Roberto Marino

Different therapeutic strategies for burning mouth syndrome: preliminary data.

BACKGROUND To compare different therapeutic supportive approaches in patients with burning mouth syndrome. A prospective study was carried out for this purpose. MATERIALS AND METHODS The study involved 56 patients with burning mouth syndrome. They were randomly assigned to treatment with capsaicin, alpha-lipoic acid or lysozyme-lactoperoxidase (test drugs) or boric acid (control group). Symptoms were scored after 60 days treatment and 60 days after drug discontinuation. RESULTS At the end of the treatment period, there was a significant reduction in the symptom scores of all of the patients who received the test drugs (P<0.01), and at the end of the follow-up period in the test groups as a whole (P<0.01); the reduction was not significant when considering each test group separately after the treatment period. All of the treatments were more effective than boric acid and there was no significant difference in the symptom scores of the control group at either of the study time-points. CONCLUSIONS Our results demonstrate the similar effectiveness of capsaicin and alpha-lipoic acid in controlling the symptoms of burning mouth syndrome. Lysozyme-lactoperoxidase may be effective in the supportive care of BMS patients with xerostomia. The transitory effect observed after discontinuing drug administration justifies the use of prolonged therapy in chronically affected patients.

Genomic aberrations in normal appearing mucosa fields distal from oral potentially malignant lesions

ObjectivesOral fields of visually normal and non-dysplastic mucosa (ODFs) may represent the precursors of oral potentially malignant lesions (OPMLs). Aim of the study was to provide new evidence for the concept of the “field carcinogenesis” model by comparing the ODF and OPML genomic aberration profiles obtained by high resolution DNA flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). A second aim was to investigate if specific CGH aberrations were associated with DNA aneuploidy.MethodsNineteen patients with single OPMLs were recruited for the study. In parallel with obtaining samples of OPML tissue from 11 leukoplakias without dysplasia (nd-OPMLs) and 8 with dysplasia (d-OPMLs), we also obtained samples from distant ODFs. DNA aneuploid nuclei detected by hr DNA-FCM were physically separated, based on DNA content, from the DNA diploid components with a DNA-FCM-Sorter. These relatively pure subpopulations of epithelial nuclei were then submitted to DNA extraction and a-CGH for a genome-wide analysis of DNA copy number aberrations (CNAs).ResultsThe frequencies of DNA aneuploidy (DI ≠ 1) among ODFs and OPMLs were respectively 5.3% and 32%. The DI aneuploid values of ODFs and nd-OPMLs were all near-diploid (DI ≠ 1 and DI ≤ 1.4), while for d-OPMLs were high-aneuploid (DI > 1.4) in 40% of the cases. CNA averages were 1.9 in ODFs and 6.5 in OPMLs. The gain of the chromosomal region 20q13.33-qter was observed in 37% of both ODFs and corresponding OPMLs. Additional common regions included 7p22.2-pter, 11p15.5-pter and 16p13.3-pter where gains were observed. Furthermore, gains of 20q13.31–q13.33 and of 5p13.33-pter and loss of 9p21.3 were detected at high frequency (respectively, at 62.5%, 50% and 50%) only in d-OPMLs. In particular, loss at 9p21.3, gain at 5p13.33-pter and gain of 20q13.31–q13.33 were associated with DNA aneuploidy (p = 0.00004; p = 0.0005; p = 0.01).ConclusionsODFs and OPMLs showed common CNAs in specific chromosomal regions suggesting that they may represent early events of the natural history of oral carcinogenesis according to the field effect cancerization and may contribute to the ODF-OPML transition. In addition, loss at 9p21.3 and gains at 5p13.33-pter and 20q13.31–q13.33 may contribute to DNA aneuploidization.

Osteonecrosis of the jaw in a patient receiving cabozantinib

Since the discovery of bisphosphonate-related osteonecrosis of the jaw, there has been increasing evidence in recent years of osteonecrosis induced by drugs other than bisphosphonates, mainly agents with antiangiogenic and antiosteoclastic activity. Mandibular osteonecrosis was observed in a 51-year-old female with medullary thyroid cancer receiving cabozantinib, a new tyrosine kinase inhibitor having antiangiogenic activity. The bone necrosis appeared after a dental extraction. The clinical, radiographic and histologic picture of a chronic non-healing extraction socket was consistent with drug-induced osteonecrosis of the jaw. Healing was achieved by segmental ostectomy. The osteonecrosis was likely associated with a vascular endothelial growth factor (VEGF) pathway inhibition, implying inhibition of angiogenesis and hampering of the local host defence mechanisms.

Clinical features of microinvasive stage I oral carcinoma

BACKGROUND This study aimed to analyse a case series of microinvasive (tumour thickness <4 mm) stage I oral squamous cell carcinoma (OSCC), with an emphasis on the clinical features of the tumours. METHODS In total, 32 microinvasive and 67 non-microinvasive stage I lesions, which had been surgically treated, were retrospectively studied and compared. The data analysed included gender, age, risk habits, clinical appearance, lesion site, symptoms, nodal involvement and outcome. RESULTS The clinical features of microinvasive lesions meant that, more often than not, they resembled premalignant lesions (P = 0.008), and diagnosis was mainly based on accurate clinical examination rather than the presence of symptoms (P = 0.029). During a median follow-up of 4.5 years, one nodal involvement and one cancer-related death were observed in patients with microinvasive lesions. A significantly higher (P = 0.044) level of nodal involvement was observed in the non-microinvasive lesion group. CONCLUSIONS   Stage I OSCC has a favourable prognosis overall, but nodal recurrence is more common in non-microinvasive cancers. As microinvasive lesions tend to present clinically as premalignant lesions, accurate clinical examination is essential if misdiagnosis of early lesions is to be avoided.

Distinctive chromosomal instability patterns in oral verrucous and squamous cell carcinomas detected by high-resolution DNA flow cytometry.

Oral verrucous carcinomas (OVCs) are characterized by better prognosis than oral squamous cell carcinomas (OSCCs). Because chromosomal instability (CIN) in solid tumors is indicative of prognosis, this study investigated whether OVCs and OSCCs were characterized by differences in CIN biomarkers.

Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs.

Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.

Microbiopsy a novel sampling technique to early detect dysplastic/malignant alterations in oral mucosal lesions: practicability by general dentists.

BACKGROUND When used in oral medicine clinics, microbiopsy is able to obtain tissue fragments suitable for a highly sensitive first-level diagnosis of dysplastic/malignant alterations in oral mucosal lesions. If feasible by general dentists, this sampling technique could reduce the diagnostic delay for oral malignant and premalignant lesions. This study assesses the adequacy of microbiopsy samples when taken by general dentists. METHODS Fifty dentists, without specific training on oral medicine, volunteered for enrolment. They were given brief training and asked to prospectively sample any mucosal lesion observed during their routine practice. The sample adequacy features were assessed. RESULTS The dentists sampled 152 lesions; there were 92.1% of adequate samples (140/152), and the BMZ was visible in 78.6% of these (110/140). Neither the clinical aspect nor lesion site affected either the adequacy or the presence of BMZ. CONCLUSIONS The high adequacy rate observed and the advantages histological specimens have over cytological ones go to support the feasibility of microbiopsy taken by general dentists for the characterization of oral mucosal lesions and in selecting those requiring further assessment in specialized oral medicine centres.

Choristoma Involving the Floor of the Mouth and the Anterior Tongue: A Case of Teratoid Cyst With Gastric and Respiratory Epithelia

Oral dysontogenic cysts result from defective embryonic development. Among them teratoid cysts are the most unusual presentation and may be lined by gastric, intestinal, respiratory, squamous, ciliated epithelium or even pancreatic structures. Teratoid cysts containing respiratory and gastrointestinal epithelium have typically been called choristomas. This article describes a 15-year-old boy presenting a choristoma involving both the floor of the mouth and the anterior tongue and characterized by the presence of squamous epithelium with skin adnexa, gastric and respiratory epithelium.

High-resolution DNA content analysis of microbiopsy samples in oral lichen planus.

OBJECTIVES DNA aneuploidy has been reported to be a predictor of poor prognosis in both premalignant and malignant lesions. In oral lichen planus (OLP), this hypothesis remains to be proved. This study aimed to determine the rate of occurrence of DNA aneuploidy in patients with OLP by high-resolution DNA flow cytometry. METHODS Patients with OLP were consecutively enrolled. Tissue samples were subdivided for formalin fixation and routine histological assessment and for immediate storage at -20°C for later DNA ploidy analysis, which was performed by DAPI staining of the extracted nuclei and excitation with a UV lamp. The DNA aneuploid sublines were characterized by the DNA Index. RESULTS A DNA aneuploid status was observed in two of 77 patients with OLP (2.6%). When considering the clinical aspect of the OLP lesions, both DNA aneuploid cases had a reticular clinical aspect. CONCLUSIONS DNA aneuploidy is an uncommon event in OLP and less frequent compared to other non-dysplastic and non-OLP oral potentially malignant disorders. The extremely low rate of DNA aneuploidy could represent an occasional finding or reflect the low rate of malignant transformation observed in patients with OLP even if the real prognostic value of DNA ploidy analysis in patients with OLP remains to be confirmed.

DNA aneuploidy relationship with patient age and tobacco smoke in OPMDs/OSCCs

The aim of this study was to investigate the relationship between tobacco smoke habit, patient age, DNA aneuploidy and genomic DNA copy number aberrations (CNAs) in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) patients. DNA aneuploidy was detected by high-resolution DNA flow cytometry (hr DNA-FCM) on DAPI stained nuclei obtained from multiple tissue samples from OPMDs/OSCCs in 220 consecutive patients. Nuclear genomic aberrations were determined in a subset of 65 patients by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. DNA aneuploidy and mean nuclear genomic aberrations were associated with patients’ age. In particular, DNA aneuploidy strongly associated with age in non-smoker OPMDs/OSCCs patients. OSCCs from smokers showed a lower prevalence of DNA aneuploidy compared to OSCCs from non-smokers. A higher occurrence of DNA aneuploidy (particularly in smokers’ OPMDs) was observed in patients characterized by involvement of a single oral subsite. Our study suggests that: 1) DNA aneuploidy in non-smokers is mainly related to aging; 2) OPMDs/OSCCs involving multiple oral subsites in smokers are less likely to develop DNA aneuploidy compared to non-smokers; 3) OSCC development is characterized by both CIN and CIN-independent mechanisms and that the latter are more relevant in smokers. This study provides evidence that DNA diploid OPMDs may be considered at lower risk of cancerization than DNA aneuploid ones in non-smokers but not in smokers.