Adjuvant antiangiogenic therapy for giant cell tumors of the jaws.

PURPOSE: To further evaluate a novel treatment protocol for the management of aggressive giant cell lesions (GCLs) consisting of enucleation followed by adjuvant subcutaneous interferon alpha therapy. PATIENTS AND METHODS: Using a retrospective case series study design, a sample of patients with aggressive GCLs was enrolled between April 1995 and June 2006. Lesions were enucleated with preservation of vital structures. Postoperatively, the patients received daily subcutaneous interferon alpha (3 million units/m2 of body surface area). Interferon treatment continued with regular clinical and radiographic follow-up until the surgical defects filled in with bone, as demonstrated by panoramic radiographs and confirmed by computed tomography. Side effects, such as fever, fatigue, weight loss, decreased white blood cell count, decreased platelet count and elevated liver enzymes, were monitored. After completion of interferon therapy, patients followed for 2 years without evidence of recurrence were considered cured of disease. RESULTS: The study sample was comprised of 26 subjects (65% female) with a mean age of 18.5 years. At the time of this writing, 16 of the subjects have completed the protocol and are cured of disease, 6 are in remission, and 4 are in active treatment. Four subjects experienced significant side effects from the interferon, requiring modification of treatment. CONCLUSIONS: Enucleation of aggressive GCLs with preservation of vital structures and adjuvant interferon is an excellent strategy for managing aggressive GCLs. Approximately 15% of subjects developed significant side effects limiting interferon administration and necessitating alternative therapies.     

Clonality analysis of giant cell lesions of the jaws

Despite the importance of clonality to understand the pathogenesis and progression of tumors, it has not been investigated yet in giant cell lesions of the jaws. The aim of this study was to analyze the clonality of peripheral giant cell lesions (PGCL) and central giant cell lesions (CGCL) of the jaws. Six samples of PGCL and 5 samples of CGCL were analyzed in this study using the polymorphic human androgen receptor locus (HUMARA) assay. Three out of the 5 samples of the CGCL and 3 out of 6 samples of PGCL exhibited a monoclonal pattern. Our findings demonstrate that some giant cell lesions of the jaws are clonal, which indicate that these lesions may have a common genetic mechanism of development. Further studies are necessary to better elucidate the molecular mechanisms involved in the pathogenesis of such lesions.     

Central giant cell lesions of the jaws: A clinicopathologic study

The biologic behavior of central giant cell lesions of the jaws ranges from quiescent to aggressive with destructive expansion. To date, these variations have not been explained by the findings of routine histologic examination. This retrospective clinicopathologic study of giant cell lesions was performed to search for histologic correlates of biologic behavior. Lesions in 17 patients were classified clinically as nonaggressive (group I) or aggressive (group II). In general, group II lesions affected children at an earlier age, were larger at the time of diagnosis, and recurred more frequently. The following histologic parameters were assessed: fractional surface area occupied by giant cells (FSA), relative size index of giant cells (RSI), stromal characteristics, mitotic index, inflammatory cells, and hemosiderin content. Histologic differences between the two groups were not as clear as the differences in biologic behavior. However, aggressive lesions had a higher RSI, and recurrent giant cells lesions had a higher RSI and FSA; these parameters warrant further study. In addition, electron microscopic differences in a small number of aggressive and nonaggressive lesions were documented.     

Estrogen and progesterone receptor status of central giant cell lesions of the jaws

It is well known that the central giant cell lesion (granuloma) of the jaws has a distinct female predilection. In addition, occasional cases of central giant cell lesion have been reported to have undergone marked proliferation in pregnant patients and in those undergoing hormonal therapy. As such, we have evaluated 10 central giant cell lesions for the detection of estrogen and progesterone receptor proteins with the use of immunoperoxidase staining. Surprisingly, however, immunostaining for estrogen receptor protein was essentially negative in all cases examined. Although an occasional mononuclear cell stained weakly positive for estrogen receptor protein, these findings suggest that in most cases, factors other than a direct influence of the ovarian hormones, estrogen and progesterone, are responsible for the development and growth of these lesions.     

31例颌骨中心性巨细胞肉芽肿的临床病理研究

目的 观察分析颌骨中心性巨细胞肉芽肿(CGCG)的临床病理学特点及病变生物学行为问的关系，探讨颌骨CGCG的性质及诊断。方法 采用组织病理学方法，结合临床随访对比分析31例颌骨CGCG的临床病理学特点及其与病变性质的关系。结果 31例颌骨CGCG以30岁以下的女性多见，病变多见于下颌，X线表现无特异性。病变中的多核巨细胞(MGC)分布较不均匀，核数较少，以10～19个核多见，病变出血明显，纤维成分丰富，常有含铁血黄素沉积，骨及类骨质多见。比较病变复发组与非复发组问的临床病理学特点，结果提示差异无统计学意义。根据临床和X线特点病变分为侵袭组与非侵袭组，侵袭组与复发关系密切。结论 颌骨CGCG是一种非瘤性病变，在病变性质上有别于骨巨细胞瘤，其病理学特点在两者的鉴别上缺乏客观标准并且与其生物学行为无关，结合临床分析对治疗更加有意义。     

Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts

BACKGROUND: The nature and the mechanism involved in the formation of the multinucleated giant cells (MGCs) in various giant cell-containing lesions of the jaws are not fully understood. The aim of this study is to clarify the osteoclastic features of the MGCs in central giant cell granuloma (CGCG), peripheral giant cell granuloma (PGCG), cherubism, and aneurysmal bone cyst (ABC), and the mechanism underlying the interrelations between cellular components in the formation of the MGCs. METHODS: Immunohistochemical study with a panel of antibodies including vacuolar H+-ATPase (V-ATPase), carbonic anhydrase II (CA II), Cathepsin K, matrix metalloproteinases-9 (MMP-9), CD68, and proliferating cell nuclear antigen (PCNA), and enzyme histochemical staining for tartarate-resistant acid phosphatase (TRAP) were applied on a total number of 53 cases of giant cell-containing lesions including CGCG (n = 34), PGCG (n = 6), cherubism (n = 7), and ABC (n = 6). In situ hybridization was also carried out to detect the mRNA expression of the receptor activator of NF-kappaB ligand (RANKL), a newly identified cytokine that is shown to be essential in the osteoclastogenesis, its receptor RANK (receptor activator of NF-kappaB ligand), and its decoy receptor OPG (osteoprotegerin) in these four types of lesions. RESULTS: Immunohistochemical and enzyme histochemical studies showed that both the MGCs and a fraction of mononuclear cells in these lesions were strongly positive for TRAP, V-ATPase, CA II, Cathepsin K, MMP-9, and CD68, while the spindle-shaped mononuclear cells were positive for PCNA. The results with in situ hybridization indicated that RANKL mRNA was mainly expressed in the spindle mononuclear cells while OPG was extensively distributed in both the MGCs and the mononuclear cells. RANK mRNA was expressed in the MGCs and some round mononuclear cells. CONCLUSIONS: These results suggest that MGCs in the four types of giant cell-containing lesions of the jaws show characteristics of the osteoclast phenotype. The mononuclear stromal cells, which show TRAP positively, may be the precursors of the MGCs. RANKL, OPG, and RANK expressed in these lesions may play important roles in the formation of the MGCs. The similar characteristics and mechanisms in the differentiation of MGCs in these lesions also suggest that there might be a similar kind of pathogenesis involved in the formation of the MGCs in these lesions     

Quantitative analysis of argyrophilic nuclear organizer regions in giant cell lesions of jaws

J Oral Pathol Med (2010) 39 : 431–434 Background: Giant cell lesions of the jaws are considerably similar according to histopathologic characteristics yet show different clinical behaviors. These lesions include central giant cell granuloma (CGCG), aneurysmal bone cyst, Cherubism, and Brown tumor associated with hyperparathyroidism. The present study aimed to investigate AgNORs count in these lesions as a proliferative marker and to determine whether it can be used to discriminate between them or not. Methods: Forty‐one cases of giant cell lesions of jaws were retrived from Oral Pathology Department (1987–2007). They included 21 cases of CGCG, eight cases of aneurysmal bone cyst (ABC), six cases of Cherubism, six cases of Brown tumor. The mean AgNORs count was calculated for all cases. To compare mean AgNORs in groups of lesions, ANOVA test was performed. Results: Mean AgNOR counts were: (0/85 ± 0/29) in CGCG, (0/76 ± 0/32) in ABC (0/87 ± 0/10) in Cherubism and (0/82 ± 0/16) in Brown tumor. A significant difference was not observed in AgNOR counts among these groups of lesions. Conclusions: Jaws giant cell containing lesions have no acceptable differences in mean AgNORs.     

Surgical therapy for osteonecotic lesions of the jaws in patients in therapy with bisphosphonates

OBJECTIVE: Surgical therapy to improve the symptoms and the lesions in osteonecrosis (ON) of the jaws in patients in therapy with bisphosphonates.Design: to evaluate the patient's therapeutic protocols, performance status, and factors promoting ON to prevent surgical failure. MATERIALS AND METHODS: 18 patients affected by osteonecrotic lesions of the jaws associated to BF, were treated by surgery. RESULTS: The results were recorded after 6 months. All the patients showed improvement of symptoms, in particular the pain. In addition, all the patients referred to a sensation of fresh and clean mouth, the disappearance of fetor ex ore, and a healthy mouth. CONCLUSIONS: The management and the resolution of BF osteonecrotic lesions is arguable and complex because in most cases, the patients are affected by oncologic disease when the better approach is prevention, but when the ON lesion is clear, surgery can improve the symptoms and in some cases, it can be resolute. To prevent surgical failure, it can be useful to evaluate the patient's therapeutic protocols, performance status, and factors promoting ON.     

颌骨巨细胞瘤和巨细胞肉芽肿病变中多核巨细胞性质的探讨

目的 探讨颌骨巨细胞瘤(Giant cell tumor，GCT)和巨细胞肉芽肿(Giant cell granuloma，GCG)病变中多核巨细胞(Multinucleated giant cells，MGCs)的性质及组织来源。方法 对8例颌骨GET和8例GCG(中心性4例、外周性4例)进行酶组织化学和免疫组织化学观察，并与其它含MGICs的口腔病变(如异物反应、淋巴结结核等)进行比较。结果 颌骨GCT和GCG中的MGCs既可表达组织细胞／单核巨噬细胞相关抗原[如CD68、αl-抗胰蛋白酶(Alpha-1-antitrypsin，AAT)、α1-抗糜蛋白酶(Alpha-1-antichymotrypsin，AACT)、溶菌酶等]，又具有破骨细胞特异性酶-抗酒石酸酸性磷酸酶[Tartrate-resistant acid phosphatase(TRAP)]的活性，但不表达增殖细胞标记Ki-67抗原。结论 颌骨GCT和GCG中的MGCs可能是反应性终末分化细胞，由病变中处于不同分化阶段的前体破骨细胞融合而成．同时具有单核巨噬细胞和破骨细胞的某些表型特征。     

Central giant cell lesions of the jaws: A clinical,radiologic, and histopathologic study

The histology, radiographs, and follow-up information for 142 cases of central giant cell lesions of the jaws were reviewed in an effort to determine which, if any, microscopic features could be correlated with clinical behavior. The majority of these lesions were asymptomatic and relatively innocuous. However, some displayed a more aggressive clinical course characterized by root resorption, pain or paresthesia, and cortical perforation. The over-all recurrence rate in the 142 cases was 16%. Adequate follow-up information (mean, 48 months) was only obtained for 47 patients, and 23 (46%) of these experienced one or more recurrences. Statistically significant histologic differences in distribution of giant cells and frequency of osteoid within the lesions were found in lesions that recurred as opposed to those that did not. The concept that giant cell lesions of the jaws are not totally different entities from giant cell tumors is discussed.     

Multiple recurrent central giant cell granulomas of the jaws. Case report.

A case of a 31-year-old Caucasian female with multiple recurrent central giant cell granulomas of the maxilla and mandible is presented. The patient's mother was also treated for an extensive giant cell granuloma of the maxilla. Hyperparathyroidism was excluded.     

Noonan syndrome with giant cell lesions

Noonan syndrome is characterised by short stature, unusual facies, congenital heart disease, chest deformity and mild mental retardation. It may be sporadic or inherited as an autosomal dominant trait and occurs between one in 1000-2500. Cherubism is a giant cell lesion of the jaws thought to be transmitted as an autosomal dominant trait. It is usually recognised by age two to four years, follows a variable course, and is not known to be related to other genetic disorders. The purpose of this article is to report a case of multiple giant cell lesions of the mandible that occurred in a patient with phenotypic features of Noonan syndrome. The emerging relationship between these cherubism-like findings and Noonan syndrome will be discussed.     

Stromal myofibroblasts in central giant cell granuloma of the jaws cannot distinguish between non-aggressive and aggressive lesions

OBJECTIVE: To investigate correlations between myofibroblast density (MFD) and biological behavior of a large series of non-aggressive and aggressive central giant cell granuloma lesions (CGCGs). METHODS: Twenty-four non-aggressive and 17 aggressive lesions were immunohistochemically stained with alpha smooth muscle actin. MFD was assessed using the point counting method in the lesions' core tissue and in control areas that consisted of non-involved, connective tissue surrounding the lesion. RESULTS: All CGCGs contained myofibroblasts among the stromal cells. No significant differences were found in the mean percentage of MFD (%MFD) of non-aggressive (20.8 +/- 15.7%) and aggressive (23.7 +/- 22.9%) lesions (P > 0.05) or in the mean %MFD of the respective control areas (1.4 +/- 2.2% and 1.7 +/- 4.1%; P > 0.05). The mean core tissue %MFD of both lesion types was significantly higher than that of the control areas (P < 0.001). CONCLUSION: Myofibroblasts were an integral component of CGCG stromal cells, but their density could not distinguish between non-aggressive and aggressive lesions.