A dinosaurian facial deformity and the first occurrence of ameloblastoma in the fossil record

Abstract

Despite documentation of various types of neoplastic pathologies encountered in the vertebrate fossil record, no ameloblastic tumours have been recognised so far. Ameloblastoma is a benign neoplasic tumour with a strong preponderance for the mandible. Here, we report for the first time the presence of an ameloblastoma neoplasm in the lower jaw of a specimen referred to the derived non-hadrosaurid hadrosauroid dinosaur Telmatosaurus transsylvanicus from the uppermost Cretaceous of the Haeg Basin in Romania. The location, external appearance and internal structure of the pathological outgrowth provide clear evidence for the diagnosis of ameloblastoma in Telmatosaurus. This report extends the range of pathologies encountered in hadrosauroid dinosaurs. In addition, recognition of an ameloblastoma neoplasm in a taxon lying close to the origin of 'duck-billed' hadrosaurid dinosaurs confirms the predisposition of this clade towards neoplasia pathologies already in its basal members.

A dinosaurian facial deformity ameloblastoma in the fossil record

OPEN

Mihai D. , Bruce M. Rothschild, David B.Weishampel, Zoltn Csiki-Sava, Andrei, Katharine A. Acheson & Vlad A. Codrea

Despite documentation of various types of neoplastic pathologies encountered in the vertebrate fossil record, no ameloblastic tumours have been recognised so far. Ameloblastoma is a benign neoplasic an ameloblastoma neoplasm in the lower jaw of a specimen referred to the derived non-hadrosaurid hadrosauroid dinosaur Telmatosaurus transsylvanicus from the uppermost Cretaceous of the Hat.eg

Basin in Romania. The location, external appearance and internal structure of the pathological outgrowth provide clear evidence for the diagnosis of ameloblastoma in Telmatosaurus. This report extends the range of pathologies encountered in hadrosauroid dinosaurs. In addition, recognition of an ameloblastoma neoplasm in a taxon lying close to the origin of duck-billed hadrosaurid dinosaurs

Ancient diseases have been recognised for well over a century1 in dinosaurs1,2 and other pre-Cenozoic fossil vertebrate groups such as pterosaurs3, crurotarsans4, plesiosaurs5, mosasaurs6, ichthyosaurs7, turtles8, or synapsids9. Beside their intrinsic value in revealing a very particular facet of dinosaurian life and death that is, the existence of certain diseases and their taxonomic and anatomic specicity, as well as of pathogenic agents responsible for them, studies into dinosaurian palaeopathologies have also contributed signicantly to a more profound understanding of dinosaur behaviour.

The current range of documented dinosaurian pathologies is very wide2. Examples range from healed wounds from failed predator attacks10, intraspecic combat11 or daily routine activity leading to accidental injury and breakage2, to congenital and developmental defects1214, cases of severe bacterial or fungal infection such as osteomyelitis12 following exogenous traumatic events, chronic diseases like osteoarthritis15, and neoplasms16,17.

Hadrosauroids were one of the most ecologically important, specious, and widespread clades of herbivorous dinosaurs during the middle to Late Cretaceous. Hadrosauroids also rank among the most frequently cited examples of dinosaurs presenting pathological modications12,16. This clade has been reported from the uppermost Cretaceous of western Romania based on remains collected for over a century from the Maastrichtian formations of the Ha.teg Basin and its surrounding areas1820 (see Supplementary Figs 2 and 3). Despite early claims of pathological individuals from the Transylvanian record of dinosaurs (in accordance with the perceived ecologically strained nature of the local fauna21), subsequent research failed to substantiate such claims. Now, a hadrosauroid specimen from the Maastrichtian of the Ha.teg Basin provides the first evidence of a pathological condition (a neoplasm) previously unrecognized in the dinosaurian fossil record, and at the same time of a well-documented pathological modication in a Romanian dinosaur.

The specimen under consideration (Laboratory of Palaeontology Bucharest, Faculty of Geology and Geophysics, University of Bucharest [LPB (FGGUB) R.1305] was discovered in an outcrop of the Snpetru Formation along the banks of the Sibiel River, in the central part of the Ha.teg Basin (see Supplementary Figs S2 and S3). The specimen is represented by a pair of well-preserved, associated lower jaws with in situ dentition

P

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(Fig.1A) belonging to a sub-adult individual of the hadrosauroid Telmatosaurus transsylvanicus (Nopcsa, 1900; see Supplementary Text S1). The elements are relatively small (right ramus: L-129mm, W-34mm, H-57mm; le ramus: L-143mm, W-58mm, H-76mm) only about half the size of the largest known Telmatosaurus individuals, including the lectotype skull [Natural History Museum, United Kingdom (NHMUK R.3386)]18,19. Although found in isolation, the dentaries were discovered close to their natural articular position, and not as part of a bone-pocket assemblage, the most typical taphonomic mode described for this lithostratigraphic unit (see Supplementary Text S1). The less complete right ramus is broken posteriorly, level with the rostral edge of the coronoid process, while the better preserved le ramus preserves part of the coronoid process.

The labial surface of the le dentary has a smooth and shiny periosteum, except for an area covered by a thin crust of iron hydroxide deposits. It is also largely unworn and unabraded (Fig.1AD), only showing mainly transverse diagenetic fractures that fragmented the dentary into several parts that could be easily recombined to reveal the original morphology of the element. It is moderately convex dorsoventrally and roughly straight rostrodistally.

The pathology identied in LPB (FGGUB) R.1305, at a macroscopic examination, is represented by a prominent, rostroventrally slanting ridge-like bulge (exostosis) on the ventral two-thirds of the labial surface of the le dentary, close to its midline (Fig.1A,C,D). The right counterpart of this dentary is similarly well-preserved, excepting some diagenetic fractures (see Supplementary Figs S5 and 3D Fig. S5). However, it does not show any external sign of a comparable deformation, neither on its labial face mirroring the bulge on the le side, nor in other parts of the element. As a result, the unilateral bony excrescence of the le dentary was considered pathological in nature and thus worthy of further investigations.

To investigate the precise nature of the lesion and to identify the pathogenic process responsible for producing it, detailed X-ray micro-CT scanning of the two jaw rami of LPB (FGGUB) R.1305 was employed (see Supplementary Fig. 1). Micro-CT examination of the left dentary segment showing the pathological bulge revealed a unique internal structure associated spatially with the external deformation visible by gross examination and has provided the necessary characteristics for a tentative diagnosis. Concurrent micro-CT investigation of the right ramus in the same area revealed no signs of any internal pathological features, thus conrming the unilateral presence of the observed lesion, localised exclusively around mid-length of the le dentary.

Results

Description of the pathology. The cortical bone surface at the site of the exostosis displays a locally lytic density (Fig.1C,H,I, and Supplementary Figs S6f, S7e, S8f and 3D Fig. S4). Ventrally, the cortical bone shows moderate thinning (Fig.1F) in the lower third of the le dentary, compared to the normal cortical thickness visible elsewhere in the specimen; at the ventral edge of the exostosis, however, there is a fair amount of expansion of the cortical bone (Fig.1E). Between the modied cortical wall of the dentary labially, and the primary neurovascular canal and secondary neurovascular pathways (Fig.1E,G,I) lingually, the internal structure of the pathological area consists of a pattern of large vacuolae separated by thin bony struts or internal trabeculae (Fig.1J), reminiscent of a soap bubble texture2227 (Fig.1F,H). At the dorsal apex of the exostosis, the cortical bone is expanded (Fig.1E). The exostosis is separated from the normal trabecular bone by a thin layer of longitudinally expanded bony struts forming the internal margin of the lesion (Fig.1G,I).

Although preliminary macroscopic assessment of the exostotic lesion on the le dentary suggested a callus resulting from healed fracture, micro-CT scanning failed to support such a cause. No displacement of the bone surface is visible on its exterior and, more importantly, no discernible internal disruption or fracture line aects the trabeculae and/or the teeth, anomalies that are generally associated with a fracture-induced lesion of the mandible as reported previously in the case of ceratopsian11 and derived hadrosauroid12 dinosaurs. Although some of the teeth in the pathological jaw section show partial resorption of roots (see Supplementary Figs S7d and S9g) and crowns (Fig.1I), no obvious alteration is visible in the regular tooth replacement pattern characteristic of the typical hadrosauroid dental battery. There are no signs of tooth loss or misalignment, either.

The dierential diagnosis for the pathology of the le dentary of Telmatosaurus LPB (FGGUB) R.1305 includes abscesses, odontogenic and non-odontogenic cysts, and neoplasia (see Supplementary Table 1). Intra-osseous odontogenic cysts include developmental cysts (follicular cysts, keratocysts and lateral periodontal cysts), inammatory cysts (radicular cysts and paradental cysts), ameloblastoma, ameloblastic broma, odontogenic myxoma, primordial cyst and central odontogenic broma23,24,26. Inammatory cysts derive from pulp necrosis induced by dental caries. Non-odontogenic cysts include traumatic bone cysts, solitary bone cysts, hemorrhagic cysts, unicameral bone cysts and traumatic bone cysts. Non-odontogenic neoplasia includes metastatic cancer, multiple myeloma/plasma cell tumour lymphoma, leukemia, hemangioma, neurobroma, and schwannoma.

The localisation, external appearance and topology, and especially the internal osseous structure corresponding to the exostotic bulge, are consistent with a diagnosis of ameloblastoma, a benign odontogenic neoplasia28.

Ameloblastomas are described as expansile multiloculated cystic or mixed cystic and solid areas with cortical thinning (Fig.1K), and may be associated with tooth root resorption (Fig.1J)29,30. Internal septations produce a honeycomb or soap bubble appearance22,24,31. They represent about 10% of odontogenic tumours in humans, and are usually characteristic to young adults32.

The identied pathologic structure resembles a dental abscess, a pathology reported previously to occur as early as the Permian in the captorhinid Labidosaurus9, and which is also recognised in Late Cretaceous hadrosauroids12. Development of a marked labial bony overgrowth on the dentary is a feature shared between the pathology of the Romanian hadrosauroid dentary and that of a Canadian latest Cretaceous hadrosaur rst documented in detail31 to represent a case of dental abscess. However, the irregular borders and septate nature of the inner structure presented by the pathologic le dentary of LPB (FGGUB) R.1305 are not compatible with

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Figure 1. External morphology and internal structure of the pathological Telmatosaurus transsylvanicus dentary (LPB (FGGUB) R.1305). (A) Surface scans of the le and right rami positioned in anatomical articulation; (B) segmented internal structures of the le ramus exhibiting the pathology (red - primary neurovascular canal, yellow - secondary neurovascular pathways, orange - functional teeth, blue - replacement teeth, light blue - segmented dentary bone, purple - lytic density areas); (C) Three-dimensional micro-CT image with rectangular cutout in the area of the exostosis; (D) Three-dimensional micro-CT image of the investigated portion of the dentary showing the external appearance of the exostosis (E) transverse cross-section no. 260 micro-CT image in the coronal plane; (F) close-up detail of E. (G) Transverse cross-section no. 648 micro-CT image in the coronal plane; (H) close-up detail of G. (I) Transverse cross-section no. 775 micro-CT imagein the sagittal plane; (J) comparative human panoramic radiograph of the le mandibular ramus exhibiting ameloblastoma (modied from28); (K) comparative human tomographic slice in the coronal plane of thele mandibular ramus exhibiting ameloblastoma (modied from28). Abbreviations: cb=cortical bone;cbe= cortical bone expansion; cbt= cortical bone thinning; dt= dentary tooth; exo=exostosis; im=internal margin; itrb= internal trabeculae; lda= lytic density areas; mgr= mandibular groove; pnvc=primary neurovascular canal; rb= resorbed bone; rt= resorbed tooth; rtr= resorbed tooth roots; sba=soap bubble appearance; snvc= secondary neurovascular pathways. Scale bars (A,B): 50mm. Scale bars (CI): 5mm. Scale for (J,K) not reported in the ref. 28.

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that diagnosis; moreover, tooth loss that is usually associated with dental abscesses is not noted in the Romanian dentary.

Osteomyelitis, a disease oen spread from traumatised and/or infected teeth more deeply into the dentary, has a lengthy fossil record, recognised in the Early Permian captorhinid Labidosaurus9 as well as in the Early Jurassic basal theropod Sinosaurus32 and in Late Cretaceous ceratopsians11. Acute suppurative osteomyelitis, while osteolytic, is non-expansile, in contrast to chronic osteomyelitis in which osteolytic expansion is accompanied by bony sequestra28,33, whereas sclerosing osteomyelitis is characterised by diuse sclerotic expansion; neither of these features are present in the Romanian dentary. Osteomyelitis is also oen associated with development of draining sinuses, the presence of which cannot be documented in LPB (FGGUB) R.1305.

The pathological condition recognised in the Telmatosaurus dentary is distinguished from ameloblastic broma by lack of the internal calcications characteristic of the latter, and from ameloblastic carcinoma by absence of bone destruction31,3334. The pathology in the dentary is clearly distinguished from dentrinous tumours, odontoma, enameloma, periapical cement dysplasia, ossifying broma, and renal osteodystrophy, which have increased, rather than decreased density on X-ray examination28,33.

Osteosarcomatous lesions are ill-dened and tend to be osteoblastic, unlike the pathology in LPB (FGGUB) R.1305. While there are similarities of this pathology to giant cell reparative granuloma28,33,35, the latter do not have internal septations. Furthermore, the pathology in Telmatosaurus does not have the scalloped appearance of tuberculosis, the topographic appearance of eosinophilic granuloma, the ill-dened surface of odontogenic myxoma, brosarcoma, and intraosseous hematoma, the rough surface of metastatic malignancies, the internal trabecular pattern (Fig.1J) of hemangioma and osteosarcoma, or the ground glass appearance of brous dysplasia, ossifying broma, Pagets disease and hyperparathyroidism28,33,36. Root resorption in ameloblastoma clearly distinguishes it from the preserved, but oating teeth of eosinophilic granuloma. The specimen lacks the increased tooth separation of globulomaxillary cysts. Follicular cysts contain unerupted teeth with bone remodelling rather than expansion33. The pathology in LPB (FGGUB) R.1305 is also clearly distinguished from the lingual cortical defect referred to as a Stafne cyst, and from the spheroid expansile lesions of multiple myeloma which penetrate rather than expand bone2628.

In conclusion, although the pathological condition reported here in the dentary of the hadrosauroid Telmatosaurus transsylvanicus is by no means unequivocally pathognomonic, its characteristics nevertheless suggest identication as an ameloblastoma. The presence of this benign neoplasic modication is reported here for the rst time in the dinosaurian fossil record, as well as in the fossil record overall. The occurrence of ameloblastoma is a well-known phenomenon in humans37 and other mammals38, yet has only recently been identied among reptiles in the living wild black rat snake39. A related disorder, adenoameloblastoma, was noted in the Indian rock python40.

Discussion

When rst suggesting the insular nature of the latest Cretaceous Ha.teg fauna, Nopcsa21 noted several palaeobio-logical features in support of his views, including what he perceived as the common presence of pathological individuals. He considered this condition a reasonable consequence of the ecologically impoverished and stressed environment inhabited by this fauna. Identication of pathological individuals was, however, largely unsuccessful subsequently; there is, as yet, no thoroughly described and diagnosed case of dinosaurian pathology reported from the Transylvanian fossil record, although possible cases of dinosaur neoplasm pathologies have been noted previously4143.

Now, recognition of ameloblastoma in a Telmatosaurus dentary discovered from the same area represents the fourth reported, and best documented, case of pathological modication identied in Transylvanian dinosaurs, all of which appear to represent neoplasic diseases4143. Our report might lend some support to Nopcsas21 view about high incidence of pathologies in the Transylvanian dinosaur fauna, although these cases remain still scarce.

Even more remarkable is the taxonomic preference and nature of these Transylvanian pathologies. All reported cases belong to hadrosauroids, and all appear to represent tumoural modications of neoplasic origin. Although neoplasia pathologies have been reported from as early as the Late Jurassic43, tumoural modications appear to be relatively rare in the dinosaurian fossil record2,44. While the neoplasia incidence rates in dinosaurs appear to be statistically comparable with that known in Recent animals45, neoplasic modications demonstrate a high level of taxonomic selectivity for hadrosauroids. The study of Rothschild et al.16 showed that neoplasia pathologies (including malignant forms) were restricted to hadrosauroids in their extensive sample covering all major dinosaur clades; the rst case of dinosaurian neoplasia occurring outside the Hadrosauroidea was reported only recently, in the form of haemangioma and osteoma identied in a Late Cretaceous titanosaur from Brazil17.

Haemangiomas have been identied in several hadrosauroids16, including the derived non-hadrosaurid hadrosauroids Gilmoreosaurus and Bactrosaurus, as well as the saurolophines Edmontosaurus and Brachylophosaurus. Meanwhile, cases of benign neoplasia such as desmoplastic broma and osteoblastoma, as well as of metastatic cancer were found only in Edmontosaurus16.

This report of an ameloblastic Telmatosaurus dentary not only expands the spectrum of neoplasia reported in dinosaurs (and more specically in hadrosauroids), but it provides further support for an apparent predisposition of hadrosauroids for neoplasia pathologies16. Since dierent types of neoplasia are reported to occur already in diverse derived non-hadrosaurid hadrosauroids (Telmatosaurus, Bactrosaurus and Gilmoreosaurus), it appears that this particular predisposition had already arisen in the ancestors of the true hadrosaurs.

Due to the limited nature of the fossil material referable to individual LPB (FGGUB) R.1305, no clear evidence for a cause of death is discernible in this subadult hadrosauroid specimen. Nevertheless, even if ameloblastoma itself is not lethal, its uncontrolled development and potential spread to other areas of the muzzle can eventually led to more severe abnormalities of the buccal and narial areas. Such abnormalities could become severely

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Figure 2. Artistic reconstruction of the pathological individual of the hadrosauroid Telmatosaurus transsylvanicus (LPB [FGGUB] R.1305) in rostral view, showing the probable life appearance of the mandibular deformity caused by ameloblastoma. (Reconstruction by M.D. D.).

debilitating, and might have nally contributed to the demise of this individual. Furthermore, the in vivo appearance of the exostosis (Fig.2) would have set this particular individual apart from other herd members, possibly leaving it vulnerable to predator attack. Such a predisposition of predators to select and attack individuals bearing malformations has been noted before in the case of Antarctic penguin chicks preyed upon by Skua (Stercorarius sp.)46. Another example of selective predation upon malformed individuals was described by Goodman and Johnson47, where individuals of the Pacic chorus frog (Pseudacris regilla) which showed parasite-induced limb malformations underwent alterations in predator avoidance behaviour; such alterations, in turn, allow predators to approach closer than normal their crippled frog prey, thereby severely reducing its chances of escape. Also, there is a considerable body of evidence correlating bilateral symmetry and sexual selection across several major taxa and a variety of species48. Whether such a selective intra-specic behaviour would further imply that malformed individuals such as the sub-adult Telmatosaurus LPB (FGGUB) R.1305 reported here were also marginalized within their group, and therefore made more exposed to predators, is not known but can be certainly conjectured.

Methods

Micro-CT Scanning. Given the rarity of pathological specimens in the dinosaurian material from the Ha.teg Basin, the non-destructive method of micro-CT scanning was chosen to investigate the internal nature of the identied surface pathology. Both le (see Supplementary Figs 1 and 4) and right (see Supplementary Fig. 5) rami were scanned with a SCANCO Medical CT 100 machine at SCANCO Medical AG headquarters in Zrich, Switzerland. The scanning was supervised by Dr. Rzvan Andrei and conducted by Dr. Lisa Falco. Due to the large dimensions of the specimens and the prohibitive size of the resulting dataset, only the region of interest (L-32.22mm, W-28.28mm, H-55.38mm) exhibiting the pathology was scanned on the pathological le dentary (see Supplementary Fig. 1e). To facilitate comparison and help determine the type of pathological change encountered, the corresponding areas of both dentaries were scanned using the same equipment parameters.

Scanning was made with a reection micro focus X-ray source having a focal spot size of 12 , powered by a current of 90kVp at an intensity of 150mAs providing a spatial resolution of 4 m per voxel. Beam hardening was accomplished by the use of a 0.5 mm copper lter. The specimens were rotated by 0.25 between successive projections. At each 0.25 increment, three exposures were made with a at panel X-ray detector and the resulting images were digitally stacked to enhance the signal to noise ratio and suppress random digital noise. A total of 720 images were generated for a complete 180 rotation. The images were subsequently reconstructed

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using a back-projection algorithm to obtain the full 360 view. The 3D volume thus obtained was sliced axially in the region of the exostosis, resulting in 1249 individual slices for the right ramus and 1305 slices for the le. Each 0.025 mm thick slice was saved as a grayscale, 16-bit 1200 dpi DICOM and TIF le with a resolution of 2048 2048 pixels (see Supplementary Fig. 1c). The TIF les were saved with an LZW compression algorithm. The DICOM dataset is 4.8Gb for the right ramus and 3.3Gb for the le one. The TIF les were imported into Adobe Photoshop CS3 and processed globally for contrast improvement and saved as 8-bit JPEG les to reduce the size of the dataset (see Supplementary Fig. 1d). The two datasets were imported individually into FEI Amira 5.3.3 (Visualization Sciences Group) for viewing, analysis and segmentation (see Supplementary Fig. 1c). All micro-CT datasets were analysed on a Lenovo ThinkPad W520 64-bit mobile workstation with 32 Gb of RAM and an nVidia Quadro 2000M graphics card with 2Gb of RAM running Windows 7 Professional Edition. Structures of interest such as the teeth, external mandibular artery, primary neuro-vascular canal and cortical bone surface were highlighted and labelled (see Supplementary Fig. 1f) using the manual segmentation tools in Amira. Each structure was then saved in STL format and aligned relative to the other structures. The datasets are available for download upon request, from the Morphosource website (http://morphosource.org/index.php/ Detail/SpecimenDetail/Show/specimen_id/2089).

To integrate the micro-CT data into the complete element, both rami were surface scanned by one of the authors (M. D. D.) using the 3D photogrammetry soware Photoscan PRO 1.1.6 (Agiso LLC).

The 360 photographic coverage was repeated from 4 dierent orientations to record the complete surface. The individual surface scans (see Supplementary Fig. 1g) were subsequently aligned in Photoscan to obtain a closed mesh. The 3D surface (see Supplementary Fig. 1h) was saved as an STL format.

Both the segmented internal structures and the 3D surface scan were subsequently imported into Rhinoceros 5.0 (Robert McNeill and Associates 2015, Release 2015-8-10) where the segmented structures were aligned within the 3D surface scan of the mandible and assigned levels of opacity and colour to dierentiate between the various structures and emphasise their spatial and dimensional relationships (see Supplementary Fig. 1i). The aligned structures were then combined into 3D PDF les using Adobe Acrobat 10 and the 3D PDF plugin (Tech So 3D, Inc. DBA tetra 4D). The micro-CT datasets were animated in Photoshop CS3 to produce Supplementary Movies 1 and 2. The two DICOM datasets were saved as 3D .tif images for online repository storage and access (see Acknowledgements).

Photography. The specimen was also photographed in standard anatomical orientations with a Canon EOS 500D DSLR camera equipped with a Nikon DG 60mm EDX lens and a macro ring light. Prior to photographing, the specimens were lightly coated with ammonium chloride (NH3Cl) to improve contrast. All photographs were processed globally in Adobe Photoshop CS3 to improve contrast and suppress camera noise (see Supplementary Fig. 1b). The entire workow (see Supplementary Fig. 1) was identical for both mandibles.

References

1. Rothschild, B. M. In The Complete Dinosaur. 427448 (Bloomington, University of Indiana Press, 1997).2. Tanke, D. H. & Rothschild, B. M. An annotated bibliography of palaeopathology and related topics 18382001. New Mexico Mus. Nat. Hist. Sci. Bull. 20, 197 (2002).

3. Bennett, S. C. A survey of pathologies of large pterodactyloid pterosaurs. Palaeontology 46, 185198 (2003).4. Witzmann, F., Schwarz-Wings, D., Hampe, O., Fritsch. G. & Asbach, P. Evidence of spondyloarthropathy in the spine of a phytosaur (Reptilia: Archosauriformes) from the Late Triassic of Halberstadt, Germany. PLoS ONE 9, 113 (2014).

5. Rothschild, B. M. & Storrs, G. W. Decompression syndrome in plesiosaurs (Sauropterygia: Reptilia). J. Vertebr. Paleontol. 23, 234328 (2003).

6. Schulp, A. S., Walenkamp, G. H., Hofman, P. A., Stuip, Y. & Rothschild, B. M. Chronic bone infection in the jaw of Mosasaurus homanni (Squamata). Oryctos 6, 4152 (2006).

7. Rothschild, B. M., Schultze, H.-P. & Peligrini, R. Herpetological Osteopathology: Annotated Bibliography of Amphibians and Reptiles (Heidelberg, Springer-Verlag, 2012).

8. Rothschild, B. M. & Naples, V. Decompression syndrome and diving behaviour in Odontochelys, the rst turtle. Acta Palaeontol. Pol. 60, 163167 (2015).

9. Reisz, R. R., Scott, D. M., Pynn D. B. & Modesto, S. P. Osteomyelitis in a Paleozoic reptile: ancient evidence for bacterial infection and its evolutionary signicance. Naturwissenschaen 98, 551555 (2011).

10. Rothschild, B. M. & DePalma, R. Skin pathology in the Cretaceous: Evidence for probable failed predation in a dinosaur. Cretac. Res. 42, 4447 (2013).

11. Tanke, D. H. & Rothschild, B. M. In New Perspectives on Horned Dinosaurs: The Royal Tyrrell Museum Ceratopsian Symposium. Life in the Past 355384 (Bloomington and Indianapolis, Indiana University Press, 2010).

12. Tanke, D. H. & Rothschild, B. M. In Hadrosaurs. Life of the Past 540571 (Bloomington and Indianapolis, Indiana University Press,

2014).

13. Witzmann, F. et al. Vertebral pathology in an ornithopod dinosaur: a hemivertebra in Dysalotosaurus lettowvorbecki from the Jurassic of Tanzania. Anat. Rec. 29, 11491155 (2008).

14. Lovelace, D. M. Developmental failure of segmentation in a caudal vertebra of Apatosaurus (Sauropoda). Anat. Rec. 297, 12621269 (2014).

15. Rothschild, B. M., Zheng, X.-T. & Martin, L. D. Osteoarthritis in the early avian radiation: Earliest recognition of the disease in birds. Cretac. Res. 35, 178180 (2012).

16. Rothschild, B. M., Tanke, D. H., Helbling M. & Martin, L. D. Epidemiologic study of tumors in dinosaurs. Naturwissenschaen 90, 495500 (2003).

17. de Souza Barbosa, F. H., da Costa Pereira, P. V., Bergqvist, L. P. & Rothschild, B. M. Multiple neoplasms in a single sauropod dinosaur from the Upper Cretaceous of Brazil. Cretac. Res. 62, 1317 (2016).

18. Nopcsa, F. Dinosaurierreste aus Siebenbrgen I. Schdel von Limnosaurus transsylvanicus nov. gen.et nov. spec. Denkschr. K. Akad. Wiss. Math.-naturwiss. Klasse 68, 555591 (1900).

SCIENTIFIC REPORTS

6

www.nature.com/scientificreports/

19. Weishampel, D. B., Norman, D. B. & Grigorescu, D. Telmatosaurus transsylvanicus from the Late Cretaceous of Romania: the most basal hadrosaurid dinosaur. Palaeontology 36, 361386 (1993).

20. Dalla Vecchia, F. M. In Hadrosaurs. Life of the Past 268297 (Bloomington and Indianapolis, Indiana Universitry Press, 2014).21. Nopcsa, F. Die Dinosaurier der Siebenbrgischen Landesteile Ungarns. Mitt. Jahr. Tc. -ung. geol. Reichsanstalt 23, 124 (1915).22. Pasler, F. A. & Visser, H. Pocket Atlas of Dental Radiology (New York, Thieme New York, 2007).23. Pasler, F. A. In Radiology 200202 (New York, Thieme New York, 1993).24. Regezi, J. A. Odontogenic Cysts, Odontogenic Tumors, Fibroosseous, and Giant Cell Lesions of the Jaws. Modern Pathol. 15,

331341 (2002).

25. Cankurtaran, C. Z., Branstetter, B. F., Chiosea, S. I. & Barnes, E. L. Ameloblastoma and Dentigerous Cyst Associated with Impacted Mandibular Third Molar Tooth. RadioGraphics 30, 14151420 (2010).

26. Meyer, K. A., Bancro, L. W., Dietrich, T. J., Kransdorf, M. J. & Peterson, J. J. Imaging characteristics of Benign, Malignant and Infectious Jaw Lesions: A Pictoral Review. Amer. J. Roentgenol. 197, 412421 (2011).

27. Devenney-Cakir, B. et al. Cystic and Cystic-Appearing Lesions of the Mandible: Review. Amer. J. Roentgenol. 196, 6667 (2011).28. Brooks, S. L. In Cone Beam Computed Tomography: Oral and Maxillofacial Diagnosis and Application 4364 (New Jersey, Wiley & Sons, 2014).

29. Avon, S. L., McComb, J. & Clokie, C. Ameloblastic Carcinoma: Case Report and Literature Review. J. Can. Dent. Assoc. 69, 573576 (2003).

30. Reichart, P. A., Philipsen, H. P. & Sonner, S. Ameloblastoma: biological prole of 3677 cases. Eur. J. Cancer B. Oral Oncol. 31B, 8699 (1995).

31. Moodie, R. L. Studies in paleodontology - dental abscesses in a dinosaur millions of years old, and the oldest yet known. Pac. Dent. Gaz. 38, 435440 (1930).

32. Xing, L.-D. et al. Tooth loss and alveolar remodelling in Sinosaurus triassicus (Dinosauria: Theropoda) from the Lower Jurassic strata of the Lufeng Basin, China. Chin. Sci. Bull. 58, 19311935 (2013).

33. Dunfee, B. L., Sakai, O., Pistey, R. & Gohel, A. Radiologic and pathologic characteristics of benign and malignant lesions of the mandible. RadioGraphics 26, 17511768 (2006).

34. Ram, H., Mohammad, S., Hussain, N. & Gupta, P. N. Ameloblastic Carcinoma. J. Maxillofac. Oral. Surg. 9, 415419 (2010).35. Murphey, M. D. et al. Imaging of Giant Cell Tumor and Giant Cell Reparative Granuloma of the Bone: Radiologic-Pathologic Correlation. RadioGraphics 21, 12831309 (2001).

36. Witzmann, F. et al. Paget disease of bone in a Jurassic dinosaur. Curr. Biol. 21, 647648 (2011).37. Philipsen, H. P., Reichart, P. A. & Takata, T. Desmoplastic ameloblastoma (including hybrid lesion of ameloblastoma). Biological prole based on 100 cases from the literature and own les. Oral Oncol. 37, 455460 (2001).

38. Das, S., Nath, B. K., Alim, A., Sikder, S. & Pallab, M. S. Acanthomatous ameloblastoma in a female Spitz dog with a rare atypical histomorphology: A Case Study. Vet. World 6, 219222 (2013).

39. Comolli, J. R. et al. Ameloblastoma in a wild black rat snake (Patherophis alleghaniensis). J. Vet. Diagn. Invest. 27, 536539 (2015).40. Mehler, S. J. & Bennet, R. A. Oral, dental and beak disorders of reptiles. Vet. Clinics: Exot. Anim. Pract. 6, 477503 (2003).41. Campbell, J. G. A dinosaur bone lesion resembling avian osteopetrosis and some remarks on the mode of development of the lesions. Jour. Roy. Microsc. Soc. 85, 163174 (1966).

42. Reid, R. E. Zonal growth rings in dinosaurs. Modern Geol. 15, 1948 (1990).43. Rothschild, B. M., Tanke, D. H., Hershkovitz, I. & Schultz, M. Mesozoic neoplasia: origins of haemangioma in the Jurassic age. Lancet 351, 1862 (1998).

44. Rothschild, B. M. & Martin, L. D. Skeletal impact of disease. New Mexico Mus. Nat. Hist. Sci. Bull 33, 1226 (2006).45. Natarajan, L. C., Mellott, A. L., Rothschild, B. M. & Martin, L. D. Bone cancer rates in dinosaurs compared with modern vertebrates. Trans. Kansas Acad. Sci. 110. 155158 (2007).

46. Young, E. Skua and penguin: Predator and prey, Ch. 6, 110154 (New York, Cambridge University Press, 1994).47. Goodman, B. A. & Johnson, P. T. J. Ecomorphology and disease: cryptic eects of parasitism on host habitat use, thermoregulation, and predator avoidance. Ecology 92, 542548 (2011).

48. Moller, A. P. & Thornhill, R. Bilateral symmetry and sexual selection: a meta-analysis. Amer. Nat. 151. 174192.

Acknowledgements

The authors thank Mr. Enrico Zamparo of SCANCO Medical AG for the invitation to use their micro-CT scanning facilities, and Dr. Lisa Falco (SCANCO Medical AG) for performing the micro-CT scans. Funding was provided in part by CNCS grant PN-II-ID-PCE-2011-3-0381 (to V.A.C., Z.Cs.-S.), and grant POSDRU/159/1.5/S/132400 (to M.D.D.).

Author Contributions

M.D.D. conceived the research, wrote the main manuscript and supplementary materials, processed the micro-CT data and prepared the gures. B.M.R. analysed the pathology, wrote the manuscript and supplementary materials. and compiled Table S1. D.B.W. wrote the manuscript and formatted the text and supplementary materials. Z.C.-S. provided the specimens, wrote the manuscript and supplementary materials, created the geological map of the Ha.teg Basin, R.A.A. supervised the micro-CT scanning and provided the hardware and soware for data processing, K.A.A. processed the micro-CT data, wrote and formatted the manuscript and supplementary materials, created the maps and the lithostratigraphic log, V.A.C. wrote the manuscript. All authors reviewed the manuscript.

Additional Information

Supplementary information accompanies this paper at http://www.nature.com/srep

Competing nancial interests: The authors declare no competing nancial interests.

How to cite this article: Dumbrav, M. D. et al. A dinosaurian facial deformity and the rst occurrence of ameloblastoma in the fossil record. Sci. Rep. 6, 29271; doi: 10.1038/srep29271 (2016).

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