Gianfranco Favia

Human herpesvirus 8 variants in sarcoid tissues

BACKGROUND The cause of sarcoidosis is unknown, although mycobacteria have been implicated. We examined sarcoid tissues for human herpesvirus 8 (HHV-8) in addition to mycobacterial genomic sequences. METHODS Biopsy samples from 17 patients with sarcoidosis were studied (eight transbronchial, 27 lymph node, two skin, and two oral mucosa). We used tissues (n = 137) from 96 patients without sarcoidosis as negative controls. A nested PCR was applied to amplify a segment of open reading frame (ORF) 26 of the HHV-8 genome, and a heminested PCR was to amplify a segment of ORF 25 of HHV-8 and of the 16 S rRNA gene of mycobacteria. Differences in base sequences of the amplified fragments were resolved with single-strand conformation polymorphism and dideoxy sequencing. FINDINGS HHV-8 ORF 26 DNA was detected in significantly higher proportions of sarcoid than of non-sarcoid tissue samples from lung (8/8 vs 0/54; p < 0.0001), lymph nodes (26/27 vs 6/29; p < 0.0001), skin (2/2 vs 0/17; p = 0.006), and oral tissues (2/2 vs 1/13; p = 0.029). 31 (82%) of the 38 ORF 26 DNA-positive sarcoid specimens were also positive for ORF 25 DNA. For mycobacteria-like 16 S rRNA DNA, the proportion positive was significantly higher in sarcoid than non-sarcoid tissues for lymph node samples (11/27 vs 2/29; p = 0.003) but not for other tissues (lung 3/8 vs 22/54; skin 2/2 vs 15/17; and oral tissues 1/2 vs 0/13). Overall, the prevalence of HHV-8 ORF 26 sequences was higher in sarcoid tissues than in non-sarcoid tissues (p < 0.0001). When patients whose tissues were included in a masked phase of the study were treated as units of analysis, eight of eight sarcoidosis patients were positive for HHV-8 ORF 26 DNA, compared with three of 56 control patients (p < 0.0001); for mycobacteria-like sequences, three of eight sarcoidosis patients were positive, compared with four of 56 controls (p = 0.0464). The HHV-8 ORF 26 sequences, ten of which were unique, could be segregated into four groups according to peptide motifs. In seven of nine patients from whom biopsy samples were taken from various sites, different sequences were recovered. The mycobacterial sequences amplified from sarcoid tissues were also varied, but none was homologous to those of known species. INTERPRETATION Variant HHV-8 DNA sequences are found in a wide range of sarcoid but not non-sarcoid tissues. Mycobacteria-like 16 S rRNA sequences are more frequently present in sarcoid lymph nodes and not in other tissue types, but do not indicate infection by a particular mycobacterial species.

Oral lichen planus and HCV infection: a clinical evaluation of 263 cases

Background Hepatitis C virus (HCV) infection induces variable dermatologic manifestations. Our purpose was to determine whether there is an association between HCV infection and oral lichen planus (OLP).

Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected individuals

Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary condition transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. The syndrome is characterised by numerous basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, palmar and/or plantar pits, skeletal abnormalities and intracranial calcifications.In this paper, the clinical features of 37 Italian patients are reviewed. Jaw cysts and calcification of falx cerebri were the most frequently observed anomalies, followed by BCCs and palmar/plantar pits. Similar to the case of African–Americans, the relatively low frequency of BCCs in the Italian population is probably due to protective skin pigmentation. A future search based on mutation screening might establish a possible genotype–phenotype correlation in Italian patients.

Histologic and histomorphometric features of bisphosphonate-related osteonecrosis of the jaws: An analysis of 31 cases with confocal laser scanning microscopy

INTRODUCTION Patients undergoing bisphosphonate therapies may develop jaw lesions, mainly consisting in bone necrosis. No effective treatment has been proposed so far for such lesions, nor is there a uniform concept on the possible pathogenesis of this entity. METHODS The study population included 31 patients with bisphosphonate-related osteonecrosis of the jaws and 10 healthy donors. All patients underwent to jaw bone biopsy and the tissue samples were divided into two parts, one of which was fixed, decalcified and routinely processed. The second part was fixed, embedded in methylmetacrylate, cut and stained with methylene blue and basic fuchsine. All samples were subjected to light and confocal microscopic examination and to histomorphometric analyses to evaluate differences in bone structure between the two samples groups. RESULTS Three main histological patterns were identified in ONJ patients: 1 - Areas with active acute inflammation, characterized by predominance of soft tissues, inflammatory infiltrate, acellular necrotic debris, thin-walled and dilated blood vessel, intensely basophilic bone spiculae with scalloped borders showing prominent bone resorption. 2 - Areas characterized by predominance of bony structures showing wide acellular necrotic sequestra and large, scalloped Haversian canals containing inflammatory cells. 3 - Non-necrotic areas contained larger amounts of bone, showing increased trabecular thickness, inter-osteonic bone deposition and smaller and fewer Haversian canals. These differences were more evident after comparing the histomorphometrical data of samples from ONJ patients with controls. Also, lamellar bone from treated patients was composed of bigger osteones containing larger osteocytes. Two different types of newly-formed woven bone, mainly showing centrifugal spatial orientation, were easily detectable in these areas. Osteoclast-like cells detected in inflammatory areas from treated patients were small and contained few nuclei, but they were rare to absent in non-necrotic bone from the same patients. CONCLUSIONS These features point at a peculiar process of bone remodeling in patients undergoing bisphosphonate therapy, which showed scarce osteoclastic activity and subsequent deposition of newly-formed bone. The latter would be made up of thicker bone structures supplied by fewer blood vessels. Consequently, in case of increased metabolic requests, this modified bone would not be supported by adequate blood supply, thus leading to necrosis and superinfection.

Warthin's tumour: a study of 78 cases with emphasis on bilaterality, multifocality and association with other malignancies

The authors reviewed the clinical records and the histopathological preparations of 78 cases of Warthins tumours (WTs), treated at the Department of Dental Sciences, Centre for the Study of Oral Tumours, of the University of Bari. All the surgical specimens had been fixed in neutral buffered formalin, sampled according to the step-serial, whole-specimen sectioning technique, embedded in paraffin and stained with haematoxylin-eosin, periodic acid Schiff and Gomoris reticulin. The results showed that Warthins tumours characteristically affect the parotid gland, and most frequently arise in adults (mean age=57 years) and in males (95%). Multiple tumours were detected in 16 cases (20.5%), and five of these were bilateral (6.5%). One of the multifocal tumours involved an intra-parotideal lymph node and the laryngeal piriform sinus. In addition, 13 cases (16.6%) were associated with other malignancies. These data indicate that multiple (synchronous or metachronous) WTs may occur more frequently than previously reported. The high rate of multiple WTs detected in the current study may result from extensive and accurate sampling of these neoplasms for histopathological evaluation. Consequently, complete preoperative work-up of patients harbouring parotideal tumours consistent with or suspicious for WT is necessary. The work-up should include CT scans and/or magnetic resonance imaging of both parotid glands, to exclude the occurrence of multiple tumours, which may be clinically undetectable. Also, fine needle aspiration biopsy may be an accurate tool for excluding malignant neoplasms and for better planning subsequent surgical procedures. These usually consist in (bilateral) superficial parotidectomy and should be followed by long term follow up of the patients, in view of possible metachronous WTs, even after prolonged time intervals.

Surgery-triggered and non surgery-triggered Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ): A retrospective analysis of 567 cases in an Italian multicenter study

Invasive local procedures are often reported in clinical history of patients suffering from Bisphosphonates-Related Osteonecrosis of the Jaws (BRONJ) but over 40% of spontaneous forms have been also described in literature. We compared age, gender, underlying bone disorders, bisphosphonate therapy, clinical features and surgical outcome of 205 cases (36.2%) of BRONJ non surgery-triggered (group 1) with 362 (63.8%) cases of surgery-triggered forms (group 2). Differences between group 1 and 2 were analysed using Mann-Whitney U and χ(2) tests. Statistical analysis was performed using STATA 8. Zoledronate was the most used type of bisphosphonate (63.4% versus 69.0%) and the mandible was the most frequently involved site (63.9% versus 63.4%) in both groups. BRONJ in group 1 was more frequently multicentric (9.3% versus 5%, p<0.05), had a lower clinical stage (45.9% versus 13.8% in stage 1, p<0.01) and had a better outcome after surgical therapy (improvement in 74.1% versus 58.6%, p<0.05). The high prevalence of non surgery-triggered forms of BRONJ should be considered by oncologists, haematologists and general physicians who are advised to inform their patients regarding the importance of preventive dental protocols to control the possible causes of osteonecrosis not related to dental invasive procedures.

Resective surgical approach shows a high performance in the management of advanced cases of bisphosphonate-related osteonecrosis of the jaws: a retrospective survey of 347 cases.

PURPOSE The aim of this study was to evaluate the results of the surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a large cohort. MATERIALS AND METHODS A retrospective cohort multicenter study was designed. Patients were enrolled if they were diagnosed with BRONJ and received operative treatment. Data on demographic, health status, perioperative, and surgical factors were collected retrospectively. The primary outcome variable was a change in BRONJ staging (improvement, worsening, or no change). Interventions were grouped by local debridement and resective surgery. Data were collected for other variables as cofactors. Univariate analysis and logistic regressions were then performed. RESULTS Of the 347 BRONJ-affected subjects, 59% showed improvement, 30% showed no change, and 11% showed worsening. Improvement was observed in 49% of cases treated with local debridement and 68% of cases treated with resective surgery. Multivariate analysis indicated that maxillary location, resective surgery, and no additional corticosteroid treatment were associated with a positive outcome. CONCLUSIONS Surgical treatment of BRONJ appeared to be more effective when resective procedures were performed. Nonetheless, other factors, such as the absence of symptoms and the types of drug administration, should be taken into account before clinical decisions are made.

Use of calretinin in the differential diagnosis of unicystic ameloblastomas.

Aims: Calretinin, a 29‐kDa calcium‐binding protein is expressed widely in normal human tissues and tumours including both unicystic and solid and multicystic ameloblastomas. The histological distinction between unicystic ameloblastomas and certain non‐neoplastic odontogenic cysts can be problematic. The objective of this study was to determine whether calretinin was expressed in the lining epithelium of odontogenic keratocysts, residual and dentigerous cysts and to determine whether this calcium‐binding protein could be used to distinguish these cysts from the unicystic ameloblastoma.

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.

Calretinin expression in ameloblastomas

Calretinin is a 29‐kDa calcium‐binding protein which is expressed in the central and peripheral nervous systems as well as in many other normal and pathological human tissues. The objective of this study was to determine whether calretinin was expressed in the epithelium of ameloblastomas.