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Background Emerging evidence points toward the idea that oral squamous cell carcinoma (OSCC) invasiveness can be attributed to the existence of a small subpopulation of cancer stem cells (CSCs) in the bulk of the tumor. However, knowledge about the existence of CSCs in the OSCC close margins and their possible role in determining OSCC phenotypes is still far from being satisfactory. Methods We analyzed the expression of 13 CSCs marker genes in 72 primary tissue specimens (24 core tumors, 24 pathologically negative close margins, and 24 healthy distant margins), obtained from 24 OSCC patients upon surgical resection, by using Real-Time PCR. TGCA and GEO databases were used to confirm gene expression analyses. CAL27 and SCC15 OSCC cell lines were used to perform in vitro siRNA-mediated knockdown of SOX2 both in 2D and 3D cultures. The effects of SOX2 knockdown on OSCC cell lines were assessed by wound healing assays and 3D tumor spheroids formation assays. Cytofluorimetric apoptosis assays were used to test the effects of SOX2 knockdown on cisplatin sensitivity. Live imaging was used to monitor OSCC cells migration and spheroidogenesis. Results We found that BMI1, CD44, SOX2, OCT4, UBE2C, CXCR4 were significantly up-regulated, while IGF1-R, KLF4, ALDH1A1, CD133, FAM3Cappeared down-regulated in the tumor core vs healthy distant margin. No differences were observed for NANOG and RRM2. SOX2, CD44, and CXCR4 were upregulated also in the close margin vs healthy distant margin. The high expression of SOX2 both in the tumor core and in the close margin significantly correlated with tumor size and lymph node compromise. In vitro experiments further showed that SOX2knockdown i) promotes the mesenchymal-to-epithelial transition and smooths the invasiveness, ii) attenuates the 3D tumor sphere-forming capacity and stemness-associated traits and iii) partially increases the sensitivity to cisplatin treatment of CAL27 and SCC15 cell lines. Conclusions Overall, our study shows that the OSCC close margins can retain CSC-specific markers even in the setting of negative histopathological diagnosis. In particular, SOX2 may represent a promising marker useful to predict a more aggressive OSCC phenotype and a suitable target to prevent local invasiveness.

Background: Medication-related osteonecrosis of the jaw (MRONJ) may be a severe side effect of bone-modifying agents. Objective: Pathologic fractures treatment in patients with MRONJ remains challenging. The authors reported a unique case of successful non-surgical management of a mandible fracture secondary to MRONJ. Methods: A 78-year-old osteoporotic woman with a 4-year history of oral bisphosphonate therapy and a compromised dental condition developed an MRONJ-related right mandibular body fracture. Treatment consisted of systemic antibiotic administration (amoxiclav and metronidazole) and chlorhexidine mouthwash. Results: Follow-up visits revealed progressive healing of the mandibular fracture with bone callus formation and complete recovery of the ipsilateral lip and chin sensitivity after one year. Conclusion: Non-surgical management of pathological fractures related to MRONJ might be of interest in patients that refuse any type of surgery, but preventive measures, such as careful dental examination, should be taken before start antiresorptive therapy and during the treatment. The authors reported the first case in the literature of successful management of a mandibular fracture secondary to MRONJ with only antibiotics and mouthwashes.

This study aimed to retrospectively evaluate the incidence of oral non-Hodgkin lymphoma (NHL) in patients referred to the Academic Hospital of the Magna Graecia University of Catanzaro from 2002 to 2020. A retrospective single-center study was performed. Patients with a histologically confirmed diagnosis of oral NHL were included. Demographic data and clinical parameters were digitally recorded, focusing on the NHL-specific localization and symptomatology. The study sample was evaluated by analyzing descriptive statistics with absolute and relative frequencies. A total of 26 patients with intraoral NHL were identified with a progressive increase in NHL occurrence during the observation period. Clinical manifestations included swelling/mass (80.7%), eventually associated with pain and ulcerations. The most common localizations were in soft tissues: buccal mucosa (38.4%), tongue (19.2%), gingiva (11.5%), cheek (11.5%). Oral NHL is rare. Clinical manifestations were unspecific, so a misdiagnosis could occur. The extranodal B-cell form of oral NHL, particularly diffuse large B-cell lymphoma, was the most common frequent oral NHL in this southern Italian population, with a progressively increased occurrence in almost 20 years.

Medication-related osteonecrosis of the jaw (MRONJ) is a well-recognized complication of drug therapies for bone metabolic disorders or cancer related to administration of antiresorptive (bisphosphonates and denosumab) and antiangiogenic drugs. This report describes an advanced and unusual case of stage III peri-implantitis-induced MRONJ involving the right upper jaw which was attempting to self-exfoliate. A 61-year-old male patient, rehabilitated with the placement of two implants when he was still healthy, was suffering from metastatic renal cancer previously treated with bevacizumab, interleukin-2, zoledronic acid, denosumab, cabozantinib and nivolumab. He had been under treatment of nonsurgical therapy over a year, based on antibiotic and antiseptic mouth rinse, without improvement of oral conditions. Surgical treatment consisted of massive sequestrectomy and complete surgical debridement of necrotic bone tissues. The specimen was sent for histopathologic analysis, which confirmed bone tissue necrosis with no evidence of metastatic disease. Two-month follow-up revealed a considerable life quality improvement. Although this complication is well known, the uniqueness of this case is given by its severity, related to the administration of multiple antiresorptive and antiangiogenic drugs, by the natural response of the oral cavity with the almost complete self-exfoliation of the massive necrotic zone. This case is emblematic in highlighting the controversies in the management of MRONJ, which certainly require effective collaboration of the multidisciplinary health care team that could improve patient safety and reduce the risk of developing MRONJ.

Oral lichen planus (OLP) is a chronic immune-mediated disease that affects the oral cavity. Topical steroids are considered the treatment of choice for painful lesions of OLP. The aim of this split-mouth study was to compare the efficacy of platelet-rich fibrin (PRF) and triamcinolone acetonide (TA) injective therapies in patients with symptomatic OLP.Participants with symptomatic OLP were recruited in the Academic Hospital of Magna Graecia University of Catanzaro, Italy. Once a week for a month, patients randomly received a 0.5-mL TA injection in one buccal mucosa and 1-mL PRF injection in the opposite side. The measured outcomes were reduction of the lesions area and symptomatology modifications using visual analogue scale (VAS) score RESULTS: Four weeks after the last injections, an average reduction of 59.8% in the lesion extension and an average reduction of 47.6% in the VAS score for PRF-treated sites were observed; the same variation for TA-treated sites was respectively of 59.2% and 40%. There were no statistically significant differences between the two groups.PRF was effective in reducing OLP lesions extension and symptomatology, and it seems to be as effective as TA. Additional data should be collected with a larger sample size, at a longer follow-up and on the PRF lowest effective dose.Current treatment options for OLP are limited. The study proved benefits of PRF injections in management of painful lesions of OLP comparable with TA.

The COVID‐19, which appeared to originate in China in December 2019, has spread worldwide pandemically. In this commentary, authors described this new challenge for dental education using the recent literature and experience gained in the Italian University of Catanzaro.

Interleukin-6 (IL-6) is a potent inflammatory cytokine that appears to play a key role in cancer growth and metastasis. In the present study, the effects of IL-6 receptor (IL-6R) on breast cancer aggressiveness and bone metastases were investigated.MDA-MB-231 (MDA-231) cells were treated in the presence or absence of anti-human IL-6 receptor (IL-6R) monoclonal antibody and examined with respect to cell survival. The expressions of signal transducer and activator of transcription 3 (Stat3), vascular endothelial growth factor (VEGF), and receptor activator of NF-κB (RANK) were analyzed by SDS-PAGE and immunoblotting. MDA-231 cells were injected into the left ventricle of mice, and then anti-human IL-6R monoclonal antibody or saline was administered intraperitoneally for 28 days. After 28 days, the incidence of bone metastases was evaluated in the hind limbs by radiography and histology.Anti-human IL-6R monoclonal antibody reduced bone metastases in an animal model injected with MDA-231 cells on radiological and histomorphometric analyses. The mechanism of bone metastasis inhibition involved inhibited cell proliferation and decreased expressions of phospho-Stat3, VEGF, and RANK in MDA-231 cells.The results of the present study suggest that inhibition of IL-6 signaling may become a preventive therapeutic option for breast cancer and bone metastases.

OBJECTIVES Autofluorescence is considered a useful technique in the early detection of oral mucosal alterations. However, its efficacy to discriminate tumor margins is still under debate. The purpose of this pilot study was to confirm the existence of molecular divergence from the center of a lesion compared to white light and autofluorescence (VELscopeTM ) visualized margins in leukoplakia and oral carcinoma. MATERIALS AND METHODS Molecular divergence from the center of the lesion to white light and VELscopeTM defined margins was compared in patients with leukoplakia (n = 3) and oral carcinoma (n = 4). Expression profiling of 45 selected genes was performed through custom-made TaqMan arrays. Gene Ontology was used for biological pathway analysis. RESULTS Irrespective of pathology, the greatest molecular divergence existed between the center of the lesion and both white light and VELscopeTM margins. VELscopeTM and white light margins were also molecularly distinct in oral carcinoma samples. Indeed, the white light margin retained molecular abnormalities observed in the center of the lesion thus suggesting the existence of a "partially transformed" cell population. CONCLUSION Despite the limited low number of patients, our data confirm the benefit of combining autofluorescence with conventional oral examination in identifying surgical margins during biopsy procedures for leukoplakia and oral carcinoma.

Oral squamous cell carcinoma (OSCC) is often. [...]

The aim of this systematic review was to answer the question: Is the application of autologous platelet concentrates (APCs) effective in the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ)? A literature search of PubMed, Scopus, and Web of Science databases (articles published until June 30, 2019) was conducted, in accordance with the PRISMA statement, using search terms related to “platelet concentrate” and “osteonecrosis”. The Jadad scale was used to assess the quality of the articles. Fisher's exact test was used to evaluate eventual differences between groups. Of 594 articles, 43 were included in the review (8 for MRONJ prevention and 35 for MRONJ treatment). Out of a total of 1219 dental extractions recorded (786 with APCs), only 12 cases of MRONJ have been reported (1%), all in patients with a history of high-dose antiresorptive treatment, and regardless of the use of APCs (p = 0.7634). Regarding MRONJ treatment, there were no statistically significant differences in terms of improvement between APC application and surgical treatment alone (p = 0.0788). Results are not sufficient to establish the effectiveness of APCs in the prevention and treatment of MRONJ. Randomized controlled trials with large sample size are needed.

Angioleiomyoma (AL) is an uncommon benign soft tissue neoplasia arising from the tunica media of the smooth muscle cells. AL appears as a solitary and slow-growing mass and seldom is observed in oral tissues. We reported a rare case of AL involving the cheek of a 17-year-old young woman. A review of the English-language literature was performed entering the keywords “angioleiomyoma” and “oral” in the search fields of PubMed. 70 results were identified. Excluded were cases that were not in the oral cavity or not compatible with the AL diagnosis or report lacking immunohistochemical analysis. According to the exclusion criteria, we selected 30 studies that included 63 cases of AL. The results of the review showed an average age of 42.97 years with a prevalence between the fourth and fifth decade of life with a male-to-female ratio of 1.95 : 1. The most affected sites were palate, buccal mucosa of the cheek, lip, tongue, and gingiva. Surgical excision was the treatment of choice, and diagnosis was possible through histopathological and immunohistochemical analysis. SMA, vimentin, CD34, desmin, and S-100 were the most common markers to guide the histopathological diagnosis of oral AL. In conclusion, oral AL is a rare entity, especially in adolescence as in the reported case of AL of the cheek in a 17-year-old woman. The clinical aspects of AL did not allow clinicians to make a correct presumptive diagnosis. A scrupulous histopathological analysis and immunohistochemical examinations are fundamental to differentiate AL from other lesions.