Increased beta 2 defensin in recurrent aphthous ulcer.

OBJECTIVES: It was hypothesized that beta 2 defensin (BD-2) is increased in RAU lesions compared with healthy controls to promote anti-microbial host defence. METHODS: RAU and control mucosa samples were subjected to quantitative real-time PCR and immunostained for BD-2, CD68, mast cell tryptase and 4-hydroxynonenal (4HNE). The effect of tumour necrosis factor-α (TNF-α) ± interleukin-17C (IL-17C), without and with vitamin K3, was studied on BD-2 expression in epithelial SCC-25 cells. RESULTS: Although BD-2 mRNA did not differ between healthy and RAU mucosa, BD-2 stained strongly in acute-phase RAU epithelium (P = 0.001). In controls, subepithelial BD-2(+) cells were mast cells and macrophages, whereas in RAU, most infiltrating leucocytes were BD-2(+) (P = 0.004). In cell culture, BD-2 was increased 124-fold by TNF-α (P < 0.0001) and 208-fold synergistically together with IL-17C (P < 0.0001). 4HNE staining of RAU epithelium was not significantly increased, and vitamin K3-induced reactive oxygen species (ROS) did not affect BD-2. CONCLUSIONS: Anti-microbial BD-2 was not affected by oxidative stress but was highly increased in the epithelial and immigrant cells in the acute-phase RAU lesions, probably in part synergistically by TNF-α and epithelial IL-17C, which are known to be induced by activation of danger-signal receptors by pathogen- and/or damage-associated molecular patterns.

Histamine H4 receptor in oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines. MATERIALS AND METHODS: Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes. RESULTS: H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts. CONCLUSION: Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: guidelines for oral pathology and oral medicine in the dental curriculum.

In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: statement on oral pathology and oral medicine in the European Dental Curriculum.

BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD. METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD. RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation. PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.

Soft tissue reactions to bioactive glass 13-93 combined with chitosan.

The aim of this study was to evaluate rabbit soft tissue reactions to bioactive glass 13-93 mesh by using a histological and immunohistochemical analysis. Bioactive glass (13-93) mesh fixed with 3 wt % chitosan was implanted into the dorsal subcutaneous space of New Zealand White rabbits (n=18) for six, 12, and 24 weeks, respectively. After 6 weeks the bioactive glass remnants were surrounded by foreign-body granuloma with eosinophilic granulocytes. After 12 and 24 weeks the implanted material was mainly absorbed, but, if any particles still remained the foreign-body reaction was notably milder. Yet, a mild chronic inflammatory infiltrate was present. Matrix metalloproteinase (MMP) -2, -3, -13 and tissue inhibitory protein (TIMP-1 and -2) expressions were studied by immunohistochemistry. MMP-3, -13, TIMP-1, and -2 positivity were detected throughout the follow-up period. MMP-2 positivity was only occasionally seen in the 24 week samples, which is constitutively expressed but is not related to inductive MMP-3 and -13 cascade. The presence of eosinophilic granulocytes in some of the samples raises the possibility of an allergic reaction to the materials. MMP-3 and -13 are suggested to participate in the host reaction to either bioactive glass or chitosan.

A histological and immunohistochemical study of tissue reactions to solid poly(ortho ester) in rabbits.

In many cases only the temporary presence of a biomaterial is needed in tissue support, augmentation or replacement. In such cases biodegradable materials are better alternatives than biostable ones. At present, biodegradable polymers are widely used in the field of maxillofacial surgery as sutures, fracture fixation devices and as absorbable membranes. The most often used polymers are aliphatic polyesters, such as polyglycolic acid (PGA) and polylactic acid (PLA). Poly(ortho ester) is a surface eroding polymer, which has been under development since 1970, but is used mostly in drug delivery systems in semisolid form. The aim of this study was to evaluate the tissue reactions of solid poly(ortho ester) (POE), histologically and immunohistochemically. Resorption times and the effect of 2 different sterilization methods (gamma radiation and ethylene oxide) upon resorption were also evaluated. Material was implanted into the tibia and subcutaneously into the mandibular ramus area of 24 rabbits. Follow-up times were 1-10, 14 and 24 weeks. Histological studies showed that POE induces a moderate inflammation in soft tissue and in bone. At 24 week follow-up, inflammation was mild in soft tissue and moderate in bone. In immunohistochemical studies, no highly fluorescent layer of tenascin or fibronectin was found adjacent to the implant. Resorption of gamma-sterilized rods was faster than ethylene oxide-sterilized rods. The total resorption time was more than 24 weeks in both groups. Clinically the healing was uneventful and the implants the well tolerated by the living tissue. This encourages these authors to continue studies with this interesting new material to search for the ideal material for bone filling and fracture fixation.

Epithelial Cell Apoptosis in Recurrent Aphthous Ulcers.

A recurrent aphthous ulcer (RAU) is a common inflammatory ulcerative lesion affecting oral mucosa. We studied the eventual apoptosis of epithelial cells from the point of view of ulcer and inflammation. RAU lesions and healthy mucosa samples were immunostained for caspase-3 and high-mobility group box 1 (HMGB1). DNA nicks were identified using TUNEL staining. We studied the effects of tumor necrosis factor α (TNFα) and interferon γ (IFNγ) on the toll-like receptor 2 and 4 (TLR2 and TLR4) expression of human oral SCC-25 keratinocytes. We also studied the effects of self-DNA, all-thiol-HMGB1, and disulfide-HMGB1 on epithelial cells, with or without IFNγ. At the edge of RAU lesions, all epithelial cell layers were caspase-3(+), TUNEL(+), and HMGB-1(+) and had widened intercellular spaces. In contrast, healthy epithelial cells were negative for caspase-3 and TUNEL staining. HMGB1 was seen in only the basal cell layers, and the cells retained close cell-to-cell contacts. Self-DNA increased TNF-α mRNA (P = 0.02) in SCC-25 cells. Both TNFα and IFNγ (P = 0.01) increased TLR2. Upon TNFα stimulation, SCC-25 cells lost their nuclear HMGB1 staining. HMGB1 did not increase IL-8, IL-6, or TNF-α mRNA in SCC-25 cells, which was unaffected by the presence of IFNγ. We conclude that in healthy epithelium, the most superficial cells at the end of their life cycle are simply desquamated. In contrast, RAU is characterized by top-to-bottom apoptosis such that dead cells may slough off, leading to an ulcer. Because of a lack of scavenging anti-inflammatory macrophages, apoptotic cells probably undergo secondary necrosis releasing proinflammatory danger signals, which may contribute to the peripheral inflammatory halo. This is supported by self-DNA-induced TNFα synthesis. In contrast to TLR4- and TLR2-binding lipopolysaccharide used as a positive control, disulfide-HMGB1 did not stimulate proinflammatory cytokines.

Sjögren's syndome and extragonadal sex steroid formation: a clue to a better disease control?

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphoplasmacytoid focal adenitis leading to mucosal dryness, with 9:1 female dominance and peak incidence at menopause. Due to autoimmune adenitis it can be speculated that the normal epithelial cell renewal has failed, possibly as a result of local intracrine failure to process dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). Local intracrine/-cellular DHT deficiency seems to predispose to SS if estrogens are low, in menopausal women and in men. This intracrine failure could be the initial noxious stimulus, factor X, initiating the development of SS. Abnormal release and presentation of exocrine gland-derived antigens (Ag-epitopes), in a complex with major histocompatibility complex class II (MHC II), by migratory dendritic cells (DC) activates T-cells in the regional lymph nodes. B-cells with the same specificity capture and present self-Ag to Th-cells which provide T-cell help. B-cells transform to plasma cells and start to produce autoantibodies (Ab) against these T-cell-dependent Ag. Ab against SS-A/Ro and SS-B/La ribonucleoproteins occur only in HLA-DQw2.1/DQw6 heterozygous individuals, but hY-RNA and RNA polymerase III transcripts in these Ag may in all SS patients stimulate toll-like receptors (TLR) 7 and 9 of the plasmacytoid DCs, because IFN-α and IFN-signature are produced. CD8+αEß7+cytotoxic T-cells activated via cross-presentation recirculate to attack intracrine-deficient, apoptotic epithelial cells expressing self-Ag on their surface. Exocrine glands fall into the sphere of mucosal/gut-associated lymphatic tissue. This together with immune complexes spreads the immunological memory/aggression to extra-glandular sites explaining the systemic nature of the syndrome. Secondary SS could be explained by disturbed lymphocyte recirculation. There is no conclusive evidence that SS in those few men affected is more severe than in women, suggesting that sex steroid endo-/intracrinology has its major impact on the target tissue, not on immune modulation. This article is part of a Special Issue entitled 'Essential role of DHEA'.

Matrix metalloproteinase (MMP)-9 type IV collagenase/gelatinase implicated in the pathogenesis of Sjögren's syndrome.

Type IV collagenases/gelatinases (matrix metalloproteinases MMP-2 and MMP-9) in labial salivary glands (LSG) and saliva in Sjögren's syndrome (SS) and healthy controls were studied. Zymograms and Western blots disclosed that SS saliva contained 92/82 kD MMP-9/type IV collagenase duplex. Specific activity measurement disclosed 53.1+/-9.8 U/mg protein MMP-9 in SS compared to 16.5+/-2.6 U/mg in healthy controls (p=0.01). MMP-2 did not differ between SS and controls. In SS salivary glands, MMP-2 and MMP-9 were also expressed, in addition to stromal fibroblasts and occasional infiltrating neutrophils, respectively, in acinar end piece cells. In addition, an effective proMMP-9 activator, human trypsin-2 (also known as tumor-associated trypsin-2 or TAT-2), was found in acinar end piece cells and in saliva. Interestingly, proteolytically processed MMP-9 was found in saliva (vide supra), and in vivo activated MMP-9 was significantly higher in SS than in controls (p=0.002). LSGs, particularly in SS, were characterized ultrastructurally by areas containing small cytoplasmic vesicles in the basal parts of the epithelial cells associated with areas of disordered and thickened basal lamina. Based on our results, we conclude here that SS saliva contains increased concentrations of MMP-9, which is of glandular origin in part. Pro MMP-9 is to a large extent proteolytically activated. This is probably mediated by the most potent pro MMP-9 activator found in vivo thus far, namely trypsin-2. Therefore, the MMP 9/trypsin-2 cascade may be responsible for the increased remodelling and/or structural destruction of the basement membrane scaffolding in salivary glands in SS. Due to the role of basal lamina as an important molecular sieve and extracellular matrix-cell signal, these pathological changes may contribute to the pathogenesis of the syndrome.

Face-specific responses from the human inferior occipito-temporal cortex.

Whole-head neuromagnetic responses were recorded from seven subjects to pictures of faces and to various control stimuli. Four subjects displayed signals specific to faces. The combination of functional information from magnetoencephalography and anatomical data from magnetic resonance images suggests that the face-specific activity was generated in the inferior occipitotemporal cortex. All four subjects showed the face-specific response in the right hemisphere, one of them also in the left. Our results, together with recent position emission tomography and lesion studies, suggest a right-hemisphere preponderance of face processing in the inferior occipitotemporal cortex.

Autopsy analysis of clinically unilateral exfoliation syndrome.

PURPOSE: To study the pathogenesis of clinically unilateral exfoliation syndrome by localizing exfoliation deposits in involved and fellow eyes during autopsy. METHODS: The formalin-fixed and paraffin-embedded involved and fellow eyes were obtained at autopsy from five patients (age range, 72 to 88 years) with clinically unilateral exfoliation. Exfoliation deposits were identified with monoclonal antibodies (mAb) HNK-1 and NC-1 to the HNK-1 carbohydrate epitope, and with five lectins (Bauhinia purpurea agglutinin, Concanavalin A, Lens culinaris agglutinin, Phaseolus vulgaris erythroagglutinin, and Ricinus communis agglutinin I) using the avidin-biotinylated peroxidase complex (ABC) method. RESULTS: Marked exfoliation deposits in all involved eyes, and weak exfoliation deposits in one fellow eye were consistently detected in light microscopic, immunohistochemical, and lectin histochemical examinations. Similarly labeled deposits were present around a population of blood vessels of the iris in every involved and fellow eye. Particularly in fellow eyes, these subendothelial deposits were better visualized with mAbs to the HNK-1 epitope than they were with lectins. In the only fellow eye with early exfoliation, the reactivity around blood vessels was more conspicuous than the exfoliation deposits, whereas the reverse was true in the involved eyes. CONCLUSIONS: Clinically unilateral exfoliation is asymmetric, rather than truly monocular. The findings in fellow eyes suggest that iris blood vessels become abnormal early in the process, even before exfoliation deposits are histopathologically seen in the posterior chamber. Marked asymmetry in exfoliation indicates an influence of modulating local factors that may be internal or external to the eye, and that also may be functional in bilateral exfoliation.

Histological study of tissue reactions to epsilon-caprolactone-lactide copolymer in paste form.

In previous studies, epsilon-caprolactone-lactide copolymer in solid form has been used in experimental animals as suture material, and as a biodegradable nerve guide. The aim of the study reported here was to assess tissue reactions to epsilon-caprolactone-lactide copolymer in paste form, histologically, and to compare bone healing at the sites of implantation versus that at control sites. The other purpose of the study was to evaluate the properties of the implanted material as a filling material for bone defects. Resorption time and intensity of inflammatory reaction were also evaluated. Material was implanted into the abdominal walls and femurs of 34 rats. Follow-up times were from 2 weeks to 1 year. The results showed that epsilon-caprolactone-lactide copolymer in paste form induces a severe inflammatory reaction when placed in muscle, and moderate inflammation when implanted into bone. The resorption time was more than 1 year. Bone healing at sites of implantation was slower than at control sites.

Modulation of human auditory information processing by emotional visual stimuli.

Auditory event-related potentials mismatch negativity (MMN) and N100 were recorded from seven subjects while they read text and watched emotionally negative, neutral, and positive pictures varying in valence and arousal. The MMN reflects automatic detection of change in auditory stimulus stream. Functionally different N100 is triggered by onset of various auditory stimuli. The N100 was stabile during all visual conditions. The MMN was very similar during text reading, and neutral and negative slide viewing, but was significantly attenuated during viewing of positively valenced slides. We suggest that visual emotional information of high positive valence and low arousal is a signal of nonthreatening and nonappetitive environment. This kind of environment probably reduces the need for auditory change detection.

Does your gaze direction and head orientation shift my visual attention?

The effects of another person's gaze direction and head orientation on the observer's attentional processes were investigated. Subjects responded to visual, laterally presented reaction signals. The presentation of the reaction signal was preceded by a facial cue stimulus signaling a direction which was either congruent, neutral, or incongruent with the laterality of the reaction signal. A head (front and profile views) with an averted gaze affected the response times in comparison to the front view of a face with a straight gaze. In contrast, a profile view of a head with a compatible gaze direction did not result in such an effect. The results indicate that visual information from the other individual's gaze direction and head orientation is integrated, and the integrated information is fed to the brain areas subserving visual attention orienting.

Motion sensitive cells in the macaque superior temporal polysensory area: response discrimination between self-generated and externally generated pattern motion.

It was previously shown [17] that visual movement sensitive neurons lacking selectivity in the anterior parts of the dorsal superior temporal sulcus (STP) of monkeys exhibited selective responses to externally moved objects and failed to respond to the sight of the animal's own limb movements. This paper describes a series of experiments in which a monkey was trained to operate an apparatus that produced visual motion of a projected two-dimensional patterned stimulus. Single unit responses from STP were recorded and responses to visual motion, produced externally by the experimenter, were compared to the responses to visual motion (of the same pattern) produced by the monkey itself. The majority of the movement sensitive cells giving reliable responses to the pattern motion responded statistically more strongly to the experimenter-induced motion than to the motion induced by the monkey itself. The cell responses were observed not to be affected by the motion velocity and the monkey's motor activity (handle rotation without any visual stimulation) did not affect the cell's spontaneous activity. The results indicate that the response discrimination of STP cells between externally and self-induced stimulus motion is not based on form sensitivity. Moreover, the mechanism which produces the described response selectivity is not only limited to naturally occurring visual consequences of the monkey's own motor activity but is plastic and can extend to arbitrary associations between the monkey's movements and consequent visual motion.

Face-selective processing in human extrastriate cortex around 120 ms after stimulus onset revealed by magneto- and electroencephalography.

Quick recognition of faces is crucial to a variety of human interactions, and highly specialized pathways may be involved in the processing of faces. To reveal selectivity to faces in early cortical processing, whole-scalp magnetoencephalography (MEG) and electroencephalography (EEG) were used to record event-related responses to faces and degraded faces and their inverted counterparts. We observed increases in the peak latency and amplitude of the early 120-ms component (P120) for the inverted faces. These effects were enhanced for the 1 70-ms component (N170). For the degraded counterparts, a significant effect of the inversion was observed only for the N170, which was strongly delayed. Source modelling suggested that the early response originated at the posterior occipital areas whereas the later response was generated anterior and lateral to this location. We conclude that under sufficiently good conditions face-selective activity may be taking place during the P120.

Tumor necrosis factor-alpha and its receptors, p55 and p75, in gingiva of adult periodontitis.

Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, can stimulate matrix metalloproteinase synthesis and osteoclastic bone resorption. We hypothesized that elevated expression of TNF-alpha and its p55 and p75 receptors (TNF-R) in gingival tissue might associate with periodontitis. Immunohistochemistry was used for the study of the localization of TNF-alpha and its p55 and p75 TNF-R in adult periodontitis (AP) gingival tissue, in comparison with that in healthy control specimens. TNF-alpha and p55 TNF-R were detected in sulcular epithelial basal cells and in monocyte/macrophages, fibroblasts, and endothelial cells in the AP gingival tissue specimens, but mainly in fibroblasts and endothelial cells in control specimens. P75 TNF-R was occasionally found in monocyte/macrophage-like cells in gingival tissue specimens. The percentage of TNF-alpha-containing cells was not increased in AP compared with controls (13.2%+/-6.1% vs. 12.8%+/-7.6%), but, due to the increased cellularity of AP samples, the number of TNF-alpha positive cells/mm2 was clearly increased (1621+/-663 vs. 664+/-191, p > 0.001). Thus, AP gingival tissue has an elevated expression of TNF-alpha and especially its p55 receptor, suggesting that TNF-alpha may contribute to tissue degradation in periodontitis.

Lectin and immunohistochemical comparison of glycoconjugates in the conjunctiva of patients with and without exfoliation syndrome.

AIMS--The study was carried out to search for labelling similar to that of intraocular exfoliation material in the conjunctiva by light microscopy using lectin and immunohistochemistry. METHODS--Ten formalin fixed and paraffin embedded conjunctival biopsy specimens both from patients with and without exfoliation syndrome were studied with a panel of 11 lectins and with three monoclonal antibodies to the HNK-1 carbohydrate epitope, all of which react with intraocular exfoliation material. RESULTS--The lectin binding profile was essentially the same in specimens from patients with and without exfoliation syndrome. The superficial epithelium reacted similarly with Phaseolus vulgaris (PHA-E), Caragana arborescens (CAA), Helix pomatia (HPA), concanavalin A (ConA), and wheat germ (WGA) agglutinins. Binding was also detected with peanut (PNA) and Bauhinia purpurea (BPA) agglutinins, particularly in patients with exfoliation. The basement membrane generally reacted with Ricinus communis (RCA-I), PHA-E, Vicia villosa (VVA), ConA, and Lens culinaris (LCA) agglutinins. The stroma was weakly labelled with RCA-I, PHA-E, ConA, and LCA. Lectin binding to the vascular endothelium was moderate with RCA-I, PHA-E, CAA, ConA, LCA, and WGA. Inconsistent labelling was also detected with PNA, BPA, and Erythrina cristagalli agglutinin (ECA). The subendothelial region reacted weakly but consistently with PHA-E, ConA, and LCA, and inconsistently with PNA. Pretreatment with neuraminidase did not change that pattern. Antibodies to the HNK-1 epitope reacted only with myelinated stromal nerve branches. CONCLUSION--No evidence of abnormal deposits in any specimen was found. The carbohydrate composition of intraocular exfoliation material may differ from that of exfoliation-like fibres often detected in the conjunctiva by electron microscopy.

Otitis externa sicca/fibrotising external otitis (FEO) as a complication of Sjögren's syndrome.

Sjögren's syndrome (SS) is a condition characterized by sicca symptoms and by autoimmune features. We describe two SS patients with otitis externa fibroticans/sicca. One of these 2 patients developed a lesion of the tympanic membrane making it necessary to perform a tympantomy and meatoplasty. Our findings suggest firstly that the epithelial cell-mediated secretion of lamellar bodies and the production of the permeability barrier are defective in SS. Secondly, local moisturing and/or topical corticosteroid treatment in SS patients with sicca symptoms in the auditory canal could help to avoid reconstructive surgical treatment.

A retrospective study of oral lichen planus patients with concurrent or subsequent development of malignancy.

Oral lichen planus (OLP) carries a very small probability of becoming malignant. Our Finnish series comprised eight patients suffering from OLP and concurrent or subsequent oral squamous cell carcinoma over a 10-year period. The mean interval between the histologically suggested initial diagnosis of OLP and carcinoma was 3.4 years. An oral ulcer as a clinical manifestation of malignant change appeared in seven of these eight patients; five of the eight died of carcinoma on average 13 months (range 7-20) after the final squamous cell carcinoma diagnosis. These eight patients were compared to eight control OLP patients without malignant transformation matched as to follow-up time, age, gender, sites of the lesions, etc. We could discover no histological features leading to malignant development. However, the clinically unilateral atrophic/erosive type of OLP more often preceded the malignant change, compared to the situation for control patients, in whom the most prevalent type was the bilateral reticular OLP. However, the probability seems to be very small.