Correlation of clinical, histological and immunopathological findings in oral inflammatory mucosal diseases

There is an array of immune-mediated chronic ulcerative conditions that affect the oral mucosa. Many of them share clinical and microscopic characteristics and only through immunopathological studies such as direct immunofluorescence (DIF), a correct diagnosis can be rendered. This study aimed to determine the specificity and sensitivity of clinical, and histological parameters of chronic ulcerative conditions of the oral cavity particularly lichen planus, using DIF as the gold standard. In addition, we endeavor to investigate the ability of four board certified oral pathologists to diagnose correctly oral lichen planus, pemphigoid, pemhigus vulgaris and squamous cell carcinoma when only the site of the biopsy and light microscopy of hematolylin and eosin (H&E) stained tissue sections were provided. We designed a two-stages retrospective study of 100 consecutive oral biopsies submitted to an immunopathological referral center (IMMCO Diagnostics. Buffalo, NY). Ninety-seven H&E biopsies were included in our study. The specific microscopic findings for all 97 cases were tabulated for comparison. In the first stage of this research project we found that sixty-two cases yielded a DIF immunopathological profile consistent with lichen planus while seven cases were diagnosed as mucous membrane pemphigoid; two cases were diagnosed as pemphigus vulgaris, and one case each of linear IgA disease and systemic connective tissue disease. Thirty-four cases had negative DIF findings. These cases included 10 lichen planus, 4 premalignant or malignant epithelial changes and the rest represented miscellaneous entities. Sensitivity and specificity of clinical diagnosis was 88% and 72%, respectively. The sensitivity and specificity for H&E diagnosis was 88% and 93%. The sensitivity and specificity for DIF diagnosis was 88% and 100%, respectively. For the second stage of this project, 97 H&E slides were sent to a panel of 4 board certified oral pathologists. Only the site of the biopsy was included. The pathologists were asked to render a diagnosis and to provide a comment, if they thought that it was indicated. The responses of the panel were not uniform regarding the terms used for the diagnosis. In addition, there was a wide variation in the number and the degree of detail used in the comments. It became clear that the term lichen planus was not used as a "sign-out" diagnosis by three of the pathologists, with only one using the term lichen planus in the final diagnosis. The terms chronic mucositis or lichenoid mucositis were used as sign out diagnosis for most cases. In these cases, comments such as "DIF and/or clinical correlation are indicated to arrive to a more precise diagnosis." Interestingly, one of the pathologists only commented that DIF was indicated if she/he diagnosed the case as mucous membrane pemphigoid. Because the term lichen planus was rarely used in this study as a final diagnosis, it became apparent that the comments used by the pathologists were very important. These comments pointed out to the need of using DIF and/or a clinical correlation to rule-out lichen planus ultimately, securing a precise diagnosis resulting in using the proper treatment for the patient. We also found that mucous membrane pemphigoid was difficult to separate from lichen planus on H&E examination. In these cases most pathologists requested DIF to secure a correct diagnosis. Superimposed inflammation also distracted the pathologists, diverting them from a diagnosis of lichen planus. Our study emphasizes the importance of DIF to segregate immune-mediated chronic ulcerative conditions of the oral cavity. In addition, this study also emphasizes the need to include H&E studies, particularly in cases where DIF is noncontributory to the final diagnosis.