Cell adhesion molecules' altered profile in benign and malignant salivary gland tumors. The paradigm of beta4-integrin, desmoglein-2, ICAM-1 and CD44s.

BACKGROUND: Alterations in intercellular and cell-extracellular matrix connections contribute to tumour development. This study investigates the expression of specific cell adhesion molecules (CAMs) in salivary gland tumors (SGTs). METHODS: Formalin-fixed, paraffin- embedded tissue specimens of different types of 34 benign and 31 malignant SGTs and normal salivary glands were studied using Envision/HRP immunohistochemical technique for Desmoglein-2 (Dsg-2), beta4-integrin, CD44s and ICAM-1. Intensity of staining was evaluated in a semi-quantitative manner. Results were analyzed using Kendall's τ and Spearman's ρ as correlation criteria. RESULTS: Dsg-2 in intercellular space, beta4-integrin in cell-basal membrane, and CD44s in both types of contacts were strongly expressed in normal acinar and ductal cells, whereas ICAM-1 was expressed only at the endothelium and sparse stromal cells and monocytes. Strong correlation was found between Dsg-2 expression in adenomas and controls and between adenocarcinomas and controls. In adenomas, a distinct cytoplasmic presence of Dsg-2 was observed in addition to the usual membranous expression, with decreased expression in comparison with normal tissue. In malignant SGTs, Dsg-2 expression was absent. In most SGTs, beta4-integrin was expressed also with a distinct pattern, involving the cytoplasm and the unpolarised membrane, while CD44 was found only on the membrane. Strong correlation between beta4-integrin expression in adenomas and controls was noted, while CD44 expression was found to be correlated significantly between adenocarcinomas and controls (p < 0.001). Regarding ICAM-1, its expression was found increased in adenomas, with non-specific distribution in malignant SGTs and strong correlation between the histological subtypes and controls (p < 0.001). CONCLUSION: The different expression profile of CAMs in SGTs could possibly suggest a role on their pathogenesis, representing a model of how neoplastic cells can take advantage of normal tissue architecture and cell-extracellular matrix interactions.

Desmoglein-3/γ-catenin and E-cadherin/ß-catenin differential expression in oral leukoplakia and squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to investigate gene/protein expression alterations of intercellular connections' components in oral leukoplakia (OLs) and squamous-cell carcinoma (OSCCs). MATERIALS AND METHODS: Expression of desmogleins-2,3 (Dsg2/Dsg3), E-cadherin, and their cytoplasmic ligand, ß/γ-catenins were quantitatively assessed in HSC-3 cells growing as monolayer cultures (ML)/multicellular aggregates (MCAs), using RT-PCR/Western blot, whereas their localization was detected by immunofluorescence. Furthermore, their expression was semi-quantitatively investigated in tissues from 25 OLs/25 OSCCs, using automated immunohistochemistry. RESULTS: The steady-state levels of Dsg3 RNA transcripts increased as HSC-3 cells enter their exponential phase of growth, before a dramatic decrease to be observed as cells reached their plateau phase especially in MCAs. Upon the same period of time, Dsg2 levels have been increased. The expression of γ-catenin but not that of ß-catenin was increased after 48 h in both MLs and MCAs. In clinical samples, Dsg3, Ε-cadherin, ß/γ-catenin down-regulation was observed to be associated with the grade of OLs-dysplasia and OSCCs. Importantly, a membrane-to-cytoplasmic switch of expression and strong perinuclear aggregation of Dsg3/γ-catenin was seen in both HSC-3 cells and OLs/OSCCs. CONCLUSIONS: The altered expression of Dsg3/γ-catenin and E-cadherin/ß-catenin, in vitro and in ODs/OSCC imply their involvement in growth regulation and phenotype of dysplastic/malignant oral epithelial cells, contributing to the better understanding of epithelial dysplasia and OSCCs. CLINICAL RELEVANCE: The observed alterations of their expression suggest a role of Dsg3 and γ-catenin (additionally to E-cadherin/ß-catenin) as biomarkers of malignant transformation risk of oral dysplasia and the biological behavior (aggressiveness) of oral cancer, respectively.

Myofibroblasts and transforming growth factor-beta1 in reactive gingival overgrowths.

OBJECTIVES: The purpose of this study was to evaluate the oral health-related quality of life of patients treated with implant-supported mandibular overdentures and to compare the attachment systems used. MATERIAL AND METHODS: The presence of myofibroblasts as well as transforming growth factor-beta1 was examined in twenty cases of fibrous epulis and 22 ossifying fibrous epulis, using immunohistochemistry. RESULTS: Myofibroblasts positive for alpha smooth muscle actin and vimentin but negative to desmin were found in 20% and 45% in fibrous epulis and ossifying fibrous epulis, respectively. Myofibroblasts were distributed in areas with and without inflammatory infiltration and their presence in inflammatory areas was not related with the degree of inflammatory infiltration. A percentage of 21 - 60% of fibroblasts and chronic inflammatory cells expressed transforming growth factor-beta1 in all cases. CONCLUSIONS: These data suggest that transforming growth factor-beta1 and myofibroblasts contribute to the formation of collagenous connective tissue in fibrous epulis and ossifying fibrous epulis. Myofibroblasts are mainly presented in ossifying fibrous epulis than in fibrous epulis. It seems to be no relationship between the presence of myofibroblasts and the degree of inflammatory infiltration of the lesions.

Central odontogenic fibroma: report of case with immunohistochemical study.

OBJECTIVES: To report a case of central odontogenic fibroma (COF) with immunohistochemical study. CLINICAL PRESENTATION: We describe a case of epithelium-rich type of COF in the posterior region of the mandible of a 39-year-old woman. Immunohistochemical examination showed the odontogenic epithelium to be positive for high-molecular-weight cytokeratins, vimentin and CD99, and negative for CAM5.2. The stroma contained some myofibroblasts and many fibroblast-like cells positive for CD99. CONCLUSION: Our immunohistochemical findings, and especially the positive expression of vimentin from the epithelial cells of COF suggests that these cells are primordial. Last but not least, the presence of a relative small number of myofibroblasts in the stroma justifies the non-aggressive behavior of the neoplasm and supports that a part of stromal collagen of COF is produced by these cells.

Pleomorphic adenoma of the sublingual salivary gland: an unusual diagnostic challenge.

OBJECTIVES: To describe a rare case of pleomorphic adenoma of the sublingual gland. CLINICAL PRESENTATION AND INTERVENTION: An 80-year-old patient presented with a painless solid submucosal mass of 4 months' duration in the anterior floor of the mouth, appearing as a distinct homogeneous, radiolucent lesion in CT imaging. Histologic findings after complete removal were suggestive of a pleomorphic adenoma almost completely surrounded by a fibrous capsule. No recurrence was observed after a 12-month follow-up. CONCLUSION: This case showed the possibility of sublingual salivary gland tumors and highlighted the need to consider them when making a differential diagnosis of masses located in the floor of the mouth.

Lip ulceration associated with intravenous administration of zoledronic acid: report of a case.

Although osteonecrosis of the jaw is a well-known adverse reaction of bisphosphonates (BPs), random cases of oral mucosal ulceration after per os administration of BP-aledronate have been attributed to prolonged mucosal irritation. This report, for the first time, describes the mucosal ulceration related to intravenous use of zoledronic acid (ZA). A 52-year-old female patient presented with painful ulcers on both cutaneous/mucosal surfaces of the lower lip and a 2-month history of osteonecrosis of the mandible beside the right lower canine. Her medical record included intravenous administration of ZA for 10 months for primary breast cancer metastatic to bone. Examination of the peripheral blood showed severe anemia and a slightly increased white blood cell count, due to urinary tract infection by E. coli, but no evidence of a viral infection. The treatment of anemia and E. coli infection did not improve the labial ulcers. Biopsy from the mucosal lesion revealed a non-specific ulceration with moderate inflammatory infiltration. There was no evidence of infection or malignancy. ZA administration was discontinued and within 3 months the lesions were resolved after treatment with systemic antibiotics (amoxicillin), vitamins A and E, chlorexidine and H(2)O(2) (hydrogen peroxide) solutions and local pantothenic acid/vitamin A creams. Recurrence was detected a month after ZA re-administration. Nevertheless, after new treatment, the patient was free of oral/skin lesions 18 months later. This case, which is the first report of ulceration associated with intravenous administration of bisphosphonates, suggests that systemic mechanisms may be implicated in BP-induced oral mucosal ulceration. Furthermore, ZA appears to cause the same oral mucosal manifestations as alendronate. This emphasizes the need for oral examination in all cases of BP therapy, whether per os or intravenously administrated.

Tenascin-C in chronic sclerosing sialadenitis.

Tenascin-C is an extracellular matrix glycoprotein that has been implicated in the development of fibrosis in certain chronic inflammatory/sclerosing conditions. This study was undertaken to expand our understanding of the processes involved in fibrosis that occurs in chronic sclerosing sialadenitis (CSS) by investigating the distribution of tenascin-C. Fifteen specimens of CSS with varying degrees of fibrosis and five normal submandibular glands were retrospectively examined immunohistochemically for the distribution of TNC. Linear deposition of TNC was found around collecting ducts in normal glands and around collecting ducts without surrounding fibrotic tissue in CSS; percentage incidences were not statistically different. In contrast, broader, band-like deposition of TNC was found in the fibrous tissue around collecting ducts in CSS with widespread degree of fibrosis compared to little or no fibrosis; the percentage incidence was statistically different. In addition, deposition of TNC was found around duct-like structures and extremely atrophic acini but, interestingly, however, was not found in fibrotic interlobular septa. The results of this investigation suggest that TNC is likely involved in the fibrosis that occurs around collecting ducts in CSS.

Localized tongue Amyloidosis in a Patient with Neurofibromatosis type II.

BACKGROUND: Localized Amyloidosis (AL) may rarely involve oral mucosa. This is the first known reported case describing the development of tongue AL in a 30-year-old patient with Neurofibromatosis (NF) type-2. CASE: A female patient presented with a painless, well-circumscribed nodule of the tongue. Her medical history included NF type-2 with chromosome-22 abnormal karyotype (mosaicism), multiple intracranial and spinal meningiomas/schwannomas and unilateral blindness/deafness. The biopsy of the excised lesion of the tongue revealed subepithelial accumulation of an amorphous, nodular, fibrillar material positive for Congo red. Blood examination showed increased Thyroxine-T4 due to thyroid multinodular colloid goiter, but excluded any other hematological/immunological disorder or organ dysfunction. No recurrence was observed after a six-month follow-up. CONCLUSION: This case highlights the possibility of oral manifestations as the only sign of AL and reveals the unexpected co-existence of AL and NF 2, for the first time.

Angiofibrolipoma of the oral cavity.

We describe an unusual and rare case of a lipoma variant known as angiofibrolipoma. A literature search revealed only a few cases of angiofibrolipoma which were located in different anatomical sites; no case of angiofibrolipoma in the oral cavity has been previously reported. We present and discuss the histopatholological-immunohistological findings and features. Angiofibrolipoma histologically consists of mature adipocytes, blood vessels, and bundles of collagenous connective tissue with low to moderate cellularity. It is not encapsulated, but is histologically distinct from surrounding tissue. Positive immunohistological staining with CD-34 presented a large number of blood vessels of different sizes located between collagen fibers and adipocytes. The treatment of choice for a patient with angiofibrolipoma is surgical excision, which is expected to be curative.

Black hairy tongue in a 2-month-old infant.

Black hairy tongue (BHT) is an unusual condition in adults, and is characterised by marked accumulation of keratin on the filiform papillae of the dorsum of the tongue resulting in a hairlike appearance. The colour of the papillae may vary from brown to black. We describe a case of BHT in a 2-month-old infant. An extended review of the literature suggests that our case is the youngest ever reported. In conclusion, although BHT is considered benign, clinical, haematological and histological, evaluation is recommended to exclude several entities which can present as pigmented lesions of the oral mucosa.

Increased anxiety level and high salivary and serum cortisol concentrations in patients with recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal disorders. The aim of the study was to determine any association between anxiety levels and concentrations of salivary and serum cortisol in patients with RAS. It has been suggested that stress with its presumed effects on the immune system, constitutes one of the major causative agents of RAS. The concentrations of salivary and serum cortisol were measured in 38 patients with recurrent aphthous stomatitis, and 38 healthy controls. Salivary and serum cortisol levels were measured using a Luminenscent Immunoassay (LIA) method. Anxiety levels were evaluated using Spielberger's State-Trait Anxiety Inventory which measures both trait anxiety as a general aspect of personality (STAI-T) and state anxiety as a response to a specific situation (STAI-S). The salivary cortisol levels were 1.44 (+/- 0.58) microg dl(-1) in RAS patients and 0.91 (+/- 0.56) microg dl(-1) in controls (p = 0.001), while the serum cortisol levels were 3.13 (+/- 1.59) microg dl(-1) in RAS patients and 1.89 (+/- 1.11) microg dl(-1) in controls (p = 0.001). The state anxiety levels (STAI-S) were 48.85 (+/- 9.7) in RAS group and 39.45 (+/- 7.5) in control group (p = 0.001). The trait anxiety levels (STAI-T) were 49.78 (+/- 13.02) in RAS group and 38.49 (+/- 10.31) in control group (p = 0.001). Salivary and serum cortisol concentrations and state and trait anxiety levels in RAS were significantly higher than those in the control group. Our results suggest that stress may be involved in the pathogenesis of RAS.

Application of alpha-smooth muscle actin and c-kit in the differential diagnosis of adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma.

The expression of vimentin, alpha-smooth muscle actin (alpha-SMA) and c-kit in adenoid cystic carcinomas (AdCCs) and polymorphous low-grade adenocarcinomas (PLGAs) was investigated immunohistochemically to evaluate the application of these markers to distinguish AdCCs from PLGAs when the histological features are equivocal. Tissue specimens of AdCCs and of PLGAs, formalin-fixed and paraffin-embedded were retrospectively studied using vimentin, alpha-SMA and c-kit. Positive staining for alpha-SMA was identified in all AdCCs and 25% of PLGAs. The immunoreactivity of c-kit in all positive cases of AdCCs (83%) and PLGAs (41%) was more than 50% and less than 50% of tumor cells respectively. The expression pattern for both alpha-SMA and c-kit, in tubular structures of AdCCs was different of that seen in the same structures in PLGAs. The results of this study support the potential application of alpha-SMA and c-kit as an adjunctive aid in the differential diagnosis of AdCCs from PLGAs.

Detection of C-KIT (CD117) molecule in benign and malignant salivary gland tumours.

C-KIT (CD117), a tyrosine kinase receptor, is involved in the growth and development of normal tissues and some types of neoplasms. In the present study we analysed the expression of this molecule in salivary gland tumours. Archival formalin-fixed, paraffin-embedded sections of 40 benign and 57 malignant salivary gland tumours were retrieved and retrospectively studied immunohistochemically using a polyclonal C-KIT antibody in an Envision/HRP technique. In addition five samples of chronic submandibular sialadenitis, five normal minor salivary glands and parotid or submandibular gland tissue adjacent to benign tumour were also studied. C-KIT expression was observed in cases of adenoid cystic, acinic cell polymorphous low grade, epithelial-myoepithelial, carcinosarcoma and basal cell adenocarcinomas, as in luminal cells of pleomorphic adenomas, in serous acinar and only in intercalated and a small number of striated ductal cells of inflammatory salivary gland tissue, whereas normal salivary lobules were generally negative except a weak positivity of intercalated cells. Contrary to other reports, this study suggests that, C-KIT protein does not appear to be an exclusively specific marker for benign or malignant salivary gland neoplasms, but may be useful in differential diagnosis of adenoid cystic carcinoma from polymorphous low grade adenocarcinoma. Furthermore its expression in serous acinar cells in sialadenitis and intercalated ductal cells in normal and inflammatory lesions may indicate a possible participation in pathogenesis of both neoplastic and non-neoplastic salivary gland diseases.

Facial and perioral primary impetigo: a clinical study.

Impetigo is the most common skin infection in children. The face, especially the perioral region, is one of the most frequently involved areas. Impetigo is a disease that interests the pediatric dentist, as it poses significant problems in its differential diagnosis from other conditions. Sixteen otherwise healthy children were examined suffering from facial and perioral impetigo. The typical clinical appearance was scattered, painless, slightly pruritic erosions covered by "honey-colored" crusts. In 4 children impetigo was localized in the facial and perioral area, whereas in all other cases lesions were diffused in perioral area and several regions throughout the body. Four children exhibited neck lymphadenopathy and one had mild fever. The treatment of impetigo included the application of topical measures with the systemic antibiotic chemotherapy.

Immunohistochemical detection of the expression of the cell adhesion molecules E-cadherin, desmoglein-2, beta4-integrin, ICAM-1 and HCAM (CD44s) in Warthin's tumour of the parotid gland.

The study of the expression of cell adhesion molecules (CAMs), E-cadherin, desmoglein-2, beta4-integrin, HCAM (CD44s) and ICAM-1 in Warthin's tumours. Twenty formalin--fixed, paraffin--embedded parotid Warthin's tumours were studied using an Envision/HRP immunohistochemical technique. Beta4-integrin was strongly expressed in all cell-basement membrane and intercellular contacts of the epithelium, E-cadherin and desmoglein-2 in cell-cell contacts, but not in basal cell-basement membrane connections and on columnar cells' luminal surfaces, HCAM (CD44s) in intercellular contacts of both luminal (mainly), basal cells and also in the periphery of monocytic-lymphocytic stroma, and ICAM-1 was weak to moderate expressed in both luminal and basal epithelial cells and strongly in the germinal lymphocytic centres. CAM expression suggests a bilayered excretory ductal structure of the neoplastic epithelium in Warthin's tumour, as a result of hyperplastic process of the glandular epithelium that interacts with the excessive lymphoid tissue of the stroma.

Pyogenic granuloma of the oral cavity: comparative study of its clinicopathological and immunohistochemical features.

There are two histological types of pyogenic granuloma (PG) of the oral cavity: the lobular capillary hemangioma (LCH) and non-LCH type. The aim of the present study was to examine and compare the clinical features, etiological factors, diameter of vascular elements and immunohistochemical features of LCH and non-LCH histological types of PG to determine whether they are two distinct entities. Thirty cases of LCH and 26 cases of non-LCH PG were retrieved and retrospectively studied. Clinically, LCH PG occurred more frequently (66.4%) as sessile lesion whereas non-LCH PG occurred as pedunculated (77%). Non-LCH PG was associated more frequently (86.4%) with etiological factors. The lobular area of the LCH PG contained a greater number of blood vessels with small luminal diameter than did the central area of non-LCH PG. In the central area of non-LCH PG a significantly greater number of vessels with perivascular mesenchymal cells non-reactive for alpha-smooth muscle actin and muscle-specific actin was present than in the lobular area of LCH PG. The differences found in the present study suggest that the two histological types of PG represent distinct entities.