Monostotic fibrous dysplasia of jaw bones: a case series.

BACKGROUND: Fibrous dysplasia (FD) is a benign fibro-osseous lesion, a skeletal developmental anomaly of the bone-forming mesenchyme. The diagnosis of fibro-osseous lesions, particularly those of the jaw bones, poses significant challenges to clinicians and pathologists since it requires a correlation of clinical, radiological, histological, and surgical findings. Accurate and specific diagnosis is crucial as treatment modalities differ with different fibro-osseous lesions. METHODS: This retrospective analysis presents a case series of a rare condition of monostotic FD in the maxillofacial region affecting jaw bones diagnosed and/or treated over period of 10 years. RESULTS: Five cases of monostotic FD were diagnosed and treated between a period of 2013 and 2023. The cases from the 2nd to 8th decade were included in the analysis with equal involvement of males and females. Out of five cases, four cases were involving maxilla and 1 showed involvement of mandible. CONCLUSION: FD is a rare entity affecting the jaw bones which often lead to disfigurement of face. Early detection is warranted to decrease potential complications. In addition, genetic analysis could help in understanding the occurrence in certain population.

Giant Cell Lesions of the Jaws: A Work on Current Concepts and Making Through a Working Classification.

INTRODUCTION: Giant cell-rich lesions are a diverse group of lesions that usually occur in bone and contain varying numbers of reactive osteoclastic-type multinucleate giant cells. These lesions present a challenge in pathologic diagnosis, often requiring a combination of clinical, radiographic, and histopathological assessments. The present retrospective observational study aims to provide a concise diagnostic criterion by combining all these parameters, which will aid in effective diagnosis and targeted treatment planning in the future. MATERIAL AND METHOD: Previously diagnosed cases of these lesions were taken from the archives and categorized as Central Giant Cell Granuloma (CGCG), CGCG with secondary Aneurysmal Bone Cyst (ABC), primary ABC, and Brown's Tumour. Their demographic characteristics along with clinical, radiological, and histological data were retrieved and compiled into the table. The data was then analyzed and classified into aggressive and non-aggressive CGCG according to the criteria set in the study. RESULT: 10 reported cases were of isolated CGCG, 5 were CGCG with secondary ABC, 5 of Brown's tumor and 3 were that of conventional ABC. Out of these, the lesions showing extensive size along with an increased number of giant cells were categorized under aggressive CGCG, whereas those with less aggressive characteristics were categorized under non-aggressive CGCG. The aggressive category comprised 5 cases of isolated CGCG, 2 cases of CGCG with secondary ABC, 3 cases of primary ABC, and 5 of brown tumor, whilst the rest of the cases were categorized under non-aggressive CGCG. CONCLUSION: Since all these share overlapping features, thereby this type of concise categorization is the dire need so that the lesions can have a precise diagnosis with treatment and follow-up intervals for aggressive lesions.

Florid Cemento-Osseous Dysplasia with a Concurrent Glandular Odontogenic Cyst.

The presence of non-odontogenic cysts associated with benign fibro-osseous lesions of the jaws has been well documented. However, literature is scant when describing benign fibro-osseous lesions with associated odontogenic cysts. This case report highlights the presence of a concurrent developmental odontogenic cyst, glandular odontogenic cyst with extensive squamous metaplasia, in a patient with florid cemento-osseous dysplasia (COD). The postulated pathogenesis of these synchronous lesions is discussed along with a review of current literature. Surgical treatment is discouraged for florid COD, however, radiological follow-up is recommended, especially in lesions with associated cysts.

Dystrophic calcification and respiratory metaplasia in the epithelial lining of odontogenic cysts: a study of 362 odontogenic cysts in a Brazilian population and literature review.

PURPOSE: Main study: undertake a histological study of odontogenic cysts (OC) to determine the prevalence of dystrophic calcification and metaplasia to respiratory epithelium on a Brazilian population. LITERATURE REVIEW: to review the literature for studies that investigated the prevalence of respiratory metaplasia and dystrophic calcification on OC. METHODS: Main study: a retrospective histopathological evaluation was made of the archives from a pathology laboratory. A total of 362 cases diagnosed as OC were identified; they were analyzed by two expert observers to determine the presence of dystrophic calcification and respiratory metaplasia. The association with sex, age and anatomic location was performed through statistical analysis. LITERATURE REVIEW: a critical literature review was undertaken. Two main electronic databases (PubMed and LILACS) were searched. Retrospective studies of histological evaluation that determined the prevalence of epithelial metaplasia and dystrophic calcification on OC, with at least 10 cases, were included; their findings were summarized and discussed. RESULTS: Main study: the histological evaluation of OC revealed the presence of respiratory epithelium in 25 cases (6.9%) and dystrophic calcification in 24 cases (6.6%). Positive association was found to dystrophic calcification on residual cyst and age; respiratory metaplasia on OC and sex; respiratory metaplasia on residual cyst and gnatic bone; respiratory metaplasia in OC and gnatic bone; dystrophic calcification in OC and anatomic site of mandible. LITERATURE REVIEW: eleven studies were included in the literature review, and respiratory metaplasia ranged from 0.0% to 19.2% while dystrophic calcification ranged from 2.5% to 40.5%. CONCLUSIONS: the histological evaluation of this study found 6.9% of prevalence of respiratory metaplasia and 6.6% of dystrophic calcification, which is in accordance with the literature reviewed. Therefore, these phenomena must be taken into account in routine diagnosis services.

Central giant cell granuloma: A clinicopathological and immunohistochemical study of macrophages, blood vessels, lymphatic vessels and regulatory proteins.

OBJECTIVE: This study seeks to investigate immunohistochemical parameters that could distinguish non-aggressive Central giant cell granuloma (CGCG) from aggressive CGCG, two groups of lesions which differ in their clinical and radiographic features and prognosis. MATERIAL AND METHODS: 12 cases of non-aggressive CGCG and 11 cases of aggressive CGCG were investigated and associated the immunohistochemical expression of macrophages (CD68 and CD163), blood vessels (CD34 and CD105), lymphatic vessels (D2-40) and regulator proteins (p63 and Ki-67). Clinical and radiographic features were also studied. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (p > 0.05). With respect to non-aggressive CGCG, there were no significant correlations, while in aggressive CGCG there was a significant positive correlation between CD68 and CD163 (p = 0.031), between CD34 and D2-40 proteins (p = 0.04), whereas a significant negative correlation was observed between CD105 and CD68 (p = 0.040). However, regardless of aggressiveness of CGCG, there was a significant positive correlation between CD68 and CD163 (p = 0,04). Among the clinical and immunohistochemical aspects, only the symptomatology was a significant risk factor for the occurrence of aggressive CGCG (OR = 12.00/p = 0.016). CONCLUSION: Macrophages and angiogenesis contribute to their maintenance and development of CGCG. In addition, immunohistochemistry used here was not able to differentiate their aggressiveness. However, symptomatology was proved to be a risk factor for the occurrence of aggressive CGCG. It is possible that clinical features, particularly symptomatology, represent the most appropriate parameter to attempt to distinguish GCCG.

Evaluation of SPECT/CT in the assessment of inflammatory jaw pathologies.

PURPOSE: Since accurate diagnosis of inflammatory jaw diseases is still challenging, this study investigated the performance of three phase bone scintigraphy including SPECT/CT in the assessment of correct diagnosis and size of the affected bone tissue. METHOD: This retrospective study contained 31 patients with suspected jaw-related osteoradionecrosis, osteomyelitis or medication-related osteonecrosis of the jaw, which underwent 3-phase bone scintigraphy including SPECT/CT. Results were reviewed by two nuclear medicine physicians. Positive cases received surgery; negative ones were followed-up for six months. Both served as reference standard. Inflamed bone length was measured in the SPECT/CT images and postoperatively by a pathologist. RESULTS: 19 out of 20 positive cases and 10 out of 11 negative ones were classified correctly by SPECT/CT (sensitivity 95 %, specificity 91 %, accuracy 94 %, positive predictive value 95 %, negative predictive value 91 %). Regarding the length of affected bone, no significant difference (p = 0.23) could be observed between SPECT/CT and postoperative obtained values. Both correlated significantly (r = 0.86, p = 0.0001). CONCLUSION: SPECT/CT can safely detect different kinds of inflammatory jaw pathologies compared to other conventional imaging modalities. Lack of specificity of conventional scintigraphy ranging from 17 % to 71 % in earlier studies could be improved by adding CT-analysis. Additionally, SPECT/CT assists the surgeon in determining the expansion of the process (with focus on the length) preoperatively and thereby optimizing surgery planning.

Differential expression of nicotinamide N-methyltransferase in primary and recurrent ameloblastomas and odontogenic keratocysts.

BACKGROUND: Odontogenic tumours are a group of rare heterogeneous diseases that range from hamartomatous tissue proliferations to benign and malignant neoplasms. Recurrences can occur after 10 years, so long-term clinical and radiological follow-up is required. The study of the molecular mechanisms involved in the development of these lesions is necessary to identify new prognostic markers. In this study, we evaluate the possible role of nicotinamide N-methyltransferase (NNMT) in ameloblastomas (AM) and odontogenic keratocysts (OKC). MATERIALS AND METHODS: A total of 105 surgical specimens of primary and recurrent lesions were obtained from 55 patients (25 AM, 30 OKC). In particular, 50 AMs (25 primary, 25 recurrences) and 55 OKCs (30 primary, 25 recurrences) were retrieved. We carried out immunohistochemical analyses to evaluate the cytoplasmic expression of NNMT, measuring the percentage of positive cells and the value of NNMT expression intensity. RESULTS: NNMT expression was significantly higher in recurrent than primary AMs (P = .0430). This result was confirmed by staining intensity, showing more cases with moderate/intense staining in recurrent AMs (P = .0470). NNMT expression was significantly lower in recurrent than primary OKC (P = .0014). Staining intensity showed more cases with moderate/intense staining in primary OKCs (P = .0276). CONCLUSIONS: This report is the first to evaluate NNMT expression in odontogenic lesions and to demonstrate a differential expression in recurrent AMs and OKCs, suggesting that there is potential for use of NNMT as prognostic marker.

Benign Alveolar Ridge Keratosis: Clinical and Histopathologic Analysis of 167 Cases.

Benign alveolar ridge keratosis (BARK), the intraoral counterpart of cutaneous lichen simplex chronicus, is a reactive hyperkeratosis caused by trauma or friction that presents as a poorly demarcated white papule or plaque on the keratinized mucosa of the retromolar pad or alveolar ridge mucosa (often edentulous). This is a clinical and histopathologic analysis of BARK including evaluation of p53 expression in selected cases. One hundred and sixty-seven cases of BARK were identified from 2016 to 2017 and 112 (67.1%) occurred in males with a median age of 56 years (range 15-86). The retromolar pad was affected in 107 (64.1%) cases and the edentulous alveolar mucosa in 60 (35.9%) cases, with 17.4% of the cases presenting bilaterally. BARK showed hyperkeratosis often with wedge-shaped hypergranulosis and occasional focal parakeratosis. The epithelium exhibited acanthosis and surface corrugation with tapered rete ridges often interconnected at the tips. The study for p53 performed in 12 cases showed less than 25% nuclear positivity. BARK is a distinct benign clinicopathologic entity caused by friction, which should be clearly distinguished from true leukoplakia, a potentially malignant disorder.

Giant Cell Lesions of the Jaws:A Review and Comparative Histopathological Study.

BACKGROUND AND OBJECTIVES: Giant cell lesions (GCLs) are rare lesions which prominently feature multinucleated giant cells in their histology. They include central giant cell granuloma (CGCG), giant cell tumour of bone (GCT), peripheral giant cell granuloma (PGCG), Cherubism (CHB), e.t.c. This study reviewed the clinico-demographic parameters of GCLs of the jaws and assessed the giant cells. METHODS: This was a retrospective study examining the histopathology records of which part of the body of two tertiary institutions. All entries of cases diagnosed as GCLs were retrieved and data were extracted. Also, the giant cells in tissue sections were assessed. Data were analysed using SPSS Inc. version 20 while Chi square test was used to test for association. This was considered significant quand p < 0.05. RESULTS: Over the study period, 2,862 biopsy reports were reviewed. GCLs constituted 48(1.7%) and M: F ratio was 1:1.6 while majority occurred in the 2nd and 3rd decades. The mandible was the most common site recording 27(56.3%) cases and CGCG was the most frequently diagnosed GCL constituting 22(45.8%). Assessment of the giant cells revealed CGCG had predominantly large giant cells, a dense dispersal of giant cells and irregularly shaped giant cells, while CHB mainly had large giant cells with dense dispersal, but round shaped giant cells. CONCLUSION: GCLs are rare lesions commonly seen in females in the 2nd and 3rd decades of life with preference for the mandible. CGCG was the most commonly encountered lesion, while the giant cells in CGCG and CHB were similar in size as well as dispersal.

A Comparative Analysis of p63 Expression in Giant Cell Tumour (GCT), Central Giant Cell Granuloma (CGCG) and Peripheral Giant Cell Granuloma (PGCG).

Giant cell tumour (GCT) is locally aggressive benign neoplasm of long bones whereas giant cell granulomas; central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG); are tumour-like conditions of the oral cavity. This study aimed to evaluate and compare the immunohistochemical expression of p63 in GCT, CGCG, PGCG and determine whether p63 can be used as a diagnostic, prognostic and differential biomarker between these entities. Histopathologically diagnosed 10 cases of GCT, 20 cases of CGCG and 20 cases of PGCG were subjected to p63 immunohistochemical staining. The percentage of p63-positive cells was semi-quantitatively assessed on the whole section. Intergroup comparison was done using Kruskal-Wallis test and one-way ANOVA. The value p < 0.05 was considered to be statistically significant and value p < 0.01 was considered to be statistically highly significant. p63 immunoexpression was seen in 100% (10/10) cases of GCT whereas CGCG and PGCG revealed the complete absence of p63 immunopositivity. These results showed a highly significant difference in p63 expression between GCT, CGCG and PGCG (p < 0.01). No difference was noted between CGCG and PGCG. GCT is a distinct entity when compared with CGCG and PGCG. Even aggressive CGCG also did not show p63 immunopositivity, so it is not a prognostic marker. Also, p63 cannot differentiate between CGCG and PGCG.

A comparative study of osteopontin and MMP-2 protein expression in peripheral and central giant cell granuloma of the jaw / Estudo comparativo da expressão das proteínas osteopontina e MMP-2 no granuloma central e periférico de células gigantes de mandíbula

Abstract Introduction: Oral peripheral and central giant cell granulomas are lesions with little-known etiology and pathogenesis. Objective: The aim of this study was to compare matrix metalloproteinases-2 and osteopontin protein expression in the multinucleated giant cells and mononuclear cells of the peripheral and central giant cell granuloma lesions. Methods: In this retrospective study, the presence of matrix metalloproteinases-2 and osteopontin in 37 cases of central giant cell granuloma and 37 cases of peripheral giant cell granuloma paraffin blocks were assessed by streptavidin-biotin immunohistochemistry. Independent sample t-test, Chi-square, Mann-Whitney tests and Spearman's rank correlation coefficient were used. Results: The osteopontin was expressed in both multinucleated giant cells and mononuclear cells in all cases of peripheral and central giant cells granulomas. However, the matrix metalloproteinases-2 expression was positive in 86.5% of giant cells and it was positive in all of mononuclear cells in peripheral giant cells granuloma. In central giant cells granulomas, 91.8% of giant cells and all mononuclear cells were positive for matrix metalloproteinases-2 marker. Percentage and Intensity of staining were significantly higher in central than peripheral giant cells lesions, for both markers (p ˂ 0.05). Conclusion: This study showed that the expression of osteopontin in giant cells supports the theory of osteolcastic nature of these cells. Also, the presence of osteopontin and matrix metalloproteinases-2 in mononuclear cells may indicate the monocyte-macrophage origin of these cells, as the differentiation of the precursors of the mononuclear stromal monocyte/macrophage to osteoclasts is possibly affected by the expression of osteolytic factors. Also, may be differences in biological behaviors of these lesions are associated with the level of osteopontin and matrix metalloproteinases-2 expression.

Resumo Introdução: Os granulomas periféricos e centrais de células gigantes são lesões com etiologia e patogênese pouco conhecidas. Objetivo: Comparar a expressão das proteínas metaloproteinases da matriz-2 e osteopontina nas células gigantes multinucleadas e células mononucleares no granuloma periférico e central de células gigantes. Método: Neste estudo retrospectivo, a presença de metaloproteinases da matriz-2 e osteopontina em 37 casos de granuloma central de células gigantes e 37 casos de granuloma periférico de células gigantes em blocos de parafina foi avaliada por imuno-histoquímica pela estreptavidina-biotina. Foram usados teste t para amostra independente, teste de qui-quadrado, Mann-Whitney e coeficiente de correlação de Spearman. Resultados: A osteopontina foi expressa em células gigantes multinucleadas e células mononucleares em todos os casos de granuloma periférico de células gigantes e granuloma central de células gigantes. No entanto, a expressão de metaloproteinases da matriz-2 foi positiva em 86,5% de células gigantes e foi positiva em todas as células mononucleares em granuloma periférico de células gigantes. Em granuloma central de células gigantes, 91,8% das células gigantes e todas as células mononucleares foram positivas para o marcador metaloproteinases da matriz-2. A porcentagem e intensidade de coloração em granuloma central de células gigantes foram significantemente maiores do que em granuloma periférico de células gigantes para ambos os marcadores (p ˂ 0,05). Conclusão: Este estudo mostrou que a expressão de osteopontina em células gigantes apoia a teoria da natureza osteoclástica dessas células. Além disso, a presença de osteopontina e metaloproteinases da matriz-2 em células mononucleares pode indicar a origem dos monócitos-macrófagos dessas células, uma vez que a diferenciação dos precursores do monócito/macrófago estromal mononuclear em osteoclastos é possivelmente afetada pela expressão de fatores osteolíticos. Além disso, as diferenças nos comportamentos biológicos dessas lesões estão associadas ao nível de expressão de osteopontina e metaloproteinases da matriz-2.

ACE Gene Variant Causing High Blood Pressure May Be Associated With Medication-related Jaw Osteonecrosis.

The association of the high blood pressure D variant of the angiotensin-converting enzyme (ACE) gene with medication-related jaw osteonecrosis (MRONJ) is described in two Greek patients. The first patient, a 73-year-old man, took zolendronate, 4 mg/100 ml IV once per month for two years for prostate cancer and bone metastases. Three months after drug discontinuation, extraction of the first premolar was performed. After the intervention, he suffered from osteonecrosis of the mandible. He presented with hypertension and genetic testing revealed that he was homozygous for the high blood pressure D variant of the ACE gene. The second patient, a 65 years old woman, took denosumab, 120 mg subcutaneously once per month for 6 months for possible bone metastases from breast cancer. Three months after extraction of the first molar, she suffered from MRONJ. He also presented with hypertension and genetic testing revealed that she had the high blood pressure D variant of the ACE gene in a heterozygous state, which moderately predisposes to hypertension. To our knowledge, this is the first report indicating that genetic predisposition to hypertension may increase risk for MRONJ.

Fibrous dysplasia of the jaws: Integrating molecular pathogenesis with clinical, radiological, and histopathological features.

Fibrous dysplasia is a non-neoplastic developmental process that affects the craniofacial bones, characterized by painless enlargement as a result of bone substitution by abnormal fibrous tissue. Postzygotic somatic activating mutations in the GNAS1 gene cause fibrous dysplasia and have been extensively investigated, as well as being helpful in the differential diagnosis of the disease. Fibrous dysplasia may involve one (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune-Albright syndrome, Jeffe-Lichenstein syndrome, or Mazabreud syndrome. This review summarizes the current knowledge on fibrous dysplasia, emphasizing the value of integrating the understanding of its molecular pathogenesis with the clinical, radiological, and histopathological features. In addition, we address important aspects related to the differential diagnosis and patient management.

A comparative study of osteopontin and MMP-2 protein expression in peripheral and central giant cell granuloma of the jaw.

INTRODUCTION: Oral peripheral and central giant cell granulomas are lesions with little-known etiology and pathogenesis. OBJECTIVE: The aim of this study was to compare matrix metalloproteinases-2 and osteopontin protein expression in the multinucleated giant cells and mononuclear cells of the peripheral and central giant cell granuloma lesions. METHODS: In this retrospective study, the presence of matrix metalloproteinases-2 and osteopontin in 37 cases of central giant cell granuloma and 37 cases of peripheral giant cell granuloma paraffin blocks were assessed by streptavidin-biotin immunohistochemistry. Independent sample t-test, Chi-square, Mann-Whitney tests and Spearman's rank correlation coefficient were used. RESULTS: The osteopontin was expressed in both multinucleated giant cells and mononuclear cells in all cases of peripheral and central giant cells granulomas. However, the matrix metalloproteinases-2 expression was positive in 86.5% of giant cells and it was positive in all of mononuclear cells in peripheral giant cells granuloma. In central giant cells granulomas, 91.8% of giant cells and all mononuclear cells were positive for matrix metalloproteinases-2 marker. Percentage and Intensity of staining were significantly higher in central than peripheral giant cells lesions, for both markers (p˂0.05). CONCLUSION: This study showed that the expression of osteopontin in giant cells supports the theory of osteolcastic nature of these cells. Also, the presence of osteopontin and matrix metalloproteinases-2 in mononuclear cells may indicate the monocyte-macrophage origin of these cells, as the differentiation of the precursors of the mononuclear stromal monocyte/macrophage to osteoclasts is possibly affected by the expression of osteolytic factors. Also, may be differences in biological behaviors of these lesions are associated with the level of osteopontin and matrix metalloproteinases-2 expression.

Immunohistochemical expression of RANKL in oral giant cell lesions is predictive of aggressiveness.

The aim of this study was to evaluate the immunohistochemical expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and of osteoprotegerin (OPG), important proteins correlated with osteoclastogenesis, in central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) and to compare their expression with the histological and clinical parameters for quantification of multinucleated giant cells (MGC) and their nuclei, lesion size, and recurrences. Twenty cases of each lesion type were selected to quantify the number of MGCs and nuclei/mm2 of connective tissue. The immunoreactivity of RANKL and OPG was expressed as a percentage of the marked area in the stroma. Clinical data were collected from pathoanatomical and medical reports. No statistical differences were found for the number of MGCs (p = 0.24) between PGCL and CGCL, but the number of nuclei within the MGCs was higher in CGCL (p = 0.01). RANKL expression was higher in CGCL than in PGCL (p = 0.04) and all recurrent lesions showed higher RANKL and OPG expressions than nonrecurrent lesions. We report higher RANKL expression and a greater number of nuclei in CGCL, which may explain the difference in clinical behaviour between these lesions and their pathogenesis.

Life threatening bleeding from an osteonecrosis of the jaw: Are bisphosphonates safe in irradiated head and neck cancer patients?

Osteonecrosis of the jaw is a significant complication secondary to radiation therapy or drug therapy, most commonly bisphosphonates. Safety data regarding the administration of bisphosphonates in bone metastatic head and neck cancer patients with history of jaw irradiation are almost non-existent. In this paper, we report the case of a Head and Neck (HNC) patient, with history of radiation therapy to the mandible region, treated with intravenous bisphosphonates for bone metastases that resulted in gross, life threatening mouth hemorrhage secondary to advanced, locally invasive ONJ.