Bu-Yuan Liu

Central Ossifying Fibroma: A Clinicopathologic Study of 28 Cases

BACKGROUND/PURPOSE Central ossifying fibroma (COF) is the most common benign fibro-osseous lesion of the jaw. This retrospective study evaluated the clinical and histopathologic features of 28 COFs in Taiwanese patients. METHODS Twenty-eight consecutive cases of COF were collected from 1988 to 2006. The clinical data and microscopic features of these cases were reviewed and analyzed. RESULTS The mean age of patients at the time of diagnosis was 34 years. There were six male and 22 female patients. Twenty-six (93%) cases were found in the mandible and two (7%) in the maxilla. The most common sites for COFs were the molar region (17 cases, 61%), followed by the premolar (8 cases, 28%), and incisor/canine (3 cases, 11%) regions. Bone swelling or expansion (96%, 26/27) was the most frequent clinical presentation. Six (21%) COFs presented as a radiolucent lesion, 17 (61%) as a mixed lesion, and five (18%) as a radio-opaque lesion. No recurrence of the lesion was found after surgical excision in this series. Microscopically, COFs showed trabeculae of woven bone (25 cases) and/or lamellar bone (5 cases) and/or spherules of cementoid (19 cases) in a cellular fibrous connective tissue stroma. The stromal component was highly cellular in 21 cases, moderately cellular in seven cases, prominently vascular in 11, and collagenous in six. CONCLUSION COFs occur more frequently in female patients and in those in the second to fourth decades of life. The most commonly affected site is the mandible, especially the molar region. The majority of COF lesions present as a well-defined, mixed lesion radiographically. Most COFs can be treated by conservative surgical excision without subsequent recurrence.

Expression of proliferating cell nuclear antigen (PCNA) in oral submucous fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan

To test whether the oral epithelia of oral submucous fibrosis (OSF), epithelial hyperkeratosis (EH) and epithelial dysplasia (ED) may have increased proliferative activity under the long-term exposure to areca quid ingredients and whether there is an increased expression of proliferating cell nuclear antigen (PCNA) in oral premalignant lesions with disease progression, we used an immunohistochemical technique with the mouse monoclonal antibody PC10 to investigate PCNA expression in histologic sections of OSF, EH, ED and normal oral mucosa (NOM). Positive PCNA staining was found mainly in basal and parabasal epithelial cells in all specimens of OSF, EH, ED and NOM. The mean PCNA labeling indices (LI) in NOM, OSF, EH and ED were 8.8+/-2.7%, 22.1+/-12.5%, 25.5+/-5. 2% and 44.9+/-15.4%, respectively. Significant differences in the PCNA LI were noted between NOM and OSF (P<0.01), EH (P<0.001) or ED (P<0.001), as well as between ED and OSF (P<0.001) or EH (P<0.01). The gradual increase of PCNA expression with the morphologic transformation of normal epithelial cells into dysplastic epithelial cells suggests that there is increased proliferative activity in oral premalignant lesions with disease progression. However, no significant correlation was found between PCNA LI in OSF epithelium and the clinicohistologic parameters of OSF. In addition, the mean PCNA LI of p53-positive OSF cases (23.7+/-12.0%) was very close to that of p53-negative OSF cases (23.9+/-13.1%), suggesting that there was no association between PCNA and p53 expression in OSF.

Oral verrucous hyperplasia: histologic classification, prognosis, and clinical implications

BACKGROUND Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. METHODS Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed. RESULTS We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 +/- 7 months. The mean time for malignant transformation was 22 +/- 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy. CONCLUSIONS We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.

Odontoma: A clinicopathologic study of 81 cases

BACKGROUND AND PURPOSE Odontoma is the most common odontogenic tumor. It includes 2 types, the compound and complex odontomas. There has not been a series study of the clinical and histologic features of odontomas from Taiwan. This study evaluated the clinicopathologic features of odontoma in Taiwanese. METHODS Cases of odontoma treated from 1998 to 2002 identified from medical records were included. The microscopic features, radiographic features, and clinical history of the patients were reviewed and analyzed. RESULTS A total of 81 odontomas in 81 patients (36 males and 45 females) were included. There were 62 compound and 19 complex odontomas. The mean age of the patients was 18 years with the majority of odontomas occurring in the first (32%) and second decade (38%) of life. Odontomas had a marked predilection for the maxilla (70%) and for the anterior region of the jaw (83%), particularly for the anterior maxilla (62%). Sixty four (79%) of the 81 odontomas were associated with 80 impacted teeth, including 71 permanent teeth, 2 deciduous teeth, and 7 supernumerary teeth. Of the 71 impacted permanent teeth, the maxillary central incisor (27%) was most commonly affected, followed by the maxillary canine (26%) and mandibular canine (24%). Histologic examination revealed enamel matrix in 90%, dentin in 100%, cementum in 88%, pulp tissue in 96%, fibrous capsule in 93%, ghost cells in 83%, reduced enamel epithelium in 86%, and nests of odontogenic epithelium in 58% of odontomas. Dentigerous cyst was associated with 9% of odontomas. CONCLUSIONS In this series, odontomas occurred most often in the first and second decade of life. Although complex odontomas are usually found in the posterior jaw, in this Taiwanese series they were most commonly found in the anterior maxilla. Odontoma is frequently associated with an impacted tooth and occasionally with a dentigerous cyst. No recurrence of odontomas was found after surgical excision with follow-up of 1 to 15 years.

Quantitative analysis of immunocompetent cells in oral submucous fibrosis in Taiwan

Previous studies have shown that the local and systemic upregulation of inflammatory and fibrogenic cytokines and downregulation of antifibrotic cytokines are central to the pathogenesis of oral submucous fibrosis (OSF). The immunocompetent cells, especially the macrophages and lymphocytes, are likely the main source of cytokine synthesis. Therefore, this study used an immunohistochemical method to quantify the T lymphocyte, B lymphocyte and macrophage densities in the epithelium and subepithelial connective tissue of 50 specimens of moderately advanced and advanced OSF and 10 specimens of normal oral mucosa (NOM). The mean T lymphocyte, B lymphocyte and macrophage densities in OSF specimens were 555.2+/-417.4, 63.4+/-44.3 and 66.9+/-76.4 cells/mm(2) in the subepithelial connective tissue and 308.1+/-261.1, 1.4+/-3.5 and 6.6+/-11.9 cells/mm(2) in the epithelium, respectively. These findings suggest that T lymphocytes were the major immunocompetent cells in both the subepithelial connective tissue and epithelium of OSF specimens. Macrophages and B lymphocytes are the minor immunocompetent cells in the subepithelial connective tissue and are only occasionally found in the epithelium of OSF specimens. Similar distribution of immunocompetent cells was also found in NOM specimens. However, the mean T lymphocyte, B lymphocyte and macrophage densities in the subepithelial connective tissue (271.2+/-107.0, 13.3+/-18.4 and 17.3+/-19.1 cells/mm(2), respectively) and the mean T lymphocyte density in the epithelium (97.7+/-51.4) of NOM specimens were significantly lower than the corresponding mean cell densities in OSF specimens. Using frozen tissue sections, we further quantified the CD4+ and CD8+ lymphocyte numbers in eight moderately advanced or advanced OSF specimens. It was found that the CD4+ and CD8+ lymphocyte densities were 213.3+/-140.7 and 101.5+/-72.8 cells/mm(2) in the subepithelial connective tissue of OSF specimens, respectively. The CD4+ to CD8+ lymphocyte ratio was 2.1:1. Our results showed a significant increase in the number of T lymphocytes and macrophages and a predominance of CD4+ lymphocytes over CD8+ lymphocytes in the subepithelial connective tissue of OSF specimens. We conclude that the cellular immune response may play an important role in the pathogenesis of OSF.

Clinicopathological Study of Oral Giant Cell Fibromas

BACKGROUND/PURPOSE Oral giant cell fibromas (GCFs) are found predominantly in Caucasians and rarely in other races. This retrospective study evaluated the clinicopathological features of 24 GCFs in Taiwanese patients. METHODS Twenty-four consecutive cases of oral GCF were investigated from 1987 to 2008. Clinical data and microscopic features were reviewed and analyzed. RESULTS The mean age of patients at the time of diagnosis was 29 years. Oral GCF occurred more commonly in patients between 11 and 40 years of age. There were 12 male and 12 female patients. The lesions were found more frequently on the tongue (8 cases) and gingiva (7 cases). The mean size of the lesion was 5.5mm (range, 2-10 mm) in greatest dimension. GCF is misdiagnosed frequently as fibroma (19 cases) or papilloma (5 cases). All tumors were treated by total surgical excision and no recurrence was found after treatment. Microscopically, the GCF was a sessile or pedunculated mass covered with a thin layer of parakeratinized or orthokeratinized stratified squamous epithelium. The tumor was composed mainly of loose or dense fibrous connective tissue with well-formed capillaries and no inflammation. The consistent and diagnostic feature was the presence of large stellate giant cells, usually with one or two nuclei. Multinucleated giant cells were seen occasionally. These giant cells were most numerous in the connective tissue just beneath the epithelium. CONCLUSION Oral GCFs show no significant sex predilection and occur in patients in the second to fourth decades of life. Usually, the lesions are < 1 cm in diameter and are found more frequently on the tongue and gingiva. GCF resembles fibroma or papilloma and is difficult to diagnose correctly at the first glance. All GCFs can be treated by conservative surgical excision without subsequent recurrence.

High Expression of Osteopontin and CD44v6 in Odontogenic Keratocysts

BACKGROUND/PURPOSE Odontogenic keratocysts (OKCs) are more aggressive and more osteolytic lesions than dentigerous cysts (DCs) and radicular cysts (RCs). Osteopontin (OPN) is related to cancer metastasis and bone destruction. Binding of OPN to its cell membrane receptors integrin alphav and CD44v6 can enhance tumor cell motility, migration, invasion and spread. This study assessed the possible contribution of OPN, integrin alphav and CD44v6 to the local aggressive behavior and osteolytic ability of OKCs. METHODS We used an immunohistochemical method to examine the expression of OPN, integrin alphav and CD44v6 in tissue sections of 20 OKCs, eight DCs and 10 RCs. RESULTS We found strong cytoplasmic OPN immunostaining in lining epithelial cells of 8 of 20 OKCs but not in any DCs and RCs. Positive OPN staining was also noted in the subepithelial connective tissue of four OKCs with intraepithelial expression of OPN. Diffuse and strong membranous integrin alphav staining was discovered in osteoclasts in all our tissue sections and in nearly all lining epithelial cells of DCs and RCs, but not in OKCs. In addition, diffuse and strong membranous CD44v6 staining was also observed in nearly all lining epithelial cells of OKCs, DCs and RCs. CONCLUSION Binding of OPN to osteoclast cell membrane receptor integrin alphav can activate the osteoclasts and increase their osteolytic activity. In addition, binding of OPN to OKC lining epithelial cell membrane receptor CD44v6 can enhance the motility, migration, invasion and spread of lining epithelial cells into the surrounding cancellous bone. Therefore, we suggest that the local aggressive behavior and high osteolytic ability of OKCs in the jawbone can be explained at least partially by high expression of OPN and CD44v6 in lining epithelial cells of OKCs and high expression of integrin alphav in osteoclasts.

Expression of osteopontin and its receptors in ameloblastomas

This study used an immunohistochemical method to examine the expression of osteopontin (OPN) in 30 ameloblastomas and of integrin alpha(v) and CD44v6 in 20 of these 30 ameloblastomas. We found that the positive staining rate in ameloblastomas was 87% for OPN, 45% for integrin alpha(v), and 90% for CD44v6. Both ameloblast-like and stellate reticulum-like cells showed a high expression of OPN and CD44v6. There was also a strong integrin alpha(v) immunostaining on the cell membrane of osteoclasts. Binding of OPN to osteoclast cell membrane receptor integrin alpha(v) can activate the osteoclast and increase its osteolytic activity. In addition, binding of OPN to ameloblastoma tumor cell membrane receptor CD44v6 can enhance tumor cell migration, invasion and spread. Therefore, we suggest that the local aggressive behavior and high osteolytic ability of ameloblastomas in the jawbones can be explained by the high expression of OPN and CD44v6 in ameloblastoma cells and the high expression of integrin alpha(v) in osteoclasts.

Nuclear Expression of metastasis-associated Protein 1 (MTA1) is Inversely Related to Progression of Oral Squamous Cell Carcinoma in Taiwan

Overexpression of metastasis-associated protein 1 (MTA1) has been demonstrated in a variety of human cancers and found to be significantly associated with the tumor size, lymph node metastasis, clinical stage, tumor invasion, and prognosis of these cancers. In this study, we examined the expression of MTA1 in 74 specimens of oral squamous cell carcinoma (OSCC), 100 specimens of oral epithelial dysplasia (OED; 33 mild, 44 moderate, and 23 severe OED cases), and 21 specimens of normal oral mucosa (NOM) by immunohistochemistry. The cytoplasmic and nuclear MTA1 labeling indices (LIs) in OSCC, OED, and NOM samples were calculated and compared among these groups. Correlations of the cytoplasmic and nuclear MTA1 LIs in OSCC with clinicopathological parameters and survival of OSCC patients were statistically analyzed. We found that the mean cytoplasmic MTA1 LIs were all over 95% for the NOM, OED, and OSCC samples. There were no significant associations of the cytoplasmic MTA1 LI with any of the clinicopathological parameters of OSCC patients. The mean nuclear MTA1 LIs significantly decreased from NOM (73%±13%) to mild OED (71%±16%), moderate OED (60%±22%), and severe OED (46%±25%) and OSCC samples (30%±30%, p＜0.001). A significant correlation was found between the lower mean nuclear MTA1 LIs and OSCCs located on the buccal mucosa and tongue (p=0.001), with larger tumor sizes (T3 and T4, p=0.020), with regional lymph node metastases (N1, N2, and N3, p=0.024), and with more-advanced clinical stages (stages 3 and 4, p=0.045). Our results suggest that MTA1 is universally expressed in the cytoplasm of normal, dysplastic, and malignant oral epithelial cells. The nuclear expression of MTA1 significantly dropped from NOM through OED to OSCC samples, and was inversely related to the T status, N status, and clinical staging of OSCCs. Therefore, the nuclear MTA1 LI can be used to predict the progression of OSCCs in Taiwan.

Characteristics of calcifying odontogenic cyst in Taiwanese

BACKGROUND AND PURPOSE Calcifying odontogenic cyst (COC) is a rare type of odontogenic cyst. This retrospective study analyzed the clinical, radiographic, and histopathologic features of COC in Taiwanese. METHODS Ten cases of COC in 2 male and 8 female patients with a mean age of 29 years (range, 11 to 48 years) treated from January 1985 to December 2002 were included. Microscopic slides, clinical histories, and radiographic features of these 10 COC cases were reviewed and analyzed. RESULTS COCs occurred in the maxilla in 3 cases and in the mandible in 7 cases. COCs were associated with impacted teeth in 6 cases and with odontomas in 3 cases. All COCs appeared as either unilocular (9 cases) or multilocular (1 case) radiolucencies. In 7 cases, spotty radiopaque materials were scattered throughout the radiolucency. Histologically, all of the lesions were at least partially lined by epithelium with cuboidal to columnar basal cells and stellate reticulum-like suprabasal cells. Variable numbers of ghost cells, some of which were calcified, were observed in the lining epithelium or in the fibrous connective tissue wall of all 10 cases. Juxta-epithelial dentinoid was also found in all cases. However, proliferation of ameloblastoma-like tumor nests was observed in only 1 case. Based on the above histologic findings, 6 COC lesions were classified as simple unicystic type, 3 as unicystic odontoma-producing type, and 1 as unicystic ameloblastomatous proliferating type. CONCLUSIONS COC occurs frequently in the second and third decades and is commonly associated with an impacted tooth or an odontoma. It usually appears as a mixed radiolucent and radiopaque lesion radiographically. Simple unicystic type is the most common type of COC. No recurrences were found after conservative surgical removal in this series.