Description

The aim of the Journal of Oral Pathology & Medicine is to publish manuscripts of high scientific quality representing original clinical, diagnostic or experimental work in oral pathology and oral medicine. Papers advancing the science or practice of these disciplines will be welcomed, especially those which bring new knowledge and observations from the application of techniques within the spheres of light and electron microscopy, tissue and organ culture, immunology, histochemistry and immunocytochemistry, microbiology, genetics and biochemistry. Review papers on topical and relevant subjects will receive a high priority and articles requiring rapid publication because of their significance and timeliness will be included as "Short Communications" not exceeding two printed pages. All submitted manuscripts falling within the overall scope of the Journal will be assessed by at least two suitably qualified referees.

Publisher details

Blackwell Publishing

Publications in this journal

• Oral malignant melanoma: a review of the literature.

  Authors: Felice Femiano, Alessandro Lanza, Curzio Buonaiuto, Fernando Gombos, Federica Di Spirito, Nicola Cirillo

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

  Primary oral melanoma (POM) is an uncommon malignant tumor that originates from the proliferation of melanocytes. Such tumors can be present at any location in the oral cavity; however, it affectsPrimary oral melanoma (POM) is an uncommon malignant tumor that originates from the proliferation of melanocytes. Such tumors can be present at any location in the oral cavity; however, it affects more frequently the hard palate and the maxillary alveolar mucosa. POM is usually asymptomatic in the early stages and it presents normally as a pigmented patch or as a mass with a rapid growth rate. In the advanced stages, it can show ulceration, swelling, bleeding, rapid enlargement and loosening of teeth. Melanoma of the mouth is rare, most commonly occurring in the upper jaw of patients more than 65 years. Because of a frequent delay in diagnosis, the tumors are often diagnosed when they are deeper than the average cutaneous melanoma. The prognosis is extremely poor, especially in advanced stages. Therefore, pigmented lesions of undetermined origin should be routinely subjected to a biopsy examination. In this study, we aimed to present a review on primary malignancy.

• Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of beta-catenin.

  Authors: Jin Tanahashi, Tsutomu Daa, Naomi Yada, Kenji Kashima, Yoshiyuki Kondoh, Shigeo Yokoyama

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

  Background: To clarify the genetic background of ameloblastoma, expression of beta-catenin, and mutational status of genes involved in Wnt signaling pathway were investigated. Methods: We analyzedBackground: To clarify the genetic background of ameloblastoma, expression of beta-catenin, and mutational status of genes involved in Wnt signaling pathway were investigated. Methods: We analyzed beta-catenin and cyclin D1 in 18 cases of ameloblastoma by immunohistochemical staining, and searched for mutations in CTNNB1 (gene for beta-catenin), APC, AXIN1, and AXIN2 by polymerase chain reaction (PCR) and direct sequencing method. Result: We detected membranous and occasionally cytoplasmic expression of beta-catenin in 16 of 18 cases (89%), and nuclear expression of beta-catenin principally in the peripheral columnar cells in 11 of 18 cases (61%). In nine of the 18 cases (50%), we detected the expression of cyclin D1 principally in the peripheral columnar cells. However, there was no correlation between nuclear expressions of beta-catenin and cyclin D1. No missense mutations were found in CTNNB1, APC, AXIN1, and AXIN2 in all cases except for silent mutation and already-known single nucleotide polymorphism. Conclusion: Mutations in CTNNB1, APC, AXIN1, and AXIN2 are not implicated in nuclear accumulation of beta-catenin, and that the expression of cyclin D1 is accelerated independently of beta-catenin in ameloblastomas. Other Wnt signaling members or alternative pathways involved in the degradation of beta-catenin should be subject of further investigation.

• Fingerprinting genomic instability in oral submucous fibrosis.

  Authors: M T Teh, W M Tilakaratne, T Chaplin, B D Young, A Ariyawardana, G Pitiyage, A Lalli, J E Stewart, E Hagi-Pavli, A Cruchley, A Waseem, F Fortune

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

  Background: Oral submucous fibrosis (OSF) is a high-risk pre-cancerous condition where 7-13% of these patients develop head and neck squamous cell carcinoma (HNSCC). To date there is no cancerBackground: Oral submucous fibrosis (OSF) is a high-risk pre-cancerous condition where 7-13% of these patients develop head and neck squamous cell carcinoma (HNSCC). To date there is no cancer predictive markers for OSF patients. Genomic instability hallmarks early genetic events during malignant transformation causing loss of heterozygosity (LOH) and chromosomal copy number abnormality. However, to date there is no study on genomic instability in OSF. Although this condition is known as a high-risk pre-cancerous condition, there is no data regarding the genomic status of this disease in terms of genetic susceptibility to malignant transformation. Methods: In this study, we investigated the existence of genetic signatures for carcinogenesis in OSF. We employed the high-resolution genome-wide Affymetrix Mapping single nucleotide polymorphism microarray technique to 'fingerprint' global genomic instability in the form of LOH in 15 patient-matched OSF-blood genomic DNA samples. Results: This rapid high-resolution mapping technique has revealed for the first time that a small number of discrete hot-spot LOH loci appeared in 47-53% of the OSF tissues studied. Many of these LOH loci were previously identified regions of genomic instability associated with carcinogenesis of the HNSCC. Conclusion: To our knowledge, this is the first evidence that genomic instability in the form of LOH is present in OSF. We hypothesize that the genomic instability detected in OSF may play an important role in malignant transformation. Further functional association studies on these putative genes may reveal potential predictive oral cancer markers for OSF patients.

• High frequency of hypermethylation of p14, p15 and p16 in oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka.

  Authors: Maiko Takeshima, Masato Saitoh, Kaoru Kusano, Hiroki Nagayasu, Yoshihito Kurashige, Muthumala Malsantha, Toshiya Arakawa, Taishin Takuma, Itsuo Chiba, Tohru Kaku, Toshiyuki Shibata, Yoshihiro Abiko

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

  Background: Oral squamous cell carcinoma and the most common oral pre-malignancies appear to be related to the habit of betel-quid chewing in Sri Lanka. Although hypermethylation of the tumourBackground: Oral squamous cell carcinoma and the most common oral pre-malignancies appear to be related to the habit of betel-quid chewing in Sri Lanka. Although hypermethylation of the tumour suppressor genes in oral cancer have been well documented, little information has been available concerning hypermethylation in oral pre-cancerous lesions. In the present study, we investigated the hypermethylation of p14, p15 and p16 in pre-cancerous lesions including epithelial dysplasia and submucous fibrosis. Methods: All samples were obtained from patients with a betel-quid chewing habit in Sri Lanka. Sixty-four patients were clinically diagnosed with leukoplakia, and histopathologically diagnosed with mild or severe dysplasia. Ten patients were diagnosed with submucous fibrosis without epithelial dysplasia. CpG island hypermethylation was assessed by a methylation-specific PCR method. Immunohistochemical staining was performed using anti-p53 antibodies. Results: A high frequency of hypermethylation of p14, p15 and p16 was detected in the pre-cancerous lesions, although no hypermethylation was found in normal epithelium. The frequency of hypermethylation was higher than that of positive staining for p53 mutation except in the case of p16 in mild dysplasia. No significant correlation was observed between p53-positive reactions and hypermethylation in any lesions. The hypermethylation was highly detectable even in p53-negative lesions, suggesting that hypermethylation of p14, p15 and p16 occur regardless of whether the lesions have p53 mutations or not. Conclusions: The present study indicates that hypermethylation may be involved in the pathogenesis of oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka.

• A study of phosphorylated ERK1/2 and COX-2 in early stage (T1-T2) oral squamous cell carcinomas.

  Authors: Tine M Søland, Camilla Husvik, Hanna Strømme Koppang, Morten Boysen, Leiv Sandvik, Ole Petter Fraas Clausen, Thoralf Christoffersen, Magne Bryne

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

  Background: Histomorphological grading at the invasive front of oral squamous cell carcinomas (OSCCs) may provide useful prognostic information. In the present study, we investigated the presence andBackground: Histomorphological grading at the invasive front of oral squamous cell carcinomas (OSCCs) may provide useful prognostic information. In the present study, we investigated the presence and prognostic value of activated phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2) and cyclo-oxygenase-2 (COX-2) both at the invasive front and in central/superficial parts of OSCCs. Methods: Using immunohistochemistry, we assessed the presence of p-ERK1/2 and COX-2 in 53 early stage OSCCs. Clinical data were recorded prospectively. The end point was disease-free survival. Results: p-ERK1/2 staining was present in almost all tumours. The staining was mostly nuclear in the cells of the invasive front and either nuclear or nuclear/cytoplasmic in central/superficial tumour parts. COX-2 was observed in almost all tumours (98%) and the staining was often restricted to focal areas. Most tumours were COX-2 negative at the invasive front. The lowest P-value in survival analyses was P = 0.06 for p-ERK1/2 at the invasive front. COX-2, the histomorphological grading systems and TNM stage were of no prognostic value. Conclusion: p-ERK1/2 was present in almost all tumours and p-ERK1/2 may be a prognostic marker at the invasive front of OSCCs. In early stage OSCCs, most tumours did not express COX-2 at the invasive front.

• Quantitative histological changes of repeated antigen-induced arthritis in the temporomandibular joints of rabbits treated with intra-articular corticosteroid.

  Authors: Kasper Dahl Kristensen, Peter Stoustrup, Annelise Küseler, Thomas Klit Pedersen, Jens Randel Nyengaard, Ellen-Margrethe Hauge, Troels Herlin

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

  Background: To compare the inflammatory changes of antigen-induced temporomandibular joint (TMJ) arthritis in rabbits by different histological methods and to evaluate the immunomodulatory effect ofBackground: To compare the inflammatory changes of antigen-induced temporomandibular joint (TMJ) arthritis in rabbits by different histological methods and to evaluate the immunomodulatory effect of intra-articular corticosteroid injections histologically. Methods: 35 rabbits (10 weeks old) pre-sensibilized with ovalbumin were divided into three groups: a placebo group of five (saline), an arthritis group of 15 (ovalbumin) and a steroid-treated group of 15 (ovalbumin + corticosteroid). Additionally, a group of seven rabbits receiving no sensibilization with ovalbumin and no intra-articular injections served as controls. Histomorphometry of the inflammatory changes in the subsynovial connective tissue (SSCT) of the TMJ included: (i) semi-quantitative (S-Q) scoring of inflammation and synovial proliferation, (ii) thickness measurements and fractional surface and (iii) stereological quantitative assessment of volume and plasma cells in thick sections of the SSCT by an optical fractionator. Results: The histomorphometry showed synovial proliferation in both the arthritis and the steroid groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating the TMJ with corticosteroids. However, the thickness of the synovial lining and volume of the SSCT as well as S-Q scoring of inflammation showed no difference between the arthritis and the steroid-treated groups. The optical fractionator proved a superior tool compared to S-Q assessments. Conclusion: Counting of plasma cells in the SSCT showed that corticosteroids reduced the inflammation, but did not eliminate it. Semiquantitative scoring of synovial proliferation and inflammation demonstrated low sensitivity regarding changes in immunomodulation in antigen-induced arthritis compared to stereological quantitative estimations using an optical fractionator.

• Prevalence of oral cancer and pre-cancer and associated risk factors among tea estate workers in the central Sri Lanka.

  Authors: A Ariyawardana, M A M Sitheeque, A W Ranasinghe, I Perera, W M Tilakaratne, E A P D Amaratunga, Yi-Hsin Yang, S Warnakulasuriya

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):581-7.

  BACKGROUND: To screen for oral cancer or not is being debated, but for high-risk populations with minimal access to regular dental care systematic oral examinations could provide some benefit.BACKGROUND: To screen for oral cancer or not is being debated, but for high-risk populations with minimal access to regular dental care systematic oral examinations could provide some benefit. METHODS: We undertook oral mucosal examinations of labourers employed in tea estate plantations in Sri Lanka. In a two-stage screening procedure, first by estate medical officers and then by visiting specialists, we examined 12 716 persons at their workplaces achieving a coverage of one-sixth of the total workforce. RESULTS: Fourteen oral cancers and 848 subjects with oral pre-cancer (6.7%) were detected giving population prevalences of 46.1 per 1000 for leukoplakia and 16.4 per 1000 for oral submucous fibrosis. Among subjects with any oral mucosal disorder (n = 1159) proportions of current users of betel quid, smokers and alcohol use was recorded at 92%, 31% and 61% respectively. The synergistic effect of these three risk habits on the development of oral leukoplakia was evident in mixed habit groups. CONCLUSIONS: The prevalence of oral pre-cancer in tea estate labourers was higher than estimates reported in previous studies. In the absence of state-sponsored preventive activities, it is necessary to improve the capacity of individual health practitioners and small medical centres to participate in oral health promotion and oral cancer/pre-cancer screening.

• Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma.

  Authors: Lisa J Harper, Kim Piper, John Common, Farida Fortune, Ian C Mackenzie

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):594-603.

  The initiation, growth, recurrence and metastasis of solid tumours, including squamous cell carcinoma of the head and neck region, have been related to the behaviour of a small subpopulation ofThe initiation, growth, recurrence and metastasis of solid tumours, including squamous cell carcinoma of the head and neck region, have been related to the behaviour of a small subpopulation of 'tumour-initiating' cells. Cells with stem cell characteristics have also been identified in cell lines derived from cancers and the aim of the present work was to extend examination of such cells. Established cell lines were examined for their patterns of colony morphologies and staining, the presence of a Hoechst dye-excluding 'side population', expression of the putative stem cell markers CD44, CD133 and CD29, and their ability to grow as 'cancer spheroids'. Two cell lines, CaLH2 and CaLH3, recently generated from HNSCC tumour biopsies, were similarly examined. All cell lines showed a holoclone/meroclone/paraclone series of colony morphologies and cell sorting indicated that CD44 marker expression was related to clonogenicity. FACS analysis after exposure to Hoechst dye indicated that the CA1, H357 and UK1 cell lines contain a dye-excluding 'side population', a property associated with stem-like subpopulations. When held in suspension, all cell lines formed spheroids that could be re-passaged. These observations indicate that cell lines derived from HNSCC contain cells with stem cell properties and that such cell lines may provide experimental systems relevant to the behaviour of stem cells present in the tumours of origin and to their responses to therapy.

• Immunolocalization of cell signaling molecules in the granular cell ameloblastoma.

  Authors: Gul San Ara Sathi, Phuu Pwint Han, Ryo Tamamura, Hitoshi Nagatsuka, Hailong Hu, Naoki Katase, Noriyuki Nagai

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):609-14.

  BACKGROUND: Bone morphogenic protein (BMP) and Wnt signaling pathway molecules play important roles in cytodifferentiation and cell proliferation. We attempted to localize these signaling moleculesBACKGROUND: Bone morphogenic protein (BMP) and Wnt signaling pathway molecules play important roles in cytodifferentiation and cell proliferation. We attempted to localize these signaling molecules in the granular cell ameloblastoma. MATERIALS AND METHODS: Four samples of paraffin-embedded ameloblastoma with granular cells were studied. Immunohistochemistry was performed to detect basement membrane type heparan sulfate (HS) (JM403), cell surface type HS (10E4), heparanase, Wnt-5a, Wnt-2, beta-catenin, and BMP-4. RESULTS: In all four samples, strong expression of beta-catenin and Wnt-5a was detected within the granular cells, while BMP-4 expression was weak and Wnt-2 was negative. Immunoreactivities of basement membrane type HS, cell surface type HS, and heparanase were variable within granular cells in ameloblastoma. CONCLUSION: Granular cells in ameloblastoma exhibit abnormal biological behaviors, particularly synthesis and secretion of protein. Synthesis of signaling molecules is upregulated, but secretion is arrested in some cases, while both are lost in other cases.

• Possible involvement of stem cell factor and endothelin-1 in the emergence of pigmented squamous cell carcinoma in oral mucosa.

  Authors: Kazuhito Satomura, Reiko Tokuyama, Yasuhumi Yamasaki, Tetsuya Yuasa, Seiko Tatehara, Naozumi Ishimaru, Yoshio Hayashi, Masaru Nagayama

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):621-4.

  We present here the clinical, morphological and immunohistochemical features of a pigmented squamous cell carcinoma (SCC) in the oral mucosa of the hard palate of a 76-year-old Japanese man. HeWe present here the clinical, morphological and immunohistochemical features of a pigmented squamous cell carcinoma (SCC) in the oral mucosa of the hard palate of a 76-year-old Japanese man. He underwent a partial resection of the maxilla subsequent to radiotherapy. The tumor was typical, moderately well-differentiated SCC but had many melanocytes (melanocytosis) within it. Immunohistochemical analysis for stem cell factor (SCF) and endothelin-1, both of which are known to stimulate proliferation and differentiation of melanocytes, revealed prominent expression of both factors in the neoplastic squamous cells of the pigmented SCC, while the non-pigmented oral SCC showed little sign of either factor. These findings strongly suggest that SCF and endothelin-1 secreted by neoplasmic squamous cells are involved in the emergence of a rare variant of oral SCC.

• Nomenclature and classification of potentially malignant disorders of the oral mucosa.

  Authors: S Warnakulasuriya, Newell W Johnson, I van der Waal

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):575-80.

  At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by anAt a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term, 'potentially malignant disorders', was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize 'white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer'. An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia. The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades. The terminology presented in this report reflects our best understanding of multi-step carcinogenesis in the oral mucosa, and aspires to engender consistency in use.

• Epigallocatechin-3-gallate inhibits the invasion of human oral cancer cells and decreases the productions of matrix metalloproteinases and urokinase-plasminogen activator.

  Authors: Yung-Chuan Ho, Shun-Fa Yang, Chih-Yu Peng, Ming-Yung Chou, Yu-Chao Chang

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):588-93.

  BACKGROUND: Green tea polyphenols are considered beneficial to human health, especially as cancer chemopreventive agents in recent years. Epigallocatechin- 3-gallate (EGCG), the most abundantBACKGROUND: Green tea polyphenols are considered beneficial to human health, especially as cancer chemopreventive agents in recent years. Epigallocatechin- 3-gallate (EGCG), the most abundant polyphenol in green tea, has been proven to suppress colonic tumorigenesis in animal and epidemiological studies, whereas its role in the oral carcinogenesis remains to be elucidated. METHODS: Cytotoxicity, invasion, and migration assays were used to investigate the effects of human oral cancer cell line OC2 cells exposed to EGCG. To look at the precise involvement of EGCG in cancer metastasis, gelatin zymography and casein zymography were performed to evaluate the impacts of EGCG on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion in OC2 cells. RESULTS: EGCG exhibited a dose-dependent inhibitory effect on the invasion and migration of OC2 cells in the absence of cytotoxicity (P < 0.05). EGCG was also found to decrease the expressions of MMP-2, MMP-9, and uPA in a concentration-dependent manner (P < 0.05). CONCLUSION: Taken together, these results suggest that EGCG could inhibit the invasion and migration of human oral cancer cells and that the effects may partially because of the decreased productions of MMP-2, MMP-9, and uPA.

• Oral lichen planus in relation to transaminase levels and hepatitis C virus.

  Authors: A A Ali, C S Suresh

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):604-8.

  BACKGROUND: Elevation of transaminase levels was reported earlier in patients with oral lichen planus. The association between hepatitis C virus (HCV) and lichen planus had given positive andBACKGROUND: Elevation of transaminase levels was reported earlier in patients with oral lichen planus. The association between hepatitis C virus (HCV) and lichen planus had given positive and negative results. The controversies and uncertainties regarding the association of HCV and the liver function status (transaminase levels) in oral lichen planus inspired us to conduct this study. PATIENTS AND METHODS: This study was performed on 40 patients with different types of oral lichen planus as a study group and 40 healthy cases as control group. All patients were subjected to routine blood test and urine analysis and the estimation of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels. The values of SGOT and SGPT levels < or =40 IU / l were considered within normal limits. Anti-HCV titer was estimated in all cases. RESULTS: Fourteen patients (35%) with oral lichen planus had diabetes mellitus, while six (15%) cases of the control group had diabetes mellitus (P = 0.04). Regarding SGOT and SGPT levels, it was elevated in 19 cases (47.5%) and in 4 cases (10%) of the study group and control group, respectively (P = 0.0002). In relation to the type of oral lichen planus, out of 15 erosive cases, 80% (12 cases) showed elevated SGOT/SGPT levels. Out of 25 non-erosive cases, 7 (28%) patients showed elevated SGOT/SGPT levels (P < 0.01). Anti-HCV titer was negative in all cases. CONCLUSION: We can conclude that diabetes mellitus and elevated transaminase levels might be related to the development of oral lichen planus lesions. There is a strong association between elevated SGOT/SGPT levels and detection of erosive type of such lesions. However, no correlation between oral lichen planus and HCV infection could be assessed in the present study.

• Recurrent aphthous stomatitis revisited; clinical features, associations, and new association with infant feeding practices?

  Authors: Michael John McCullough, Samah Abdel-Hafeth, Crispian Scully

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):615-20.

  BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease, characterized by painful oral ulcerations whose causes is poorly understood. The aim of the present study was toBACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease, characterized by painful oral ulcerations whose causes is poorly understood. The aim of the present study was to assess the characteristics of patients suffering from RAS. METHODS: Five hundred and twenty-eight consecutive patients attending an Oral Medicine Specialist Clinic in the UK were examined and 143 specific attributes recorded. RESULTS: Patients with a clinical diagnosis of RAS were significantly more often males (P = 0.001) younger (P < 0.001). Significant correlations were observed between a diagnosis of RAS and trauma (P = 0.044), stress (P = 0.006), non-smoking (P < 0.001), a family history (P < 0.001), breast feeding (P = 0.017) and the site in the mouth (buccal, labial, floor of mouth) (P < 0.007). CONCLUSION: This retrospective analysis of patients attending a tertiary referral center provides evidence to support some long held beliefs about RAS, such as young age of onset, sites affected, and associations with trauma, stress, familial history and hormonal changes, while raising a new and interesting decreased incidence with breast feeding.

• Amelogenesis imperfecta with renal disease--a report of two cases.

  Authors: J Elizabeth, E Lakshmi Priya, K M R Umadevi, K Ranganathan

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(10):625-8.

  Amelogenesis imperfecta (AI) is a collective term for a number of developmental conditions characterized by abnormal enamel formation. AI is usually not associated with generalized findings; however,Amelogenesis imperfecta (AI) is a collective term for a number of developmental conditions characterized by abnormal enamel formation. AI is usually not associated with generalized findings; however, a few cases of AI associated with syndromes and metabolic disorders have been reported in the literature. We report two cases of AI presenting with renal disease and thereby highlight the importance of recognizing this possible association at an early stage, as AI in some cases, may be a marker of renal disease.

• Fcgamma receptors mediate internalization of anti-Ro and anti-La autoantibodies from Sjögren's syndrome and apoptosis in human salivary gland cell line A-253.

  Authors: Sabrina Lisi, Margherita Sisto, Raffaella Soleti, Concetta Saponaro, Pasquale Scagliusi, Massimo D'Amore, Matteo Saccia, Angela B Maffione, Vincenzo Mitolo

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):511-23.

  BACKGROUND: The presence of serum anti-Ro and anti-La autoantibodies directed against the ribonucleoproteins Ro and La has been associated with Sjögren's syndrome (SS), an autoimmune rheumaticBACKGROUND: The presence of serum anti-Ro and anti-La autoantibodies directed against the ribonucleoproteins Ro and La has been associated with Sjögren's syndrome (SS), an autoimmune rheumatic disease that targets salivary and lachrymal glands. There is increasing evidence of the direct involvement of autoantibodies in the pathogenesis of tissue injury and correlation of their presence with clinical manifestations in SS. The focus of this work was to explore the cellular apoptotic pathway triggered by binding and penetration of anti-Ro and anti-La autoantibodies in human salivary gland cell line A-253 and to identify the membrane receptors through which anti-Ro and anti-La could exert their effect. METHODS: Anti-Ro and anti-La autoantibodies were purified from IgG fractions, obtained from eleven healthy volunteers and patients with primary Sjögren's syndrome, using Sepharose 4B-Ro and Sepharose 4B-La affinity columns. Flow cytometry, RT-PCR, western blot and confocal microscopy analysis were used to visualize the FCgammaRI, FCgammaRII and FCgammaRIII receptors on the A-253 cell membrane. DNA laddering and western blot analysis of caspases activation were studied to evaluate in A-253 cells treated with anti-Ro and anti-La autoantibodies. RESULTS: The results yeilded the evidence of the presence of members of the Fcgamma receptors (FcgammaRs) family on the cell membrane of the human salivary gland cell line A-253. Furthermore, we demonstrated that, in the A-253 cell line, anti-Ro and anti-La autoantibodies can access the cells probably through Fcgamma receptors, and trigger apoptotis. CONCLUSIONS: We conclude that anti-Ro and anti-La autoantibodies have pathogenic effects that could depend on binding to Fcgamma receptors.

• Oral manifestation of chronic mucocutaneous candidiasis: seven case reports.

  Authors: Xiaosong Liu, Hong Hua

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):528-32.

  BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is a rare disorder characterized by persistent or recurrent candidal infections of the skin, nails and mucous membranes or by a variableBACKGROUND: Chronic mucocutaneous candidiasis (CMC) is a rare disorder characterized by persistent or recurrent candidal infections of the skin, nails and mucous membranes or by a variable combination of endocrine failure as well as immunodeficiency. Oral clinicopathological features of CMC have seldom been described in detail. METHODS: Seven patients with CMC were reported in the study. The clinical and histological findings, etiological Candida species, immunological evaluation, and therapeutic pattern of oral lesions, were analyzed. RESULTS: Long-standing whitish hyperplastic and nodule-like lesions with exaggerated deep fissure were the typical and characteristic oral manifestations presented by all patients. The tongue was the most common site affected. Histologically, no obvious distinction was found between CMC and other forms of candidal infection. Abnormal proportions of T-lymphocyte subsets and positive titers of autoantibody were observed in three subjects (42.9%) and one patient (14.3%) respectively. Meanwhile, four subjects (57.1%) showed decreased albumin and increased globulin, three cases (42.9%) had high levels of ESR. But no iron deficiency was found. Candida albicans was the microorganism isolated from these patients. CONCLUSIONS: Multiple and widespread candidal infectious lesions can be observed on the oral cavity of CMC patients. Hyperplastic and nodule-like lesion with irremovable whitish patches and deep fissure are the most common oral manifestations of these patients. Dentists, otolaryngologists and pediatricians should be familiar with the clinical appearances of CMC to make an accurate diagnosis. Potential systemic disorders should be concerned to avoid the reoccurrence of oral candidiasis.

• Solitary fibrous tumor of the oral cavity: the need for an extensive sampling for a correct diagnosis.

  Authors: Lorenzo Lo Muzio, Massimo Mascolo, Saverio Capodiferro, Gianfranco Favia, Eugenio Maiorano

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):538-42.

  BACKGROUND: Solitary fibrous tumor (SFT) is an uncommon but well-characterized soft tissue tumor that was first described as a pleural lesion and now is considered ubiquitous, having been detected atBACKGROUND: Solitary fibrous tumor (SFT) is an uncommon but well-characterized soft tissue tumor that was first described as a pleural lesion and now is considered ubiquitous, having been detected at many extra-pleural sites (abdominal cavity, orbit, upper respiratory tract, and oral cavity). Histologically, SFT may show wide morphological variability of both its cellular and stromal components, which may lead to incorrect diagnosis especially when dealing with small incisional biopsies. MATERIALS: We report on the clinical, morphological and immunohistochemical features of eight SFT occurring in the oral cavity. RESULTS: Microscopically all eight tumors showed widely variable morphological features in terms of cellular density and stromal architecture, thus simulating benign fibrous histiocytoma, schwannoma, hemangiopericytoma or low-grade sarcoma in distinct areas of the same lesion. Among these eight cases, five had been diagnosed as SFT, two as benign fibrous histiocytoma and one as low-grade sarcoma. CONCLUSIONS: In consideration of the heterogeneous morphological appearance of SFT, inaccurate sampling of the mass may lead to misdiagnosis and inappropriate treatment. Therefore, an accurate histological examination of multiple tissue sections is advised, along with the use of appropriate immunostains.

• Analysis of the neoplastic nature and biological potential of sporadic and nevoid basal cell carcinoma syndrome-associated keratocystic odontogenic tumor.

  Authors: Naoki Katase, Hitoshi Nagatsuka, Hidetsugu Tsujigiwa, Mehmet Gunduz, Ryo Tamamura, Han Phuu Pwint, Rosario Santos Rivera, Motowo Nakajima, Yoshio Naomoto, Noriyuki Nagai

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):550-4.

  BACKGROUND: Keratocystic odontogenic tumor (KCOT), also known as odontogenic keratocyst, is a benign cystic neoplasm, which may be associated with nevoid basal cell carcinoma syndrome (NBCCS) and ifBACKGROUND: Keratocystic odontogenic tumor (KCOT), also known as odontogenic keratocyst, is a benign cystic neoplasm, which may be associated with nevoid basal cell carcinoma syndrome (NBCCS) and if it does, will occur as multiple cystic lesions. KCOT is locally destructive despite its bland histological features. However, the neoplastic nature of KCOT is not well established. Heparanase is an endo-d-glucuronidase enzyme that specifically cleaves heparan sulfate (HS) and the increase of its level in tumors promotes invasion, angiogenesis, and metastasis. METHODS: To investigate the neoplastic character of KCOT, we studied the localization patterns of heparanase in KCOT, focusing on the differences between sporadic and NBCCS-associated KCOTs, by immunohistochemistry and in situ hybridization. To compare the expression pattern of these cysts with non-tumorous odontogenic developmental cyst, dentigerous cyst was included. RESULTS: All the odontogenic cysts showed positive immunoreaction for heparanase protein in various intensities. The expression pattern of heparanase gene corresponded to that of protein expression. Interestingly, intense gene and protein expressions were observed in KCOT associated with NBCCS compared with sporadic ones and dentigerous cyst. CONCLUSIONS: The results implied that heparanase expression may be correlated with the neoplastic properties of KCOT, particularly in NBCCS-associated cases.

• Island of salivary gland in adipose tissue: a report of three cases.

  Authors: I Ponniah, N Lavanya, P SureshKumar

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):558-62.

  Although uncommon, many variants of lipomatous lesions in or around salivary glands have been reported in the literature. We report a series of three such cases in the minor salivary gland region.Although uncommon, many variants of lipomatous lesions in or around salivary glands have been reported in the literature. We report a series of three such cases in the minor salivary gland region. The first case (oral floor) is a well-circumscribed lipocytic lesion admixed with glandular components (mucous acini, serous demilunes and ducts). The second case (alveolar mucosa) is a diffuse lipomatous proliferation with entrapped salivary glandular elements, muscles and blood vessels. The third case (palate) is similar to the first case but the gland is located at the periphery of the lesion. The purpose of the article was to report these three lesions and discuss in relation to other pertaining lipomatous lesions (sialolipoma, lipoadenoma, lipomatosis, lipometaplasia in pleomorphic adenoma and infiltrating lipoma).

• Calcineurin inhibitor-associated oral inflammatory polyps after transplantation.

  Authors: Maha Al-Mohaya, Nathaniel Treister, Ons Al-Khadra, Leslie Lehmann, Bonnie Padwa, Sook-Bin Woo

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):570-4.

  Calcineurin inhibitors (cyclosporine and tacrolimus) have been used as the mainstay immunosuppressive therapy for solid organ and hematopoietic cell transplantations (HCT) to prevent allograftCalcineurin inhibitors (cyclosporine and tacrolimus) have been used as the mainstay immunosuppressive therapy for solid organ and hematopoietic cell transplantations (HCT) to prevent allograft rejection and for prophylaxis and treatment of the chronic graft-versus-host disease. Adverse effects of these drugs include nephrotoxicity, hepatotoxicity, neurotoxicity, hypertension and gingival hyperplasia. Association of oral non-gingival soft tissue hyperplasia with calcineurin inhibitor therapy has only recently been recognized and is thought to occur infrequently. We present four cases of oral non-gingival inflammatory fibro-vascular hyperplasias attributed to the use of calcineurin inhibitors following solid organ transplantation and HCT. These lesions interfere with function and must be differentiated from other oral lesions, and therefore should be surgically excised.

• Oral manifestations of systemic and cutaneous lupus erythematosus in a Venezuelan population.

  Authors: Jeaneth López-Labady, Mariana Villarroel Dorrego, Nieves González, Ricardo Pérez, Magdalena Mata de Henning

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):524-7.

  BACKGROUND: The aim of this study was to characterize oral lesions in patients with systemic and cutaneous lupus erythematosus (LE) in a Venezuelan group. METHODS: Ninety patients with LE wereBACKGROUND: The aim of this study was to characterize oral lesions in patients with systemic and cutaneous lupus erythematosus (LE) in a Venezuelan group. METHODS: Ninety patients with LE were studied. Oral biopsies were taken from patients who showed oral mucosal involvement. Tissue samples were investigated with histology and direct immunofluorescence techniques for the presence of immunoglobulins G, M, A and complement factor C3. RESULTS: In 90 patients with LE, 10 patients showed oral lesions related to the disease. Sixteen lesions were investigated. Oral ulcerations accompanied by white irradiating striae occurred in five patients, erythema was observed in five patients and a white homogeneous plaque in one patient. Fifteen lesions demonstrated vacuolar basal degeneration and 12 thickening of the basement membrane histologically. Direct immunofluorescence was negative in three samples. CONCLUSIONS: These findings corroborated that ulcers are not the only manifestation of LE in the oral mucosa. Clinical and histological examinations are significant as immunoproteins are not always found on the oral sample.

• Immunohistochemical detection of phosphorylated JNK, p38 MAPK, and ERK5 in ameloblastic tumors.

  Authors: H Kumamoto, K Ooya

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):543-9.

  BACKGROUND: To evaluate roles of mitogen-activated protein kinases (MAPKs) in oncogenesis and cytodifferentiation of odontogenic tumors, expression of phosphorylated JNK (p-JNK), p38 MAPK (p-p38BACKGROUND: To evaluate roles of mitogen-activated protein kinases (MAPKs) in oncogenesis and cytodifferentiation of odontogenic tumors, expression of phosphorylated JNK (p-JNK), p38 MAPK (p-p38 MAPK), and ERK5 (p-ERK5) was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: Ten tooth germs, 47 ameloblastomas, and 5 malignant ameloblastic tumors were examined immunohistochemically with the antibodies against p-JNK, p-p38 MAPK, and p-ERK5. RESULTS: Immunoreactivity for p-JNK was detected in epithelial or neoplastic cells detached from the basement membrane in 7 tooth germs and 7 ameloblastomas, and the expression levels of p-JNK in ameloblastic tumors were significantly lower than that in tooth germs. Expression of p-p38 MAPK was found in epithelial or neoplastic cells in tooth germs and ameloblastic tumors except for two ameloblastomas, and increased expression was found in keratinizing cells of acanthomatous ameloblastomas. The expression level of p-p38 MAPK in ameloblastomas was significantly higher than the levels in tooth germs and malignant ameloblastic tumors. Immunoreactivity for p-ERK5 was found predominantly in epithelial or neoplastic cells near the basement membrane in tooth germs and ameloblastic tumors. The expression levels of p-ERK5 in ameloblastic tumors were slightly higher than that in tooth germs, and plexiform ameloblastomas showed significantly higher p-ERK5 expression than follicular ameloblastomas. CONCLUSION: Expression of p-JNK, p-p38 MAPK, and p-ERK5 in tooth germs and ameloblastic tumors suggests that these MAPK signaling pathways contribute to cell proliferation, differentiation, or apoptosis in both normal and neoplastic odontogenic tissues. Altered expression of these phosphorylated MAPKs in ameloblastic tumors may be involved in oncogenesis and tumor cell differentiation.

• Oromandibular limb hypogenesis syndrome, type IIA, hypoglossia-hypodactylia: a case report.

  Authors: Puneet Wadhwani, Shadab Mohammad, Ruchi Sahu

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):555-7.

  A patient with oromandibular limb hypogenesis syndrome, type IIA hypoglossia-hypodactylia, is reported. The features essential for the diagnosis of this congenital defect include a reduction inA patient with oromandibular limb hypogenesis syndrome, type IIA hypoglossia-hypodactylia, is reported. The features essential for the diagnosis of this congenital defect include a reduction in tongue size (microglossia), micrognathic mandible and limb abnormalities of varying severity. Parents and the other sibling were normal. Past medical history for exposure of the mother to drugs during pregnancy was positive.

• How to name it: a rare case of odontogenic cyst.

  Authors: I Ponniah, G V Murali Gopika Manoharan, P SureshKumar, K Karthikeyan

  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 36(9):563-9.

  Odontogenic cysts and tumors are well-recognized entities to the specialist oral pathologist and they seldom pose problems in differential diagnosis. This paper deals with an aggressive cystic lesionOdontogenic cysts and tumors are well-recognized entities to the specialist oral pathologist and they seldom pose problems in differential diagnosis. This paper deals with an aggressive cystic lesion in the maxilla of a 65-year-old male that was characterized by a large radiographically multilocular lesion and a multicystic pattern microscopically. The categorization of this lesion was complicated by the presence of features suggestive of both glandular odontogenic cyst and cystic ameloblastoma with aggressive histologic phenotypes.

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