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Biological tissues (including oral mucosa) can absorb and re-emit specific light wavelengths, detectable through spectrophotometric devices. Such a phenomenon is known as "autofluorescence" (AF). Several devices evaluating tissue AF have been developed and commercialized in the last two decades. Among these, the VELscope® system has been proposed as a visual diagnostic aid for potentially malignant disorders and malignant lesions of the oral mucosa. In the present pilot study, we investigated which are the main histopathological features possibly related to variations in AF patterns in a set of 20 oral squamous cell verrucous carcinoma. Among all the histological features investigated, only the mean width of keratin was significantly different between hypofluorescent and hyperfluorescent carcinomas. The results of the present study demonstrate that AF features of oral malignant lesions are significantly associated with the width of their keratin layer.

Non-melanoma skin cancer (NMSC) is the most common malignant tumor affecting fair-skinned people. Increasing incidence rates of NMSC have been reported worldwide, which is an important challenge in terms of public health management. Surgical excision with pre-operatively identified margins is one of the most common and effective treatment strategies. Incomplete tumor removal is associated with a very high risk of recurrence and re-excision. Biological tissues can absorb and re-emit specific light wave-lengths, detectable through spectrophotometric devices. Such a phenomenon is known as autofluorescence (AF). AF spectroscopy has been widely explored for non-invasive, early detection of NMSC as well as for evaluation of surgical margins before excision. Fluorescence-aided diagnosis is based on differences in spectral characteristics between healthy and neoplastic skin. Understanding the biological basis of such differences and correlating AF intensity to histological features could improve the diagnostic accuracy of skin fluorescence spectroscopy. The primary objective of the present pre-clinical ex vivo study is to investigate the correlation between the intensity of cutaneous AF and the histopathological features of NMSC. Ninety-eight lesions suggestive for NMSCs were radically excised from 75 patients (46 M; 29 F; mean age: 79 years). After removal, 115 specific reference points on lesions (“cases”; 59 on BBC, 53 on SCC and 3 on other lesions) and on peri-lesional healthy skin (controls; 115 healthy skin) were identified and marked through suture stitches. Such reference points were irradiated at 400–430 nm wavelength, and resulting emission AF spectra were acquired through spectrophotometry. For each case, AFIR (autofluorescence intensity ratio) was measured as the ratio between the number of photons emitted at a wavelength ranging between 450 and 700 nm (peak: 500 nm) in the healthy skin and that was captured in the pathological tissue. At the histological level, hyperkeratosis, neoangiogenesis, cellular atypia, epithelial thickening, fibrosis and elastosis were quantified by light microscopy and were assessed through a previously validated grading system. Statistical correlation between histologic variables and AFIR was calculated through linear regression. Spectrometric evaluation was performed on 230 (115 cases + 115 controls) reference points. The mean AFIR for BCC group was 4.5, while the mean AFIR for SCC group was 4.4 and the fluorescence peaks at 500 nm were approximately 4 times lower (hypo-fluorescent) in BCCs and in SCCs than in healthy skin. Histological variables significantly associated with alteration of AFIR were fibrosis and elastosis (p < 0.05), neoangiogenesis, hyperkeratosis and epithelial thickening. Cellular atypia was not significantly associated with alteration of AFIR. The intensity of fluorescence emission in neoplastic tissues was approximately 4 times lower than that in healthy tissues. Histopathological features such as hyperkeratosis, neoangiogenesis, fibrosis and elastosis are statistically associated with the decrease in AFIR. We hypothesize that such tissue alterations are among the possible biophysical and biochemical bases of difference in emission AF between neoplastic and healthy tissue. The results of the present evaluation highlighted the possible usefulness of autofluorescence as diagnostic, non-invasive and real-time tool for NMSCs.

Objectives The present review provides information about which molecules appear to be the main fluorophores in skin and oral mucosa, together with their clinical applications. Design The MEDLINE database was searched, using “oral mucosa AND fluorophores”, “skin AND fluorophores”, “epidermal AND fluorophores”, “dermal AND fluorophores” and “cutaneous AND fluorophores” as entry terms. We searched the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The level of evidence in the studies was assessed using the Classification of the Oxford Centre for Evidence-based Medicine (CEBM) Levels for Diagnosis. Results Five papers and 17 were primarily focused on description of fluorophores in oral mucosa and skin Evidence exists that fluorophores of oral mucosa and skin are mainly proteins such as collagen, elastin, keratin and tryptophan. Other possible fluorophores identified are: porphyrins, advanced glycation end products, flavins, lipopigment, nicotinamide adenine dinucleotide, flavin adenine dinucleotide, pheomelanin, eumelanin and components of lipofuscin. Clinical applications of oral mucosal autofluorescence (AF) are related to management of malignant and potentially malignant lesions. In the skin, AF has been used for acne assessment, diagnosis of sweat-gland pathologies, glycemic control and management of malignant lesions and as a marker for skin aging. Conclusion Fluorophores stimulated through AF devices are implied in different physiologic and pathologic processes. AF seems to be useful for several clinical applications, especially in skin department. Because most of the studies show a low level of evidence, further studies are necessary in such a promising and fascinating field.

Background: Several noninvasive diagnostic tools have been developed to aid the early detection of oral cancer and for evaluation before definitive biopsy. Among these, devices evaluating a tissues...

The diagnostic pathway for oral suspicious lesions usually starts with the clinical examination based on inspection and palpation of the oral mucosa. Such a phase is strongly related to the experience of the operator. Moreover, oral epithelial dysplasia and early oral carcinomas may already be present within areas of macroscopically intact oral mucosa. A great interest for techniques potentially improving the diagnostic accuracy has developed in several fields of surgical oncology in order to increase the specificity and sensitivity of the conventional diagnostic pathway. The development of noninvasive methods for real-time screening of neoplastic changes in oral cavity may be associated with the improvement of patients’ quality of life and survival rate. The analysis of tissue autofluorescence (AF) for improving sensitivity and specificity in cancer diagnosis has been proposed for different organs, including colon, lung, cervix, and esophagus. Particularly, there are several evidences supporting the effectiveness of this technique in head and neck cancer diagnosis. Autofluorescence shows high specificity and sensitivity for oral cancer and precancerous lesions: 72.4% and 63.79%, respectively. It can also provide valuable information for diagnosis, for planning of margin resection in surgical excision, and for monitoring the therapeutic response during follow-up. Direct visual fluorescence examination (DVFE) is based on the action of irradiation of specific wavelengths, between 375 and 440 nm, which excites some natural fluorochromes which show fluorescence in the range of the green color. The analysis of the lesions with AF tools must be performed in a dark environment to avoid the interference of white light wavelengths and to improve the quality of recorded images. Healthy oral mucosa emits fluorescence, detectable as green light. Cell and tissues within dysplastic and malignant lesions display modifications of the amount, distribution, and chemical–physical properties of the endogenous fluorophores. This results in an autofluorescence pattern variation that can be potentially used at diagnostic level. Loss of autofluorescence (LAF) seems to increase in correspondence to the progression of dysplasia, and altered tissue appears dark (brown to black). LAF in dysplasia and carcinoma seems to be connected to different mechanisms, such as altered metabolic activity of dysplastic keratinocytes, altered structure of subepithelial collagen, and absorbance of light by increased blood circulation due to inflammatory phenomena in dysplastic tissue and cancer. AF can be used for guiding incisional biopsy and in the excision to identify the resection margins.

INTRODUCTION Different osteotomy techniques have been proposed in order to improve postoperative course of impacted third molar extraction. The aim is to evaluate the possible advantages achieved with erbium yttrium-aluminum-garnet (Er:YAG) laser osteotomy compared with traditional burs. MATERIALS AND METHODS Seventy-six extractions were randomly classified into 2 groups according to osteotomy instrument: group 1 (G1)-Er:YAG laser: 35 patients; group 2 (G2)-traditional bur: 41 patients. Intraoperative parameters: total time, stitches number, and patient compliance. Postoperative: pain, health-related quality of life (HR-QoL), need for analgesics, edema, trismus, intra- and extraoral hematoma, and postoperative complications. RESULTS Mean time for G1 resulted 1069.4 seconds; for G2 1913.5 seconds (P

Auto-fluorescence (AF) of healthy bone tissue has recently been described. Loss of AF (LAF) has, on the contrary, been reported in necrotic bone. Further, the use of LAF as a possible guidance to distinguish viable from necrotic bone during surgical treatment of osteonecrosis has been proposed. The aim of this study is to detail 8 patients of medication-related osteonecrosis of the jaws treated through an AF-guided surgical resection. The authors also provide the histopathologic description of hypo-fluorescent and hyper-fluorescent bone in each patient. After removal of necrotic bone block, Er:YAG laser was used for vaporizing further necrotic bone, up to the detection of strongly hyper-fluorescent bone. Samples of hyper-fluorescent bone were collected around areas of necrosis. Histopathologic evaluation revealed viable bone tissue in all hyper-fluorescent specimens. On the basis of these data, AF-guided surgical resection could be effective in highlighting surgical margins of necrotic bone tissue and it might have some utility in a range of applications of bone surgery.

Dentoalveolar surgery including tooth extractions and dental implants placement is considered the major risk factor for developing medication-related osteonecrosis of the jaw (MRONJ).In this study, a patient series of MRONJ around dental implants were carefully analyzed to describe the findings and to assess the possible risk factors.Fifteen patients with peri-implant bone osteonecrosis were selected out of a group of 250 patients (6%). Patients were divided into 2 groups according to the temporal relationship. Group 1 (G1)-necrosis immediately after implant placement (from 2 to 10 months) and defined as "implant surgery-triggered" MRONJ. Group 2-necrosis distant (from 1 to 15 years) from implant placement and defined as "implant presence-triggered" MRONJ. Epidemiological and pharmacological variables were recorded as well as specific data about osteonecrosis and dental implants.G1 included 6 patients: 5 (83.4%) treated with oral bisphosphonates (BPs) for osteoporosis and 1 (16.6%) with intravenous BPs for breast cancer. Mean duration of BP therapy (BPT) was 83.7 months. G2 included 9 patients: 8 patients (88.89%) treated with intravenous BPs for malignant disease and 1 (11.11%) with oral BPs for osteoporosis.Data confirms that not only surgical insertion of dental implants is a potential risk factor for the development of osteonecrosis but also the presence itself of the implant into the bone can be associated with this disease. Therefore, it is necessary to inform of the increased risk for MRONJ also the patients who have already osteointegrated implants and are going to start the BPT.The risk is lower for patients receiving oral BPs but it exists and seems to be higher if the implant is located in the posterior areas, if the duration of BPT is more than 3 years and if the patient is under corticosteroid therapy.

Riassunto Obiettivi Il presente articolo descrive la tecnica di immunofluorescenza diretta (IFD) come ausilio diagnostico in numerose patologie immunomediate del cavo orale. Materiali e Metodi E stata eseguita una revisione critica della letteratura disponibile sull’argomento al fine di approfondire i vari passaggi dell’esame di IFD, dalle indicazioni fino all’interpretazione dei risultati. Risultati L’IFD e indicata tutte le volte in cui si sospetti una patologia immunomediata a carico della mucosa del cavo orale. I disordini di questo tipo possono avere manifestazioni cliniche e istologiche sovrapponibili. La scelta del sito di prelievo, la tecnica bioptica e la modalita di trasporto del tessuto al laboratorio risultano fondamentali per ottenere risultati affidabili. Conclusioni L’IFD richiede un’adeguata preparazione da parte dei diversi operatori (medici, altro personale sanitario e tecnici di laboratorio) che sono coinvolti dal momento del prelievo bioptico fino alla consegna del referto.

Background The etiology of traumatic ulcerative granulomas with stromal eosinophilia (TUGSE) is not clear, traumatic irritation having advocated as the most likely cause. TUGSEs are typically self-limiting slow-healing lesions of the oral mucosa with unclear pathogenesis, commonly manifesting as a rapidly developing, long-lasting ulcer. Case presentation Here we report a controversial case of a self-healing lesion of the tongue in a 57 year-old woman. A clonal T-cell proliferation and CD30 negative immunohistochemical (IHC) profile could be documented. Discussion and conclusion In view of the very peculiar clinical and histological features, a retrospective diagnosis of a TUGSE with scarce eosinophilic infiltrate (possibly in regression), displaying CD30- T-clonal proliferation was eventually rendered. The patient did not report signs of recurrence after a 3-year follow-up period.

Background Biphosphonate-related osteonecrosis of the jaw (BRONJ) is a potential side effect associated with the administration of bisphosphonates; the aim of this work is to highlight the possible epidemiological differences between two groups of patients affected by medication related osteonecrosis of the jaw (MRONJ) treated at the Center of Oral Medicine, Pathology and Laser Surgery of the Academic Hospital at the University of Parma, Italy, between January 2004 and June 2016. Methods Medical charts of 303 patients (214 females and 89 males, mean age: 67 years old) treated at the Center of Oral Medicine, Pathology and Laser Surgery of the Academic Hospital at the University of Parma, between January 2004 and June 2016, were retrospectively analyzed. Patients were divided in 2 groups according to drugs therapy they underwent: group 1 (G1) including patients treated with bisphosphonates alone and group 2 (G2) including patients receiving antiresorptive-antiangiogenic drugs in association with bisphosphonates or antiresorptive-antiangiogenic drugs alone. Than 269 MRONJ sites treated with 5 different therapeutical approaches were analyzed. Results Results showed G1 consisting mainly in female patients undergoing bisphosphonates for oncologic disease, stage II was most frequently diagnosed and MRONJ developed mainly after dental extraction or bone surgery. G2 consisted mainly in males patients, whom took antiresorptive-antiangiogenic drugs in association with bisphosphonate or antiresorptive-antiangiogenic drugs alone for oncologic disease. Stage II was most frequently diagnosed and MRONJ developed most frequently "spontaneous". Conclusions This study showed how a new population affected by MRONJ is emerging. Men affected by kidney cancer treated with new antiresorptive-antiangiogenic drugs will represent a growing portion of the pool of patients at risk. In our experience, a strict follow-up is of outmost importance to early detect MRONJ also in patients with spontaneous cases. When MRONJ occurs, surgical laser treatment with Er:YAG seems to represent the option with highest percentage of success; for patients with contraindication to surgery, LLLT helps to improve outcomes of the medical therapy.

Medication-related osteonecrosis of the jaws (MRONJ) is an adverse side effect of several drug therapies, including bisphosphonates (BPs). Osteonecrosis of the jaw specifically related to BP therapy is usually referred to using the acronym BRONJ. However, no consensus has yet been reached regarding the most appropriate management of BRONJ. The greatest success rates have been recorded with surgical removal of necrotic bone. In particular, erbium:yttrium-aluminum-garnet (Er:YAG) laser-assisted surgery has shown significantly better results than conventional surgical approaches. According to a position paper reported by the American Association of Oral and Maxillofacial Surgeons in 2007, the identification of necrotic bone margins during osteonecrosis removal can be very difficult. In 2015, a review of treatment perspectives for MRONJ reported that both surgical debridement and resection cannot be standardized owing to the lack of guidance to define the necrotic margins. Recently, the use of autofluorescence (AF) of the bone as a possible suitable guide to visualize necrotic bone during surgical debridement or resection was proposed. It seems that vital bone could be highlighted by its very strong AF. In contrast, necrotic bone loses AF and, thus, appears much darker. The molecular sources of the phenomenon of AF are the specific amino acids of the collagen molecules that show AF when irradiated by ultraviolet or blue light. The use of AF as an intraoperative diagnostic tool is entirely new in the management of MRONJ, although it has been used for several years in other fields (eg, intervertebral disc surgery). The aim of the present report was to describe a case of mandibular BRONJ treated with a new surgical approach performed with an Er:YAG laser and guided by AF. The histopathologic evaluation of the removed hypofluorescent bone block and hyperfluorescent surrounding bone has also been reported in detail.

Background: Gold standard for the diagnosis of oral dysplasia (OD) oral squamous cell carcinoma (OSCC) and malignant lesions is the histological examination. Several adjunctive diagnostic techniques have been proposed in order to increase the sensitivity (SE) and specificity (SP) of conventional oral examination and to improve the diagnostic first level accuracy. The aim of this study is to perform a systematic review on non-invasive tools for diagnosis of OD and early OSCC. Material and Methods: Medline, Scopus, Web of Knowledge databases were searched, using as entry terms “oral dysplasia AND diagnosis” / ”oral cancer AND diagnosis”. Data extracted from each study included number of lesions evaluated, histopathological diagnosis, SE, SP, positive and negative predictive values (PPV and NPV), diagnostic accuracy (DA) and the main conclusions. Results: After title and abstract scanning of 11.080 records, we selected 35 articles for full text evaluation. Most evaluated tools were autofluorescence (AF), chemiluminescence (CL), toluidine blu (TL) and chemiluminescence associated with toluidine blue (CLTB). Conclusions: There is a great inhomogeneity of the reported values and there is no significant evidence of superiority of one tool over the other. Further clinical trials with a higher level of evidence are necessary in order to assess the real usefulness visual diagnostic tools.

The aim of this study was to propose an autofluorescence (AF)-guided surgical approach performed with Er:YAG laser and Nd:YAG low-level laser therapy (LLLT).Medication-related osteonecrosis of the jaw (MRONJ) therapy remains an unresolved problem. The proposed conservative and surgical treatment regimens are associated with contradictory success rates. However, the increased experience with MRONJ management suggests that surgical therapy can halt disease progression, and can allow a histology-based diagnosis of osteonecrosis. Surgical approach with Er:YAG laser is associated with significantly better results compared with medical treatment and traditional surgical approaches. One of the difficulties encountered during surgical removal of a MRONJ is the precise individuation of necrotic bone margins.A case of Stage III maxillary osteonecrosis treated with a new surgical approach is presented.After 7 months of follow-up, complete mucosal healing was evident, and the patient was free of symptoms. Such a technique allowed a highly accurate and minimally invasive approach through the selective ablation of the non-/hypofluorescent areas.Taking into account the advantages of laser therapy and the possible effectiveness of AF in highlighting surgical margins, this approach would probably achieve excellent outcomes.

Purpose: The aim of this work is to report a review of the literature concerning epidemiology, clinical and radiographic features as well as treatment of odontogenic myxofibroma (MF). Methods: The PubMed database was searched using the following keywords: “odontogenic myxofibroma”, “odontogenic fibromyxoma”, “myxofibroma of the jaw” and “fibromyxoma of the jaw”. Results: Fifteen articles reporting the experience with 24 patients were identified. Male/female ratio was 1:1.4 and the average age was 29.5 years. The most frequent location was the mandible. In 66.7% of the cases the radiographic appearance was a multilocular radiolucency. Swelling was observed in 13 patients (92.86%), varying degrees of pain in 5 (35.71%) and paresthesia in only one patient (7.14%). Six out of 24 patients (26.09%) were treated with radical surgery and 17 (73.91%) with a conservative approach. In two out of 21 cases (9.52%) a recurrence was reported. Conclusions: MF is an extremely rare tumor and no agreement exists on the causes of its development. According to the present review, the choice of treatment should depend on variables such as localization, presence of a primary or of a recurrent lesion, age, general medical conditions and aesthetic needs of the patient. Key words:Odontogenic myxofibroma, myxofibroma of the jaw, odontogenic tumors, oral surgery, oral pathology.

To report two cases of solid type primary intraosseous carcinoma (PIOC) with a critical appraisal of one of the WHO diagnostic criteria.Both patients had radiographic and histopathologic findings showing massive mandibular destruction as well as the involvement of the inferior alveolar nerve, without lip or chin paresthesia. Patients were treated through hemimandibulectomy followed by reconstruction through fibula free flap and forearm flap.Lip and/ or chin paresthesia are rather frequent in metastatic and salivary gland tumors but not in primary tumors of the jaws. Reasons for such a discrepancy are mostly unknown. A few hypotheses are put forward here. It is the opinion of the authors that most of the diagnostic criteria for solid type PIOC are acceptable. However, the criterion "absence of ulcer formation on the overlying mucosa" mainly depends on the dimension of the tumor at diagnosis.

Chondromas are benign cartilaginous tumors usually localized within the tubular bones of the extremities. Soft tissue chondromas (STCs) are rare and only few cases have been reported in the oral cavity. The present case documents the exceptional finding of a 12-year-standing STC of the hard palate of a 63-year-old man. The tumor measured approximately 6 cm in its larger size and it was radically excised through the use of a quantic resonance molecular (QRM) lancet. No recurrence was observed during 1-year follow-up. A concise review of the relevant literature is included in the present paper.

The peripheral ossifying fibroma (POF) is a relatively uncommon, reactive gingival overgrowth usually composed of cellular fibroblastic tissue containing one or more mineralized tissues, namely bone, cementum-like material, or dystrophic calcification. The aetiology and pathogenesis of POF are yet not clear, but some authors have hypothesized a reaction originating from the periodontal ligament, as a result of irritating agents such as dental calculus, plaque, orthodontic appliances, and ill-fitting restorations. The aim of our study was to report the clinicopathologic features of a case series of POF from a single Italian institution. A total of 27 cases were collected over an 18-year period. Detailed relevant medical history, clinical and histological information were recorded for each patient. The age range of patients (m = 6; f = 21) was 17.2-80.1 years with a mean of 42.9 ± 18.1 years. Occurrence of the lesion in the mandibular and maxillary arches was similar, and 67.0% occurred in the incisor-cuspid region. The lesions ranged in size from 0.3 to 5.0 cm (mean, 1.3 cm ± 1.1 cm). All the different types of mineralization were present, with higher prevalence of lamellar bone. The lesions were treated by surgical excision and four lesions in three patients recurred after surgery. Surgeons should consider the high recurrence rate of POF and remove the lesion down to the bone involving also the adjacent periosteum and the periodontal ligament. Professional prophylaxis should precede any surgical procedure, and periodical dental hygiene recalls are important in order to remove any possible irritating factor.