Malignant transformation of oral proliferative verrucous leukoplakia: a series of 48 patients with suggestions for management.

Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral mucosal leukoplakia of unknown origin, characterized by high rates of malignant transformation. Different diagnostic criteria, terminologies, and therapeutic approaches have been proposed since the first report in 1985. There remains no general agreement regarding the clinical and histological diagnosis, prevention, and correct management of this disease. This retrospective study investigated 48 patients affected by PVL showing at least one malignant transformation and followed up at 2-month intervals. Twenty-five were female (52.1%) and 23 (47.9%) were male; their median age was 67 years (range 40-93 years). Follow-up ranged from 18 to 240 months. Clinical examination included the use of Lugol's solution to prevent clinical underestimation of the margins and toluidine blue for suspicious areas. Surgical excision by scalpel was the preferred treatment for suspicious lesions, with only five carcinomas surgically removed by diode laser and two by CO2 laser. All specimens were accurately mapped after formalin fixation. Fifteen patients (31.3%; 10 female, five male) developed one oral carcinoma, while 33 (68.7%) developed two or more primary tumours (range 3-12). Only four patients (8.3%), who developed between 2 and 8 oral squamous cell carcinomas (OSCCs), died of tumour-related causes. The pre-surgical clinical workup, subsequent surgical treatment, and follow-up are key to success for patients affected by PVL with malignant transformation into stage 1 OSCC and/or verrucous carcinoma, leading to a high overall survival rate.

Oral lesions as first clinical manifestations of Crohn's disease in paediatric patients: a report on 8 cases.

AIM: Oro-facial granulomatosis is a descriptive term commonly encompassing a variety of conditions that exhibit similar clinical and microscopic features. It is generally used to describe persistent enlargement of the soft tissues of the oral and maxillofacial region. MATERIALS AND METHODS: We report on the salient clinical features of 8 cases of Crohn's disease in paediatric patients (age range from 9 to 13 years old), with oral lesions as first clinical manifestations. RESULTS: The clinical presentation of oro-facial granulomatosis is highly variable but usually recurrent facial swelling, mainly in the lips with or without intraoral manifestations, is the single most common clinical sign at onset. The association with systemic conditions such as sarcoidosis and Crohn's disease has been widely reported in literature. In paediatric age, oro-facial granulomatosis may frequently represent an extra-intestinal manifestation of Crohn's disease and oral lesions can be the first sign of an unknown intestinal disease. The diagnosis in paediatric patients is challenging as oro-facial granulomatosis may precede Crohn's disease by several years, frequently remaining the only evident active focus of the disease. CONCLUSION: The detection of specific oral manifestations often preceded by painless gingival enlargement (diffuse lip and buccal mucosal swelling, oral cobblestoning, buccal sulcus ulceration and mucosal tags) and/or unspecific or ancillary ones (cheilitis, scaly perioral erythematous rashes and frank intraoral abscess formation, labial and tongue fissuring, glossitis and aphthous stomatitis) is mandatory for the early diagnosis of intestinal Crohn's disease.

Oral squamous cell carcinoma: a mono-institutional epidemiological study on 462 cases highlighting differences among young and adult patients.

AIM: Despite several diagnostic and therapeutic advances, an increasing incidence of oral squamous cell carcinoma (OSCC) especially among young individuals has been observed in different parts of the world. Aim of this study was to delineate the profile of patients with OSCC in particular among young people. METHODS: Between 1977-2004, the medical records of 462 patients (mean age: 64.18 years, male-to-female ratio 2.1:1) with a diagnosis of OSCC were retrieved and successively analysed, with details of demographic data, staging, histological grading, treatment modality and risk factor profile. Overall, 43 (9.3%) patients were less of 45 years old, and among these, the male-to-female ratio was 2.9:1 with the median age of 38 years. Most patients had stage II (37.5%) or III (29.2) disease, only 9.7% of the patients had stage IV. The most common histological gradings were well or moderately differentiated (98,5%). The most common involved site was the tongue (40.1%). A large number of patients (45.4%) received treatment with either surgery alone or a combination of surgery and other adjuvant therapy (45.9%). RESULTS: Collectively, these data indicate that OSCC remains a constant worldwide health problem. In addition, the occurrence of OSCC in young people is relatively high. Traditional risk habits including smoking and alcohol consumption remain the most important factors in the development of OSCC. CONCLUSION: Therefore, our data suggested that the OSCC prevention with early detection, early treatment intervention, and withdrawal from risk habits must be devised and advised also for patients in southern Italy.

N-(4-hydroxyphenyl)all-trans-retinamide (4-HPR) high dose effect on DMBA-induced hamster oral cancer: a histomorphometric evaluation.

N-(4-hydroxyphenyl)all-trans-retinamide (4-HPR) has shown cancer chemoprevention activity in many experimental and clinical situations. The purpose of this research is to evaluate the in vivo efficacy of 4-HPR in preventing 7,12-dimethylbenz(alpha)antracene (DMBA)-induced oral carcinogenesis and to study histomorphometric changes. 76 Syrian hamsters were separated into four groups: group 1, untreated controls (16 animals); group 2, 4-HPR controls (16 animals); group 3, DMBA-treated animals (28); group 4, animals treated with DMBA and 4-HPR (16). Hamsters were painted with a 0.5% solution of DMBA three times a week in their left buccal pouch. A diet of 2 mmol of 4-HPR/kg was administered. At week 9, 50% of the animals were killed; the remainder were killed at week 12. Pathology and histomorphometric tests were performed on epithelium, dysplasia and carcinomas. At week 9, 5 carcinomas were found in group 3, and 13 in group 4. Cancers in group 4 were more numerous, endophytic and infiltrating than those in group 3 animals. At week 12, 16 carcinomas were detected in group 3 animals, but group 4 developed more carcinomas per animal than group 3. Using these experimental concentrations, 4-HPR cannot express its best chemopreventive effect.

Accelerated wound healing of oral soft tissues and angiogenic effect induced by a pool of aminoacids combined to sodium hyaluronate (AMINOGAM).

In this study we investigated the property of a new medical substance, in the form of a gel compound containing four aminoacids (glycine, leucine, proline, lysine) and sodium hyaluronate (AMINOGAM), to accelerate the wound healing process of the soft oral tissues and to promote angiogenesis in vivo in the vascular proliferation in chick embryo chorioallantoic membrane (CAM) assay. Furthermore, we investigated the capacity of AMINOGAM to induce the expression of an angiogenic cytokine, namely vascular endothelial growth factor (VEGF) in human fibroblasts in vitro. Results showed that AMINOGAM promoted wound healing in post-surgical wounds (after teeth extraction, oral laser surgery with secondary healing without direct suture of the surgical wound, and after dental implant insertion). Stimulated angiogenesis in vivo in the CAM assay and the response was similar to that obtained with vascular endothelial growth factor, a well-known angiogenic cytokine, tested in the same assay, and confirmed by clinical outcomes, which showed reduction of the healing time of oral soft tissues after three different kinds of surgery and also the absence of post-operative infections.

Oral laser surgical pathology: a preliminary study on the clinical advantages of diode laser and on the histopathological features of specimens evaluated by conventional and confocal laser scanning microscopy.

AIM: The effects of diode laser therapy reported in literature are both clinical and biological. The aim of the present preliminary study was to verify the clinical benefits such as reduction of postoperative pain, inflammatory response and bleeding and also the benefits concerning wound healing and histopathological alterations of specimens related to diode laser surgery. METHODS: The study was carried out on a group of 25 patients; we evaluated histologically the surgical specimens both by conventional optical microscopy and by autofluorescence by confocal laser scanner microscopy, paying attention to the incision margins and to the eventual presence of thermally induced changes/ damages. Both benign and premalignant or malignant lesions were treated with diode laser, with an output ranging from 2 to 7 Watt. RESULTS: Clinically we had several advantages (haemostasis, reduction of pain, healing without suture) and wound healing was always complete in 20-30 days. In the specimens evaluated histologically we noticed a good precision of surgical margins while changes induced by laser such as coagulation of proteins were present only with high power density output. Considering that nowadays the use of diode laser in the treatment of premalignant or malignant lesions is still debated, in this preliminary study no difficulty occurred with the observation of the specimens and no alterations were found. CONCLUSION: Thanks to the preliminary results obtained with this study, we encourage the use of diode laser also for malignant lesions, considering that an important factor to obtain specimens without alterations is the choice of the laser setting, strictly related to clinical experience, clinical situation, site and biological nature of the lesion.

Expression of protease-activated receptor-1 and -2 in orofacial granulomatosis.

OBJECTIVE: Orofacial granulomatosis (OFG) is a rare condition characterized by non-caseating granulomas in the orofacial region. Protease-Activated Receptors (PARs) play a role in inflammatory diseases in diverse human tissues. The aim of the study was to investigate the expression of PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 in tissues taken from OFG patients. METHODS: PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 expression was evaluated by immunohistochemistry in biopsies taken from oral Crohn's disease (five cases), Melkersson-Rosenthal syndrome (MRS) (six cases), cheilitis granulomatosa (five cases) and normal oral mucosa (five cases). RESULTS: PAR-1 was observed in mononuclear inflammatory cells in edematous/lichenoid lesions, whereas a strong PAR-2 immunostaining was detected in epithelioid histiocytes and giant cells in granulomatous lesions, irrespective of the clinical features (Crohn vs MRS). MMPs and COX-2 were expressed in the inflammatory component of edematous/lichenoid lesions and markedly overexpressed in granulomatous lesions. COX-1 was weakly and variably expressed in both edematous/lichenoid and granulomatous lesions. CONCLUSION: Thus, PAR-1 and PAR-2 expressions were related to the intensity and type of inflammatory response but not to the type of clinical lesion. Simultaneous overexpression of PARs, MMPs and COXs suggests synergism among these proinflammatory receptors and enzymes.

Prognostic implications of NUMB immunoreactivity in salivary gland carcinomas.

The gene numb encodes for a protein (Numb) involved in cell fate decisions in Drosophila, with proposed endocytic and developmental functions in mammalians. The distribution pattern of Numb in human tissues however, has not been fully characterized. We set out to explore the immunohistochemical expression of Numb in normal and neoplastic (28 adenoid cystic and 34 mucoepidermoid carcinomas) salivary glands, and correlated the results with the clinico-pathologic features of the neoplasms. Intense Numb immunoreactivity was detected in normal ductal cells and in a subset of acinar cells. In salivary carcinomas, we detected diffuse and intense Numb immunostaining in 5 adenoid cystic and 8 mucoepidermoid carcinomas. By contrast, the majority of adenoid cystic and mucoepidermoid cancers showed only moderate (14 and 5 cases) or focal staining (9 and 21 cases), respectively. The corresponding expression of Numb mRNA was documented in normal parotid gland and adenoid cystic carcinoma. Numb immunoreactivity was inversely correlated with the histological grade and Ki-67 immunoreactivity of both adenoid cystic and mucoepidermoid carcinomas. In addition, while tumor grade, stage, Ki-67 and Numb immunoreactivity were associated with disease-free survival in univariate analysis, only Numb and Ki-67 immunoreactivities retained independent prognostic significance in multivariate analysis. These data suggest that loss of Numb is implicated in aberrant differentiation programs of salivary gland carcinomas and may serve as a prognostic indicator in patients treated for these neoplasms.

Multiple and giant mandibular osteomas in a Gardner's syndrome. Case report.

Though rare, Gardner's syndrome is a systemic disease with frequent jawbones involvement. Dento-maxillo-facial lesions both in early and in advanced stages should be known by dentists and other specialists. In fact, these lesions should be sought in patients with intestinal polyposis, while they could be the first sign of Gardner's syndrome not yet diagnosed.

Bilateral intraosseous adenoid cystic carcinoma of the mandible: report of a case with lung metastases at first clinical presentation.

OBJECTIVE: Malignant epithelial tumours arising in the jaws are very rare. Adenoid cystic carcinoma (ACC) represents approximately 7.5% of all carcinomas and only a few cases of intraosseous (central) ACC have been reported in the literature. MATERIALS: The salient clinico-pathological features of a case of ACC, bilaterally occurring in the mandible of a young caucasian woman who also had lung metastases are reported to appropriately characterize such unusual lesions and discriminate them from other tumours that more commonly affect the mandible. RESULTS: The patient presented with a painful swelling of the right retro-molar area and paraesthesia of the ipsilateral lower lip and radiological investigations disclosed bilateral radiolucent lesions of the mandible with unequivocal signs of malignancy but without intra-lesional calcifications or association with teeth roots or cystic component. Conventional histological examination disclosed typical ACC with solid and cribriform growth patterns and extensive infiltration of the adjacent tissues. CONCLUSIONS: The diagnosis of intraosseous malignant salivary gland type neoplasms is very difficult in view of their rarity and lack of specific signs and mainly achieved after histological examination and complete clinico-radiological work up. As surgical treatment of the patient was not indicated, due to extensive neoplastic disease, the patient is being controlled with multimodal treatment, including chemo- and radiotherapy and is alive with persistent disease 3 years after the original diagnosis.

Liposarcoma circumscriptum (lipoma-like) of the tongue: report of a case.

Liposarcoma, first described by Virchow in 1857, is the second most frequent sarcoma of soft tissues, although it is rare both in the head and neck and the oral cavity. Intra-orally, liposarcoma has been reported in the jawbones (particularly the maxilla) and the soft tissues -- mainly the cheek and floor of mouth, but it is rare in the tongue. A case of well-differentiated, superficial liposarcoma circumscriptum of the tongue is reported. The authors underline the difficulties in the clinical and histopathological diagnosis, as this tumour may be confused with lipoma. In view of the indolent behaviour of this tumour type, local recurrence or metastasis rarely occur; consequently, conservative surgical therapy is advised without adjuvant chemo-radio therapy.

Multiple parotid lymphoepithelial cysts in patients with HIV-infection: report of two cases.

OBJECTIVE: Bilateral and multiple lymphoepithelial cysts (LECs) of major salivary glands, in particular of parotid glands, are quite rare and have been reported in human immunodeficiency virus (HIV) infected patients with an incidence of about 3-6%. These lesions represent an early manifestation of HIV infection and are rarely found in patients with advanced acquired immunodeficiency syndrome. MATERIALS: Two cases of parotid LECs, the first occurring in a middle-age white woman and the second in a young white boy, both in advanced phases of HIV infection, are reported. RESULTS: Clinical, cytological, histological and immunohistochemical (cytokeratin AE1/AE3, CD20, CD45RA, CD8, kappa and lambda immunoglobulin light chains, S-100, MLA and Ki67) features are described. CONCLUSIONS: Fine needle aspiration (FNA), a relatively non-traumatic procedure, could represent both a diagnostic and a therapeutic tool in parotid LECs. No surgical therapy is usually required for these lesions and aspiration of cystic fluid with FNA is quite resolutive, although evidence of further relapses does exist. Surgical excision may become necessary when pain, because of persistent and progressive swelling of the parotid gland, occurs.

Lithiasis of minor salivary glands of the upper lip. Clinico-pathological report of a case with unusual presentation.

We report a rare case of lithiasis of the minor salivary glands (LMSG) of the upper lip, with a very atypical clinical presentation, firstly as a left hemifacial cellulitis and later, after antibiotic therapy, as a solid, firm and hard intramural nodule of the retrocommissural side of the upper lip; the needs of a wide spectrum of clinical differential diagnosis with calcified angiomas, salivary tumors, soft tissue tumors, phlogistic and neoplastic pathology of the local lymphnode, foreign body lesions, is underlined. The histological aspects of the lesion are described.