Pigmented ameloblastic fibrodentinoma: a novel melanin-pigmented intraosseous odontogenic lesion

This paper reports about an ameloblastic fibrodentinoma with macroscopically visible pigmentation, resulting in the clinical appearance of a melanotic lesion in a 21-year-old Japanese male. In addition to the characteristic histopathologic features of ameloblastic fibrodentinoma, various-formed and -sized cells, which were considered to be melanophages containing numerous aggregates of melanin pigment in their cytoplasm, were densely distributed throughout the mesenchymal component. In addition, melanin pigment was deposited in dentin. Some of the pigmented cells showed dendritic form and were regarded as melanocytes. Furthermore, pigmented cells were frequently distributed in the epithelial component, and melanin pigment was seen in some epithelial cells. Perusal of the English language literature revealed 30 cases of pigmented odontogenic tumors: 18 were calcifying odontogenic cysts, three were ameloblastic fibro-odontomas, three were adenomatoid odontogenic tumors, two were odontomas, one was an ameloblastic fibroma and one was an odontogenic fibroma. However, all of these reported lesions did not show macroscopically visible pigmentation. The possible histogenesis of melanocytes in the odontogenic lesions is discussed, although no firm conclusion could be drawn. Received: 13 January 2000 / Accepted: 27 March 2000     

Immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in a case of ameloblastic fibrosarcoma

Ameloblastic fibrosarcoma (AFS), regarded as the malignant counterpart of the benign ameloblastic fibroma, is an extremely rare odontogenic neoplasm with only 68 cases reported in the English literature up to 2009. It is composed of a benign odontogenic epithelium, resembling that of ameloblastoma, and a malignant mesenchymal part exhibiting features of fibrosarcoma. Due to the rarity of the lesion, little is known about its molecular pathogenesis; therefore, in the current study, we sought to evaluate the immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in AFS, comparing the results obtained with its benign counterpart, as well as to report a new case of this rare entity affecting a 19-year-old female patient. The results obtained revealed that all the proteins evaluated were overexpressed in the malignant mesenchymal portion of AFS if compared with ameloblastic fibroma, suggesting that nuclear proliferative factors such as Ki67 and proliferative cell nuclear antigen, in association to histopathologic features, may be useful markers for identifying the malignancy and that, despite the lack of molecular analysis in the case reported, Bcl-2 alteration may play a role in AFS pathogenesis.     

Maligne odontogene Tumoren

Malignant odontogenic tumors are extremely rare. As with benign odontogenic tumors, malignant epithelial odontogenic tumors or odontogenic carcinomas are distinguished from the even rarer mesenchymal ones, the odontogenic sarcomas. The existence of odontogenic carcinosarcomas is not yet acknowledged by the World Health Organization. Odontogenic carcinomas comprise ameloblastic carcinoma (AmCa), primary intraosseous carcinoma (PIOC), clear cell odontogenic carcinoma, odontogenic ghost cell carcinoma (OGCC), and the special case of metastasizing ameloblastoma. Odontogenic sarcomas consist of ameloblastic fibrosarcoma and ameloblastic fibrodentinosarcoma and fibroodontosarcoma. Whereas metastasizing ameloblastoma can be diagnosed only after having metastasized, all other malignant odontogenic tumors present with atypia, increased cellularity and mitoses, and invasion. Odontogenic sarcomas are regarded as low-grade tumors that rarely metastasize. Odontogenic carcinomas, however, especially AmCa, OGCC, and PIOC, are more aggressive, with a 5-year survival rate of about 70% for AmCa and OGCC and a 3-year survival rate of about 37% for PIOC. Radical surgery, eventually in combination with radiotherapy, is the treatment of choice.     

Ameloblastic fibrosarcoma in the maxilla,malignant transformation of ameloblastic fibroma

Summary This report presents a fatal case of ameloblastic fibrosarcoma arising from an ameloblastic fibroma, originating in the maxilla of 19-year-old Japanese male. An analysis of previously reported fatal cases of ameloblastic fibrosarcoma is included.In the course of the disease, the mesenchymal component of ameloblastic fibroma showed a dramatic histopathological transformation into sarcoma following multiple recurrence and the patient died of uncontrollable local infiltration of the cranial base. Although many cases have seemed to show disappearance of the epithelial component as malignant transformation progressed, many benign appearing ameloblastoid epithelial masses were scattered throughout the sarcomatous area even in the fatal stage in the present case. No distant metastases were found at autopsy. During multiple recurrences of the lesion, a little dysplastic dentin which was closely associated with both epithelial and mesenchymal components was found, though it could not be observed in autopsy material. Ultrastructural findings in autopsy material showed that the mesenchymal component consisted of undifferentiated mesenchymal cells, fibroblastic and fibrocytic cells with marked cellular and nuclear pleomorphism and that the epithelial component closely resembled the enamel organ.     

Odontogenic sarcoma and carcinosarcoma

Odontogenic sarcoma is a gnathic malignant connective tissue tumor containing epithelium similar to that seen in an ameloblastoma or ameloblastic fibroma. It is a mixed odontogenic tumor in which the epithelial component is benign and the proliferative mesenchymal component is malignant. With each recurrence, the ameloblastic fibrosarcoma demonstrates increasing evidence of stromal cellularity and mitotic activity but diminishing evidence of odontogenic epithelium. If an ameloblastic fibrosarcoma exhibits dysplastic dentin, it can be called an ameloblastic fibrodentinosarcoma, and if it additionally shows focal deposits of dysplastic enamel proteins, it can be designated an ameloblastic fibro-odontosarcoma. A jaw tumor displaying both a carcinomatous and a malignant spindle cell component can be termed an odontogenic carcinosarcoma if it reveals an ameloblastic fibroma-like pattern. If it lacks this pattern, the appellations "spindle-cell ameloblastic carcinoma" or "biphasic ameloblastic sarcomatoid carcinoma" might be preferable. This is a US government work. There are no restrictions on its use.     

Differential expression of collagen IV alpha1 to alpha6 chains in basement membranes of benign and malignant odontogenic tumors

Type IV collagen, the major component of basement membrane (BM), demonstrates a stage- and position-specific distribution of its isoforms during tooth development. To determine its localization in BM of odontogenic neoplasms, immunohistochemistry using six anti-alpha(IV) chain-specific monoclonal antibodies was performed. Results disclosed that BM demonstrated an irregular alpha(IV) chain profile in malignant odontogenic tumors as compared to benign odontogenic neoplasms. No alpha3(IV) chains were detected. Expression of alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) chains was stronger in desmoplastic ( n=3) than in ordinary (n=5) ameloblastomas. The adenomatoid odontogenic tumor ( n=2) distinctly expressed these chains in BM of cribriform areas and hyaline materials (which was also alpha4(IV)-positive), but weakly around epithelial whorls/rosettes/nests and mineralized foci. These five chains also stained BM and tumor cells of ameloblastic fibroma ( n=3) and ameloblastic fibro-odontosarcoma (n=1), but not the inductive hard tissues. Ameloblastic carcinoma ( n=2) showed specific alpha1(IV)/alpha2(IV) chain loss, while primary intraosseous carcinoma ( n=1) demonstrated a discontinuous alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) staining pattern. The present results suggest that modification and remodeling of BM collagen IValpha chains occur during odontogenic neoplasms' progression.     

Co-expression of hepatocyte growth factor and c-met in epithelial odontogenic tumors

Hepatocyte growth factor (HGF) and its receptor, c-met, have been shown to regulate cell proliferation, motility and morphology in a variety of cell types. A significant role of the HGF/c-met pathway has been demonstrated in various tumors, however, little is known about the role of HGF/c-met pathway in odontogenic tumors. The aim of this study was to characterize the expression of HGF and c-met in 30 ameloblastomas, 7 unicystic ameloblastomas (luminal type), 10 calcifying cystic odontogenic tumors, 10 adenomatoid odontogenic tumors (AOTs), 30 keratocytic odontogenic tumors (KCOTs) and 6 ameloblastic carcinomas using an immunohistochemical method. HGF and c-met were generally immunolocalized in the cytoplasm of all epithelial tumor cells, except for keratinizing cells in acanthomatous ameloblastoma, in all the examined odontogenic tumors. These results, together with the expression of these two proteins in the epithelium of tooth germs, suggest that the HGF/c-met pathway is involved in the differentiation of odontogenic tumors. This pathway may also promote tumor proliferation in odontogenic tumors due to its potent mitogenic effect. The consistent and strong immunolocalization of HGF and c-met in squamous cells present in acanthomatous ameloblastomas, AOTs and ameloblastic carcinomas, and in the linings of KCOTs suggests that the HGF/c-met interaction may have an influence on squamous differentiation in these odontogenic tumors.     

Benigne „gemischte“ odontogene Tumoren

Benign "mixed"odontogenic tumors consist of an epithelial and ectomesenchymal tumor component, distinguishing them from pure epithelial and pure ectomesenchymal odontogenic tumors. In addition, they may have the ability to produce dentin, enamel or cementum. Therefore, they can sometimes already be differentiated radiologically from epithelial odontogenic tumors. Some of the mixed odontogenic lesions are regarded as true tumors (ameloblastic fibroma, odontoameloblastoma, dentinogenic ghost cell tumor), while others are assumed to represent hamartomatous lesions (complex and compound odontoma, probably also ameloblastic fibrodentinoma and ameloblastic fibroodontoma). Preceded by keratocystic odontogenic tumor, complex and compound odontomas are the second most common odontogenic tumors, while other members of the "mixed" odontogenic tumor group are far less frequently diagnosed. Odontoameloblastoma and dentinogenic ghost cell tumors are locally aggressive lesions that require total resection. All other lesions of this group are treated by local excision. Since ameloblastic fibrosarcoma may evolve from ameloblastic fibroma, patients with ameloblastic fibroma should remain in long-term follow-up.     

Nestin expression in odontoblasts and odontogenic ectomesenchymal tissue of odontogenic tumours

BACKGROUND: Nestin, one of the intermediate filaments constituting the cytoskeleton, is a marker of neural stem cells or progenitor cells. Its expression is also related to tooth development and repair of dentine. AIMS: The aim of this study was to investigate nestin expression in various odontogenic tumours and evaluate its usefulness for histopathological diagnosis. METHODS: We studied formalin fixed, paraffin embedded specimens from 129 cases of odontogenic tumours and 9 of mandibular intraosseous myxoma. After characterisation of odontogenic ectomesenchymal tissues in these tumours using antibodies to vimentin, desmin, neurofilament, and glial fibrillary acidic protein, we immunohistochemically examined nestin expression. RESULTS: No differentiation towards muscle and nervous tissues was found in the odontogenic ectomesenchymal tissues. Although almost all the ameloblastomas and malignant ameloblastomas were negative for nestin, odontogenic ectomesenchyme in the odontogenic mixed tumours demonstrated nestin immunolocalisation, particularly in the region adjacent to the odontogenic epithelium. Odontoblasts and their processes, pulp cells near the positive odontoblasts, and flat cells adhering to the dentine showed immunoreaction with nestin in the odontomas and odontoma-like component in the ameloblastic fibro-odontomas. Neoplastic cells in almost half cases of jaw myxoma and one case of odontogenic fibroma expressed nestin. CONCLUSIONS: The distribution of nestin in the odontogenic mixed tumours suggests that nestin expression in the odontogenic ectomesenchyme is upregulated by stimulation from odontogenic epithelium. In addition, nestin may also be involved in the differentiation from pulp cells to odontoblasts in odontogenic tumours. Therefore, nestin is a useful marker for the odontogenic ectomesenchyme and odontoblasts in odontogenic tumours. Nestin, one of the intermediate filaments constituting the cytoskeleton, is a marker of neural stem cells or progenitor cells. Its expression is also related to tooth development and repair of dentine.     

牙源性钙化囊性瘤临床病理研究

目的探讨牙源性钙化囊性瘤(calcifying cystic odontogenic tumor,CCOT)的临床病理分型对治疗预后的影响。方法对39例CCOT的临床表现、X线影象、病理特征及治疗随访资料等进行回顾性分析。结果 39例中男性26例,女性13例,平均年龄29.6岁;病变位于下颌骨21例,上颌骨18例;临床多以颜面部肿胀就诊。X线主要表现为颌骨内界限清楚的放射透光区,单房或多房,其中伴有钙化斑点或团块。镜下均可见到特征性的影细胞,可分为4种类型:单纯囊肿型(17例)、CCOT伴牙瘤型(12例)、CCOT伴成釉细胞瘤增生型(7例)、CCOT伴其他良性牙源性肿瘤型(3例:伴成釉细胞纤维瘤2例,伴成釉细胞纤维牙瘤1例)。治疗均采用囊肿摘除术或刮治术,获得随访33例,复发6例,其中3例复发者均为CCOT伴成釉细胞瘤增生型且有囊壁内浸润(1例复发为牙源性影细胞瘤,1例20年后复发恶变为牙源性影细胞癌)。结论 CCOT伴成釉细胞瘤增生且有囊壁内浸润型行单纯囊肿摘除术或刮治术容易复发,可形成牙源性影细胞瘤或恶变成牙源性影细胞癌,此型肿瘤的手术范围应适当扩大并进行长期随访。     

Gene mutation analysis and immunohistochemical study of beta-catenin in odontogenic tumors

In the present study the significance of nuclear/cytoplasmic expression of beta-catenin (CTNNB1) and mutation of the CTNNB1 gene (CTNNB1) in odontogenic tumors was examined. Six ameloblastomas (five follicular ameloblastomas and one plexiform ameloblastoma) and three malignant odontogenic tumors (one metastasizing ameloblastoma, one ameloblastic carcinoma, and one primary intraosseous odontogenic carcinoma) were investigated for CTNNB1 expression and CTNNB1 mutation. Immunohistochemically, all follicular ameloblastomas and one primary intraosseous odontogenic carcinoma exhibited focal and moderate nuclear/cytoplasmic expression of CTNNB1, whereas the plexiform ameloblastoma and the remaining two malignant odontogenic tumors had entirely membranous expression. CTNNB1 mutation at codon 40 of exon 3 was found in one of the six follicular ameloblastomas. The other five follicular ameloblastomas, the plexiform ameloblastoma, and the three malignant odontogenic tumors did not show mutation in exon 3 of CTNNB1. These findings further confirmed that CTNNB1 mutation is not frequent in ameloblastoma and malignant odontogenic tumors, although the abnormality of Wnt signaling may be associated with some of these tumors.     

Desmoplastic ameloblastoma: a case report with fine-needle aspiration cytologic findings

A case of desmoplastic ameloblastoma of the maxilla in a 25-yr-old woman is presented. Smears prepared from fine-needle aspiration cytology showed two populations of cellular elements: cohesive epithelial clusters with basaloid morphology present, mostly in bidimensional, irregularly outlined clusters with ill-formed palisading of nuclei at the periphery in some, and a mesenchymal component represented by 1) a sparse chunk of moderate-sized tissue fragments made up of spindle- or ovoid-shaped nuclei entrapped in mesenchymal matrix, and 2) many dissociated naked oval-to-spindle-shaped nuclei. The presence of epithelial and mesenchymal components and their benign nature lead us to consider the possibility of benign odontogenic tumors 1) of epithelial origin, such as ameloblastma with a stromal component, e.g., desmoplastic ameloblastoma; 2) of mesenchymal origin, such as odontogenic fibroma; and 3) of mixed epithelial and mesenchymal origin, such as ameloblastic fibroma. Excision and histopathological examination of this lesion confirmed the diagnosis of desmoplastic ameloblastoma. In the given clinical setting and radiological examination, the above cytological features suggest a benign odontogenic tumor, rather than precisely diagnosing any of the entities mentioned above. However, it is important to distinguish between these, since the treatment varies accordingly. The differential diagnosis is discussed.     

Immunohistochemical expression of neural tissue markers (neuron-specific enolase, glial fibrillary acidic protein, S100 protein) in ameloblastic fibrodentinoma: a comparative study with ameloblastic fibroma

Formalin-fixed paraffin-embedded sections of three cases of ameloblastic fibrodentinoma (AFD) were studied by the avidin-biotin-peroxidase complex method using antibodies against neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and S100 protein and the results were compared with those in ameloblastic fibroma (AF). A striking histopathological characteristic of AFD was the formation of abortive dentin with various degrees of maturation at the epithelial-mesenchymal tissue interface. Central cells of enamel organ-like epithelia with various stages of abortive dentin induction in AFD were generally positive for NSE. Dental lamina-like epithelial cells also showed positive staining in some areas. No cells were positive for NSE in AF. Positive staining for GFAP was observed in the juxta-epithelial mesenchymal tissue of the formation stage of immature dentin with various numbers of entrapped cells in AFD, but GFAP staining was negative in other mesenchymal and epithelial tissues at other stages. In AF, no GFAP-positive cells were found. There were a few S100 protein-positive cells found in the foci of epithelial components in both AFD and AF. Mesenchymal cells showing a dendritic or spindle shape were positive for S100 protein in some areas of AFD and AF. Although such cells in the mesenchymal component of pigmented AFD were more numerous than in non-pigmented AFD and AF, their distribution pattern in the former condition was basically similar to that in the latter. Although the present results, obtained from conventional immunohistochemical procedures, do not directly reflect the expression of neural crest-derived cells in the dentinogenesis of AFD, such results do not disprove the possibility of the expression of neural proteins probably related to neural crest-derived cells in dentinogenesis under certain pathologic conditions in odontogenic mixed tumors. Such a phenomenon may also occur during dentinogenesis in other odontogenic mixed tumors and in normal tooth differentiation, but at an undetectable level.     

Ameloblastic fibrosarcoma: a cytologist's perspective

Fine-needle aspiration cytology of a case of ameloblastic fibrosarcoma (AFS), an unusual odontogenic tumor related to ameloblastoma (AB), was performed in a 25-year-old female with a 1 cm swelling in the left lower orbital region along with involvement of zygomatic region. Aspiration of the tumor yielded a cellular sample composed predominantly of mesenchymal element and few clusters representing epithelial component showing tall columnar cells with peripheral palisading. Detailed cytomorphological features of AFS are discussed along with differential diagnosis from other tumors such as AB, desmoplastic AB, odontogenic fibroma, ameloblastic fibrodentinoma and ameloblastic fibro-odontoma, ameloblastic fibroma.     

Calcifying epithelial odontogenic tumor: report of two cases

Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign odontogenic tumor. It constitutes 0.4-3% of all odontogenic tumors. There is only a single case, which has been reported in the Indian literature that too in cytology. Microscopically, these are composed of large sheets of epithelial cells, amorphous amyloid-like material and calcification. Although these lesions are benign, they can be locally aggressive, but malignant transformation and metastasis is rare. Considering its locally aggressive nature, appropriate management and long-term follow-up is recommended. We describe two cases of CEOT involving the hard palate and leading to facial alterations.     

Immunohistochemical localization of large chondroitin sulfate proteoglycan in odontogenic tumor

The present study investigated the localization of versican in odontogenic tumors by immunohistochemistry, using paraffin-embedded sections obtained from 27 patients with odontogenic tumors (17 ameloblastomas, 1 adenomatoid odontogenic tumor, 4 odontogenic keratocysts, 1 calcifying odontogenic cyst, 2 ameloblastic fibromas, and 2 malignant ameloblastomas). Deparaffinized sections were immersed in a buffered 1 : 1000 solution of an antibody, 5D5 (raised against a large chondroitin sulfate proteoglycan from bovine sclera), which mainly recognizes versican. All samples showed a positive reaction for versican in connective tissues, whereas positive staining of epithelial nests was observed in only some samples. The positive staining in epithelial nests was in areas showing stellate reticulum-like, cuboidal, columnar cells at the periphery, and tear-drop structures. These results indicated that versican might be involved in, at least in part, the morphogenesis of neoplastic epithelium and mesenchymal tissues in odontogenic tumors.     

Malignant epithelial odontogenic tumors

Malignant epithelial odontogenic tumors are very rare. They may arise from the epithelial components of the odontogenic apparatus. The rests of Malassez, the reduced enamel epithelium surrounding the crown of an impacted tooth, the rests of Serres in the gingiva, and the linings of odontogenic cysts represent the precursor cells for malignant transformation. Because metastatic carcinoma is the most common malignancy of the jaws, the diagnosis of a primary intraosseous carcinoma must always be made to the exclusion of metastatic disease. Odontogenic carcinomas include malignant (metastasizing) ameloblastoma, ameloblastic carcinoma, primary intraosseous squamous cell carcinoma, clear cell odontogenic carcinoma, and malignant epithelial ghost cell tumor. There are specific histopathologic features that support the diagnosis of a primary carcinoma of odontogenic epithelium which are presented in this article. Immunohistochemical (IHC) staining is important for distinguishing clear cell odontogenic carcinoma from metastatic renal cell tumors, yet IHC stains are not particularly helpful for other lesions in this group-all of which exhibit low molecular weight cytokeratin positivity. Aggressive growth and nodal and distant metastases occur with all of these entities.     

Clear cell odontogenic carcinoma. Report of two cases and review of the literature.

This study reviews the literature and reports on the morphologic and immunophenotypic features of 2 clear cell odontogenic carcinomas occurring in the mandible of elderly women, showing extensive infiltration into adjacent tissues. The tumor cells were large, with clear cytoplasm, and arranged in irregular sheets. Some of the latter demonstrated a peripheral rim of cells with eosinophilic cytoplasm or included duct-like structures. There was no evidence of ameloblastic differentiation. Most cells contained glycogen granules and were immunoreactive for cytokeratins and epithelial membrane antigen. In the differential diagnosis other clear cell odontogenic, salivary gland, and metastatic tumors should be considered. Both cases were treated with surgical excision, and the patients are free of disease after 3 and 5 years, respectively. In the literature, however, variable behavior of these tumors has been reported, including recurrence and metastases. It is recommended that terms such as clear cell ameloblastoma and clear cell odontogenic tumor not be used to describe such tumors.     

颌骨牙源性钙化囊肿病变性质的探讨

目的：明确所谓牙源性钙化囊肿（calcifying odontogenic cyst,COC)各临床病理亚型的特点及其病变性能。方法：回顾分析21例被笼统诊断为COC病例资料,通过对临床、X线、病理、治疗及预后特点的综合分析,将本组病例分为囊肿、良性肿瘤和恶性肿瘤3类病损进行观察。结果：囊肿组16例（男性9例、女性7例）,10－19岁为高发年龄,前磨牙区好发,随访13例患者无复发。良性肿瘤组4例,临床病理表现各异,其中2例表现为所谓实性型COC,1例为COC伴发成釉细胞瘤,1例为COC伴发牙源性纤维黏液瘤;这组病例均发生于下颌,其中2例有多次复发史。恶性肿瘤组1例,肿瘤呈实性,除表现某些COC特点外,具有显著的组织学恶性特点。结论：以往被笼统归类为COC的病变可表现囊肿,良性肿瘤或恶性肿瘤等多种病理和行为特点,因此其命名和分类应作相应修改,临床治疗也应区别对待。     

Expression of p21RAS in odontogenic tumors.

Using an immunohistochemical assay 10 benign odontogenic tumors were evaluated for expression of the HRAS- and KRAS-encoded gene products p21RAS. Overexpression of p21RAS was found in ameloblastomas, ameloblastic fibromas and odontogenic myxomas compared with normal human developing teeth. The highest expression was noted in a recurrent plexiform ameloblastoma in which almost 100% of the tumor cells were brightly reactive. In general, p21RAS was preferentially expressed in ectodermal cells of odontogenic tumors, consistent with the findings in the tooth germs. The significance of p21RAS expression is considered in relation to the biological behavior of ameloblastomas.