Peripheral calcifying cystic odontogenic tumour of the maxillary gingiva

ABSTRACT: BACKGROUND: Odontogenic tumors are lesions that are derived from remnants of the components of the developing tooth germ. The calcifying cystic odontogenic tumor or calcifying odontogenic cyst is a benign cystic neoplasm of odontogenic origin that is characterized by an ameloblastoma-like epithelium. Calcifying cystic odontogenic tumor may be centrally or peripherally located, and its ghost cells may exhibit calcification, as first described by Gorlin in 1962. Most peripheral calcifying cystic odontogenic tumors are located in the anterior gingiva of the mandible or maxilla. CASE PRESENTATION: Authors report a rare case of a peripheral calcifying cystic odontogenic tumor of the maxillary gingiva. A 39-year-old male patient presented with a fibrous mass on the attached buccal gingiva of the upper left cuspid teeth. It was 0.7-cm-diameter, painless and it was clinically diagnosed as a peripheral ossifying fibroma. After an excisional biopsy, the diagnosis was peripheric calcifying cystic odontogenic tumor. The patient was monitored for five years following the excision, and no recurrence was detected. CONCLUSIONS: All biopsy material must be sent for histological examination. If the histological examination of gingival lesions with innocuous appearance is not performed, the frequency of peripheral calcifying cystic odontogenic tumor and other peripheral odontogenic tumors may be underestimated.     

Ghost cells in calcifying odontogenic cyst express enamel-related proteins

The so-called ghost cell is a unique cell type occurring in a variety of odontogenic and non-odontogenic lesions. However, the true nature of ghost cells has not been determined. In the present study, we examined the immunoreactivity of ghost cells in calcifying odontogenic cysts and dermal calcifying epitheliomas, with antibodies against amelogenin, enamelin, sheath protein (sheathlin) and enamelysin, in an attempt to clarify the nature of this unique cell. The cytoplasm of ghost cells in calcifying odontogenic cysts demonstrated distinct immunolocalization of the enamel-related proteins, while similar in the calcifying epitheliomas of the skin showed a negative reaction. The results indicate that the ghost cells in calcifying odontogenic cysts, as opposed to ghost cells in dermal calcifying epitheliomas, contain enamel-related proteins in their cytoplasm accumulated during the process of pathological transformation.     

Cytologic findings in calcifying epithelial odontogenic tumor: a case report

BACKGROUND: Calcifying epithelial odontogenic tumor (CEOT), or Pindborg's tumor, is a rare, benign, odontogenic neoplasm first described by Pindborg in 1955. It is most commonly seen in the fourth and fifth decades of life, usually arises in the mandibular premolar-molar areas and accounts for approximately 1% of all intraosseous odontogenic tumors. This report describes the cytologic findings in a case of CEOT. CASE: A 62-year-old woman was referred to the ear, nose and throat clinic with a right maxillary mass. The fine needle aspiration (FNA) smears showed numerous calcifications; amorphous, eosinophilic material; and clusters of round epithelial cells embedded in a bloody background. The smears were diagnosed as suspicious for malignancy. Maxillectomy was done. The histologic sections were diagnosed as CEOT. CONCLUSION: FNA findings of calcifying epithelial odontogenic tumor have been described rarely. The clusters of epithelial cells with prominent nucleoli are mistaken for features of a malignant tumor.     

Pilomatrixoma as a diagnostic pitfall in fine needle aspiration cytology: a case report

BACKGROUND: Pilomatrixoma (pilomatrixoma, calcifying epithelioma of Malherbe) is a relatively uncommon, benign neoplasm arising from the skin adnexa. The tumor can cause diagnostic difficulty not only for the clinician but also for the cytologist. CASE: A 62-year-old woman presented with a right submandibular swelling of 4 months' duration. The clinical findings were highly suspicious for malignancy. A fine needle aspiration biopsy was performed. Three preliminary differential diagnoses were offered: mucoepidermoid carcinoma of the submandibular salivary gland, squamous cell carcinomatous deposit in a submandibular lymph node and calcifying odontogenic tumor. Computed tomography demonstrated no bony lesion. No primary site of squamous cell carcinoma could be identified. An excisional biopsy of the swelling was performed, and the histologic diagnosis of pilomatrixoma was made. CONCLUSION: The cytologic presentation of pilomatrixoma of the right submandibular region can masquerade as that of a malignant tumor, in this case mucoepidermoid carcinoma, squamous cell carcinoma or odontogenic tumor. This case delineates the cytomorphologic features of pilomatrixoma that may mimic carcinoma.     

Calcifying odontogenic cysts (keratoameloblatomas)

Two cases of calcifying odontogenic cyst were studied in males over 50. The histopathological diagnosis was based on the presence of ghost cells, partly calcified, in the thickness of the epithelium lining the cyst. These cells contained keratin occurring without keratohyalin granules. We consider that this lesion may be primary or secondary the latter occurring in common odontogenic cysts through the secondary differentiation of epithelial cells.     

Neoplastic odontogenic epithelial cells express bone sialoprotein

Bone sialoprotein (BSP) is synthesized and secreted by bone-, dentine- and cementum-forming cells and has been implicated in de novo bone formation and mineralization. In this study, we used histological sections of odontogenic neoplasms and performed immunohi stochemical and in situ hybridization analyses. In ameloblastoma, BSP mRNA signals were seen in the neoplastic epithelial cells forming nests, strips and islands. BSP deposition was also seen in the stellate reticulum of the tumour masses revealed by immunohistochemistry using human BSP antibodies. In calcifying epithelial odontogenic tumour, the calcified masses demonstrated positive immunoreactivity to the human BSP antibodies, and the hybridization signals for BSP were located in the cells near the calcified particles. In the calcifying odontogenic cyst, strong BSP signals were seen in cells surrounding the characteristic nests of ghost cells, which often calcify subsequently. BSP protein was also found in these cells by immunohistochemistry. The active expression of BSP in the epithelial elements of the odontogenic tumours of adult patients suggests the activation of this matrix protein gene in the neoplastic process, and that BSP may play an important role in tumour formation and differentiation with respect to pathological calcification. © Chapman & Hall     

Expression of odontogenic ameloblast-associated protein (ODAM) in dental and other epithelial neoplasms

We previously have communicated our discovery that the amyloid associated with calcifying epithelial odontogenic tumors is composed of N-terminal fragments of the structurally novel odontogenic ameloblast-associated protein designated ODAM. Subsequently, it was shown by other investigators that ODAM is expressed in rodent enamel organ and is likely involved in dental development. We now report that this molecule also is found in certain human tissues, principally the salivary gland and trachea, as evidenced by RNA array analysis and immunohistochemistry-utilizing antibodies prepared against synthetic ODAM-related peptides and recombinant protein. Notably, these reagents immunostained normal and malignant ameloblasts and other types of human neoplastic cells, including those of gastric, lung, and breast origin where the presence in the latter was confirmed by in situ hybridization using gene-specific molecular probes. Moreover, significant titers of anti-ODAM IgG antibodies were detected in the sera of patients with these malignancies. Our studies have provided the first evidence in humans for the cellular expression of ODAM in normal and diseased states. Based on our findings, we posit that ODAM is a developmental antigen that has an essential role in tooth maturation and in the pathogenesis of certain odontogenic and other epithelial neoplasms; further, we suggest that ODAM may serve as a novel prognostic biomarker, as well as a potential diagnostic and therapeutic target for patients with breast and other epithelial forms of cancer.     

Odontogenic tumors in Nigerian children and adolescents- a retrospective study of 92 cases

Background

Tumours arising from odontogenic tissues are rare and constitute a heterogenous group of interesting lesions. The aim of this study was to determine the relative frequency of odontogenic tumors (OT) among Nigerian children and adolescents 19 years or younger.

Patients and methods

The histopathology records were retrospectively reviewed for all the tumors and tumor-like lesions of the oral cavity and the jaws seen in children and adolescents ≤ 19 years seen between January 1980 and December 2003. Hematoxylin and eosin-stained sections were re-evaluated and the diagnosis in each case was confirmed or modified according to World Health Organization (WHO) classification, 1992; and were subjected to analysis of age, sex, site of tumor and histopathologic type.

Results

A total of 477 tumors and tumor-like lesions were seen in patients ≤ 19 years during the period of the study. Of these, 92 (19.3%) were odontogenic tumors. Benign odontogenic tumors constituted 98.9% of the cases seen, while only 1 case (1.1%) of malignant variety was seen during the period. The mean (SD) age of patients was 14.9 (± 3.1) years (range, 4–19 years). Male-to-female ratio was 1:1; and mandible-to-maxilla ratio was 2.7:1. OT's were most frequently seen in patients aged 16–19 years (46.7%) and the least number (2.2%) were found in patients aged 0–5 years. Among nine histologic types of OT seen, ameloblastoma (48.9%), adenomatoid odontogenic tumor (19.6%) and odontogenic myxoma (8.7%) were predominant. Multicystic/solid and unicystic variants of ameloblastoma were diagnosed in 40 (89%) and 5 (11%) cases respectively.

Conclusions

Odontogenic tumors are relatively common in children and adolescents in Nigeria. One out of every 5 children and adolescents with tumors and tumor-like lesions of oral cavity and the jaws seen in this study had a diagnosis of odontogenic tumor.

     

Langerhans cells in odontogenic tumours and cysts as detected by S-100 protein immunohistochemistry

Immunohistochemical demonstration of S-100 protein in Langerhans cells (LCs) was made in odontogenic epithelial tumours (71 cases), radicular cysts (40 cases), follicular cysts (28 cases), odontogenic keratocysts (11 cases), primordial cysts (7 cases) and fissual cysts (6 cases). With the use of polyclonal antiserum against S-100 protein, positive LCs, dendrical or irregular in shape were found in tumour or cystic epithelia, and sometimes in stromal connective tissue. Incidence of positive S-100 staining LCs was 11 cases out of 61 ameloblastomas, 22 cases out of 40 radicular cysts, 3 cases of 28 follicular cysts, and other lesions in both odontogenic tumours and cystic diseases lacked LCs. The cases with S-100 protein positive LCs were usually accompanied with a high degree of inflammatory infiltration in their lesions; on the contrary, the negative cases also generally lacked inflammatory responses.     

Homocysteine potentiates calcification of cultured rat aortic smooth muscle cells

Aortic calcification was demonstrated in experimental animal models of hyperhomocysteinemia. Mild hyperhomocysteinemia was associated with aortic calcification, suggesting a relationship between homocysteine (HCY) and the pathogenesis of aortic calcification. In the present study, the effect of HCY on vascular calcification was examined in calcifying and non-calcifying vascular smooth muscle cells (VSMCs). Cell calcification was induced by incubation of VSMCs with beta-glycerophosphate. Proliferation of VSMCs was studied by cell counting, 3H-thymidine (3H-TdR) and 3H-leucine (3H-Leu) incorporation. 45Ca accumulation, cell calcium content, and alkaline phosphatase (ALP) activity were measured as indices of calcification. The results showed that the proliferation of calcifying VSMCs, which was indicated by cell counting, 3H-TdR and 3H-Leu incorporation in calcifying VSMCs, was enhanced as compared with that of non-calcifying VSMCs. HCY promoted increases in cell number, 3H-TdR and 3H-Leu incorporation in both calcifying and non-calcifying VSMCs, but with more prominent effect in calcifying VSMCs. The stimulating effects of HCY on the three parameters in calcifying VSMCs were antagonized by PD98059, a specific inhibitor of mitogen activated protein kinase kinase (MAPKK). The ALP activity, 45Ca uptake, and calcium deposition in the calcifying VSMCs were greater than those in non-calcifying VSMCs. PD98059 had no effect on ALP activity, 45Ca uptake, and calcium deposition in calcifying VSMCs. HCY caused marked increases in 45Ca uptake and calcium deposition both in calcifying and non-calcifying VSMCs. HCY, however, enhanced ALP activity in the calcified VSMCs but not in the non-calcifying VSMCs. The non-calcifying VSMCs treated with HCY showed the same low ALP activity, as did the control VSMCs. In calcifying VSMCs, the HCY-induced increases in 45Ca uptake, calcium deposition, and ALP activity were also attenuated by PD98059. The results demonstrated that HCY potentiated VSMC calcification probably through the mechanisms by which HCY promotes atherosclerosis.     

Central Mucoepidermoid carcinoma of mandible – A case report and review of the literature

BACKGROUND: Primary central mucoepidermoid carcinoma of jaws is a rare lesion comprising 2-3% of all mucoepidermoid carcinomas reported in literature. CASE PRESENTATION: The case presented here illustrates the hypothesis that its specific pathogenesis is unknown. CONCLUSIONS: Mucoepidermoid carcinoma of the jaw is a rare tumour of unknown aetiology. Although about a 100 cases has been reported in literature, the speculation on its aetiopathogenesis has mainly centred on the pluripotential capabilities of the epithelial lining of odontogenic cysts.     

Follicle‐stimulating hormone impairs dental pulp stem cells odontogenic differentiation

In addition to bone, the dentin‐pulp complex is also influenced by menopause, showing a decreased regenerative capacity. High levels of follicle‐stimulating hormone (FSH) during menopause could directly regulate bone metabolism. Here, the role of FSH in the odontogenic differentiation of the dentin‐pulp complex was investigated. Dental pulp stem cells (DPSCs) were isolated. CCK‐8 assays, cell apoptosis assays, Western blotting (WB), real‐time RT‐PCR, alkaline phosphatase activity assays, and Alizarin Red S staining were used to clarify the effects of FSH on the proliferation, apoptosis and odontogenic differentiation of the DPSCs. MAPK pathway‐related factors were explored by WB assays. FSH and its inhibitor were used in OVX rats combined with a direct pulp‐capping model. HE and immunohistochemistry were used to detect reparative dentin formation and related features. The results indicated that FSH significantly decreased the odontogenic differentiation of the DPSCs without affecting cell proliferation and apoptosis. Moreover, FSH significantly activated the JNK signalling pathway, and JNK inhibitor partly rescued the inhibitory effect of FSH on DPSC differentiation. In vivo, FSH treatment attenuated the dentin bridge formation and mineralization‐related protein expression in the OVX rats. Our findings indicated that FSH reduced the odontogenic capacity of the DPSCs and was involved in reparative dentinogenesis during menopause.     

Long non-coding RNA H19/SAHH axis epigenetically regulates odontogenic differentiation of human dental pulp stem cells

Long noncoding RNAs (lncRNAs) are emerging as important regulators in molecular processes and may play vital roles in odontogenic differentiation of human dental pulp stem cells (hDPSCs). However, their functions remain to be elucidated. As lncRNA H19 is one of the most classical lncRNA, which plays essential roles in cellular differentiation, thus we explored the effects and mechanisms of H19 in odontogenic differentiation of hDPSCs. Stable overexpression and knockdown of H19 in hDPSCs were constructed using recombinant lentiviruses containing H19 and short hairpin-H19 expression cassettes, respectively. Alkaline phosphatase (ALP) assay, Alizarin red staining assay, von kossa staining, quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescent staining results indicated that overexpression of H19 in hDPSCs positively regulates the odontogenic differentiation of hDPSCs, while knockdown of H19 in hDPSCs inhibits odontogenic differentiation of hDPSCs. Further, we found that H19 promotes the odontogenic differentiation of hDPSCs through S-adenosylhomocysteine hydrolase (SAHH) epigenetically regulates the methylation and expression of distal-less homeobox (DLX3) gene. Herein, for the first time, we determined that H19/SAHH axis epigentically regulates odontogenic differentiaiton of hDPSCs by inhibiting the DNA methyltransferase 3B (DNMT3B)-mediated methylation of DLX3. Our findings provide a new insight into how H19/SAHH axis play its role in odontogenic differentiation of hDPSCs, and would be helpful in developing therapeutic approaches for dentin regeneration based on stem cells.     

Lipids of mineralizing epiphyseal tissues in the bovine fetus

Because lipids had been consistently detected histologically at sites of new calcification, the lipids of epiphyseal cartilage and bone in various stages of mineralization were examined. Lipids were extracted before and after demineralization and analyzed. Lipid content increased during proliferation and calcification of epiphyseal cartilage. Much less was seen in the adjacent cancellous bone; this corroborates histochemical findings. Similar phospholipid compositions were seen in the total lipids of cartilage and bone. Neutral (dipolar) phospholipids accounted for nearly 90% of the total lipid P and were almost completely extracted before demineralization. Serine- and inositol-containing phospholipids and two other, unidentified, acidic lipids could not be effectively extracted from calcifying tissues until after demineralization. Since the extraction of the acidic lipids was closely related to the degree of mineralization, it is possible that they form part of a lipoprotein-mineral complex in the calcifying matrix. Lysophospholipids were detected in all extracts, but primarily in those made after decalcification. It is concluded that acidic lipids are mainly responsible for the sudanophilia detected histologically at sites of new calcification.     

Spectrum of karyotypic aberrations in cultured human meningiomas

Twenty-two unselected cases of meningioma were initiated in tissue culture on an extracellular matrix derived from bovine corneal endothelial cells. The cultures were available for karyotypic analysis at passages 1 to 5, representing cultivation periods of up to two months. Histologically, the meningiomas were meningiotheliomatous (16 cases), fibrous (1 case), angiotheliomatous (1 case), microcystic (2 cases), and parenchymatous (2 cases). Two of the meningotheliomatous cases had histological signs of malignancy, another case showed increased signs of proliferation, and two cases were recurrences, one after a complete course of irradiation. In five cases no structural chromosome aberrations were found. Monosomy of chromosome 22 was found in six cases and was associated with other random aberrations. Clonal or random aberrations without monosomy 22 were present in 11 cases, including one case with trisomy 7 and another case with a stable translocation marker, t(4;7). In these latter two cases, EGF-receptor binding was not elevated, compared to other meningiomas. Our results illustrate that, in addition to the frequent involvement of chromosome 22, numerous other individual clonal karyotype aberrations exist in meningioma cell populations, reflecting the heterogeneity of biological and pathological findings.     

Nuclear morphometric features of epithelial cells lining keratocysts

OBJECTIVE: To investigate the nuclear morphometric features of epithelial cells lining keratocysts and some other odontogenic cysts. STUDY DESIGN: All cases were selected from the archives of the Department of Pathology, Gülhane Military Medical Academy, as follows: 20 keratocysts and 10 dentigerous and 10 radicular cysts. Nuclear morphometric variables were measured on hematoxylin and eosin-stained histologic slides. Basal and intermediate cells of the epithelium were evaluated separately. Nuclei of the cells were outlined interactively and measured using a specially written macro program. Area, feret ratio (ratio of the longest nuclear axis to the shortest one) and circularity (F circle) of the nuclei were calculated. Additionally, nuclear densitometric analysis was performed on the keratocyst cases. RESULTS: The number of cells in the basal layer (cell density) was higher in keratocysts than in other cysts. The mean nuclear area of basal cells was smaller than of intermediate cells in both keratocysts and other cysts (P < .001). The feret ratio values revealed that basal cell nuclei of keratocysts were more ovoid as compared to those of other cysts (P < .001). Nuclear densitometric findings showed that the DNA indices of all keratocyst cases were close to 1.0, and the cells were considered diploid. CONCLUSION: Increased cell density, a more ovoid nuclear shape and more variation in the size of basal layer cell nuclei in keratocysts were helpful in differentiating these lesions from other odontogenic cysts.     

Morpho-functional changes in human tendon tissue

Insertion tissue biopsies of right arm common extensor tendons from 11 patients with chronic lateral epicondylitis were processed for light and electron microscopy. The subjects were aged between 38 and 54 years (only one was 25). The specimens showed a variety of structural changes such as biochemical and spatial alteration of collagen, hyaline degeneration, loss of tenocytes, fibrocartilage metaplasia, calcifying processes, neovascularization and vessel wall modifications. Tissue alterations were evident in limited zones of the tendon fibrocartilage in which the surgical resection was generally visible. The areas where the degenerative processes were localized, were restricted and in spatial contiguity with morphologically normal ones. The observed cases presented histological and electron microscopic findings that characterize lateral epicondylitis as a degenerative phenomenon involving all tendon components.     

Cholestane-3beta, 5alpha, 6beta-triol promotes vascular smooth muscle cells calcification

Oxysterols found in atherosclerotic plaque may be associated with vascular calcification. We investigated the effect of oxysterol cholestane-3beta, 5alpha, 6beta-triol (Triol) on in vitro calcification of rat vascular smooth muscle cells (VSMCs). In vitro calcification was induced by incubation of VSMCs with beta-glycerophosphate. Calcifying nodule formation, calcium deposition in extracellular matrix, and alkaline phosphatase (ALP) activity were measured as indices of calcification. Because apoptotic bodies can serve as nucleation sites for calcification, apoptosis of calcifying VSMCs was determined by Hoechst 33258 staining, TUNEL, and FITC-labeled annexin V/PI double staining. The calcium deposition and ALP activity in calcifying VSMCs were much higher than those in non-calcifying VSMCs. Triol increased calcifying nodule formation, calcium deposition, ALP activity, and apoptosis of nodular cells in calcifying VSMCs. As determined by 2,7-dichlorofluorescein fluorescence, Triol induced the generation of reactive oxygen species (ROS) in calcifying VSMCs dose- and time-dependently. Triol-induced increases in calcium deposition, ALP activity, apoptosis, and ROS generation were all attenuated by antioxidant vitamin C plus vitamin E (VC + VE). The results demonstrated that Triol promoted VSMCs calcification through direct increase of ALP activity and apoptosis, probably by ROS-related mechanism.     

Antibodies against the organic matrix in scleractinians: a new tool to study coral biomineralization

Soluble organic matrix (SOM) synthesis and secretion were investigated in two scleractinian corals using antibodies raised against this organic matrix. Results demonstrate that even if other cell types, including zooxanthellae, can supply precursors for SOM synthesis, only calicoblastic cells facing the skeleton are directly responsible for the synthesis and secretion of the SOM components. Results also indicate that, as is the case for other biominerals, skeleton formation is biologically controlled and not chemically dominated as originally believed. In addition to advancing the understanding of mechanisms of coral biomineralization, these antibodies could have numerous applications: for example as markers of skeletogenesis, as tools for cell culture, and in comparative studies among calcifying organisms.     

Pilomatrixoma presenting as a parotid mass

A rare case of calcifying epithelioma of Malherbe presenting as a large parotid mass is reported in this paper. Preoperative evaluation and considerations are discussed. An exact diagnosis and definitive treatment in this patient consisted of superficial parotidectomy and histologic study.