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.     

口腔扁平苔藓诊断标准的发展与中国化

口腔扁平苔藓(oral lichen planus,OLP)是一种常见的口腔黏膜慢性炎性疾病,其诊断标准是临床诊治和科学研究的基石,但目前对诊断标准的认识并不统一,特别是国际的诊断标准如何与我国具体国情结合,应用于临床,指导我国的临床工作和科学研究,这些问题亟待解决。本文对国际上OLP诊断标准的发展、内容特点、差异度等进行系统介绍和讨论,并结合切身临床和研究经验以及我国临床医师的具体实际,提出OLP诊断中活检适应证选择的"23原则",并对其他与OLP诊断相关的热点问题提出建议。     

朗格罕斯细胞的分布、变化与口腔扁平苔藓发病及病变程度的关系

目的：为进一步探讨口探扁平苔藓的发病机制。方法：采用免疫组织化学方法,使用朗格罕斯细胞特异性标记CD1a单克隆抗体对35例口腔扁平苔藓（oral lichen planus,OLP)进行研究,结果：CD1a^ 的朗格罕斯细胞（Langerhans cell,LC)较对照组明显增多,分布更趋于上棘层及粒层,树突增,增长,其数量和表达程度与OLP病程、病变程度相关,不同组间有高度显著性（P＜0．01）。结论：LC在OLP的发病,发展中具有重要作用。     

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环孢素(cyclosporin)是有代表性的、能选择性抑制细胞免疫的免疫抑制剂,临床主要用于肝、肾等器官移植后的抗排异反应,也可用于治疗自身免疫性疾病,如类风湿性关节炎、系统性红斑狼疮等,均取得较好疗效。在口腔疾     

EP—CAM在OLP和OSCC组织中的表达及意义

目的：观察上皮细胞黏附分子（Ep—CAM）在口腔正常黏膜、扁平苔癣（OLP）和鳞癌（OSCC）组织中表达的变化,分析Ep—CAM在口腔黏膜疾病及其癌变发病机制中的作用。方法：采用免疫组织化学法检测10例正常口腔黏膜、30例OLP（15例非糜烂型、15例糜烂型）及20例OSCC组织中Ep—CAM的表达变化。结果：Ep—CAM在正常黏膜组织阴性表达,而在非糜烂型OLP、糜烂型OLP及OSCC组织中表达逐渐增强。结论：Ep—CAM在口腔黏膜癌变的发展过程中可能具有一定的指示意义。     

CD44在口腔扁平苔藓中的表达及意义

目的 探讨口腔扁平苔藓病变中粘附分子CD44H、CD44V3表达的意义。方法 应用免疫组织化学SP法对62例口腔扁平苔藓，其中糜烂型扁平苔藓14例，非糜烂型扁平苔藓48例，21例慢性盘状红斑狼疮，10例正常粘膜CD44H、CD44V3的表达进行观察。结果 扁平苔藓病损区组织的染色以基底细胞、棘层细胞下调明显。结论 CD44参与口腔扁平苔藓的发病过程。     

Studies of the inflammatory process and malignant potential of oral mucosal lichen planus

Oral mucosal lichen planus (OMLP) is a well recognized mucosal disease with unknown aetiology. Considerable controversy exists as to whether OMLP is intrinsically premalignant, or if the disorder facilitates the development of oral mucosal squamous cell carcinoma (OMSCC) by external factors.
The aim of the present studies was to investigate the expression of c-erbB-2 protein in the keratinocytes of the initial biopsies of oral mucosal disorders diagnosed as OMLP with no evidence of epithelial dysplasia and to compare the results with the expression of c-erbB-2 protein in subsequent biopsies obtained from the same patients. These results were compared with the findings from another 26 biopsies from patiente with OMLP and control groups (patiente with dysplasia with no evidence of OMLP, patients with OMSCC with no evidence of OMLP and normal oral mucosa).
The expression of the c-erbB-2 protein was evaluated by Immunohistochemical staining of the gene product with the avidin-biotin-complex method using both fresh frozen and paraffin-embedded tissue sections.
Five of the initial biopsies from patients with OMLP expressed the c-erbB-2 protein and one did not. None of the OMLP cases that subsequently showed evidence of dysplasia expressed the c-erbB-2 protein and of the OMSCC specimens from the patients with OMLP, 2 were negative and 1 expressed c-erbB-2 protein. Within the other group of OMLP specimens 3 (3/26) were negative for c-erbB-2 staining. The specimens from the control groups all expressed the c-erbB-2 protein.
The results indicated the probability of the absence of c-erbB-2 staining being an indication of a potential for neoplastic transformation in OMLP with dysplastic changes.     

Comparison of eosinophil densities in oral mucosal lichen planus and lichenoid drug reactions

The eosinophil density in various tissue compartments in oral mucosal lichen planus and oral mucosal lichenoid drug reactions was studied using a variety of staining methods and histomorphometry. No significant differences were found, indicating that the presence of eosinophils cannot be used as a reliable histologic criterion for establishing a diagnosis of oral mucosal lichenoid drug reactions.     

口腔扁平苔藓与过敏原

目的；研究口腔扁平苔藓的发生、发展与吸入性和食物性过敏原的关系。方法：应用20种食物性过敏原溶液和18种吸入性过敏原溶液，采用皮内注射法，对95例口腔扁平苔藓患者进行过敏原过敏反应检查。结果：95例全部呈现过敏反应。其中84例同时存在食物性和吸入性过敏原过敏反应。6例单纯对食物性过敏原过敏，5例单纯对吸入性过敏原过敏。部分食物过敏原呈现迟发性超敏反应。结论：口腔扁平苔藓的发生、发展与吸入性和食物性过敏原相关。限制接触过敏物质有益于口腔扁平苔藓的治疗。     

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.     

热休克蛋白60、70在口腔扁平苔藓中表达的研究

目的　探讨热休克蛋白 (heatshockprotein ,HSP) 60和HSP70在口腔扁平苔藓病变中的作用。方法　对 62例口腔扁平苔藓、1 0例正常口腔粘膜、2 1例慢性盘状红斑狼疮、1 0例粘膜良性淋巴组织增生病 ,46例白斑进行免疫组织化学SP法染色 ,分析HSP60、HSP70在口腔扁平苔藓中的表达 ;对 1 2例口腔扁平苔藓和 5例正常粘膜进行逆转录PCR实验 ,观察HSP60、HSP70mRNA的变化。结果　HSP60在口腔扁平苔藓病损区的表达较其他各组显著增强 ,差异有显著性 (P <0 0 0 1 )。HSP70在糜烂型口腔扁平苔藓病损区的表达下调。RT PCR结果显示 ,HSP60、HSP70mRNA表达增强。结论　HSP60及HSP70在口腔扁平苔藓的发病中起重要作用     

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.     

Number V Oral lichen planus: clinical features and management

Oral lichen planus (OLP) is a relatively common chronic inflammatory disorder affecting stratified squamous epithelia. Whereas in the majority of instances, cutaneous lesions of lichen planus (LP) are self-limiting and cause itching, oral lesions in OLP are chronic, rarely undergo spontaneous remission, are potentially premalignant and are often a source of morbidity. Current data suggest that OLP is a T cell-mediated autoimmune disease in which auto-cytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. The characteristic clinical aspects of OLP may be sufficient to make a correct diagnosis if there are classic skin lesions present. An oral biopsy with histopathologic study is recommended to confirm the clinical diagnosis and mainly to exclude dysplasia and malignancy. The most commonly employed and useful agents for the treatment of lichen planus (LP) are topical corticosteroids but other newer agents are available.     

中药治疗口腔扁平苔藓的免疫调节作用

目的探讨中药治疗对口腔扁平苔藓患者免疫状况的影响。方法对３０例口腔扁平苔藓患者应用中药治疗，检查了患者治疗前后Ｔ淋巴细胞亚群的变化。结果患者治疗前ＣＤ３、ＣＤ４以及ＣＤ４／ＣＤ８比率显著低于健康人（Ｐ＜０．０１）；中药治疗后患者ＣＤ３、ＣＤ４以及ＣＤ４／ＣＤ８比率显著提高（Ｐ＜０．０１），ＣＤ４／ＣＤ８比率恢复正常。３０例中，痊愈８例，显效１４例，好转８例。结论提示口腔扁平苔藓患者Ｔ淋巴细胞功能减弱，Ｔ细胞亚群平衡失调，中药治疗对患者机体免疫有双向调节作用，免疫平衡得以恢复，并取得较好的临床疗效。     

CD133在口腔扁平苔藓和口腔鳞状细胞癌中的表达及其临床意义

目的探究肿瘤干细胞标记物CD133在口腔正常黏膜、口腔扁平苔藓（OLP）及口腔鳞状细胞癌（OSCC）中的表达情况及临床意义,评估其作为OLP恶性转化的早期诊断指标、OSCC治疗干预靶标的临床价值,为进一步研究口腔黏膜癌变机制提供基础。 方法回顾性分析10例正常口腔黏膜、60例OLP、60例OSCC患者的临床资料,运用免疫组织化学技术检测各组病理组织中CD133表达情况,采用Mann-Whiney秩和检验比较各组间CD133表达差异,卡方检验统计分析CD133与各临床因素的关系。采用免疫组织化学技术和免疫印迹技术检测人口腔癌前病变细胞株（DOK）和人OSCC细胞株（CAL-27）中CD133的表达情况,t检验比较CD133在DOK与CAL-27细胞株中含量差异。 结果口腔正常黏膜、OLP、OSCC三组中,CD133的阳性率为0（0/10）、31.67%（19/60）、63.33%（38/60）,表达逐渐增强。CD133在口腔正常黏膜与OLP表达强度差异有统计学意义（Z=-2.046,P= 0.041）。CD133在OLP与OSCC表达强度差异具有统计学意义（Z=-3.777,P<0.001）。CD133在DOK中弱阳性表达,在CAL-27中阳性表达,DOK与CAL-27中CD133含量差异有统计学意义（t=-5.029,P= 0.001）CD133与OSCC的临床分期和淋巴结转移有关。 结论CD133作为评估OLP恶性转化潜能的指标及OSCC早期治疗干预靶标可能具有重要临床价值。     

Langerhans cell distribution and keratinocyte expression of HLADR in oral lichen planus

Keratinocyte expression of the Class II major histocompatibility complex antigen HLADR, is seen in several inflammatory disorders of skin and mucosa, including lichen planus. The purpose of this study is to determine whether the distribution of Langerhans cells and their expression of CD4 in oral lichen planus is related to keratinocyte HLADR. The numbers of CD1- and CD4-positive Langerhans cells were compared in areas of keratinocyte HLADR and areas showing no expression in oral lichen planus and with normal oral mucosa. Cells were identified using an immunoalkaline phosphatase technique and numbers were expressed per mm epithelial surface length. In lichen planus, an increase both in the number of Langerhans cells and the numbers expressing CD4 were found in areas of keratinocyte HLADR expression compared with HLADR negative areas and with normal oral mucosa. There was no difference in the numbers of Langerhans cells or their expression of CD4 between HLADR-negative areas in LP and normal oral mucosa. These results show that the distribution of Langerhans cells is related to keratinocyte expression of HLADR and suggest that Langerhans cell entry may be enhanced in these areas. Whilst it is possible this enhancement is mediated by CD4/HLADR interaction, other molecules are also likely to be important in controlling Langerhans cell entry into oral mucosa.     

口腔扁平苔藓中基质金属蛋白酶及其组织抑制剂的表达

目的 分析基质金属蛋白酶（MMP）2，膜型基质金属蛋白酶1（MT1-MMP），基质金属蛋白酶抑制剂（TIMP）2在口腔扁平苔藓（OLP）中的表达及意义。方法通过免疫组化检测其在OLP中的表达并与口腔鳞状细胞癌（OSCC）及正常口腔黏膜进行比较。结果从正常口腔黏膜（NOM）、非萎缩型OLP，到萎缩型OLP和OSCC3种酶表达依次增加。萎缩型OLP中MMP-2和MTl．MMP的表达明显高于NOM和非萎缩型OLP，与OSCC表达相似。TIMP-2的表达亦随着MMP的增高而增加，但与MMP-2和MT1-MMP相比，其增加量相对较低。结论MMP表达的高低可能成为判断OLP恶变潜能的检测指标之一。     

Immunoelectron microscopic study of distribution of T cell subsets in oral lichen planus

Abstract – Monoclonal anti-CD4, anti-CD8, and anti-GD18 antibodies were applied in avidinbiotin-peroxidase complex staining using a pre-embedding immunoelectron microscopy technique. Although most of the local T cells in situ were of CD4⁺ subtype, local CD8⁺ cells generally had a lower nucleus/cytoplasm ratio and contained more cell organelles than CD4⁺ cells. This suggests a local activation of CD8⁺ subpopulation, rather than activation of the numerically predominant CD4⁺ cells. Topographical analysis disclosed that all lymphocytes, regardless of location, were CD18⁺ and that most of the CD8 ⁺ cells were located subbasally and intraepithelially, whereas CD4⁺ cells often occurred in small clusters deeper down in the subepithelial lymphocyte-rich band. Furthermore, CD8⁺ cells were often in close contact with macrophages, whereas CD4⁺ cells were in some instances in direct contact with plasma cells. This indicates that CD4⁺ cells may be involved in T cell-dependent B cell-mediated immunoglobulin synthesis, whereas CD8⁺ cytotoxic lymphocytes and tissue macrophages may be involved in the local pathogenetic process leading to basement membrane alterations.