Possible premalignant character of oral lichen planus the Amsterdam experience

In the present paper the 21-yr experience of the Department of Oral and Maxillofacial Surgery and Oral Pathology, and the Department of Otorhinolaryngology of the Free University Hospital, Amsterdam, is reported with regard to the possible premalignant character of oral lichen planus. The study consists of two parts: 1) the follow-up of 113 patients with histopathologically proven oral lichen planus, and 2) a search for lichen planus in 727 patients who have been admitted for oral cancer. Three patients with histopathologically proven lichen planus developed a squamous cell carcinoma in an average follow-up period of 7 yr. In the 727 patients with oral cancer, two additional patients with the simultaneous occurrence of oral lichen planus were observed. Our experience gives some but not very strong support to the hypothesis that oral lichen planus is a premalignant condition.     

The malignant transformation of oral lichen planus and oral lichenoid lesions: A systematic review

BackgroundDetermining the potential for malignant transformation of oral lichen planus (OLP) is complicated by difficulties in diagnosis, differentiation from oral lichenoid lesions (OLLs) and the phenomenon of premalignant lesions' exhibiting lichenoid characteristics. The authors of this systematic review evaluated evidence regarding malignant transformation of OLP and characterized transformation prevalence, clinical characteristics of OLP lesions developing into squamous cell carcinoma (SCC) and time to transformation.Types of Studies ReviewedThe authors searched PubMed, Embase and Thomson Reuters Web of Science in a systematic approach. They evaluated observational English-language studies involving human participants published in peer-reviewed journals. Inclusion required patients to have the diagnosis of OLP or OLL as confirmed with biopsy results on initial enrollment. They excluded all patients who had dysplasia on initial biopsy of OLP or OLL lesions.ResultsSixteen studies were eligible. Among 7,806 patients with OLP, 85 developed SCC. Among 125 patients with OLL, four developed SCC. The rate of transformation in individual studies ranged from 0 to 3.5 percent. The overall rate of transformation was 1.09 percent for OLP; in the solitary study in which investigators evaluated OLL, the rate of transformation was 3.2 percent. Patients' average age at onset of SCC was 60.8 years. The authors noted a slight predominance of female patients among those who experienced malignant transformation. The most common subsite of malignant transformation was the tongue. The average time from diagnosis of OLP or OLL to transformation was 51.4 months.Practical ImplicationsA small subset of patients with a diagnosis of OLP eventually developed SCC. The most common demographic characteristics of patients in this subset were similar to the most common demographic characteristics associated with OLP in general (that is, being female, being older and being affected in areas common to this condition). It is prudent for clinicians to pursue continued regular observation and follow-up in patients with these conditions, even in patients who do not fit a traditional high-risk category for oral SCC.     

Nuclear and cellular volumetric alterations in oral lichen planus and lichenoid lesions: a histomorphometric study.

There is presently no line of distinction between oral lichen planus and other oral lichenoid lesions. The aim of this study is to determine using histomorphometry, the differences between these lesions. Paraffin sections from 7 normal buccal epithelium, 19 oral lichen planus (LP), 14 oral lichenoid lesions (LL) and 7 discoid lupus erythematosus-like lesions (DLE-ll) were selected. The nuclear volume (V(N)) and cellular-volume (V(CELL)) of the epithelium were assessed using an image analyser. The V(N) and V(CELL), derived for both basal and spinal strata in LP and DLE-ll were 2.3 times more than that of normal tissues. There was a significant difference between LP and LL (P < 0.005) and between LL and DLE-ll (P < 0.001), but not between LP and DLE-ll. In conclusion, there appears to be a difference between LP, LL and DLE-ll and V(N) and V(CELL) may serve as potential discriminators between these groups of lesions.     

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.     

The frequency of different T-cell receptor V-families in oral lichen planus and lichenoid contact lesions: an immunohistochemical study

Oral lichen planus (OLP) and lichenoid contact lesions (CL) are recognized as different pathological conditions of the oral mucosa. Cutaneous delayed-type hypersensitivity to mercury displayed by patients with CL but not by OLP patients supports the concept of different etiological mechanisms behind the two lesions. It is not possible to reveal this difference by histopathological assessments, and differences in clinical appearances are at present the only way to discriminate between the two conditions. It has recently been observed that T cells in OLP lesions express T-cell receptors (TCR) belonging to the Vβ3 family in a higher frequency than expected from a random distribution, suggesting an involvement of superantigens as an etiologic factor behind this condition. In an effort to discriminate more clearly between OLP and CL, and to provide clues to the etiological mechanisms behind the two lesions, the TCR V-family distributions in the inflammatory infiltrates of OLP and CL were compared. Biopsies were taken from 10 patients with manifest OLP and 10 patients with CL. Frozen sections were incubated with antibodies against TCR Vβ3, Vα2 and Vβ5a utilizing a standard immunoperoxidase technique. The frequency of Vβ3.1 (clone 8F10) was calculated as 7%, and for Vα2 less than 3%, and the results did not reveal any differences between OLP and CL regarding the frequencies of T-cell V-families. Thus, it was not possible to discriminate between OLP and CL by immunohistochemistry staining for different V families.     

Direct immunofluorescence in oral lichen planus and oral lichenoid reactions.

OBJECTIVE: To aid in differentiation of the two lesions, direct immunofluorescence was used to examine the fluorescence patterns in oral lichen planus and oral lichenoid reactions and to compare the degree of intensity of their fluorescence. METHOD AND MATERIALS: Thirty patients participated in this study. Oral mucosal biopsy specimens were obtained from the edge of fresh lesions and were hemisected. One of the sections was placed in 10% neutral buffered formalin for standard light microscopic examination and the other was washed in phosphate-buffered saline and transferred to Michel's transport media for direct immunofluorescence examination. RESULTS: Fibrinogen was deposited in specimens from 14 of 15 patients diagnosed with oral lichen planus; lesions showed an intense positive fluorescence that outlined the basement membrane zone. Eight of 10 sections from oral lichenoid reactions exhibited fibrinogen deposition along the basement membrane zone; the specimens showed a less intense, homogeneous linear fluorescence. Specimens from five control samples showed no fluorescence. CONCLUSION: Fibrinogen was deposited at the basement membrane zone in both oral lichen planus and suspected oral lichenoid reactions, but the fluorescence was less intense in the oral lichenoid lesions.     

Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection,oral lichenoid contact sensitivity reaction and idiopathic oral lichen planus

OBJECTIVES: Oral lichen planus (OLP) is a common mucocutaneous disorder and might be associated to a possible pathogenic relationship with hepatitis C virus (HCV) infection or hypersensitivity to dental alloy. We examined the clinical and immunohistochemical features of OLP associated with HCV infection (OLP-HCV), oral lichenoid contact sensitivity reaction (OLCSR), and idiopathic oral lichen planus (iOLP). The immunohistochemical expressions of CD4, CD8, B cells, Class II major histocompatibility complex antigen (HLA-DR), S-100, HSP60, Proliferating cell nuclear antigen (PCNA) and Ki-67 were compared to study the pathogenic differences of the three OLP groups. MATERIALS AND METHODS: Three groups of OLP patients, (I) OLP-HCV patients (n = 17), (2) OLCSR patients (n = 10) and (3) iOLP patients (n = 14) were retrieved from clinical records and tissues examined immunohistochemically by the avidin-biotin-complex technique. RESULTS: The patients with OLP-HCV showed widespread lesions. The proportion of CD8+ cells was found to be significantly higher in the lamina propria of the OLP-HCV patients and a significantly lower proportion of CD8+ cells of the OLCSR patients was noticed in the epithelium or the connective tissue papillae than in the iOLP patients. There were no significant differences in either the number of CD4+ cells or B cells between the three OLP groups. No significant differences in the number of HLA-DR+ cells were found between the three OLP groups and some OLP-HCV patients showed a significant increase of S-100+ cells in the epithelium compared with iOLP patients. There were no significant differences in either the number of PCNA+ or Ki-67+ cells between the groups. The patients showed similar weak expressions of HSP60 in the three OLP groups. CONCLUSION: The different distributions of the CD8+ cells that could have functionally different roles might be related to the distinct pathogenic mechanisms in the three OLP groups.     

HLA-DR3 antigens in erosive oral lichen planus, cutaneous lichen planus, and lichenoid reactions

HLA antigens were examined in patients with erosive oral lichen planus (OLPe), cutaneous lichen planus (CLP), or lichenoid reactions (LR) adjacent to amalgam fillings. The control group had amalgam restorations in contact with the oral mucosa but without any reactions. A strong association was found between HLA-DR3 and OLPe, with an RR value of 21.0 (p less than 0.05). The corresponding values for CLP and LR were 2.3 and 1.5, respectively (NS). The haplotype A1-B8-DR3 was more frequently found in OLPe (p less than 0.05) and CLP (p less than 0.05) than in LR and controls (NS). The data indicate that OLPe, CLP, and LR, which present with virtually the same histopathologic features, are different in their association with HLA-DR3. Moreover, the increased frequency of HLA-DR3 in OLPe suggests an autoimmune component in the pathogenesis of this disorder.     

Lichen planus--specific antigen in oral lichen planus and oral lichenoid drug eruptions

OBJECTIVE: To investigate the usefulness of lichen planus-specific antigen as a marker to distinguish idiopathic oral lichen planus from oral lichenoid drug eruptions.Study Design: Biopsy samples were taken from 6 patients with oral lichenoid drug eruptions and 6 patients with idiopathic oral lichen planus. Each biopsy sample was examined for the presence of lichen planus-specific antigen by using a modification of a previously described immunofluorescence method that uses autologous serum and also allogenic sera from the remaining 11 cases. RESULTS: All autologous and allogenic immunofluorescence tests showed negative findings for lichen planus-specific antigen. CONCLUSIONS: Lichen planus-specific antigen is not a useful marker to distinguish oral lichenoid drug eruptions from idiopathic lichen planus. This finding is in contrast with our findings in an earlier study of basal cell cytoplasmic autoantibodies.     

Amalgam-contact hypersensitivity lesions and oral lichen planus

OBJECTIVE: The purpose of this study was to investigate the relationship between amalgam restorations and oral lichen planus. STUDY DESIGN: Eighty-one patients with oral lichenoid lesions were characterized clinically and skin patch tested for amalgam or mercury hypersensitivity. Thirty-three of these patients had amalgam fillings in contact with oral lesions replaced and were followed to determine the outcome. RESULTS: Clinically, 2 patient groups were identified: (1) 30 patients with probable amalgam-contact hypersensitivity lesions (ACHLs) and (2) 51 patients with oral lichen planus (OLP) but no clear relationship with amalgam. Seventy percent of ACHL cases were patch test positive for amalgam or mercury compared with only 3.9% of OLP cases (P < .0001). Amalgam replacement resulted in lesion improvement in 93% of ACHL cases. No such improvement was observed in the OLP cases treated (P < .001). CONCLUSION: OLP is a heterogeneous condition within which an ACHL subgroup can be identified. ACHLs, but not other OLP lesions, respond favorably to amalgam replacement. A strong clinical association between lesions and amalgam restorations plus a positive patch test result was a good predictor of lesion improvement on amalgam replacement.     

Thermal sensation and pain in oral lichen planus and lichenoid reaction

BACKGROUND: Our previous findings in oral lichen planus (OLP) and lichenoid reactions (LR) raised the question whether the histopathological changes observed in sensory and autonomic innervation produce oral sensory disorders. METHODS: Spontaneous pain was assessed using the Visual Analogue Scale (VAS). Thermal pain thresholds were measured with a contact thermostimulator and mechanical pain thresholds with an electronic algometer. RESULTS: Patients with OLP reported a higher intensity of spontaneous pain than LR patients (P = 0.001). Even erosive LRs were relatively painless. No thermal or mechanical hyperalgesia was detected in oral lesions. Highest separate cold pain threshold was measured in lesions affected by intense Candida growth. CONCLUSION: Together with previous histological findings, the present data suggest that increased somatic innervation and sympathetic denervation do not promote clinical pain sensitivity or hyperalgesia in oral mucosa and that these sensory functions are not affected by OLP and LR. Candida growth may function as secondary irritant modulating the pain responses.     

The role of histopathological characteristics in distinguishing amalgam-associated oral lichenoid reactions and oral lichen planus

OBJECTIVES: To identify histological features that distinguish amalgam-associated oral lichenoid reactions (AAOLR) from oral lichen planus (OLP). METHODS: Oral pathologists provided their opinion as to the possibility of distinguishing AAOLR and OLP histologically, the features important in distinguishing AAOLR from OLP and the diagnosis of 12 AAOLR and 12 OLP cases including the features that drew them to their conclusion. RESULTS: There was considerable variation between pathologists in their ability to distinguish the AAOLR and OLP cases. The sensitivity and specificity for histological diagnosis were 40% and 32% respectively. There were four features that were used most commonly to discriminate between AAOLR and OLP: an inflammatory infiltrate located deep to superficial infiltrate in some or all areas; a focal perivascular infiltrate; plasma cells in the connective tissue and neutrophils in the connective tissue. Each was independently predictive of AAOLR or OLP (P < 0.028). CONCLUSIONS: This study confirms the uncertainty of the diagnostic histological differences between AAOLR and OLP. Distinguishing these conditions should not rely on histology alone, but should be based on a synthesis of all available information including history, examination, histopathology and skin patch testing.     

Disorder-specific changes in innervation in oral lichen planus and lichenoid reactions

The peripheral nervous system was analysed in the oral mucosa of eight patients with oral lichen planus (OLP), five with a lichenoid reaction (LR) and three with mild chronic inflammation (MCI), by morphometric analysis of nerve fibres containing immunoreactive PGP 9.5, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), or C-flanking peptide of neuropeptide Y (CPON). Overall nerve fibre density was higher in OLP (P=0.039) and LR (P=0.026) compared with healthy oral mucosa and was compatible with sprouting and collateral formation. In contrast to the innervation visualized with structural nerve fibre-marker PGP 9.5, the densities of neuropeptide-immunoreactive nerves were low in inflamed tissue. This is consistent with depletion via local release. Retraction and local loss of innervation were found in areas coinciding with the most severe inflammation and basal membrane (BM) damage. Interestingly, LR showed a twenty-eight-fold loss of post-ganglionic CPON-ir sympathetic nerve fibres (P=0.044). In LR, CPON-ir innervation was markedly lower than in OLP. Finally, the pattern of innervation in relation to inflammatory cell infiltrates and tissue structures differed between OLP and LR. In conclusion, the peripheral nervous system is implicated in the immunopathogenesis of lichen planus and lichenoid reactions, with a disorder-specific difference in this involvement.     

High percentage of oral lichen planus and lichenoid lesion in oral squamous cell carcinomas

Objective: Oral lichen planus (OLP) and lichenoid lesions (OLL) are regarded as precursor lesions of oral squamous cell carcinoma (OSCC) with potential for malignant transformation. This potential is not clear due to difficulties in diagnosis of OLP and OLL. Our aim was therefore to evaluate previously identified OLP and OLL as precursor lesions in OSCC and to identify cancer related etiological factors such as smoking and alcohol consumption.

Material and methods: We retrospectively reviewed all cases (total 323, comprising 164 females and 159 males) with OSCC treated at the Department of Oral and Maxillofacial Diseases and Surgery, Helsinki University Hospital during 2015. Confirmed by histopathological biopsy, 58 (17.9%) had OLP and 13 had OLL (4.0%) as precursor lesion.

Results: Patients with OLP were slightly older than those without it. OLP was more common in females than in males (p?p?=?.006) and cancer relapses less common (p?=?.005). Smoking was less frequent in patients with OLP and OLL (p?p?Conclusion: Our findings confirm the importance of active follow-up of all patients with OLP and OLL even in patients who do not fit a traditional high-risk category for OSCC.