Abstract
Benign fibro-osseous lesion (BFOL) is a distinct group of jaw entities composed of fibrocellular tissue and mineralized materials. In this study, we examined the epidemiological, clinical, and pathological features of patients with BFOL. Records and microslides of 207 BFOLs submitted to pathology service were retrospectively reviewed. Overall, fibrous dysplasia (FD) was the most prevalent (36.7%), followed by ossifying fibroma (OF; 32.4%), osseous dysplasia (OD; 24.6%), and juvenile ossifying fibroma (JOF; 6.3%). Female predilection was noted. FD and JOF were common in maxilla, whereas most OF and OD affected the mandible. Most patients with FD and OF presented with painless swelling, while patients with OD were symptomless. The majority of FD specimens showed woven bone, while a mixture of woven bone and cementum-like materials was often noted in OF and OD. Our data show variations in the clinicopathologic features of BFOLs. A thorough examination of all aspects of BFOL patients is imperative for accurate diagnosis.
Keywords
Introduction
Benign fibro-osseous lesions (BFOLs) of the jaws constitute a group of conditions showing an admixed production of fibrocollagenous tissue and various mineralized materials, including woven bone, lamellar bone, and/or cementum-like materials. The classification of BFOLs has been a subject of constant modification. As proposed by various authors, multiple pathological entities have been included under the heading of BFOLs.1-5 However, the most widely accepted classification was proposed by Waldron 5 in 1993 and later modified by Brannon and Fowler, 2 which comprised fibrous dysplasia (FD), osseous dysplasia (OD), ossifying fibroma (OF), and juvenile ossifying fibroma (JOF) as BFOLs of the jaws. These lesions were included in the current World Health Organization (WHO) classification of head and neck tumors under the “bone-related lesions.” 6 Other jaw entities, such as osteoblastoma, osteoid osteoma, and Paget disease of bone, may also be incorporated in the BFOL category by various authors. 3
Benign fibro-osseous lesions are diverse in their nature, clinical courses, and treatment outcomes. FD is a developmental condition associated with a sporadic mutation of Gs protein. 7 It stabilizes over time and the optimal treatment is surgical recontouring to correct facial deformity. All forms of OD are considered reactive lesions present only in the jaw bones and no specific treatment is required. On the other hand, both OF and JOF are neoplasms and a complete surgical removal is the treatment of choice.1,4,5
Despite their diversities, this group of lesions demonstrates some similar clinical, radiographic as well as histopathologic features. This at times poses problems for the diagnosis and management.3,8,9 A handful of reported series of BFOLs was published in the literature showing some discrepancies in epidemiological and geographical information.10-15 In addition, some earlier reports or case series are likely not fitted into the current classification scheme because of the change in concept of BFOL diagnosis and the late recognition of some lesions such as focal osseous dysplasia (FOD) or JOF. Therefore, the objective of this study was to analyze the epidemiological, clinical, radiographic, and pathologic data of patients diagnosed with BFOLs of the jaws. To our knowledge, this is one of the largest reported BFOL series to date and results should complement the current knowledge and help in diagnosis of this distinct group of lesions.
Materials and Methods
Data from patients diagnosed with BFOLs of the jaws were retrieved from the archive of Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand, during the 38-year period from 1975 to 2012. Based on the clinical, radiographic, and histopathologic findings, lesions were classified according to the 2005 WHO classification of head and neck tumors criteria into 4 distinct entities: (a) FD; (b) OF; (c) JOF, subclassified into juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF); and (d) OD, subclassified into periapical osseous dysplasia (POD), focal osseous dysplasia (FOD), and florid osseous dysplasia (FLOD).
Clinical data, including patient demographics, anatomical locations, presenting symptoms, and radiographic features were collected from pathology records. Regarding anatomic location, mandible was divided into anterior region (from right canine to left canine area), posterior region (from first premolar to third molar area), angle/ramus region and a combination of these sites. Maxilla was divided into the anterior region (form right canine to left canine area), the posterior region (from first premolar to tuberosity area) and the combined anterior and posterior regions.
Panoramic, occlusal, and/or periapical radiographs of patients were also reviewed when available to confirm clinicians’ records. Radiographically, the internal structure of lesions was recorded as 4 different types, namely complete radiolucency, mixed radiolucency-radiopacity, complete radiopacity and ground-glass appearance. Lesions were categorized as ground-glass in appearance when they showed granular radiopacities of small, delicate, randomly oriented trabeculae or gave a texture of an orange peel (Figure 1). On the other hand, lesions with homogenous, densely sclerotic trabeculae are considered completely radiopaque lesions. The border of the lesions was noted as a well-defined or ill-defined border.
Radiographic appearance of benign fibro-osseous lesions (BFOLs). (A) Fibrous dysplasia (FD) showing a ground-glass appearance with poorly defined border. (B) Ossifying fibroma (OF) showing a well-defined mixed radiolucent-radiopaque lesion. (C) Focal osseous dysplasia (FOD) showing a complete radiopaque mass with a thin radiolucent rim.
All microscopic slides were examined and 6 histopathologic parameters were recorded. Types of mineralized materials were divided into woven bones, lamellar bones, and cementum-like materials. The latter was defined as basophilic, round or curvilinear, amorphous mineralizations, which sometimes showed peripheral brush border and/or formed conglomerate structures. 4 Five other histopathologic parameters were recorded as “presence” or “absence,” including the mitosis in the fibrous stroma, osteoblastic rimming, osteoclast-typed multinucleated giant cells, stromal hemorrhage, and fibrous capsule. Osteoblast rimming was recorded when a contiguous line of osteoblasts was seen surrounding lesional bone trabeculae. Care was taken to focus on bone tissue central to the lesion and not reparative bone occasionally seen peripherally.
Cases without sufficient tissue specimens were excluded from the study. Microscopic examination of each case was performed without prior knowledge of the previous diagnosis. Each parameter was assessed by experienced oral pathologist. The study protocol was approved by the Human Research Ethics Committee of the Faculty of Dentistry, Chulalongkorn University.
Results
From the total of 19 308 accessioned cases from the Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, during 1975-2012, 207 cases were diagnosed as BFOLs of the jaws, accounting for approximately 1.0% of all cases.
The most common BFOL in this study was FD (36.7%), followed by OF (32.4%). All subtypes of OD comprised 24.6% of the cases and the majority of them were FOD (15.9%), followed by FLOD (5.8%) and POD (2.9%). JOF was rare and accounted for only 6.3% of all the cases. Of the 13 JOF cases, 9 cases were JPOF and 4 cases were JTOF.
Patient Demographics
From the 207 BFOL cases in this study, there were 142 females (68.6%) and 65 males (31.4%). The female predominance was also noted when each individual lesion was considered separately. The male-to-female ratios for FD, OF, JOF and OD were 1:1.7, 1:1.8, 1:3.0, and 1:4.6, respectively. Likewise, among each OD subtype, a strong female predilection was also observed.
The age of the patients ranged from 7 to 62 years. JOF occurred in the youngest age-group (mean age = 18.2 ± 8.9 years), followed by FD (mean age = 24.9 ± 12.9 years). The majority of FD patients (81.6%) were in their second and third decades of life. OF showed a predilection in a slightly older age group (mean age = 30.8 ± 14.4 years) and its age peak spanned from the second to fourth decades of life. Notably, no OD patient in this study was younger than 20 years. The peak incidence of OD patients was in the third to fifth decades of life. Mean age of FLOD (39.5 ± 12.3 years) and FOD (35.2 ± 10.2 years) patients were approximately a decade older than that of POD (26.7 ± 6.0 years) patients. Similarly, JPOF affected older patients than JTOF. The sex and age distributions are shown in Table 1.
Sex and Age Distribution of Benign Fibro-Osseous Lesions of the Jaws.
Clinical and Radiographic Features
Fibrous dysplasia and JOF affected maxilla more frequently than mandible, showing the maxilla-to-mandible ratios of 1.5:1 and 1.6:1, respectively. OF and OD, however, showed a strong predilection for mandible. Mandible was affected 2.3-fold more often in OF and 3.5-fold more often in OD than maxilla.
The most common site for FD was the posterior maxilla (35.5%), followed by the anterior-to-posterior maxilla (19.2%). Of the mandibular cases, FD occurred most frequently involved the posterior region.
In contrast to FD, the majority of OF was localized on the posterior mandible (34.3%), followed by the anterior-to-posterior mandibular region (22.4%). Most maxillary OFs were located on the posterior region (13.4%) or the anterior-to-posterior region (10.4%).
Posterior mandible was the most common site for OD (63.3%), followed by posterior maxilla (20.0%). The majority of FLODs (54.5%) were found concurrently on both maxilla and mandible, followed by bilateral posterior mandibular regions (36.4%; Table 2).
Site Distribution of Benign Fibro-Osseous Lesions of the Jaws.
The overwhelming majority of the FD (90.8%) and OF (85.1%) patients presented with painless swelling of the jaws. In contrast, 38.5% of the JOF patients reported swelling associated with pain. Nearly half of the OD patients (44.1%) were asymptomatic at the time of diagnosis and lesions were found incidentally on radiographs.
Radiographically, the majority of the FD cases (59.2%) were described as ground-glass appearance (Figure 1A). This feature was seen in a much lesser extent in OF (25.4%) and OD (3.0). The mixed radiolucency-radiopacity was the most common radiographic appearance in both OF (50.7%) and JOF (69.2%), while only 19.7% of the FD cases showed this feature (Figure 1B). Most ODs presented as a complete radiopacity (47.1%), closely followed by a mixed radiolucency-radiopacity (39.2%; Table 3).
Clinical and Radiographic Presentations of Benign Fibro-Osseous Lesions of the Jaws.
Histopathologic Features
Table 4 presents the microscopic features commonly described in BFOLs of the jaws. All OD subtypes were similar histopathologically; therefore, they were grouped together for comparison.
Histopathologic Features of Benign Fibro-Osseous Lesions of the Jaws.
We found that the majority of FD specimens consisted of woven bone only (67.1%), followed by a mixture of woven and lamellar bones (14.5%). On the other hand, most OF and OD specimens contained a mixture of both woven bone and cementum-like tissue (59.7% of OF and 56.9% of OD), followed by cementum-like materials only (37.3% of OF and 19.6% of OD).
Osteoblastic rimming of lesional bone trabeculae was observed most often in OF (23.9%), followed by FD (10.5%). Stromal hemorrhage was a common feature in OD (58.8%), but could also be present in a significant percentage in other lesions. Stromal mitosis was a rare finding in all BFOLs except for JOF (86.1%). The presence of multinucleated osteoclast-typed giant cells was varied among lesions. This feature is common in JTOF (75.0%), followed by OF (20.9%). Fibrous capsule was seen in 38.8% of OF and 36.1% of JOF specimens; whereas no FD or OD cases showed this feature (Figure 2).
Histopathologic features of benign fibro-osseous lesions (BFOLs). (A) Fibrous dysplasia (FD) showing irregular trabeculae of woven bone. (B) Ossifying fibroma (OF) showing a mixture of woven bone and cementum-like materials. (C) Osseous dysplasia (OD) showing round-to-curvilinear cementum-like materials and bone trabeculae. Some of these mineralized materials form conglomerate masses. Also noted are free hemorrhages within fibrous stroma. (D) Juvenile trabecular ossifying fibroma (JTOF) showing interconnecting woven bone trabeculae within a cellular connective tissue stroma. Multiple osteoclast-typed multinucleated giant cells are present (arrow). (E) Juvenile psammomatoid ossifying fibroma (JPOF) consisting of numerous small psammomatoid (cementum-like) spherules. Hematoxylin and eosin stain, original magnification 100×.
Discussion
In this study, we examined epidemiological, clinical, radiological, and pathological aspects of patients with BFOLs of the jaws diagnosed in our surgical pathology unit during the 38-year period. A total of 207 cases were retrospectively reviewed and classified according to the current description of WHO classification of head and neck tumors. 6
The classification of BFOLs has been a subject of controversy and continuing update. FOD was first described as a distinct entity in 1985 by Waldron. 4 Its detailed descriptions were additionally documented later on.8,9,16 We therefore use limited data from earlier reported series for the basis of discussion and comparison.
This study represents one of the largest BFOL series reported to date. Similar to Ogunsalu et al, 12 we found FD to be the most common BFOL of the jaws, followed by OF and OD. JOF is rare, representing only 6.1% of the cases.
Osseous dysplasia comprised 24.6% of all BFOLs and the majority of them were focal type. This result is in contrasted to that of Worawongvasu and Songkampol, 13 which reported OD in only 4.1% of BFOL cases and none in FOD category. The number of OD cases in this study is also higher than that of Ogunsalu et al, 12 which found OD in 15.6% of the cases. As previously mentioned, this could be due to the late recognition of FOD. A number of OD cases diagnosed earlier were likely classified into other lesions. In particular, we found in our series that several FOD cases were previously diagnosed as OF in earlier years.
Nonetheless, the number of OD cases in this study may still be underestimated, considering that OD is now regarded as the most common BFOL in clinical practice.5,8,9,16 One reason is that OD can often be recognized clinically and radiographically by experienced clinicians. Since asymptomatic OD does not require treatment, clinically diagnosed cases may not be biopsied, and therefore they are not included in this study. Another explanation could be the ethnic variation. The periapical and florid subtypes of OD show strong predilection for black population, whereas all subjects in this study are Asians (Thais). At present, there are very limited data on the prevalence of OD lesions in Asians, therefore studies of OD prevalence comparing among various ethnic backgrounds may be of interest.
Overall, we found that BFOLs affected females more frequently than males. This is in line with previous reports.8,9,11-13,16-25 OD showed the strongest female predominance with the male-to-female ratio of 1:4.2, followed by JOF (1:3), OF (1:1.8), and FD (1:1.6). The female predilection in OD and OF is well documented in the literature.8,16,18-25 The reason for this is still unknown. However, in contrast to the review by MacDonald-Jankowski, 26 which showed equal sex distribution in FD, we also found a slight female predominance as well.
Apart from the differences in sex predilection, our data on clinical characteristics of FD patients support those reported previously.26-28 The majority of FD affected patients are in their second and third decades of life. Maxilla was affected more often than mandible with the predilection in the posterior region. The most frequent presenting symptom was slow, painless swelling and the ground-glass appearance was the most common pattern seen radiographically in FD patients.
Notably, a complete radiolucency is often described as the early radiographic manifestation of all BFOLs. This feature was seen most often in JOF (23.1%). However, we found that this was an uncommon finding in other BFOLs. No FD case was reported as a completely radiolucent lesion at the time of presentation and only a minority of OF (10.4%) and OD (11.8%) cases were reported as such. This may partly be due to the fact that most patients seek treatment when lesion develops later in its course to become noticeable or symptomatic. Most FDs, OFs, and ODs, which show no symptom at the radiographic radiolucency stage, may be unrecognized. On the other hand, JOF is locally aggressive and can grow rapidly producing clinical symptoms in its earlier stage.
Unlike FD, OF was more common in the posterior mandible. It affected patients in a slight older age group than FD. The most common radiographic presentation was a mixed radiolucent-radiopaque pattern (50.7%). Notably, 25.4% of OF lesions showed a ground-glass appearance radiographically, a considerably smaller percentage than that of FD patients (57.5%).
In addition to the internal appearance, the border of lesion is another important radiographic feature used to distinguish FD and OF. The majority of OF lesions demonstrate well-defined border, whereas borders of FD tend to be poorly defined. Our data on radiographic border also confirm this finding.
Compared with other BFOLs, OD affected the oldest age-group. From our observation, OD was most commonly found as an incidental finding on radiographs, since most patients were asymptomatic at the time of diagnosis. Radiographically, all OD subtypes most often presented radiographically as a complete radiopacity, representing the mature stage of development.
Pain was an uncommon complaint in patients with FD (7.9%) and OF (11.9%). On the other hand, we found that 15 OD cases (29.4%) reported pain with or without associated swelling. Detailed review showed that 11 of these painful cases (71.4%) had signs of infection at the time of presentation. This is likely because of the susceptibility of OD to infection, which subsequently produces the painful symptom.
Juvenile ossifying fibroma is a rare tumor. As noted in previous studies,29,30 both JOF subtypes showed strong predominance in young individuals and affected maxilla more common than mandible. We found that JPOF patients were approximately a decade older than JTOF patients. All cases reported swelling of the jaw and as high as 46.2% of JOF patients presented with pain or paresthesia. This is distinctly in contrast to other BFOLs as mentioned previously.
In this study, microscopic slides of all BFOL cases were revisited to examine features commonly noted in each group. In general, some overlaps in various microscopic parameters were observed. Regarding types of mineralized materials, we found that the majority of OF and OD cases showed a mixture of mineralized tissue, most commonly the woven bone and cementum-like materials, whereas most FD cases consisted only of woven bone. The presence of cementum-like materials as the only type of mineralized material was observed in a portion of OF (37.3%) and OD (19.6%) specimens, while no FD cases showed this feature.
Of note is a small percentage of FD specimens consisted of few cementum-like materials together with lamellar or woven bone. Although the presence of cementum-like materials has been described, it is considered unusual in FD. Our data supports the observation from previous studies that these small, round, basophilic mineralized materials similar to cementum can be seen in the minority of FD.31,32 However, it should be emphasized that when this material is present, it comprises a minor portion of the entire FD specimen. In any BFOL specimen that consists of a considerable amount of cementum-like materials, the diagnosis of OF and OD should be primarily considered.
Osteoblastic rimming around lesional bone is a feature frequently described in OF. We observed this feature most often in JTOF and OF. Interestingly, the osteoblastic rimming was also seen in at least some parts of a number of FD specimens (10.5%); therefore, this finding is not entirely specific for OF. In addition, we found that 9 FD cases consisted of lamellar bone. This observation is consistent with the previous reports that lamellar bone can be present in FD of the jaw bones4, 31. Examination of our cases revealed that all of them were diagnosed at an older age, ranging from 31 to 62 years. Therefore, the presence of lamellar bone may correspond to the mature stage of FD specimens of the jaws.
Also noteworthy is the presence of free hemorrhage within the connective tissue stroma or surrounding mineralized materials. This feature could be seen in all BFOLs; however, it was much more common in OD than OF and FD. Fibrous capsule is another important feature. It is considered present when the compressed dense fibrocollagenous band is noted surrounding lesional tissue. Its presence also depends on the areas as well as the methods of biopsy; therefore, our numbers would be underrepresented. Even so, it is of note that the fibrous capsule was present in as high as 36.9% of OF specimens, whereas neither FD nor OD lesions had this feature.
Mitosis is a rare finding in FD, OF, and OD lesions. Interestingly, we found stromal mitosis in 4 out of 13 cases of JOF, representing 30.8% of the cases. This number is far greater than that of other BFOLs, and may parallel its aggressive nature. Multinucleated osteoclast-typed giant cells are common in JTOF and may be present in various fractions of other BFOLs.
In summary, our study reported variations in clinicopathologic characteristics of BFOLs of the jaws. These lesions are not uncommon. Despite some overlapping features, each member of BFOLs is unique in its manifestation and requires different treatment modalities. Sufficient clinical, radiographic information as well as a thorough examination of histopathologic findings are critical to obtain an accurate diagnosis for this group of lesions.
Footnotes
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Dental Research Fund, Dental Research Project 3205-312 #46/2011, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.