Role of osteopontin in oral epithelial dysplasia, oral submucous fibrosis and oral squamous cell carcinoma.

Background: Inflammatory cells and cytokines in the chronically injured mucosa promote fibrosis in the oral submucous fibrosis (OSF) fibrotic milieu. Osteopontin (OPN) is a wound-healing mediator that upregulates the inflammatory response and is involved in the malignancy and fibrosis of multiple organ systems. Objectives: We investigated the expression of OPN in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs) to determine its role in the malignant transformation and fibrosis of oral tissues. The expression of OPN in OPMDs and OSCCs was compared and correlated, and the role of OPN as a fibrotic mediator in OSF was explained. Study Design: A total of 30 cases of normal mucosa and OPMDs (mild dysplasia, severe dysplasia, OSF and OSCCs) were studied by purposive sampling. In these groups, OPN immunoreactivity was examined and correlated with clinical findings. Results: In mild dysplasia, OPN expression was restricted to the basal cell layer with moderate staining intensity. In severe dysplasia, it was extremely intense and extended throughout the epithelium. In the OSF, OPN expression was moderate in the perinuclear areas of the basal cell layer. The expression of OPN was very strong in OSCC. A flow diagram explaining the profibrotic role of OPN in OSF has been provided. Conclusion: A positive role of OPN in both pathogenesis and malignant transformation of OPMDs and OSCC has been demonstrated.

Rare case of giant unicystic ameloblastoma: Luminal variant.

OBJECTIVE AND IMPORTANCE: Ameloblastoma is a locally aggressive benign tumor, commonly occurring in the mandible. While giant ameloblastoma of multicystic or plexiform variant have been reported, the authors report a rare case of giant unicystic ameloblastoma of luminal variant, which was treated by compartmental resection and planned for delayed reconstruction. CLINICAL PRESENTATION: A 46 year old male patient reported to the oral surgery out-patient department with a swelling of the left side mandible region of 2 years duration. He had undergone ayurvedic treatment for the same with no improvement. The size of the lesion on presenting was approximately 9 × 12 cm. INTERVENTION: Compartmental resection with plan for secondary reconstruction, after adequate follow up period. CONCLUSION: While conservative management is being explored as a treatment option for unicystic ameloblastoma, resection is still the standard of care regardless of the histopathological subtype for giant lesions.

An Erupted Silent Tumour.

Odontomas are the most common odontogenic tumors of the oral cavity which are nonaggressive, hamartomatous in nature consisting of enamel, dentin and cementum. They are called as composite because they contain more than one type of tissue. They are generally asymptomatic, hence recognised on routine radiologic examination. The compound odontoma is composed of multiple small tooth like structures, whereas the complex odontoma consists of a conglomerate mass of enamel and dentine, which bears no anatomical similarity to the tooth. The eruption and infection of odontoma are uncommon, only few cases of erupted complex odontoma are reported in the literature. We report a case of silent erupting complex odontoma.

Immunohistochemical analysis of tenascin expression in different grades of oral submucous fibrosis.

AIM: Tenascin, a glycoprotein, is one of the major constituents of extracellular matrix, which may function in organizing the stroma in normal and pathological conditions. The study aimed to correlate the structural organization of tenascin with the pathological progression of disease from early, moderate and advanced changes in oral submucous fibrosis (OSMF). STUDY DESIGN: A retrospective cross-sectional immunohistochemical (IHC) analysis of OSMF cases was performed. Total 70 slide samples were prepared for the study from 35 formalin-fixed paraffin-embedded tissue blocks with 10 each from histologically proven and graded as early, moderate and advanced OSMF and 5 of normal oral mucosa. The IHC sections were analyzed for the intensity and pattern of tenascin expression at the junction of epithelium and connective tissue (ECJ) and deeper connective tissue (CT), as well as presence or absence of staining around inflammatory cells, fibroblast and endothelial cells using anti-human tenascin. RESULT: Most of the OSMF cases showed retention of antigen at ECJ and in deeper CT. Its expression varied in different grades as well as around inflammatory cells, fibroblast and endothelial cells in same tissue section. Highly significant P values of 0.001 and 0.003 were obtained for tenascin intensity and pattern, respectively, at ECJ in different OSMF grades. In addition, for the expression of tenascin pattern in deeper CT among different OSMF grades, a significant P value of 0.018 was obtained. CONCLUSION: A differential expression of tenascin was observed with the progression of disease. The expression of tenascin as bright and continuous deposition at ECJ in early and moderate stages of OSMF signifies either proliferative organization within the overlying epithelium or an epithelial-mesenchymal interaction. However, a weak immunoreactivity of tenascin at ECJ was observed in advanced stage of OSMF.

Immunohistochemical characterization of cyclin dependent kinase-4 in different histological grades of oral leukoplakia and oral squamous cell carcinoma.

BACKGROUND: Cyclin dependent kinase-4 (CDK4) encoded by CDK gene, is a heterodimer protein of cell cycle in G1-S transition. This study aimed to characterize the CDK4 immunoreactivity in different histological grades of oral leukoplakias (OLs) and oral squamous cell carcinomas (OSCCs) and also aims to discuss its probable role in the tumor biogenesis. MATERIALS AND METHODS: Expression of CDK4 was investigated in total of 52 samples including OL (15), OSCCs (30) and normal oral tissues (07). A labeled Streptavidin-Biotin immunohistochemistry assay was performed and staining intensity was evaluated. RESULTS: The staining pattern was similar in all tissues and was located in both nuclei and cytoplasm. Dysplastic epithelium displayed a progressive increase in nuclear expression of CDK4 when compared to normal tissues. Also, positive staining cytoplasm was highly evident in OSCC with loss of differentiation. CONCLUSION: Our study indicated a progressive over expression of CDK4 from normal to leukoplakias (various histological grades of dysplasias) and OSCCs.

Analysis of gonial angle in relation to age, gender, and dentition status by radiological and anthropometric methods.

BACKGROUND: With development and function, the mandibular angle has shown changes in size and shape. A variation in mandibular angle with age, gender, and even the dental status has been observed, which is supported by radiographic and anthropometric studies. AIMS: The aim of this study were to evaluate relationship between complete loss of teeth and changes in the gonial angle; the study further intends to evaluate any variation in gonial angle with age and gender. The study intends to assess the reliability and accuracy of age and gender determination using gonial angle as a parameter. MATERIALS AND METHODS: A total of 185 subjects (91 males; 89 females) were included in the study and were divided into five groups on the basis of the chronological age. Physico-forensic anthropometry and lateral cephalometric methods were used to record the gonial angle. RESULTS: The present study shows a definite decrease in the gonial angle with advancing age, but the intergroup analysis does not follow a significant pattern. The study showed no correlation of gonial angle with gender. However, the study observed a 6° increase in gonial angle for edentulous subjects. CONCLUSION: Gonial angle has been used as an adjuvant forensic parameter, but its reliability is questionable, as the mandible does not follow one characteristic pattern. Gonial angle does show changes with dentition status, which may be attributed to physiologic function of the mandible. However, when evidence is scanty, it can be used to direct the investigation.

Bisphosphonate-associated osteonecrosis of the jaws.

Bisphosphonates constitute a group of drugs capable of modulating bone turnover and reduce its remodeling when an excessive resorption occurs. This is why they are indicated in a large group of bone diseases like postmenopausal osteoporosis or osteolysis associated with breast cancer or multiple myeloma. Over the last few years and due to their extensive use, many cases of complications associated with their use have been published. Among the most important possible adverse effects are the oral ones, with the appearance of ulcerations and, especially, osteonecrosis of the jaws associated with this therapy. In this paper, we have analyzed the general characteristics of these drugs and their mechanisms of action as well as the described adverse effects, especially oral and maxillofacial, have been made special reference, regarding the prevention of osteonecrosis of the jaws, heightened by cases described in the medical and odontological literature. The preventive protocol backs up the fundamental role of the odontologist in the effective prevention of this process before, during and after the treatment.

Expression of extracellular matrix-laminin in oral squamous cell carcinoma: an immunohistochemical study.

AIM: To evaluate the expression of laminin in various grades of oral squamous cell carcinoma (OSCC) in order to determine whether this protein can be used as a marker for early detection and elucidation of oral cancer. MATERIALS AND METHODS: Immunohistochemical staining for laminin was done on 60 selected archival blocks of histopathologically diagnosed cases of primary OSCC and the laminin expression was compared between the different histopathological grades of primary OSCC. The statistical analysis was performed by using Chi-square (X square) test and Gaussiantest with a probability of p > 0.05 was considered as significant. RESULTS: It was observed that laminin expression decreased with tumor progression which may be correlated to the tumor aggressiveness. CONCLUSION: There was a gradual decrease of laminin staining with decreasing cellular differentiation, with differentiated lesions showing a more conspicuous staining of basement membrane glycoprotein than less differentiated lesions. CLINICAL SIGNIFICANCE: An understanding of how the extracellular matrix influences tumor development and invasion is fundamental in the development of new prognostic indicators and treatment strategies for oral squamous cell carcinoma..

A comparative analysis of langerhans cell in oral epithelial dysplasia and oral squamous cell carcinoma using antibody CD-1a.

BACKGROUND: The integrity of the immune system is necessary to control tumor progression and a compromised state contributes to tumor escape. AIMS: The study intends to evaluate the presence and distribution pattern of Langerhans cells (LC) in Oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) oral epithelial dysplasia and oral squamous cell carcinoma and elucidate their role. The study analyses LC in histological zones of the epithelium and connective tissue, which has seldom been attempted previously. MATERIALS AND METHODS: Forty-five microscopic sections (i.e. 5 normal, 15 OED and 25 OSCC) were examined for expression of LC marker CD1a using immunohistochemistry. LCs were counted in zones of epithelium and connective tissue. STATISTICAL ANALYSIS USED: Results were analyzed using SPSS Version 16.0 and subjected to one-way ANOVA comparison and Student's t-test and Wilcoxon Z test. RESULTS: Significant decline in LC count was observed with progressing grade of OED and OSCC. The basal and suprabasal zones in OED and superficial zone in OSCC exhibited the highest density of LCs. The low LC count in severe dysplasia was attributed to paucity in the basal zone. There was a significant paucity of LCs in the sub-epithelial zone of all the grades of OSCC, with high influx of LCs within the tumor stroma. Also, poorly differentiated OSCC exhibited a significant decrease in the LC count within the overlying epithelium as well as the tumor stroma. CONCLUSION: The present study suggests that there is a recruitment of LCs in the neoplastic process. Changes observed in LC distribution within the zones of dysplastic epithelium and tumor stroma can be interpreted as their pathophysiologic function.

Stromal response in different histological grades of oral squamous cell carcinoma: a histochemical study.

OBJECTIVES: The aim of the study is to evaluate the connective tissue changes in different grades of Oral Squamous Cell Carcinoma (OSCC's) and the influence of these changes in predicting the biological behavior of these tumors. MATERIALS AND METHODS: A total of 39 cases of OSCC's and 6 sections of controls were examined using seven connective tissue special histochemical stains. RESULTS: Staining intensity of collagen, reticulin, acid mucins, fibrin, glycoproteins, sulfated mucins, elastic fibers around the tumor islands and within the connective tissue was observed. CONCLUSIONS: Tumor cells which grow progressively in the host stroma have the capacity to pre-empt and subvert the response of host, which is essential for their growth and spread. CLINICAL RELEVANCE: The reactive changes in the tumor stroma may alter the biological aggressiveness of oral cancer, and by incorporating this concept into a prognostic system, we may help to reflect the biologic diversity of oral cancer and predict its clinical outcomes.

Reliability of toluidine blue vital staining in detection of potentially malignant oral lesions--time to reconsider.

Being simple and inexpensive toluidine blue has been in use for more than two decades for the detection of potentially malignant oral lesions (PMOL's) and malignant lesions. Although there has been concensus that staining often assists in the identification of these lesions, results have been diverse. In most studies false negative were not recorded as biopsies of lesions that did not retain toluidine blue were not performed. Thus the present study attempted to evaluate the efficacy of toluidine blue vital dye for detection of PMOL's. The study included 47 biopsies (TBP:35 and TBN:12), of which 23 cases were confirmed as dysplastic (TBP=17 and TBN=6), 7 as hyperkeratosis (TBP=4 and TBN=3), 8 as epithelial hyperplasia (TBP=6 and TBN=3) and 5 as other benign lesions (TBP=4 and TBN=1). The validity test revealed a senstivity of 73.9% and specificity of 30%. The positive predictive value was 54.8% and negative predictive value of 50%. The study intends to highlight the false negative result (26.1%) which was mainly attributed to mild dysplasia and the false positive (32.6%) which included hyperkeratosis, hyperplasia, lichen planus and traumatic ulcer. The study concludes that toluidine blue staining should not blindly direct the clinician's opinion, and strongly discourages the use of toludine blue as a screening test and the results should be interpreted with caution.

Spectrophotometric analysis of the expression of secreted aspartyl proteinases from Candida in leukoplakia and oral squamous cell carcinoma.

Candida species are a normal commensal of the oral cavity in healthy individuals, but can become an opportunistic pathogen when the oral ecosystem is unbalanced. Several virulence attributes have been identified in candidal infection, among which are the hydrolases, including the secreted aspartyl proteinases (Saps). This study evaluated and compared the in vitro level of Saps from Candida albicans in nonsmokers, smokers, and patients with leukoplakia and oral squamous cell carcinoma (OSCC). Candida cell count (CCC) at 48 h was also assessed. The Sap level was measured by spectrophotometry in 38 clinical isolates of C. albicans obtained from the oral cavity of the four different groups. Culturing was done in yeast carbon base-bovine serum albumin. Speciation of Candida was performed by using a Candida identification kit, and CCC was measured by hemocytometer. Sap levels and CCC were higher in individuals with leukoplakia and OSCC than in nonsmokers or smokers (P = 0.001); however, there was no significant difference in Sap levels or CCC between smokers and nonsmokers (P = 0.529). Further, an intragroup correlation between CCC and Sap level was also observed. The higher level of Saps from C. albicans in individuals with leukoplakia and OSCC suggests that this pathogen plays a role in disease development and could aid in identifying the pathogenic commensal.

Rhabdomyosarcoma of mandible: A diagnostic predicament.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children under 15 years of age and rare among persons older than 45 years of age. It is considered to result from malignant transformation of primitive mesenchymal cells. Although it has a relative predominance for head and neck region, it is found less often in oral cavity. Here we report a case of RMS of mandible in an adult patient, which was initially diagnosed as carcinosarcoma. Clinical and pathologic findings are described, which were confirmed by histochemical and immunohistochemical stains.

Immunohistochemical expression of EGP40, a tumor marker, in different grades of oral squamous cell carcinoma.

AIM: The aim of this study was to see the distribution and pattern of staining of epithelial glycoprotein 40 EGP-40 (also known as GA733-2, ESA, KSA, 17-1A antigen) in the different grades of OSCC. MATERIALS AND METHODS: 30 biopsy reports retrieved from the files of the Department of Oral Pathology and Microbiology, College of Dental Surgery, Manipal were used. These comprised of 10 microslides each of 3 different histological grades of Oral Squamous Cell Carcinoma, namely Well Differentiated, Moderately Differentiated and Poorly Differentiated carcinomas. Immunoperoxidase staining for IgG, was performed by the unlabelled antibody peroxidase-antiperoxidase complex (PAP) method. The criteria used to define an antigen positive area were: Homogenous /Patchy staining of the section and Cytoplasmic/ Membranous staining of the tumor cells. RESULTS: The expression of EGP 40 in different grades of OSCC showed an inverse relationship to differentiation and a direct relationship with the proliferation of the tumor cells and its expression became more pronounced as the grade worsened i.e. from well to poorly differentiated OSCC. CONCLUSION: In the present study, the surface antigen EGP40 (Ep-CAM) was detected in the different grades of OSCC with its expression becoming more pronounced as the grade worsened i.e. from well to poorly differentiated OSCC. However, further studies are required to understand the dualistic role of EGP40 (Ep-CAM) in mediating cell to cell adhesion preventing cell scattering and its heterogeneous expression in promoting tumor invasion and metastasis and also to determine its exact role and significance at a practically applicable level.

Evaluation of collagen in connective tissue walls of odontogenic cysts--a histochemical study.

BACKGROUND: The purpose of this study was to evaluate the nature of collagen in the connective tissue walls of odontogenic cysts, like the odontogenic keratocyst (OKC), dentigerous cyst and radicular cyst using picrosirius red stained sections. Furthermore, it was intended to assess if the capsular connective tissue can affect the nature of overlying epithelium, thus emphasizing the role of epithelial-mesenchymal interactions in biological behaviour of the cysts. MATERIALS AND METHOD: The material for the study included 51 formalin-fixed paraffin-embedded tissue blocks (15 odontogenic keratocyst, 15 dentigerous cysts, 15 radicular cysts and four normal mucosa and two dental follicular tissue as controls), retrieved from the Department of Oral Pathology and Microbiology, MCODS, Manipal. Tissue blocks were sectioned at 5-µm thickness, stained with picrosirius red stain and observed with polarization and light microscopy. RESULTS: Few sections of OKC and dentigerous cyst exhibited greenish-yellow birefringence in sub-epithelial region, whereas others showed a yellowish-orange birefringence under polarization microscopy. Most radicular cysts had yellowish-orange to orange birefringence. Shift in colour in case OKC and dentigerous cyst was attributed to the presence of inflammation in those sections. These regions also exhibited either a change in phenotype or thickness of overlying epithelium. CONCLUSION: This technique can be used to study the nature of collagen fibres in odontogenic cyst walls. Further studies with an increased sample size and using various epithelial and mesenchymal markers and ssDNA antibodies should be carried out to confirm the effect of epithelial-mesenchymal interactions on the nature of epithelium of odontogenic cysts.

Histochemical analysis of pathological alterations in oral lichen planus and oral lichenoid lesions.

Lichen planus is a dermatologic disease of unknown etiology characterized by keratotic plaques on the skin. Many patients also harbor white lesions of the oral mucosa. The literature contains numerous reports of lichen planus-like lesions evolving in conjunction with the administration of a variety of pharmacologic agents. It is difficult, if not impossible, to distinguish such lesions from one another. The present study evaluated the epithelial and basement membrane thickness, mast cells (intact cells and degranulated cells subepithelially) and the presence or absence of blood vessels in oral lichen planus and oral lichenoid lesions. The evaluation was done using the periodic acid-schiff (PAS) and toluidine blue staining techniques on 20 cases each of oral lichen planus and oral lichenoid lesions and 5 control specimens of normal buccal mucosa. The results showed an increased number of degranulated mast cells in areas of basement membrane degeneration, increased vascularity and increased PAS-positive basement membrane thickness in oral lichen planus as compared with oral lichenoid lesions. Reduced epithelial thickness was found in oral lichen planus. The present study emphasizes the importance of these parameters in differentiating oral lichen planus from oral lichenoid lesions using special staining techniques.

Plasmablastic lymphoma of the oral cavity in an HIV-positive child.

A 7-year-old boy with a positive history of vertical HIV transmission presented with a painful swelling over the left upper jaw of 20 days' duration. A provisional diagnosis of non-Hodgkin's lymphoma or embryonal rhabdomyosarcoma was made. Fine-needle aspiration cytology findings were inconclusive, and incisional biopsy tissue on routine stains gave an impression of small round cell tumor with plasmacytoid features. A series of histochemical stains and immunohistochemical studies was carried out to differentiate and characterize this tumor. The salient immunostaining was negativity with all routine small round cell tumor markers and positivity with CD138 and lambda light chain restriction. The heterogeneous presentation of plasmablastic lymphoma as a variant of diffuse large B-cell lymphoma and its histogenesis is documented. Potential pitfalls and differential characterization of AIDS-plasmablastic lymphoma from other closely related tumors are addressed. The importance of excluding other common pediatric small round cell tumors by immunohistochemistry is highlighted. To the best of our knowledge, this is the first report of this entity in a vertically transmitted HIV-positive child.

Mucormycosis causing extensive destruction of maxilla.

Mucormycosis is a rare, often fatal opportunistic infection caused by a saprophytic fungus belonging to a class of Phycomycetes. It is characterized by its unrelenting progression towards vital organs with marked propensity towards arterial wall by direct extension producing vascular thrombosis leading to ischaemic necrosis. In normal circumstances the saprophytes are not pathogenic but represent opportunist-requiring impairments in patient's resistance to disease. If not treated the disease may prove fatal. We report a case of Mucormycosis with extensive necrosis of the maxilla in a 57-year-old patient suffering from uncontrolled diabetes with ketoacidosis.