Congenital Epulis: A Case and Review of the Literature.

Congenital epulis is an unusual benign oral mucosal lesion in newborns with no tendency to recur after excision. The histogenesis of the lesion is unknown, but it is believed to be of mesenchymal origin. We describe a case of congenital epulis (20×10 mm) in the mandibular gingiva of a newborn. The mass, which was smooth-surfaced and pedunculated with a healthy color, was surgically removed at 5 months post-birth. Histologically, the tumor consisted mainly of large eosinophilic granular cells. Immunohistochemical studies revealed intense staining for vimentin, STRO-1, and CD44, suggesting that it was derived from mesenchymal cells. The literature and immunohistochemical profile of congenital epulis are also discussed.

A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.

In contrast to long bone osteosarcoma, mandibular osteosarcoma is highly heterogeneous and morphologically overlaps with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction and sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type 2) overexpression, GNAS (guanine nucleotide-binding protein/α subunit) mutations, and amplification of MDM2 and/or RASAL1 (RAS protein activator like 1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other 3 contained a coamplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcomas are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement for closer follow-up and more aggressive management.

Mandible ameloblastoma with lung metastasis: a rare case report.

BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region. Although the histopathological manifestation of ameloblastoma is benign, it has unique biological behavior, for example local invasion and recurrence repeatedly. A few case of ameloblastoma was locally aggressive growth, and rarely metastasis to other tissue, for example the lungs, lymph nodes, and spine. CASE REPORT: A 64-year-old Chinese man, diagnosed with metastatic ameloblastoma, was treated with palliative chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin for six cycles, and radiotherapy for 50 Gy after the last cycle chemotherapy. During the surveillance CT scan after the therapy, the tissues of the tumor were nearly complete response. CONCLUSION: The purpose of this study was to report a case of a patient with a right mandible ameloblastoma that recurred repeatedly and metastasized into bilateral lung. After the chemotherapy and radiotherapy, the tissues of the tumor were nearly complete response. This case is interesting because it investigated the diagnosis and treatment of the malignancy ameloblastoma, as this may help diagnose and treatment for clinician to the metastatic ameloblastoma.

Podoplanin, E-cadherin, ß-catenin, and CD44v6 in recurrent ameloblastoma: their distribution patterns and relevance.

BACKGROUND: Ameloblastoma is a benign but locally infiltrative odontogenic epithelial neoplasm with a high risk for recurrence. Podoplanin, a lymphatic endothelium marker, putatively promotes collective cell migration and invasiveness in this neoplasm. However, its role in the recurrent ameloblastoma (RA) remains unclear. As morphological, signaling, and genetic differences may exist between primary and recurrent tumors, clarification of their distribution patterns is of relevance. MATERIALS AND METHODS: Podoplanin was examined immunohistochemically in conjunction with E-cadherin, ß-catenin, and CD44v6 in 25 RA. Immunostaining according to tumor area, cellular type, and location, and relationship of these proteins were analyzed. Findings were compared with 25 unrelated primary ameloblastomas (UPA). RESULTS: All four proteins were detected in RA and UPA samples. Expression rates for each protein were not significantly different between these two groups. RA demonstrated significant upregulation of podoplanin at the invasive front (P < 0.05), whereas upregulation of ß-catenin and CD44v6 and downregulation of E-cadherin at this site were not statistically significant (P > 0.05). Immunolocalization for all four proteins was predominantly membranous and less frequently cytoplasmic. Pre-ameloblast-like cells were podoplanin(+) /CD44v6(-), while stellate reticulum-like cells were podoplanin(-)/CD44v6(+). Acanthomatous, granular cell, and desmoplastic variants in both RA and UPA were podoplanin(-/low) but stained weak-to-moderate for E-cadherin, ß-catenin, and CD44v6. Stromal fibroblasts and lymph channels were variably podoplanin-positive. CONCLUSIONS: Podoplanin, ß-catenin, and CD44v6 upregulation at the tumor invasive fronts in RA and UPA supports a differential regulatory role by these molecules in mediating collective cell migration and local invasiveness. E-cadherin downregulation suggests altered cell adhesion function during tumor progression.

The relationship between ezrin and podoplanin expressions in keratocystic odontogenic tumors.

BACKGROUND: The aims of this study were to investigate the immunolocalization of ezrin and its relationship with the podoplanin expression in keratocystic odontogenic tumors. MATERIAL AND METHODS: The immunohistochemical expressions of ezrin and podoplanin by odontogenic epithelium were evaluated in keratocystic odontogenic tumors using monoclonal antibodies. RESULTS: Our results showed strong cytoplasmic ezrin and membranous podoplanin expressions in basal epithelial layer of all keratocystic odontogenic tumors. The cytoplasmic and membranous ezrin expressions were also detected in suprabasal epithelial layers of tumors. Statistically significant difference between cellular immunolocalization of ezrin and podoplanin odontogenic epithelium were found by Wilcoxon's test (p < 0.05). No correlation between both proteins in keratocystic odontogenic tumors was detected by Spearman test. CONCLUSIONS: These results suggest that ezrin and podoplanin may contribute to the expansive growth and local invasiveness of keratocystic odontogenic tumors. Additionally, as both proteins were overexpressed by odontogenic epithelium, their possible roles need to be further explored in benign odontogenic tumors.

Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma.

BACKGROUND: Sonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB). METHODS: We quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non-neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry. RESULTS: We observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521). CONCLUSIONS: Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors.

Primary neuroendocrine carcinoma in oral cavity: two case reports and review of the literature.

Neuroendocrine carcinoma (NEC) is a tumor that occurs in different locations, particularly the lungs and larynx. The oral cavity is a rare site for a primary NEC. This report describes 2 cases of primary NEC in the oral cavity. Case 1 occurred in the anterior mandibular gingiva in a 25-year-old woman and presented with a special histologic appearance. This patient showed no evidence of recurrence 13 months after marginal resection of the anterior mandible. Case 2 was a primary NEC with some foci of squamous cell differentiation arising in the right buccal region in a 38-year-old woman. This patient showed no evidence of disease 8 months after tumor resection and postoperative iodine-125 brachytherapy. To the best of the authors' knowledge, case 1 is the youngest patient with NEC reported in the oral cavity to date in the English-language literature, and case 2 is the first report of a primary NEC in the buccal region.

Conventional chondrosarcoma in a survivor of rhabdoid tumor: enlarging the spectrum of tumors associated with SMARCB1 germline mutations.

SMARCB1 germline mutations mainly predispose to rhabdoid tumors. However, less aggressive tumors with a later onset have also been reported in a context of SMARCB1 constitutional mutation-that is, schwannomatosis and meningiomatosis. No other tumor type has formally been observed in such a context thus far. We report on a patient treated for a thoracic malignant rhabdoid tumor at 8 years of age who subsequently developed a mandibular conventional chondrosarcoma at 13 years of age. Both tumors showed a loss of BAF47 expression. The malignant rhabdoid tumor exhibited a large 22q11.2 deletion and an intragenic deletion of SMARCB1 (exons 1 to 3), thus leading to a biallelic inactivation. A 2.8 Mbp deletion encompassing SMARCB1 was found in the germline. This context was a strong incentive to investigate SMARCB1 alterations in the second tumor. As expected, the chondrosarcoma showed the large 22q11.2 deletion but also an additional c.243C>G(p.Tyr18X) premature stop codon in the remaining allele. This report relates for the first time a pediatric conventional chondrosarcoma to the wide family of SMARCB1-deficient tumors. Moreover, we report here the first case of conventional chondrosarcoma arising in a context of constitutional SMARCB1 deletion and, thus, enlarge the spectrum of this tumor predisposition syndrome.

Investigation of basement membrane proteins in a case of granular cell ameloblastoma.

Granular cell ameloblastoma is a rare, benign neoplasm of the odontogenic epithelium. A case of massive granular cell ameloblastoma in a 44-year-old Thai female is reported. Histopathological features displayed a follicular type of ameloblastoma with an accumulation of granular cells residing within the tumor follicles. After treatment by partial mandibulectomy, the patient showed a good prognosis without recurrence in a 2-year follow-up. To characterize the granular cells in ameloblastoma, we examined the expression of basement membrane (BM) proteins, including collagen type IV, laminins 1 and 5 and fibronectin using immunohistochemistry. Except for the granular cells, the tumor cells demonstrated a similar expression of BM proteins compared to follicular and plexiform ameloblastomas in our previous study, whereas the granular cells showed strong positivity to laminins 1 and 5 and fibronectin. The increased fibronectin expression in granular cells suggests a possibility of age-related transformation of granular cells in ameloblastoma.

Synergistic increase in osteosarcoma cell sensitivity to photodynamic therapy with aminolevulinic acid hexyl ester in the presence of hyperthermia.

OBJECTIVE: We observed that two osteosarcoma cell lines from the same tumor displayed marked differences in their sensitivities to photodynamic therapy (PDT) with aminolevulinic acid hexyl ester (hALA-PDT). We investigated why these two closely related lines had different hALA-PDT sensitivities and whether the PDT phototoxicity of the less sensitive cell line could be increased by a simultaneous application of hyperthermia (HT). METHODS: Flow cytometry was used to evaluate the intracellular accumulation of protoporphyrin IX (PpIX), a metabolic product of aminolevulinic acid, in two human mandibular osteosarcoma cell lines (HOSM-1 and HOSM-2) treated with HT, hALA-PDT, or hALA-PDT combined with HT (PDT + HT). With hALA-PDT, cells treated with 0.2 mM hALA were irradiated with a light dose of 10-80 J/cm(2) from a near-infrared irradiator. With PDT + HT, the cells were treated as for hALA-PDT except that the temperature was raised to 43.5 degrees C during irradiation. RESULTS: At 6 h after hALA treatment, HOSM-2 cells carried about 1.53-fold more PpIX than HOSM-1 cells. With hALA-PDT, the survival rate for HOSM-1 cells treated with 80 J/cm(2) irradiation was 35.7%, while that for HOSM-2 cells treated with 40-80 J/cm(2) was below 12%. With PDT + HT, the survival rate for HOSM-1 and HOSM-2 cells treated with 80 J/cm(2) irradiation was 14.1% and 10.7%, respectively. CONCLUSION: A combination therapy comprising hALA-PDT + HT treatment may be very useful for the treatment of tumors containing cells that are insensitive to hALA-PDT, such as the HOSM-1 cell line described in this study.

Low-grade gingival leiomyosarcoma in a child.

Leiomyosarcoma (LMS) of the oral cavity, a rare mesenchymal tumor exhibiting smooth-muscle differentiation, is extremely uncommon in childhood. The most frequent location of childhood LMS is the gastrointestinal tract, particularly the stomach. The purpose of this paper is to report a case of leiomyosarcoma affecting the gingival tissues and mandible of a 9-year-old girl with peculiar clinical, microscopic, and radiographic features. Clinical and radiographical examinations revealed a gingival growth affecting the primary mandibular right first molar with inflammatory features. The lesion was initially suspected to be pyogenic granuloma and was removed by excisional biopsy. Microscopic findings showed a hypercellular proliferation of mesenchymal spindle cells, suggesting malignant spindle cell neoplasm. Immunohistochemical, histochemical, and radiographic studies were undertaken, and the final diagnosis established was a low-grade leiomyosarcoma in the gingiva.

"Ameloblastoma with mucous cells": review of literature and presentation of 2 cases.

Ameloblastoma, a relatively rare benign odontogenic tumor; originates from the odontogenic epithelium and has been studied extensively for its unique clinicopathologic features. It usually exhibits a range of histopathologic features, such as follicular, plexiform, acanthomatous, granular, basal cell, and desmoplastic variants, which are well recognized. The occurrence of mucous cells in ameloblastoma is an exceptionally rare phenomenon and to date only 4 well established cases have been reported. In the present paper, 2 more cases of ameloblastoma showing evidence of mucous cells are reported, along with a review of pertinent literature. A brief clinicopathologic analysis of all the reported cases, an insight into possible histogenesis of these cells in ameloblastoma, and diagnostic difficulties encountered due to this finding are also discussed. An interesting finding in our review is that all of the the cases of ameloblastoma exhibiting mucous cells occurred in the anterior region of the jaw with a predilection to mandible. Histologically, the mucous cells in most cases were associated with areas of squamous metaplasia, suggesting a close relation between these 2 cell types.

Radiopacity in syndrome keratocystic odontogenic tumour.

Dystrophic calcification or radiopacity in syndromatic keratocystic odontogenic tumours is not uncommon although there have not been many reports. A case of dystrophic calcification in the cavity of the cyst of a patient with a syndromatic keratocystic odontogenic tumour was detected on panoramic radiograph and CT. The component of the calculus was analysed by Fourier transform infrared spectrum.

Benign fibrous histiocytoma in the condylar process of the mandible: Case report.

A 48-year-old man was referred for investigation of an asymptomatic radiolucent lesion in the mandible. The margin was partly irregular, and there was no peripheral sclerosis. The tumour was composed of histiocytic cells, spindle cells, and fibrous tissue. Immunohistochemical analysis showed that the tumour cells stained for CD68 and vimentin, and not for cytokeratin, smooth muscle actin, S-100 protein, or CD34. The tumour was therefore diagnosed as a benign fibrous histiocytoma.

[Pediatric mandibular myofibromatosis]. / Myofibromatose infantile de la mandibule.

INTRODUCTION: Pediatric myofibromatosis is a rare tumor in neonates and children. Two forms are described, solitary and multicentric, the solitary type is more common and is localized mainly on the head and the neck, mandible involvement is rare. The aim of this article was to report the anatomoclinical and therapeutic features of this pediatric tumor in a case as well as its follow-up. CASE REPORT: A 10-year-old girl was brought to consultation for a lower left gingival swelling 5 cm in diameter, forming a unit with the mandibular bone. The volume had gradually increased over the last 12 months. Imagery revealed the presence of an osteolytic tumor benign in aspect, but locally aggressive. Conservative surgery was performed. The diagnosis of pediatric myofibromatosis was confirmed. Evolution was excellent and after three years of follow-up, there was no evidence of relapse. DISCUSSION: Pediatric myofibromatosis often presents as a painless, well-circumscribed, solid nodule. Imagery is very useful to assess lesion extension and for the therapeutic follow-up. The diagnosis is made on anatomopathological findings and immunohistochemical assessment. The treatment of the solitary myofibromatosis is primarily surgical and its prognosis is excellent contrary to the multicentric form.

Mesenchymal chondrosarcoma of the left coronoid process: report of a unique case with clinical, histopathologic, and immunohistochemical findings, and a review of the literature.

Mesenchymal chondrosarcoma (MCS) is a rare malignant neoplasm of bone or soft tissue origin, locally aggressive, rare in the oral cavity, of which fewer than 100 cases have been reported in the English literature. This is the first case described of this type of tumor affecting the coronoid process. The report describes a unique case of MCS in a 64-year-old woman who presented with swelling and pain at the left preauricular area just anterior to the left tragus. An orthopantomograph showed a large mass in the temporomandibular joint involving the left coronoid process and extending to the left ramus of the mandible. Biopsy and histopathologic examination revealed a biphasic pattern, composed of an undifferentiated small round-cell component surrounding a myxoid of malignant cartilage; a focally pericytic vascular pattern resembling hemangiopericytoma was observed. Immunohistochemical studies were positive for CD99, S-100, and CD45 and negative for desmin, actin, chromogranin, epithelial membrane antigen (EMA), and cytokeratin. The tumor was treated by extensive hemimandibulectomy followed by reconstruction of the area. There was no evidence of disease at the 8-year follow-up. Previously reported cases are reviewed as well.

Nonneural granular cell tumor of the oral cavity: a case report and review of the literature.

Nonneural granular cell tumors (NNGCTs) are rare benign neoplasms originally described in 1991 by Leboit et al. Typical granular cell tumors (GCTs) are commonly encountered in the oral cavity, but NNGCTs, unlike GCTs, are S-100 negative and may display cytologic atypia, allowing for misdiagnosis as a more aggressive lesion. We report a case of a 43-year-old male with a lesion of the mandible that we believe to be the first intraoral example of an NNGCT.