses. However, conventional panoramic radiographs or CT cannot reliably discriminate between odontogenic cysts, keratocystic odontogenic tumours, and ameloblastomas MRI can, however, help.9 While some studies have reported on possible differentiation between ameloblastomas and keratocystic odontogenic tumours,5–8 or between true cysts and simple bone cysts,11 we know of little if any detailed work that has focused on discrimination between keratocystic odontogenic tumours and odontogenic cysts based on MRI. Relatively few reported cases reflect this, as none of the relevant studies has included more than 10 cases of each of keratocystic odontogenic tumours and odontogenic cysts. Statistical analysis has also not been reported, so it has not been possible to assess the
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discriminant value of features between keratocystic odontogenic tumours and odontogenic cysts. Some studies are based on out-of-date MRI machines.9 It is important to outline particularly the differentiation between keratocystic odontogenic tumours and odontogenic cysts as this can have an impact on subsequent treatment. In contrast to odontogenic cysts, keratocystic odontogenic tumours are known for having high recurrence rates,14 which is why, in addition to enucleation, either peripheral ostectomy, or application of Carnoy’s solution, or even resection, is recommended in addition to enucleation.14 In an early MRI study by Minami et al. keratocystic odontogenic tumours often showed heterogeneous signals, intermediate or high T1-weighted signal intensity, and intermediate T2-weighted signal intensity. Odontogenic cysts had low-to-intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images.9 Hisatomi et al. reported that keratocystic odontogenic tumours had a tendency towards intermediate-to-high signal intensity on T1-weighted images, and heterogeneous low-to-high signal intensity on T2-weighted images. Odontogenic cysts had similar homogeneous signal intensity on both T1 and T2-weighted images.10 Konouchi et al. reported that keratocystic odontogenic tumours tended towards heterogeneous intermediate-to-high signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Odontogenic cysts showed homogeneous low signal intensity on T1-weighted images and homogeneous high signal intensity on T2-weighted images.5 Our results have shown a tendency towards a signal intensity that was intermediate on T1-weighted images and high on T2-weighted images for both keratocystic odontogenic tumours and odontogenic cysts. This tendency towards a higher signal intensity on T2- than on T1-weighted images is in agreement with other studies. However, we found that differentiation between keratocystic odontogenic tumours and odontogenic cysts is not possible by signal intensity on T1or T2-weighted images, or STIR. Consideration of homogeneity seems to be more promising, as a tendency towards heterogeneous signal intensity in keratocystic odontogenic tumours and homogenous signal intensity in odontogenic cysts was noticable. This was most distinctive on unenhanced T1, though significance was evident from the observations of only one radiologist. Keratocystic odontogenic tumours are often thought to be multilocular, but we confirm other reports that have shown that keratocystic odontogenic tumours are as likely to be unilocular as multilocular,5,9 whereas odontogenic cysts tend to be unilocular. In most cases, both seem to be cystic or have a mixed cystic and solid character, and the diameter of the wall is usually thin.9 We could find no feature that significantly discriminated between them in the cystic character, locularity, or diameter of the wall. Consequently, these variables are of minor help in differentiating between the two. However, contrast-enhanced images seem to have the greatest potential for discriminating between keratocystic
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odontogenic tumours and odontogenic cysts on MRI. A thin enhancement of the rim with no further gradation of the enhancement has been reported by Konouchi et al. and Sumi et al. for both keratocystic odontogenic tumours and odontogenic cysts.5,6 Minami et al. have classified the enhancement of the wall as weak or strong. As a result, all keratocystic odontogenic tumours, and most odontogenic cysts, showed weak enhancement.9 The results of our study confirm that keratocystic odontogenic tumours present with low signal intensity of the enhancement of the wall. However, odontogenic cysts also show a clear trend towards high signal intensities, what is in contrast to previous reports. This difference was significant according to both our observers, and therefore seems to be an important way of discriminating between the two. This result is emphasised by substantial agreement between the observers. The homogeneity of the enhancement of the wall was also recorded. Most odontogenic cysts presented with homogeneous enhancement of the wall, whereas keratocystic odontogenic tumours presented with heterogeneous or homogeneous enhancement with nearly the same incidence. Interestingly, a subgroup of keratocystic odontogenic tumours with high signal intensities in enhancement of the wall invariably presented with heterogeneous enhancement. Contrast-enhancement in the centre of the lesions was characteristically intermediate, on a range from low and high. Keratocystic odontogenic tumours tend towards heterogeneous signals, and odontogenic cysts to homogeneous signals, with no significant distinction. Some studies have outlined discriminating features on MRI between keratocystic odontogenic tumours and ameloblastomas. Keratocystic odontogenic tumours often show heterogeneous signals, intermediate or high signal intensity on the T1-weighted image, and intermediate or high signal intensity on the T2-weighted image, 5,9,10 while ameloblastomas show a signal intensity that is low on the T1-weighted image and high (unicystic ameloblastoma) or extremely high corresponding to numerous small cysts on the T2-weighted image (multicystic ameloblastomas).5,9 Keratocystic odontogenic tumours present with thin enhancement of the rim on contrast-enhanced T1-weighted images.5,6,9 In contrast, ameloblastomas characteristically have a thick enhancement of the rim, with or without papillary projections.5,9 Diffusion-weighted MRI with calculation of apparent diffusion coefficients may be used as an adjunct for differentiation between keratocystic odontogenic tumours and ameloblastomas.6,8 The strengths of our retrospective analysis include complete radiological and histopathological correlation for each individual lesion, the significance of findings despite the small sample size, and the agreement between two independent observers on the presence of the respective distinguishing features of odontogenic cysts and keratocystic odontogenic tumours on MRI. The weaknesses include the retrospective study design, with inclusion of preselected patients whose lesions had
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been confirmed by histopathological examination to be either odontogenic cysts or keratocystic odontogenic tumours, and the use of different MRI scanners with different magnetic field strengths. The retrospective design and the restriction to patients with clear histopathological proof of either condition seemed to be necessary to prove in principle whether the two entities had any distinguishing marks on MRI. In theory, T1-relaxation times are longer and their susceptibility to changes in the concentration and binding structures of hydrogen molecules are stronger at 3.0-T than at 1.0T which could degrade the quality of the image in tissues close to cortical bone. Technically, however, read-out gradients are stronger at 3.0-T which translates into higher signal intensity or higher spatial resolution, and this could improve the quality of the image, particularly in small tissue structures such as mandibular bone marrow. In our experience the differences do not alter the clinical radiological impression. In conclusion, the results of our study disprove the hypothesis that MRI would be unable to distinguish between odontogenic cysts and keratocystic odontogenic tumours. Indeed, they indicate that odontogenic cysts regularly appear with homogeneously high signal intensity of cystic walls at contrast-enhanced MRI, while keratocystic odontogenic tumours show homogeneously or heterogeneously low signal intensity after contrast enhancement. Evaluation of a cystic mandibular lesion by MRI can have an appreciable impact on diagnosis and subsequent treatment. Nevertheless, the gold standard that establishes the diagnosis remains, of course, histopathological examination. Further research should be directed at improved differentiation by diffusion-weighted or dynamic, contrast-enhanced MRI.
Conflict of interest We have no conflict of interest.
Ethics statement/confirmation of patients’ permission The institutional ethics committee approved the protocol, and all data were anonymised.
Acknowledgements This manuscript includes results of current doctoral thesis work of Effrosyni Kaltsi at Faculty of Medicine, LudwigMaximilians-Universität München. References 1. Scholl RJ, Kellett HM, Neumann DP, et al. Cysts and cystic lesions of the mandible: clinical and radiologic–histopathologic review. Radiographics 1999;19:1107–24. 2. Dunfee BL, Sakai O, Pistey R, et al. Radiologic and pathologic characteristics of benign and malignant lesions of the mandible. Radiographics 2006;26:1751–68. 3. de Avila ED, de Molon RS, Massucato EM, et al. Relationship between the prevalence of the dentigerous cyst and the odontogenic keratocyst tumor and the current etiologic hypothesis. J Craniofac Surg 2009;20:2036–40. 4. Schussel JL, Stramandinoli RT, Dissenha JL, et al. Retrospective study of 25 cases of keratocystic odontogenic tumor: epidemiology and treatment. J Contemp Dent Pract 2011;12:100–3. 5. Konouchi H, Asaumi J, Yanagi Y, et al. Usefulness of contrast enhanced-MRI in the diagnosis of unicystic ameloblastoma. Oral Oncol 2006;42:481–6. 6. Sumi M, Ichikawa Y, Katayama I, et al. Diffusion-weighted MR imaging of ameloblastomas and keratocystic odontogenic tumors: differentiation by apparent diffusion coefficients of cystic lesions. AJNR Am J Neuroradiol 2008;29:1897–901. 7. Fujita M, Matsuzaki H, Yanagi Y, et al. Diagnostic value of MRI for odontogenic tumours. Dentomaxillofac Radiol 2013;42:20120265. 8. Srinivasan K, Seith Bhalla A, Sharma R, et al. Diffusion-weighted imaging in the evaluation of odontogenic cysts and tumours. Br J Radiol 2012;85:e864–70. 9. Minami M, Kaneda T, Ozawa K, et al. Cystic lesions of the maxillomandibular region: MR imaging distinction of odontogenic keratocysts and ameloblastomas from other cysts. Am J Roentgenol 1996;166:943–9. 10. Hisatomi M, Asaumi J, Konouchi H, et al. MR imaging of epithelial cysts of the oral and maxillofacial region. Eur J Radiol 2003;48:178–82. 11. Yanagi Y, Asaumi J, Unetsubo T, et al. Usefulness of MRI and dynamic contrast-enhanced MRI for differential diagnosis of simple bone cysts from true cysts in the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:364–9. 12. Morgenroth K. Odontogenic cysts (in German). Pathologe 2008;29: 214–20. 13. Joosse SA. Fisher’s exact test; 2013. Available from: http://in-silico.net/ statistics/fisher exact test 14. Kaczmarzyk T, Mojsa I, Stypulkowska J. A systematic review of the recurrence rate for keratocystic odontogenic tumour in relation to treatment modalities. Int J Oral Maxillofac Surg 2012;41:756–67.