Original Article
Histologic, Clinical, and Radiologic Findings of Alveolar Bone Expansion and Osteomyelitis of the Jaws in Cats
Veterinary Pathology 2015, Vol. 52(5) 910-918 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0300985815591079 vet.sagepub.com
C. M. Bell1,2 and J. W. Soukup1,3
Abstract The objective of this study was to characterize clinical, radiologic, and histologic patterns of alveolar bone expansion and osteomyelitis in cats. Based on case materials submitted as surgical biopsy specimens, alveolar bone pathology was diagnosed in 28 cats. These cats had a total of 37 oral lesions with clinical and radiologic changes that involved bone and/or teeth, including periodontitis, bone expansion, tooth resorption, and/or chronic osteomyelitis; 32 lesions were evaluated by histopathology. Canine teeth were affected in 19 cats (27 affected teeth), with bilateral lesions in 5 (26.3%) cats. The caudal premolar and/or molar regions were affected in 10 cats (10 affected sites). All biopsy sites evaluated by a review of clinical images and/or radiographs had evidence of periodontitis. Clinical photographs showed expansion of alveolar bone in 13 of 16 (81%) biopsy sites evaluated. Radiologically, rarifying osseous proliferation of alveolar bone was seen at 26 of 27 (96%) biopsy sites, and tooth resorption occurred at 15 of 18 (83%) sites. Histologically, the tissue samples from canine sites had compressed trabeculae of mature remodeled bone, loose fibrous stroma with paucicellular inflammation, and mild proliferation of woven bone. Tissue samples from the premolar/molar biopsy sites were often highly cellular with mixed lymphoplasmacytic and chronic suppurative inflammation, ulceration with granulation tissue, and robust proliferation of woven bone. Alveolar bone expansion and osteomyelitis in cats occurs in conjunction with periodontal inflammation and frequently with tooth resorption. Keywords dentistry, feline, pathology, oral, osteitis, osteomyelitis, periodontitis, radiology, tooth resorption
Periodontal disease involves inflammation of the periodontium, which includes gingiva, periodontal ligament, cementum, and alveolar bone. Defined by clinical and radiologic findings, periodontitis is one of the most common clinical diseases in cats.17,18,22 While periodontal disease may begin as gingivitis, periodontitis is defined by attachment loss (radiologic loss of alveolar bone and/or clinical periodontal pockets). Progression of periodontal inflammation can also lead to gingival recession, osteomyelitis, and tooth loss. In a study of 24 cats with mandibular swelling, 50% were malignancies (most commonly, squamous cell carcinoma), and 50% were benign, nearly all of which were osteomyelitis.14 Thus, osteomyelitis is as common as malignant processes in the jaws of cats. The diagnostic accuracy that veterinary pathologists might achieve with small biopsy specimens will significantly improve if distinctive clinicopathologic patterns of osteomyelitis are recognized. Osteomyelitis of the jaws in humans is classified by chronicity and etiology (primary and secondary). After onset of clinical symptoms, 4 weeks is accepted as the arbitrary distinction between acute/subacute osteomyelitis and chronic osteomyelitis. Clinical features of acute osteomyelitis include pain, swelling, purulent drainage, fistulous tracts, sequestrum formation,
lymphadenopathy, and febrile episodes.15 Histologically, acute osteomyelitis is characterized by necrotic bone and suppurative inflammation.15,21 Chronic suppurative osteomyelitis, or secondary chronic osteomyelitis, usually has a bacterial cause and is often a progression of acute osteomyelitis. Clinically, there is pain, swelling, and purulent discharge. Radiologic features include osteolysis, osteosclerosis, and proliferation of periosteal new bone.4 Histologically, there are variable signs of chronic infection, including medullary fibrosis, endosteal bone
1 Center for Comparative Oral and Maxillofacial Pathology, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, USA 2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, USA 3 Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, USA
Supplemental material for this article is available on the Veterinary Pathology website at http://vet.sagepub.com/supplemental. Corresponding Author: C. M. Bell, Wisconsin Veterinary Diagnostic Laboratory, 445 Easterday Lane, Madison, WI 53706, USA. Email: [email protected]
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formation, bone resorption, microabscess formation, and soft tissue involvement.4 A notable proliferation of inflamed fibrous connective tissue fills the space between bone trabeculae.21 Primary chronic osteomyelitis in humans manifests as recurrent episodes of pain and/or swelling and regional lymphadenopathy. Primary chronic osteomyelitis is nonsuppurative, usually affects the mandible, has no known etiology, and may be difficult to distinguish clinically and radiologically from a benign fibro-osseous lesion without biopsy and culture. Histologically, osteosclerosis is prominent, and the connective tissue between bone trabeculae may have low numbers of neutrophils, lymphocytes, and plasma cells.21 The highest incidence of primary chronic osteomyelitis is in patients with vascular insufficiency, immune dysfunction, or metabolic bone disorders, such as diabetes, systemic steroid therapy, renal and hepatic failure, and human immunodeficiency virus infection.15 Alveolar bone expansion, especially in the region of the canine teeth, is recognized clinically in cats and often occurs in conjunction with periodontitis and/or tooth resorption.3,16,17 Terms used to describe this condition in the veterinary dental literature include peripheral osteitis, alveolar osteitis, or peripheral buttressing.2,5,25,30 The specific objective of this study was to characterize the histopathologic, radiologic, and clinical features of alveolar osteomyelitis and alveolar bone expansion in cats, particularly as they relate to the clinical condition known as alveolar osteitis.
Materials and Methods The cases in this study were submitted as surgical biopsy specimens to the Center for Comparative Oral and Maxillofacial Pathology at the University of Wisconsin–Madison. The tissue samples were received in 10% neutral buffered formalin and decalcified as needed in standard 10% HCl solution for 2 to 48 hours. Tissues were processed by conventional methods, embedded in paraffin, sectioned at 5 mm, and stained with hematoxylin and eosin. Cases from cats with the histopathologic diagnosis of osteomyelitis of alveolar bone were considered for inclusion. Cases of feline osteomyelitis of the jaws were excluded from the study if trauma was the known or suspected cause, if neoplastic disease was present at the site of the lesion, or if an infectious process was present at the affected site, with the exception of bacterial plaque. The signalment and clinical history, clinical photographs, and radiographs were obtained at the time of submission.
Clinical Features Clinical information regarding signalment and the number and distribution of affected sites in the oral cavity was obtained from the biopsy sample submission form. These images were systematically reviewed by a board certified veterinary dentist (J.W.S.). At the biopsy site, the presence or absence of the following was recorded: in situ tooth, jaw expansion (including
direction of expansion), soft tissue swelling, clinical features of periodontal disease (eg, gingival hemorrhage, gingivomucosal erythema, root exposure), gingivomucosal ulcerations, and dental crown fracture.
Radiologic Features Radiographs were reviewed by a board-certified veterinary dentist (J.W.S.), and the presence or absence of the following was recorded at the biopsy site: rarefying osseous proliferation, incisor region involvement, radiologic type of tooth resorption (as defined by Peralta et al23), periodontitis, and endodontic disease. Criteria for evidence of periodontitis included horizontal or vertical bone loss and widening of the periodontal ligament space. Criteria for evidence of endodontic disease included rarefying or sclerosing pattern of periapical lucency or halted dentinogenesis. When the canine or carnassial tooth at the biopsy site was missing, no information regarding the presence or absence of tooth resorption, periodontitis, or endodontic disease was recorded.
Histologic Features All slides were examined by a board-certified pathologist (C.M.B.). For each sample, the histologic features of the biopsied tissues were recorded for both bone and soft tissue. The specific bony changes included the presence or absence of a distinct peripheral rim of bone and the presence of a majority of woven bone (ie, woven bone as >50% of the total bone present). These bony changes were not mutually exclusive. The evaluated soft tissues included gingiva, alveolar mucosa, intertrabecular stroma, and/or reparative tissue that replaced bone. The soft tissue changes were recorded according to the predominant type of proliferative tissue seen and the associated type of inflammation; categories were mutually exclusive: neovascular tissue with chronic suppurative inflammation vs fibrosis with lymphoplasmacytic inflammation.
Results In this study, we identified 28 cats with 37 sites of alveolar osteomyelitis with clinical and radiologic evidence of periodontitis (Suppl. Table 1). Nineteen cats had involvement of 1 canine teeth, with a total of 27 affected canine sites, 23 of which were evaluated by histopathology. Ten cats had 10 premolar/molar sites of periodontal inflammation and osteomyelitis, 9 of which were evaluated by histopathology. A total of 6 cats had multiple affected sites involving at least 2 sites of canine teeth. One of the cats with 3 affected sites had bilateral involvement of the maxillary canine regions and unilateral involvement of a maxillary premolar region. Bilateral canine involvement was noted for 5 cats (maxillary in 4 cats and mandibular in 1 cat). There was no sex difference for cats having a tissue biopsy from the premolar/molar sites. However, neutered males accounted for 22 of 27 (82%) cats having a tissue biopsy from
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Table 1. Clinical Features of Alveolar Osteomyelitis in Cats, No. (%). Tooth Missing Affected canine sites 104 (n ¼ 4) 204 (n ¼ 4) 304 (n ¼ 2) 404 (n ¼ 1) Total (n ¼ 11) Affected premolar/molar sites 107–109 (n ¼ 1) 0–209 (n ¼ 3) 309 (n ¼ 1) Total (n ¼ 5)
Labial Bone Expansion
Mesial Bone Expansion
Soft Tissue Swelling
Gingivomucosal Ulceration
1 1 0 0 2
(25) (25) (0) (0) (18)
4 (100) 4 (100) 1 (50) 0 (0) 9 (82)
0 0 2 1 3
(0) (0) (100) (100) (27)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
2 2 0 0 4
(50) (50) (0) (0) (36)
0 0 0 0
(0) (0) (0) (0)
0 (0) 2 (67) 0 (0) 2 (40)
0 0 0 0
(0) (0) (0) (0)
1 (100) 3 (100) 1 (100) 5 (100)
1 1 0 2
(100) (33) (0) (40)
the site of a canine tooth. For the study population in general and for each anatomic region, the domestic shorthair was the predominant breed, with 19 of 28 (68%) cats, yet 6 other feline breeds were represented. The age was available for 26 of the 28 cats, ranging from 5 to 20 years with a median of 10.5 years; the age distribution was similar regardless of the site of the biopsy.
Clinical Features Appropriate clinical images were available for evaluation of clinical features for 16 biopsy sites from 15 cats, including 11 sites near a canine tooth and 5 premolar/molar sites (Table 1). Specific clinical features of periodontal disease were variable yet consistent at all biopsy sites. Labial expansion of bone was present in all (n ¼ 8) sites in the region of a maxillary canine (Figs. 1, 2), of which a canine tooth was missing in 2 of 11 (18.2%). Abnormal tooth extrusion (supereruption) of the affected canine tooth was not systematically recorded but was occasionally apparent (Fig. 1). Clinically visible expansion of alveolar bone in the canine region of the mandible occurred in a mesial direction for 3 of 3 (100%) affected sites. Clinically visible jaw expansion was less common in the premolar/molar regions, seen in only 2 of 5 (40%) affected sites. None of the molar or premolar teeth was missing at these affected sites. Clinically visible swelling and erythema of the vestibular and labial soft tissues were evident in all 5 of the evaluated biopsy sites of the premolar/molar region (Figs. 3, 4), but swollen soft tissue was not apparent in any of the 11 evaluated biopsy sites in the canine region. Gingivomucosal ulcerations (Figs. 1, 3, 4) were seen in the canine and premolar/molar regions—in 4 of 11 (36%) and 2 of 5 (40%), respectively. Ulcerations were more common in the maxilla than in the mandible, as seen in 6 of 12 (50%) and 0 of 4 (0%), respectively. Bony defects occasionally occurred on the palatal aspect of affected maxillary fourth premolars (Fig. 4). Photographic evidence of a crown fracture was seen in only 1 tooth, which was a mandibular canine.
Radiologic Features Radiographs were available and evaluated for 27 biopsy sites. Of those, 18 (67%) radiographs adequately represented the pertinent canine or carnassial teeth and were assessed for features of tooth resorption, periodontitis, or endodontic disease (Table 2). Rarefying osseous proliferation at the site of biopsy was very common, occurring in 26 of 27 (96%) cases irrespective of location (Figs. 5, 6; Suppl. Figs. 2, 3). A difference was noted in the direction of bone proliferation at affected canine sites. In the maxilla, osseous proliferation remained centered on the affected canine tooth and expanded in a labial direction (Fig. 5). Involvement of the adjacent incisors was seen in only 1 case of 13 (8%) of an affected maxillary canine tooth. In contrast, osseous proliferation in the region of the mandibular canines generally extended in a mesial direction and frequently involved the incisor region, which was seen in 9 of 10 (90%) cases (Suppl. Fig. 3). Radiologic features generally associated with periodontitis were present in 100% of evaluated maxillary biopsy sites (Figs. 5, 6; Suppl. Fig. 2). In the mandible, radiographs showed features consistent with periodontitis in 4 of 6 (67%) canine sites (Suppl. Fig. 3), as did the 1 radiograph of a mandibular molar. Radiologic evidence of endodontic disease was seen at only 1 site of 18 (6%), which was a mandibular canine that had a crown fracture. The overall prevalence of radiologic changes consistent with tooth resorption was 15 of 18 (83%). Tooth resorption was commonly noted in 11 of 14 (79%) affected canine teeth and 4 of 4 (100%) affected premolars/molars. Two types of tooth resorption were seen—external inflammatory resorption (type 1) and external replacement resorption (type 2)—and the former was by far most common, as seen in 13 of 15 (92%) instances of tooth resorption (Suppl. Fig. 2).
Histologic Features Received and evaluated by histopathology were 32 formalin-fixed tissue samples of alveolar bone from 28 cats; 23 samples were from the rostral/canine region and 9 from the premolar/molar
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Figures 1–6. Figure 1. Unilateral alveolar bone expansion and osteomyelitis, left maxillary canine tooth, cat. Typical clinical features at an affected maxillary canine tooth include labial expansion of bone, tooth extrusion with root exposure (bracket), and mucosal erythema. Photograph courtesy of Kris Bannon, used with permission. Figure 2. Bilateral alveolar bone expansion and osteomyelitis with labial expansion of bone, maxillary canine teeth, cat. Photograph courtesy of Diane Carle, used with permission. Figures 3, 4. Diffuse gingivitis and regional stomatitis at the left maxillary premolars, oral cavity, cat. In the absence of obvious bone expansion, the clinical features of affected Downloaded from vet.sagepub.com at UNIVERSITE DE MONTREAL on August 27, 2015
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Table 2. Radiologic Features of Alveolar Osteomyelitis in Cats, No. (%). Rarefying Osseous Proliferation Affected canine sites 104 (n ¼ 6) 204 (n ¼ 7) 304 (n ¼ 6) 404 (n ¼ 4) Total (n ¼ 23) Affected premolar/molar sites 107-109 (n ¼ 1) 207-209 (n ¼ 2) 309 (n ¼ 1) Total (n ¼ 4)
Incisor Region Involvement
6 (100) 7 (100) 6 (100) 3 (75) 22 (96)
0 1 5 4 10
1 (100) 2 (100) 1 (100) 4 (100)
n/d n/d n/d n/d
Evidence of Tooth Resorption 3 (75; n ¼ 4) 4 (100; n ¼ 4) 3 (75; n ¼ 4) 1 (50; n ¼ 2) 11 (79; n ¼ 14)
(0) (14) (83) (100) (43)
1 (100) 2 (100) 1 (100) 4 (100)
Evidence of Periodontitis 4 4 3 1 12 1 2 1 4
(100; n ¼ 4) (100; n ¼ 4) (75; n ¼ 4) (50; n ¼ 2) (86; n ¼ 14) (100) (100) (100) (100)
Abbreviation: n/d, analysis was not done.
Table 3. Histologic Features of Alveolar Osteomyelitis in Cats, No. (%). Affected Sites Canine 104 (n ¼ 6) 204 (n ¼ 7) 304 (n ¼ 5) 404 (n ¼ 4) Total (n ¼21) Premolar/molar 107–109 (n ¼ 2) 207–209 (n ¼ 5) 309 (n ¼ 1) Total (n ¼ 8)
Peripheral Rim of Bone
Exuberant Woven Bone
Fibrosis With Lymphoplasmacytic Inflammation
6 (100) 5 (83; n ¼ 6) 2 (40) 2 (67; n ¼ 3) 15 (75; n ¼ 20)
0 0 0 0 0
(0) (0; n ¼ 6) (0) (0; n ¼ 3) (0; n ¼ 20)
6 7 3 4 20
1 (100; n ¼ 1) 2 (40) 0 (0) 3 (43; n ¼ 7)
0 3 1 4
(0; n ¼ 1) (60) (100) (57; n ¼ 7)
1 3 0 4
regions (Table 3). In general, tissue samples were small and dissociated (Suppl. Figs. 4, 5), and teeth were rarely submitted. An adequate amount of bone was present for evaluation of histologic features in 27 samples, and adequate soft tissue was present in 29 samples. A peripheral rim of bone was apparent in 15 of 20 (75%) tissue samples from canine sites and 3 of 7 (43%) samples from premolar/molar sites; for each site, maxillary samples were more likely to demonstrate this rim of bone as compared to those from the mandible (Table 3). The peripherally located rim of dense sclerotic bone had a flat or convex surface that faced an inner area of proliferative woven bone and variably inflamed fibrovascular tissue (Fig. 7, Suppl. Fig. 8). The remodeled trabeculae of sclerotic bone had irregular reversal lines and a mosaic pattern of compact lamellar bone with immature
Neovascular Tissue With Suppurative Inflammation
(100) (100) (75; n ¼ 4) (100) (95)
0 0 1 0 1
(0) (0) (25; n ¼ 4) (0) (5)
(50) (60) (0) (50)
1 2 1 4
(50) (40) (100) (50)
woven bone (Suppl. Figs. 10, 11). Osteoclastic activity was also noted but not recorded (Suppl. Fig. 7). Formation of benign woven bone was evident in all 27 samples where sufficient bone was included in the biopsy specimen. Woven bone was porous and corresponded to the rarified proliferative bone seen radiographically. A total of 4 of 27 (15%) samples—all of which were from an affected premolar/molar region—showed exuberant proliferation of woven bone. In these 4 cases, the majority of the tissue submitted for histopathologic evaluation consisted of diffuse rafts of woven bone arranged in irregular trabeculae (Fig. 10). For evaluation and reporting of the soft tissues, samples were assigned to 1 of 2 mutually exclusive categories depending on the predominant type of tissue reaction and inflammation. The majority of samples from the canine region, 20 of
Figures 3, 4. (continued) premolars/molars are signs of periodontal disease, including gingivomucosal edema and erythema, loss of alveolar bone with gingival recession (arrow), and hyperplastic gingivitis (encircling the molar; arrowhead). Photographs courtesy of Eric Davis, used with permission. Figure 5. Alveolar bone expansion and osteomyelitis, maxillary canine tooth, cat. Expanded and rarified bone is centered on the cervical region of the affected canine root. Radiograph courtesy of Chanda Miles, used with permission. Figure 6. Alveolar bone expansion and osteomyelitis, maxillary fourth premolar, cat. There is proliferation of rarified bone (arrows). Radiograph courtesy of Barden Greenfield, used with permission. Downloaded from vet.sagepub.com at UNIVERSITE DE MONTREAL on August 27, 2015
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Figures 7–12. Figures 7, 8. Chronic alveolar bone expansion and osteomyelitis, alveolar bone of a maxillary canine tooth, cat. Hematoxylin and eosin (HE). Figure 7. A rim of sclerotic bone along the peripheral edge (right of image) transitions to trabecular bone that is expanded by intertrabecular fibrosis and a small amount of woven bone (wb). In the upper left is proliferative gingiva with inflammation. Figure 8. Higher magnification of Figure 7. The outer layer of sclerotic bone (sb) is very dense; the trabecular bone (tb) is a mosaic of chronically remodeled bone; and the wb is porous. Inset: Loosely arranged intertrabecular stroma has perivascular lymphocytes and plasma cells. Figure 9. Chronic alveolar
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21 (95%), showed fibrosis with low to moderate numbers of inflammatory cells. Proliferation of fibrous connective tissue partially replaced and expanded the medullary stroma of alveolar bone (Figs. 7–9, Suppl. Fig. 10). Within areas of fibrosis were low to moderate numbers of mixed inflammatory infiltrates, including plasma cells, lymphocytes, and neutrophils (Fig. 8, inset; Suppl. Fig. 7). Although uncommon, occasional rests of odontogenic epithelium were present within the fibrous tissue. Inflammation of the periodontal apparatus was seen consistently in the gingiva and alveolar bone. In the 2 samples that included a histologic section of the tooth in situ, cementum and the periodontal ligament proper were relatively spared (Fig. 9). Tissue samples from the premolar/molar sites included 4 of 8 (50%) in each category—fibrosis with lymphoplasmacytic inflammation vs proliferative inflammatory tissue with chronic and suppurative inflammation. Although not graded quantitatively, the fibrosing reaction was subjectively more cellular in samples from the premolar/molar region (Fig. 11; Suppl. Figs. 5, 8) as compared to those from the canine region (Fig. 8, Suppl. Fig. 6). Tissue samples with chronic suppurative inflammation showed active neovascularization and dense infiltrates of neutrophils, generally accompanied by plasma cells and lymphocytes (Fig. 12, Suppl. Fig. 8). Only 1 of 21 (4.8%) canine sample had a significant amount of the densely cellular, proliferative inflammatory tissue with suppurative inflammation; this biopsy site was associated with a canine crown fracture, pulp exposure, and endodontic inflammation. Colonies of filamentous bacteria were apparent with routine hematoxylin and eosin staining in 4 of 32 (12.5%) samples, including 1 canine site of 23 (4%) and 3 of 9 (33%) premolar/molar sites (Suppl. Fig. 9). One lesion occurred in the presence of retained tooth roots and a necrotic bone sequestrum, which was confirmed histologically.
Discussion To summarize the histologic features of tissue samples from the canine biopsy sites, the alveolar bone was expanded by medullary fibrosis with mild to moderate pleocellular inflammation and modest proliferation of woven bone. The fibrous tissue surrounded and intercalated with thin noncompact trabeculae of bone (mainly lamellar rather than woven bone). Inflammatory cells were generally sparse with multifocal clusters of mixed plasma cells, lymphocytes, and neutrophils. Most samples from the maxillary canine region and half those from the mandibular canine region had a distinct peripheral rim of sclerotic bone, which ranged from dense osteonal bone to remodeled bone with a mosaic pattern of trabecular bone and woven bone. The attenuation and sclerosis were consistent with
outward compressive forces (expansion) and inflammatory remodeling of alveolar bone. Proliferation of intensely cellular granulation tissue was not a common feature of alveolar osteomyelitis in the canine region in cats. The histologic features of tissue samples from the premolar/ molar sites tended to be more variable with respect to the presence of compressed bone, presence of woven bone, fibrosis, and type and severity of inflammation. The samples that had exuberant woven bone tended to be those with proliferative and densely cellular inflamed tissue. Ulceration and erosion of the gingiva were common in those samples with granulation tissue and chronic suppurative inflammation. In cats, advanced stages of periodontitis may manifest as grossly obvious lesions, often with a distinct mass effect and involvement of bone (ie, alveolar osteomyelitis). Our results are consistent with previous descriptions of a unique pattern of chronic periodontitis in cats where there is maxillary canine tooth extrusion (supereruption) and/or labial expansion of alveolar bone.2,3,5,16,17,30 A proposed mechanism of alveolar bone expansion in cats has been eloquently described in terms of peripheral growth, or segmental alveolar bone growth, which describes proliferation of periodontal tissues (alveolar bone and gingiva) in a coronal direction.16 Our findings are consistent with the statement made by Lewis et al that alveolar bone expansion at canine teeth is easier to recognize clinically than alveolar bone expansion at premolar and molar teeth.16 Mechanical forces might also explain the characteristic pattern of expansion associated with chronic alveolar osteomyelitis of the maxillary canine teeth. Forces of translation and intrusion on teeth result in compression of the tooth against alveolar bone. This may lead to degeneration of the periodontal ligament, periodontal inflammation, and resorption of cementum and dentin.27 Lewis et al suggested that a generalized syndrome occurs in cats with periodontal ligament degeneration, tooth resorption, alveolar bone expansion, and hypercementosis with subsequent tooth extrusion.16 Given the absence of histologic inflammation in the periodontal space, they concluded that ankylosis and replacement resorption are more significant in the pathogenesis of this syndrome than is inflammatory resorption secondary to periodontitis.16 Tooth resorption was not systematically evaluated or classified for cats in the current study. Our subjective findings are consistent with recent studies that support the following conclusions: tooth resorption is common in cats, and prevalence increases with age; premolars are affected most frequently; there is a significant correlation between extrusion of canine teeth and tooth resorption; tooth resorption is not confined to the cervical portion of the tooth; tooth resorption is common in the presence of periodontitis; and tooth resorption
Figure 9. (continued) osteomyelitis, tooth and periodontal apparatus of a maxillary canine tooth, cat. The dentin (d), cementum (c), and periodontal ligament (pl) are unremarkable. On the right side of the image, low numbers of lymphocytes and plasma cells infiltrate the loose fibrovascular stroma of sclerotic alveolar bone (ab). HE. Figures 10–12. Chronic suppurative alveolar osteomyelitis, alveolar bone from a maxillary premolar, cat. HE. Figure 10. A peripheral rim of dense cortical bone (cb) is attenuated, and on the concave surface is abundant porous woven bone. Figure 11. The trabecular stroma of bone is expanded by fibrosis and dense inflammatory cell infiltrates. Inset: Inflammatory cells are mainly plasma cells. Figure 12. In some areas of the tissue, inflammation is suppurative within congested neovascularized connective tissue. Downloaded from vet.sagepub.com at UNIVERSITE DE MONTREAL on August 27, 2015
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is generalized and not a local process.9,11,16,19,23–27 Furthermore, we demonstrate that inflammation in the periodontal ligament space is not a histologic correlate of clinical periodontitis. This study shows that cats with clinical and radiologic periodontitis may have vertical segments of the tooth root that are affected by alveolar osteomyelitis but have a histologically normal periodontal ligament. In other words, involvement of the periodontal ligament may follow inflammation and remodeling of alveolar bone. Only 1 site of alveolar osteomyelitis in this study was associated with endodontic disease. In this case, there was a crown fracture of the affected tooth (a mandibular canine). While endodontic inflammation (pulpitis) is a potential cause of osteomyelitis, it appears to be considerably less common than alveolar osteomyelitis as an extension of periodontal inflammation. A broad range of bacteria has been implicated in osteomyelitis of the jaw, most of which are normal oral flora.6,7,10,13,20,28 While antimicrobial therapy is recognized as an important component of comprehensive treatment of oral osteomyelitis, aerobic and anaerobic cultures may be unrewarding in humans12,15 and cats.3,5 A combined therapy is recommended: periodontal debridement (or extraction of involved teeth), oral antibiotics, pain medication, and osteoplasty of alveolar bone.1,5 A limitation of the present study is that systemic conditions and diseases are generally unknown for this population. Based only on the submitted history, reported comorbidities for these 28 cats included diabetes mellitus, hyperthyroidism, renal insufficiency (each affecting 2 cats), chronic arthritis, and positive feline immunodeficiency status (each affecting 1 cat). As emphasized in a previous study of swollen mandibular lesions, only histologic examination can distinguish an inflammatory process from a potentially malignant tumor.14 Areas of expanded and proliferative bone may be clinically mistaken for malignancy, a benign neoplasm, or a benign condition such as fibrous dysplasia. One of the canine biopsy sites in this study was previously diagnosed by histopathology as osteosarcoma. When presenting as a hard smooth mass, inflammatory processes can resemble a benign bony tumor, such as ossifying fibroma. This is particularly true at the maxillary canine teeth where bony expansion tends to be quite pronounced. Tissue samples from the maxillary canine biopsy sites also had sparse inflammatory cell infiltrates; thus, even microscopically, the inflammatory process could be mistaken for a fibro-osseous neoplasm. In a young cat, the differential diagnosis includes benign odontogenic tumors, particularly the feline inductive ameloblastic fibroma (feline inductive odontogenic tumor) that tends to occur in association with a canine tooth.8 Squamous cell carcinoma is an important differential diagnosis for alveolar osteomyelitis of the caudal dentition in cats (Suppl. Fig. 1). Both conditions tend to arise in middle-aged and geriatric cats, and both may appear ulcerated and proliferative with soft tissue swelling and radiologic evidence of osseous proliferation and osteolysis. Within the proliferative and inflamed alveolar tissues, occasional rests of odontogenic
epithelium may be seen and should not be interpreted as neoplastic epithelium. Feline chronic gingivostomatitis is a distinct clinical entity that affects the caudal oral mucosa of cats and, histologically, features intensely cellular inflammatory tissue with abundance of plasma cells. This pattern of inflammation is very similar to the proliferative tissue seen in many samples from the premolar/molar biopsy sites in this study. Distinction between feline chronic gingivostomatitis and proliferative gingivitis due to periodontitis in cats is a challenge, and the site of the biopsied lesion must be specified. For surgical biopsy specimens, the pathologist is encouraged to obtain and rely on relevant clinical and radiologic information from the veterinary clinician to provide a clinicopathologic correlative diagnosis. Regarding nomenclature, despite its widespread use in the veterinary clinical setting, the term alveolar osteitis is potentially confusing and should be avoided. In human dentistry, alveolar osteitis specifically refers to the condition known colloquially as dry socket, which is usually a postoperative complication following tooth extraction and is attributed to premature fibrinolysis of the alveolar blood clot. This postextraction form of osteomyelitis has been reported in a dog, using the term alveolar osteitis.29 Referring to the condition as alveolar osteitis, Aller described a case of periodontitis and osteomyelitis at a maxillary canine tooth of a cat.2 The term alveolar osteitis reflected the author’s speculation that bone infection and inflammation resulted from dehiscence and fibrinolysis at the site of an extracted canine tooth, even though ‘‘excessively prominent alveolar buccal bone’’ was present prior to tooth extraction.2 Histopathologically, an appropriate diagnosis is chronic alveolar osteomyelitis. Clinically, the term alveolar bone expansion is appropriate when referring to an enlargement of bone secondary to periodontitis in cats. The results of this study contribute to a growing body of evidence that there is a likely association among tooth resorption, clinical periodontitis, and alveolar osteomyelitis in cats. A previous radiographic study of the feline jaws showed similar results where evidence of periodontitis (72% of cats), tooth resorption (67%), and expansion of alveolar bone (53%) were all common and often concurrent at 1 canine teeth.17 Acknowledgements We wish to thank the many veterinary clinicians in practice and veterinary dental specialists who support the Center for Comparative Oral and Maxillofacial Pathology through submission of surgical biopsy specimens, encouragement, and valued insight.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
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References 1. Agarwal A, Kumar N, Tyagi A, et al. Primary chronic osteomyelitis in the mandible: a conservative approach [published online April 3, 2014]. BMJ Case Rep. 2. Aller S. Veterinary dentist at work: alveolar osteitis in a cat. J Vet Dent. 1998; 15:92. 3. Arzi B, Fiani N. Diagnostic imaging in veterinary dental practice: permeative bone loss in a Himalayan cat. J Am Vet Med Assoc. 2009;235:1149–1151. 4. Baltensperger M, Gratz K, Bruder E, et al. Is primary chronic osteomyelitis a uniform disease? Proposal of a classification based on a retrospective analysis of patients treated in the past 30 years. J Craniomaxillofac Surg. 2004;32:43–50. 5. Beebe DE, Gengler WR. Osseous surgery to augment treatment of chronic periodontitis of canine teeth in a cat. J Vet Dent. 2007;24:30–38. 6. de Farias MR, Werner J, Ribeiro MG, et al. Uncommon mandibular osteomyelitis in a cat caused by Nocardia africana. BMC Vet Res. 2012;8:239–243. 7. Frid P, Tornes K, Nielsen O, et al. Primary chronic osteomyelitis of the jaw—a microbial investigation using cultivation and DNA analysis: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107:641–647. 8. Gardner DG, Dubielzig RR. Feline inductive odontogenic tumor (inductive fibroameloblastoma): a tumor unique to cats. J Oral Pathol Med. 1995;24: 185–190. 9. Girard N, Servet E, Hennet P, et al. Tooth resorption and vitamin D3 status in cats fed premium dry diets. J Vet Dent. 2010;27:142–147. 10. Goda A, Maruyama F, Michi Y, et al. Analysis of the factors affecting the formation of the microbiome associated with chronic osteomyelitis of the jaw. Clin Microbiol Infec. 2014;20:O309–O317. 11. Gorrel C, Larson A. Feline odontoclastic resorptive lesions: unveiling the early lesion. J Smll Anim Pract. 2002;43:482–488. 12. Hudson JW. Osteomyelitis of the jaws: a 50-year perspective. J Oral Maxillofac Surg. 1993;51:1294–1301. 13. Johnson KA. Osteomyelitis in dogs and cats. J Am Vet Med Assoc. 1994;204: 1882–1887. 14. Kapatkin AS, Marretta SM, Patnaik AK, et al. Mandibular swellings in cats: prospective study of 24 cats. J Am Anim Hosp Assoc. 1991;27:575–580.
15. Krakowiak PA. Alveolar osteitis and osteomyelitis of the jaws. Oral Maxillofac Surg Clin North Am. 2011;23:401–413. 16. Lewis JR, Okuda A, Shofer FS, et al. Significant association between tooth extrusion and tooth resorption in domestic cats. J Vet Dent. 2008;25:86–95. 17. Lommer MJ, Verstraete FJ. Radiographic patterns of periodontitis in cats: 147 cases (1998–1999). J Am Vet Med Assoc. 2001;218:230–234. 18. Lund EM, Armstrong JP, Kirk CA, et al. Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States. J Am Vet Med Assoc. 1999;214:1336–1341. 19. Mestrinho LA, Runhau J, Braganca M, et al. Risk assessment of feline tooth resorption: a Potuguese clinical case control study. J Vet Dent. 2013;30: 78–83. 20. Muir P, Johnson KA. Anaerobic bacteria isolated from osteomyelitis in dogs and cats. Vet Surg. 1992;21:463–466. 21. Neville BW, Damm DD, Allen CM, et al. Oral and Maxillofacial Pathology. 3rd ed. St Louis, MO: Saunders Elsevier; 2009:141–147. 22. Niemiec BA. Periodontal disease. Top Companion Anim Med. 2008;23:72–80. 23. Peralta S, Verstraete FJM, Kass PH. Radiographic evaluation of the types of tooth resorption in dogs. Am J Vet Res. 2010;71:784–793. 24. Reiter AM. Feline ‘‘odontolysis’’ in the 1920’s: the forgotten histopathological study of feline odontoclastic resorptive lesions (FORL). J Vet Dent. 1998;15: 35–41. 25. Reiter AM, Lewis JR, Okuda A. Update on the etiology of tooth resorption in domestic cats. Vet Clin Small Anim. 2005;35:913–942. 26. Reiter AM, Lyon DR, Nachreiner RF, et al. Evaluation of calciotropic hormones in cats with odontoclastic resorptive lesions. Am J Vet Res. 2005;66:1446–1452. 27. Roux P, Berger M, Stoffel M, et al. Observations of the periodontal ligament and cementum in cats with dental resorptive lesions. J Vet Dent. 2005;22:74–85. 28. Soto E, Arauz M, Gallagher CA, et al. Nocardia cyriacigeorgica as the causative agent of mandibular osteomyelitis (lumpy jaw) in a cat. J Vet Diagn Invest. 2014;26:580–584. 29. Van Cauwelaert de wyels S. Alveolar osteitis (dry socket) in a dog. J Vet Dent. 1998;15:85–87. 30. Wiggs RB, Lobprise HB. Veterinary Dentistry, Principles and Practice. Philadelphia, PA: Lippincott-Raven; 1997:482–517.
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Histologic, Clinical, and Radiologic Findings of Alveolar Bone Expansion and Osteomyelitis of the Jaws in Cats
Veterinary Pathology 2015, Vol. 52(5) 910-918 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0300985815591079 vet.sagepub.com
C. M. Bell1,2 and J. W. Soukup1,3
Abstract The objective of this study was to characterize clinical, radiologic, and histologic patterns of alveolar bone expansion and osteomyelitis in cats. Based on case materials submitted as surgical biopsy specimens, alveolar bone pathology was diagnosed in 28 cats. These cats had a total of 37 oral lesions with clinical and radiologic changes that involved bone and/or teeth, including periodontitis, bone expansion, tooth resorption, and/or chronic osteomyelitis; 32 lesions were evaluated by histopathology. Canine teeth were affected in 19 cats (27 affected teeth), with bilateral lesions in 5 (26.3%) cats. The caudal premolar and/or molar regions were affected in 10 cats (10 affected sites). All biopsy sites evaluated by a review of clinical images and/or radiographs had evidence of periodontitis. Clinical photographs showed expansion of alveolar bone in 13 of 16 (81%) biopsy sites evaluated. Radiologically, rarifying osseous proliferation of alveolar bone was seen at 26 of 27 (96%) biopsy sites, and tooth resorption occurred at 15 of 18 (83%) sites. Histologically, the tissue samples from canine sites had compressed trabeculae of mature remodeled bone, loose fibrous stroma with paucicellular inflammation, and mild proliferation of woven bone. Tissue samples from the premolar/molar biopsy sites were often highly cellular with mixed lymphoplasmacytic and chronic suppurative inflammation, ulceration with granulation tissue, and robust proliferation of woven bone. Alveolar bone expansion and osteomyelitis in cats occurs in conjunction with periodontal inflammation and frequently with tooth resorption. Keywords dentistry, feline, pathology, oral, osteitis, osteomyelitis, periodontitis, radiology, tooth resorption
Periodontal disease involves inflammation of the periodontium, which includes gingiva, periodontal ligament, cementum, and alveolar bone. Defined by clinical and radiologic findings, periodontitis is one of the most common clinical diseases in cats.17,18,22 While periodontal disease may begin as gingivitis, periodontitis is defined by attachment loss (radiologic loss of alveolar bone and/or clinical periodontal pockets). Progression of periodontal inflammation can also lead to gingival recession, osteomyelitis, and tooth loss. In a study of 24 cats with mandibular swelling, 50% were malignancies (most commonly, squamous cell carcinoma), and 50% were benign, nearly all of which were osteomyelitis.14 Thus, osteomyelitis is as common as malignant processes in the jaws of cats. The diagnostic accuracy that veterinary pathologists might achieve with small biopsy specimens will significantly improve if distinctive clinicopathologic patterns of osteomyelitis are recognized. Osteomyelitis of the jaws in humans is classified by chronicity and etiology (primary and secondary). After onset of clinical symptoms, 4 weeks is accepted as the arbitrary distinction between acute/subacute osteomyelitis and chronic osteomyelitis. Clinical features of acute osteomyelitis include pain, swelling, purulent drainage, fistulous tracts, sequestrum formation,
lymphadenopathy, and febrile episodes.15 Histologically, acute osteomyelitis is characterized by necrotic bone and suppurative inflammation.15,21 Chronic suppurative osteomyelitis, or secondary chronic osteomyelitis, usually has a bacterial cause and is often a progression of acute osteomyelitis. Clinically, there is pain, swelling, and purulent discharge. Radiologic features include osteolysis, osteosclerosis, and proliferation of periosteal new bone.4 Histologically, there are variable signs of chronic infection, including medullary fibrosis, endosteal bone
1 Center for Comparative Oral and Maxillofacial Pathology, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, USA 2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, USA 3 Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, USA
Supplemental material for this article is available on the Veterinary Pathology website at http://vet.sagepub.com/supplemental. Corresponding Author: C. M. Bell, Wisconsin Veterinary Diagnostic Laboratory, 445 Easterday Lane, Madison, WI 53706, USA. Email: [email protected]
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formation, bone resorption, microabscess formation, and soft tissue involvement.4 A notable proliferation of inflamed fibrous connective tissue fills the space between bone trabeculae.21 Primary chronic osteomyelitis in humans manifests as recurrent episodes of pain and/or swelling and regional lymphadenopathy. Primary chronic osteomyelitis is nonsuppurative, usually affects the mandible, has no known etiology, and may be difficult to distinguish clinically and radiologically from a benign fibro-osseous lesion without biopsy and culture. Histologically, osteosclerosis is prominent, and the connective tissue between bone trabeculae may have low numbers of neutrophils, lymphocytes, and plasma cells.21 The highest incidence of primary chronic osteomyelitis is in patients with vascular insufficiency, immune dysfunction, or metabolic bone disorders, such as diabetes, systemic steroid therapy, renal and hepatic failure, and human immunodeficiency virus infection.15 Alveolar bone expansion, especially in the region of the canine teeth, is recognized clinically in cats and often occurs in conjunction with periodontitis and/or tooth resorption.3,16,17 Terms used to describe this condition in the veterinary dental literature include peripheral osteitis, alveolar osteitis, or peripheral buttressing.2,5,25,30 The specific objective of this study was to characterize the histopathologic, radiologic, and clinical features of alveolar osteomyelitis and alveolar bone expansion in cats, particularly as they relate to the clinical condition known as alveolar osteitis.
Materials and Methods The cases in this study were submitted as surgical biopsy specimens to the Center for Comparative Oral and Maxillofacial Pathology at the University of Wisconsin–Madison. The tissue samples were received in 10% neutral buffered formalin and decalcified as needed in standard 10% HCl solution for 2 to 48 hours. Tissues were processed by conventional methods, embedded in paraffin, sectioned at 5 mm, and stained with hematoxylin and eosin. Cases from cats with the histopathologic diagnosis of osteomyelitis of alveolar bone were considered for inclusion. Cases of feline osteomyelitis of the jaws were excluded from the study if trauma was the known or suspected cause, if neoplastic disease was present at the site of the lesion, or if an infectious process was present at the affected site, with the exception of bacterial plaque. The signalment and clinical history, clinical photographs, and radiographs were obtained at the time of submission.
Clinical Features Clinical information regarding signalment and the number and distribution of affected sites in the oral cavity was obtained from the biopsy sample submission form. These images were systematically reviewed by a board certified veterinary dentist (J.W.S.). At the biopsy site, the presence or absence of the following was recorded: in situ tooth, jaw expansion (including
direction of expansion), soft tissue swelling, clinical features of periodontal disease (eg, gingival hemorrhage, gingivomucosal erythema, root exposure), gingivomucosal ulcerations, and dental crown fracture.
Radiologic Features Radiographs were reviewed by a board-certified veterinary dentist (J.W.S.), and the presence or absence of the following was recorded at the biopsy site: rarefying osseous proliferation, incisor region involvement, radiologic type of tooth resorption (as defined by Peralta et al23), periodontitis, and endodontic disease. Criteria for evidence of periodontitis included horizontal or vertical bone loss and widening of the periodontal ligament space. Criteria for evidence of endodontic disease included rarefying or sclerosing pattern of periapical lucency or halted dentinogenesis. When the canine or carnassial tooth at the biopsy site was missing, no information regarding the presence or absence of tooth resorption, periodontitis, or endodontic disease was recorded.
Histologic Features All slides were examined by a board-certified pathologist (C.M.B.). For each sample, the histologic features of the biopsied tissues were recorded for both bone and soft tissue. The specific bony changes included the presence or absence of a distinct peripheral rim of bone and the presence of a majority of woven bone (ie, woven bone as >50% of the total bone present). These bony changes were not mutually exclusive. The evaluated soft tissues included gingiva, alveolar mucosa, intertrabecular stroma, and/or reparative tissue that replaced bone. The soft tissue changes were recorded according to the predominant type of proliferative tissue seen and the associated type of inflammation; categories were mutually exclusive: neovascular tissue with chronic suppurative inflammation vs fibrosis with lymphoplasmacytic inflammation.
Results In this study, we identified 28 cats with 37 sites of alveolar osteomyelitis with clinical and radiologic evidence of periodontitis (Suppl. Table 1). Nineteen cats had involvement of 1 canine teeth, with a total of 27 affected canine sites, 23 of which were evaluated by histopathology. Ten cats had 10 premolar/molar sites of periodontal inflammation and osteomyelitis, 9 of which were evaluated by histopathology. A total of 6 cats had multiple affected sites involving at least 2 sites of canine teeth. One of the cats with 3 affected sites had bilateral involvement of the maxillary canine regions and unilateral involvement of a maxillary premolar region. Bilateral canine involvement was noted for 5 cats (maxillary in 4 cats and mandibular in 1 cat). There was no sex difference for cats having a tissue biopsy from the premolar/molar sites. However, neutered males accounted for 22 of 27 (82%) cats having a tissue biopsy from
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Table 1. Clinical Features of Alveolar Osteomyelitis in Cats, No. (%). Tooth Missing Affected canine sites 104 (n ¼ 4) 204 (n ¼ 4) 304 (n ¼ 2) 404 (n ¼ 1) Total (n ¼ 11) Affected premolar/molar sites 107–109 (n ¼ 1) 0–209 (n ¼ 3) 309 (n ¼ 1) Total (n ¼ 5)
Labial Bone Expansion
Mesial Bone Expansion
Soft Tissue Swelling
Gingivomucosal Ulceration
1 1 0 0 2
(25) (25) (0) (0) (18)
4 (100) 4 (100) 1 (50) 0 (0) 9 (82)
0 0 2 1 3
(0) (0) (100) (100) (27)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
2 2 0 0 4
(50) (50) (0) (0) (36)
0 0 0 0
(0) (0) (0) (0)
0 (0) 2 (67) 0 (0) 2 (40)
0 0 0 0
(0) (0) (0) (0)
1 (100) 3 (100) 1 (100) 5 (100)
1 1 0 2
(100) (33) (0) (40)
the site of a canine tooth. For the study population in general and for each anatomic region, the domestic shorthair was the predominant breed, with 19 of 28 (68%) cats, yet 6 other feline breeds were represented. The age was available for 26 of the 28 cats, ranging from 5 to 20 years with a median of 10.5 years; the age distribution was similar regardless of the site of the biopsy.
Clinical Features Appropriate clinical images were available for evaluation of clinical features for 16 biopsy sites from 15 cats, including 11 sites near a canine tooth and 5 premolar/molar sites (Table 1). Specific clinical features of periodontal disease were variable yet consistent at all biopsy sites. Labial expansion of bone was present in all (n ¼ 8) sites in the region of a maxillary canine (Figs. 1, 2), of which a canine tooth was missing in 2 of 11 (18.2%). Abnormal tooth extrusion (supereruption) of the affected canine tooth was not systematically recorded but was occasionally apparent (Fig. 1). Clinically visible expansion of alveolar bone in the canine region of the mandible occurred in a mesial direction for 3 of 3 (100%) affected sites. Clinically visible jaw expansion was less common in the premolar/molar regions, seen in only 2 of 5 (40%) affected sites. None of the molar or premolar teeth was missing at these affected sites. Clinically visible swelling and erythema of the vestibular and labial soft tissues were evident in all 5 of the evaluated biopsy sites of the premolar/molar region (Figs. 3, 4), but swollen soft tissue was not apparent in any of the 11 evaluated biopsy sites in the canine region. Gingivomucosal ulcerations (Figs. 1, 3, 4) were seen in the canine and premolar/molar regions—in 4 of 11 (36%) and 2 of 5 (40%), respectively. Ulcerations were more common in the maxilla than in the mandible, as seen in 6 of 12 (50%) and 0 of 4 (0%), respectively. Bony defects occasionally occurred on the palatal aspect of affected maxillary fourth premolars (Fig. 4). Photographic evidence of a crown fracture was seen in only 1 tooth, which was a mandibular canine.
Radiologic Features Radiographs were available and evaluated for 27 biopsy sites. Of those, 18 (67%) radiographs adequately represented the pertinent canine or carnassial teeth and were assessed for features of tooth resorption, periodontitis, or endodontic disease (Table 2). Rarefying osseous proliferation at the site of biopsy was very common, occurring in 26 of 27 (96%) cases irrespective of location (Figs. 5, 6; Suppl. Figs. 2, 3). A difference was noted in the direction of bone proliferation at affected canine sites. In the maxilla, osseous proliferation remained centered on the affected canine tooth and expanded in a labial direction (Fig. 5). Involvement of the adjacent incisors was seen in only 1 case of 13 (8%) of an affected maxillary canine tooth. In contrast, osseous proliferation in the region of the mandibular canines generally extended in a mesial direction and frequently involved the incisor region, which was seen in 9 of 10 (90%) cases (Suppl. Fig. 3). Radiologic features generally associated with periodontitis were present in 100% of evaluated maxillary biopsy sites (Figs. 5, 6; Suppl. Fig. 2). In the mandible, radiographs showed features consistent with periodontitis in 4 of 6 (67%) canine sites (Suppl. Fig. 3), as did the 1 radiograph of a mandibular molar. Radiologic evidence of endodontic disease was seen at only 1 site of 18 (6%), which was a mandibular canine that had a crown fracture. The overall prevalence of radiologic changes consistent with tooth resorption was 15 of 18 (83%). Tooth resorption was commonly noted in 11 of 14 (79%) affected canine teeth and 4 of 4 (100%) affected premolars/molars. Two types of tooth resorption were seen—external inflammatory resorption (type 1) and external replacement resorption (type 2)—and the former was by far most common, as seen in 13 of 15 (92%) instances of tooth resorption (Suppl. Fig. 2).
Histologic Features Received and evaluated by histopathology were 32 formalin-fixed tissue samples of alveolar bone from 28 cats; 23 samples were from the rostral/canine region and 9 from the premolar/molar
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Figures 1–6. Figure 1. Unilateral alveolar bone expansion and osteomyelitis, left maxillary canine tooth, cat. Typical clinical features at an affected maxillary canine tooth include labial expansion of bone, tooth extrusion with root exposure (bracket), and mucosal erythema. Photograph courtesy of Kris Bannon, used with permission. Figure 2. Bilateral alveolar bone expansion and osteomyelitis with labial expansion of bone, maxillary canine teeth, cat. Photograph courtesy of Diane Carle, used with permission. Figures 3, 4. Diffuse gingivitis and regional stomatitis at the left maxillary premolars, oral cavity, cat. In the absence of obvious bone expansion, the clinical features of affected Downloaded from vet.sagepub.com at UNIVERSITE DE MONTREAL on August 27, 2015
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Table 2. Radiologic Features of Alveolar Osteomyelitis in Cats, No. (%). Rarefying Osseous Proliferation Affected canine sites 104 (n ¼ 6) 204 (n ¼ 7) 304 (n ¼ 6) 404 (n ¼ 4) Total (n ¼ 23) Affected premolar/molar sites 107-109 (n ¼ 1) 207-209 (n ¼ 2) 309 (n ¼ 1) Total (n ¼ 4)
Incisor Region Involvement
6 (100) 7 (100) 6 (100) 3 (75) 22 (96)
0 1 5 4 10
1 (100) 2 (100) 1 (100) 4 (100)
n/d n/d n/d n/d
Evidence of Tooth Resorption 3 (75; n ¼ 4) 4 (100; n ¼ 4) 3 (75; n ¼ 4) 1 (50; n ¼ 2) 11 (79; n ¼ 14)
(0) (14) (83) (100) (43)
1 (100) 2 (100) 1 (100) 4 (100)
Evidence of Periodontitis 4 4 3 1 12 1 2 1 4
(100; n ¼ 4) (100; n ¼ 4) (75; n ¼ 4) (50; n ¼ 2) (86; n ¼ 14) (100) (100) (100) (100)
Abbreviation: n/d, analysis was not done.
Table 3. Histologic Features of Alveolar Osteomyelitis in Cats, No. (%). Affected Sites Canine 104 (n ¼ 6) 204 (n ¼ 7) 304 (n ¼ 5) 404 (n ¼ 4) Total (n ¼21) Premolar/molar 107–109 (n ¼ 2) 207–209 (n ¼ 5) 309 (n ¼ 1) Total (n ¼ 8)
Peripheral Rim of Bone
Exuberant Woven Bone
Fibrosis With Lymphoplasmacytic Inflammation
6 (100) 5 (83; n ¼ 6) 2 (40) 2 (67; n ¼ 3) 15 (75; n ¼ 20)
0 0 0 0 0
(0) (0; n ¼ 6) (0) (0; n ¼ 3) (0; n ¼ 20)
6 7 3 4 20
1 (100; n ¼ 1) 2 (40) 0 (0) 3 (43; n ¼ 7)
0 3 1 4
(0; n ¼ 1) (60) (100) (57; n ¼ 7)
1 3 0 4
regions (Table 3). In general, tissue samples were small and dissociated (Suppl. Figs. 4, 5), and teeth were rarely submitted. An adequate amount of bone was present for evaluation of histologic features in 27 samples, and adequate soft tissue was present in 29 samples. A peripheral rim of bone was apparent in 15 of 20 (75%) tissue samples from canine sites and 3 of 7 (43%) samples from premolar/molar sites; for each site, maxillary samples were more likely to demonstrate this rim of bone as compared to those from the mandible (Table 3). The peripherally located rim of dense sclerotic bone had a flat or convex surface that faced an inner area of proliferative woven bone and variably inflamed fibrovascular tissue (Fig. 7, Suppl. Fig. 8). The remodeled trabeculae of sclerotic bone had irregular reversal lines and a mosaic pattern of compact lamellar bone with immature
Neovascular Tissue With Suppurative Inflammation
(100) (100) (75; n ¼ 4) (100) (95)
0 0 1 0 1
(0) (0) (25; n ¼ 4) (0) (5)
(50) (60) (0) (50)
1 2 1 4
(50) (40) (100) (50)
woven bone (Suppl. Figs. 10, 11). Osteoclastic activity was also noted but not recorded (Suppl. Fig. 7). Formation of benign woven bone was evident in all 27 samples where sufficient bone was included in the biopsy specimen. Woven bone was porous and corresponded to the rarified proliferative bone seen radiographically. A total of 4 of 27 (15%) samples—all of which were from an affected premolar/molar region—showed exuberant proliferation of woven bone. In these 4 cases, the majority of the tissue submitted for histopathologic evaluation consisted of diffuse rafts of woven bone arranged in irregular trabeculae (Fig. 10). For evaluation and reporting of the soft tissues, samples were assigned to 1 of 2 mutually exclusive categories depending on the predominant type of tissue reaction and inflammation. The majority of samples from the canine region, 20 of
Figures 3, 4. (continued) premolars/molars are signs of periodontal disease, including gingivomucosal edema and erythema, loss of alveolar bone with gingival recession (arrow), and hyperplastic gingivitis (encircling the molar; arrowhead). Photographs courtesy of Eric Davis, used with permission. Figure 5. Alveolar bone expansion and osteomyelitis, maxillary canine tooth, cat. Expanded and rarified bone is centered on the cervical region of the affected canine root. Radiograph courtesy of Chanda Miles, used with permission. Figure 6. Alveolar bone expansion and osteomyelitis, maxillary fourth premolar, cat. There is proliferation of rarified bone (arrows). Radiograph courtesy of Barden Greenfield, used with permission. Downloaded from vet.sagepub.com at UNIVERSITE DE MONTREAL on August 27, 2015
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Figures 7–12. Figures 7, 8. Chronic alveolar bone expansion and osteomyelitis, alveolar bone of a maxillary canine tooth, cat. Hematoxylin and eosin (HE). Figure 7. A rim of sclerotic bone along the peripheral edge (right of image) transitions to trabecular bone that is expanded by intertrabecular fibrosis and a small amount of woven bone (wb). In the upper left is proliferative gingiva with inflammation. Figure 8. Higher magnification of Figure 7. The outer layer of sclerotic bone (sb) is very dense; the trabecular bone (tb) is a mosaic of chronically remodeled bone; and the wb is porous. Inset: Loosely arranged intertrabecular stroma has perivascular lymphocytes and plasma cells. Figure 9. Chronic alveolar
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21 (95%), showed fibrosis with low to moderate numbers of inflammatory cells. Proliferation of fibrous connective tissue partially replaced and expanded the medullary stroma of alveolar bone (Figs. 7–9, Suppl. Fig. 10). Within areas of fibrosis were low to moderate numbers of mixed inflammatory infiltrates, including plasma cells, lymphocytes, and neutrophils (Fig. 8, inset; Suppl. Fig. 7). Although uncommon, occasional rests of odontogenic epithelium were present within the fibrous tissue. Inflammation of the periodontal apparatus was seen consistently in the gingiva and alveolar bone. In the 2 samples that included a histologic section of the tooth in situ, cementum and the periodontal ligament proper were relatively spared (Fig. 9). Tissue samples from the premolar/molar sites included 4 of 8 (50%) in each category—fibrosis with lymphoplasmacytic inflammation vs proliferative inflammatory tissue with chronic and suppurative inflammation. Although not graded quantitatively, the fibrosing reaction was subjectively more cellular in samples from the premolar/molar region (Fig. 11; Suppl. Figs. 5, 8) as compared to those from the canine region (Fig. 8, Suppl. Fig. 6). Tissue samples with chronic suppurative inflammation showed active neovascularization and dense infiltrates of neutrophils, generally accompanied by plasma cells and lymphocytes (Fig. 12, Suppl. Fig. 8). Only 1 of 21 (4.8%) canine sample had a significant amount of the densely cellular, proliferative inflammatory tissue with suppurative inflammation; this biopsy site was associated with a canine crown fracture, pulp exposure, and endodontic inflammation. Colonies of filamentous bacteria were apparent with routine hematoxylin and eosin staining in 4 of 32 (12.5%) samples, including 1 canine site of 23 (4%) and 3 of 9 (33%) premolar/molar sites (Suppl. Fig. 9). One lesion occurred in the presence of retained tooth roots and a necrotic bone sequestrum, which was confirmed histologically.
Discussion To summarize the histologic features of tissue samples from the canine biopsy sites, the alveolar bone was expanded by medullary fibrosis with mild to moderate pleocellular inflammation and modest proliferation of woven bone. The fibrous tissue surrounded and intercalated with thin noncompact trabeculae of bone (mainly lamellar rather than woven bone). Inflammatory cells were generally sparse with multifocal clusters of mixed plasma cells, lymphocytes, and neutrophils. Most samples from the maxillary canine region and half those from the mandibular canine region had a distinct peripheral rim of sclerotic bone, which ranged from dense osteonal bone to remodeled bone with a mosaic pattern of trabecular bone and woven bone. The attenuation and sclerosis were consistent with
outward compressive forces (expansion) and inflammatory remodeling of alveolar bone. Proliferation of intensely cellular granulation tissue was not a common feature of alveolar osteomyelitis in the canine region in cats. The histologic features of tissue samples from the premolar/ molar sites tended to be more variable with respect to the presence of compressed bone, presence of woven bone, fibrosis, and type and severity of inflammation. The samples that had exuberant woven bone tended to be those with proliferative and densely cellular inflamed tissue. Ulceration and erosion of the gingiva were common in those samples with granulation tissue and chronic suppurative inflammation. In cats, advanced stages of periodontitis may manifest as grossly obvious lesions, often with a distinct mass effect and involvement of bone (ie, alveolar osteomyelitis). Our results are consistent with previous descriptions of a unique pattern of chronic periodontitis in cats where there is maxillary canine tooth extrusion (supereruption) and/or labial expansion of alveolar bone.2,3,5,16,17,30 A proposed mechanism of alveolar bone expansion in cats has been eloquently described in terms of peripheral growth, or segmental alveolar bone growth, which describes proliferation of periodontal tissues (alveolar bone and gingiva) in a coronal direction.16 Our findings are consistent with the statement made by Lewis et al that alveolar bone expansion at canine teeth is easier to recognize clinically than alveolar bone expansion at premolar and molar teeth.16 Mechanical forces might also explain the characteristic pattern of expansion associated with chronic alveolar osteomyelitis of the maxillary canine teeth. Forces of translation and intrusion on teeth result in compression of the tooth against alveolar bone. This may lead to degeneration of the periodontal ligament, periodontal inflammation, and resorption of cementum and dentin.27 Lewis et al suggested that a generalized syndrome occurs in cats with periodontal ligament degeneration, tooth resorption, alveolar bone expansion, and hypercementosis with subsequent tooth extrusion.16 Given the absence of histologic inflammation in the periodontal space, they concluded that ankylosis and replacement resorption are more significant in the pathogenesis of this syndrome than is inflammatory resorption secondary to periodontitis.16 Tooth resorption was not systematically evaluated or classified for cats in the current study. Our subjective findings are consistent with recent studies that support the following conclusions: tooth resorption is common in cats, and prevalence increases with age; premolars are affected most frequently; there is a significant correlation between extrusion of canine teeth and tooth resorption; tooth resorption is not confined to the cervical portion of the tooth; tooth resorption is common in the presence of periodontitis; and tooth resorption
Figure 9. (continued) osteomyelitis, tooth and periodontal apparatus of a maxillary canine tooth, cat. The dentin (d), cementum (c), and periodontal ligament (pl) are unremarkable. On the right side of the image, low numbers of lymphocytes and plasma cells infiltrate the loose fibrovascular stroma of sclerotic alveolar bone (ab). HE. Figures 10–12. Chronic suppurative alveolar osteomyelitis, alveolar bone from a maxillary premolar, cat. HE. Figure 10. A peripheral rim of dense cortical bone (cb) is attenuated, and on the concave surface is abundant porous woven bone. Figure 11. The trabecular stroma of bone is expanded by fibrosis and dense inflammatory cell infiltrates. Inset: Inflammatory cells are mainly plasma cells. Figure 12. In some areas of the tissue, inflammation is suppurative within congested neovascularized connective tissue. Downloaded from vet.sagepub.com at UNIVERSITE DE MONTREAL on August 27, 2015
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is generalized and not a local process.9,11,16,19,23–27 Furthermore, we demonstrate that inflammation in the periodontal ligament space is not a histologic correlate of clinical periodontitis. This study shows that cats with clinical and radiologic periodontitis may have vertical segments of the tooth root that are affected by alveolar osteomyelitis but have a histologically normal periodontal ligament. In other words, involvement of the periodontal ligament may follow inflammation and remodeling of alveolar bone. Only 1 site of alveolar osteomyelitis in this study was associated with endodontic disease. In this case, there was a crown fracture of the affected tooth (a mandibular canine). While endodontic inflammation (pulpitis) is a potential cause of osteomyelitis, it appears to be considerably less common than alveolar osteomyelitis as an extension of periodontal inflammation. A broad range of bacteria has been implicated in osteomyelitis of the jaw, most of which are normal oral flora.6,7,10,13,20,28 While antimicrobial therapy is recognized as an important component of comprehensive treatment of oral osteomyelitis, aerobic and anaerobic cultures may be unrewarding in humans12,15 and cats.3,5 A combined therapy is recommended: periodontal debridement (or extraction of involved teeth), oral antibiotics, pain medication, and osteoplasty of alveolar bone.1,5 A limitation of the present study is that systemic conditions and diseases are generally unknown for this population. Based only on the submitted history, reported comorbidities for these 28 cats included diabetes mellitus, hyperthyroidism, renal insufficiency (each affecting 2 cats), chronic arthritis, and positive feline immunodeficiency status (each affecting 1 cat). As emphasized in a previous study of swollen mandibular lesions, only histologic examination can distinguish an inflammatory process from a potentially malignant tumor.14 Areas of expanded and proliferative bone may be clinically mistaken for malignancy, a benign neoplasm, or a benign condition such as fibrous dysplasia. One of the canine biopsy sites in this study was previously diagnosed by histopathology as osteosarcoma. When presenting as a hard smooth mass, inflammatory processes can resemble a benign bony tumor, such as ossifying fibroma. This is particularly true at the maxillary canine teeth where bony expansion tends to be quite pronounced. Tissue samples from the maxillary canine biopsy sites also had sparse inflammatory cell infiltrates; thus, even microscopically, the inflammatory process could be mistaken for a fibro-osseous neoplasm. In a young cat, the differential diagnosis includes benign odontogenic tumors, particularly the feline inductive ameloblastic fibroma (feline inductive odontogenic tumor) that tends to occur in association with a canine tooth.8 Squamous cell carcinoma is an important differential diagnosis for alveolar osteomyelitis of the caudal dentition in cats (Suppl. Fig. 1). Both conditions tend to arise in middle-aged and geriatric cats, and both may appear ulcerated and proliferative with soft tissue swelling and radiologic evidence of osseous proliferation and osteolysis. Within the proliferative and inflamed alveolar tissues, occasional rests of odontogenic
epithelium may be seen and should not be interpreted as neoplastic epithelium. Feline chronic gingivostomatitis is a distinct clinical entity that affects the caudal oral mucosa of cats and, histologically, features intensely cellular inflammatory tissue with abundance of plasma cells. This pattern of inflammation is very similar to the proliferative tissue seen in many samples from the premolar/molar biopsy sites in this study. Distinction between feline chronic gingivostomatitis and proliferative gingivitis due to periodontitis in cats is a challenge, and the site of the biopsied lesion must be specified. For surgical biopsy specimens, the pathologist is encouraged to obtain and rely on relevant clinical and radiologic information from the veterinary clinician to provide a clinicopathologic correlative diagnosis. Regarding nomenclature, despite its widespread use in the veterinary clinical setting, the term alveolar osteitis is potentially confusing and should be avoided. In human dentistry, alveolar osteitis specifically refers to the condition known colloquially as dry socket, which is usually a postoperative complication following tooth extraction and is attributed to premature fibrinolysis of the alveolar blood clot. This postextraction form of osteomyelitis has been reported in a dog, using the term alveolar osteitis.29 Referring to the condition as alveolar osteitis, Aller described a case of periodontitis and osteomyelitis at a maxillary canine tooth of a cat.2 The term alveolar osteitis reflected the author’s speculation that bone infection and inflammation resulted from dehiscence and fibrinolysis at the site of an extracted canine tooth, even though ‘‘excessively prominent alveolar buccal bone’’ was present prior to tooth extraction.2 Histopathologically, an appropriate diagnosis is chronic alveolar osteomyelitis. Clinically, the term alveolar bone expansion is appropriate when referring to an enlargement of bone secondary to periodontitis in cats. The results of this study contribute to a growing body of evidence that there is a likely association among tooth resorption, clinical periodontitis, and alveolar osteomyelitis in cats. A previous radiographic study of the feline jaws showed similar results where evidence of periodontitis (72% of cats), tooth resorption (67%), and expansion of alveolar bone (53%) were all common and often concurrent at 1 canine teeth.17 Acknowledgements We wish to thank the many veterinary clinicians in practice and veterinary dental specialists who support the Center for Comparative Oral and Maxillofacial Pathology through submission of surgical biopsy specimens, encouragement, and valued insight.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
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