Proliferative Verrucous Leukoplakia Presenting as a Ring Around the Collar and Cancer: A Case Report.

Proliferative verrucous leukoplakia (PVL) is an oral mucosa lesion with a high rate of malignant transformation. The diagnosis is often difficult, especially when the initial lesion is a simple homogeneous white leukoplakia, and when located only on the gingiva or palate. Moreover, the anatomopathological analysis is non-specific in the initial stages. The gingival PVL localisation (gPVL) is described as the most aggressive form with the highest rate of malignant transformation. Cases with a unique gingival localisation are rare, described with a "ring around the collar" clinical form. Considering the difficulty of early diagnosis of gPVL, we report the case of a 72-year-old woman, who presented "white lesions on her gingiva" with a slight discomfort in February 2019. The lesion was initially limited to the buccal part of the mandibular right gingiva, but rapidly extended to all the lingual and buccal mandibular gingiva during follow-up, leading to a diagnosis of gPVL. Two biopsies were performed, which concluded a verrucous hyperplasia and papilloma with a lichenoid part. The diagnosis of gPVL was made after a six-month follow-up based on clinical and anatomopathological factors. The gPVL transformed into a squamous cell carcinoma (SCC) after 18 months of follow-up. A surgical right mandibular bone excision with an autologous left fibula graft associated with radiotherapy was performed. Three years after the surgery, the patient remains under monitoring, with several gPVL and SCC recurrences treated. This case highlights that gPVL is a rare and aggressive form of PVL, with a high risk of fast malignant transformation. Knowledge about its aetiology, anatomic pathology, and biological markers is highly needed to speed up the diagnosis and develop specific follow-up and treatment.

Epithelial-Myoepithelial Carcinoma of the Maxilla Arising From Minor Salivary Glands of Hard Palate: A Rare Case Report.

Epithelial-myoepithelial carcinoma is a rare malignant neoplasm of salivary glands. It is specifically found in the major salivary glands. The cases that emerge from minor salivary glands are rarely described. Histologically, it commonly exhibits a characteristic biphasic pattern consisting of epithelial and myoepithelial components. The histopathological resemblance to other benign and malignant neoplasms that also display myoepithelial characteristics makes the differential diagnosis challenging. Each differential diagnosis requires a very different management approach. Considering the difficulties of anatomopathological diagnosis and the rarity of epithelial-myoepithelial carcinomas emerging from minor salivary glands, we report a rare epithelial-myoepithelial carcinoma case of minor salivary glands in a 58-year-old woman. She was referred for a palatal swelling, evolving for more than 35 years, and reported recent pain and nasal obstruction. The mucosal swelling was located in the left maxilla within the hard palate, of a 45-mm-long axis crossing the medial line and extending to the premaxilla, without cervical lymph node involvement. A computed tomography scan revealed a palatal lesion involving the left and the right maxilla. Furthermore, the superior alveolar process, both left and right maxillary sinuses, the nasal cavities, and the nasal septum were included in the lesion. The final diagnosis was difficult to confirm despite multiple biopsies and was determined only from the excised specimen. The diagnosis of this tumor was challenging due to the clinical and histological similarities with other salivary tumors. The aim of this case report is to shed light on the distinctive features of these tumors and explore optimal screening and related management strategies.

Oral Cavity Squamous Cell Carcinoma Risk Factors: State of the Art.

Head and neck (HN) squamous cell carcinomas (SCCs) originate from the epithelial cells of the mucosal linings of the upper aerodigestive tract, which includes the oral cavity, the pharynx, the larynx, and the sinonasal cavities. There are many associated risk factors, including alcohol drinking coupled with tobacco use, which accounts for 70% to 80% of HNSCCs. Human papilloma virus (HPV) is another independent risk factor for oropharyngeal SCC, but it is only a minor contributor to oral cavity SCC (OSCC). Betel quid chewing is also an established risk factor in southeast Asian countries. However, OSCC, and especially oral tongue cancer, incidence has been reported to be increasing in several countries, suggesting risk factors that have not been identified yet. This review summarizes the established risk factors for oral cavity squamous cell carcinomas and examines other undemonstrated risk factors for HNSCC.

Efficient isolation of human gingival stem cells in a new serum-free medium supplemented with platelet lysate and growth hormone for osteogenic differentiation enhancement.

BACKGROUND: The use of distant autografts to restore maxillary bone defects is clinically challenging and has unpredictable outcomes. This variation may be explained by the embryonic origin of long bone donor sites, which are derived from mesoderm, whereas maxillary bones derive from neural crest. Gingival stem cells share the same embryonic origin as maxillary bones. Their stemness potential and ease of access have been repeatedly shown. One limitation in human cell therapy is the use of foetal calf serum during cell isolation and culture. To overcome this problem, a new serum-free medium enriched with an alternative to foetal calf serum, i.e., platelet lysate, needs to be adapted to clinical grade protocols. METHODS: Different serum-free media enriched with platelet lysate at various concentrations and supplemented with different growth factors were developed and compared to media containing foetal calf serum. Phenotypic markers, spontaneous DNA damage, and stem cell properties of gingival stem cells isolated in platelet lysate or in foetal calf serum were also compared, as were the immunomodulatory properties of the cells by co-culturing them with activated peripheral blood monocellular cells. T-cell proliferation and phenotype were also assessed by flow cytometry using cell proliferation dye and specific surface markers. Data were analysed with t-test for two-group comparisons, one-way ANOVA for multigroup comparisons and two-way ANOVA for repeated measures and multigroup comparisons. RESULTS: Serum-free medium enriched with 10% platelet lysate and growth hormone yielded the highest expansion rate. Gingival stem cell isolation and thawing under these conditions were successful, and no significant DNA lesions were detected. Phenotypic markers of mesenchymal stem cells and differentiation capacities were conserved. Gingival stem cells isolated in this new serum-free medium showed higher osteogenic differentiation potential compared to cells isolated in foetal calf serum. The proportion of regulatory T cells obtained by co-culturing gingival stem cells with activated peripheral blood monocellular cells was similar between the two types of media. CONCLUSIONS: This new serum-free medium is well suited for gingival stem cell isolation and proliferation, enhances osteogenic capacity and maintains immunomodulatory properties. It may allow the use of gingival stem cells in human cell therapy for bone regeneration in accordance with good manufacturing practice guidelines.

Head to Knee: Cranial Neural Crest-Derived Cells as Promising Candidates for Human Cartilage Repair.

A large array of therapeutic procedures is available to treat cartilage disorders caused by trauma or inflammatory disease. Most are invasive and may result in treatment failure or development of osteoarthritis due to extensive cartilage damage from repeated surgery. Despite encouraging results of early cell therapy trials that used chondrocytes collected during arthroscopic surgery, these approaches have serious disadvantages, including morbidity associated with cell harvesting and low predictive clinical outcomes. To overcome these limitations, adult stem cells derived from bone marrow and subsequently from other tissues are now considered as preferred sources of cells for cartilage regeneration. Moreover, with new evidence showing that the choice of cell source is one of the most important factors for successful cell therapy, there is growing interest in neural crest-derived cells in both the research and clinical communities. Neural crest-derived cells such as nasal chondrocytes and oral stem cells that exhibit chondrocyte-like properties seem particularly promising in cartilage repair. Here, we review the types of cells currently available for cartilage cell therapy, including articular chondrocytes and various mesenchymal stem cells, and then highlight recent developments in the use of neural crest-derived chondrocytes and oral stem cells for repair of cartilage lesions.

Involvement of neural crest and paraxial mesoderm in oral mucosal development and healing.

Tissue engineering therapies using adult stem cells derived from neural crest have sought accessible tissue sources of these cells because of their potential pluripotency. In this study, the gingiva and oral mucosa and their associated stem cells were investigated. Biopsies of these tissues produce neither scarring nor functional problems and are relatively painless, and fresh tissue can be obtained readily during different chairside dental procedures. However, the embryonic origin of these cells needs to be clarified, as does their evolution from the perinatal period to adulthood. In this study, the embryonic origin of gingival fibroblasts were determined, including gingival stem cells. To do this, transgenic mouse models were used to track neural crest derivatives as well as cells derived from paraxial mesoderm, spanning from embryogenesis to adulthood. These cells were compared with ones derived from abdominal dermis and facial dermis. Our results showed that gingival fibroblasts are derived from neural crest, and that paraxial mesoderm is involved in the vasculogenesis of oral tissues during development. Our in vitro studies revealed that the neuroectodermal origin of gingival fibroblasts (or gingival stem cells) endows them with multipotential properties as well as a specific migratory and contractile phenotype which may participate to the scar-free properties of the oral mucosa. Together, these results illustrate the high regenerative potential of neural crest-derived stem cells of the oral mucosa, including the gingiva, and strongly support their use in cell therapy to regenerate tissues with impaired healing.

Chronic non-suppurative mandibular osteomyelitis with proliferative periostitis: A review.

Chronic non-suppurative osteomyelitis (CNSO) is a chronic bone disease and may be associated with a reparative periosteum entity called proliferative periostitis (PP). This condition rarely affects the maxillofacial region. Mandibular cases were already described for an infectious dental cause, often with an "onion skin" radiographic aspect, but some rare reported cases showed no obvious etiology. They represent a challenge for diagnosis because of possible misdiagnosis leading to unsuccessful or inappropriate treatment attempts. An uncommon case of mandibular CNSO associated with PP in a 9-year-old boy with no obvious infectious or inflammatory causes is reported. Clinical and radiographic examinations revealed a swelling in the left hemimandible, associated with multiple osteolytic areas inside both medullary and newly formed periosteal bone and cortical bone perforations. Recovery signs were seen after a 22-month follow-up period, and radiographic signs of bone healing were observed. From this new case report, a review of the literature was performed on reported cases of mandibular CNSO with PP, and discussed the etiological, clinical, radiologic, and therapeutic aspects of this pathology. This work highlights the importance of considering CNSO with PP in the differential diagnosis of one-sided painless mandibular swellings, even in the absence of an obvious cause.

Validation of Housekeeping Genes to Study Human Gingival Stem Cells and Their In Vitro Osteogenic Differentiation Using Real-Time RT-qPCR.

Gingival stem cells (GSCs) are recently isolated multipotent cells. Their osteogenic capacity has been validated in vitro and may be transferred to human cell therapy for maxillary large bone defects, as they share a neural crest cell origin with jaw bone cells. RT-qPCR is a widely used technique to study gene expression and may help us to follow osteoblast differentiation of GSCs. For accurate results, the choice of reliable housekeeping genes (HKGs) is crucial. The aim of this study was to select the most reliable HKGs for GSCs study and their osteogenic differentiation (dGSCs). The analysis was performed with ten selected HKGs using four algorithms: ΔCt comparative method, GeNorm, BestKeeper, and NormFinder. This study demonstrated that three HKGs, SDHA, ACTB, and B2M, were the most stable to study GSC, whereas TBP, SDHA, and ALAS1 were the most reliable to study dGSCs. The comparison to stem cells of mesenchymal origin (ASCs) showed that SDHA/HPRT1 were the most appropriate for ASCs study. The choice of suitable HKGs for GSCs is important as it gave access to an accurate analysis of osteogenic differentiation. It will allow further study of this interesting stem cells source for future human therapy.