PII: S1079-2104(01)70071-6

Abstract

We would like to thank Drs Fornatora, Cale Jones, Kerpel, and Freedman for their interest in our paper; we appreciate the opportunity to reply to their letter. 1.Semantics: On the basis of the definition given by Fornatora et al (“oral lesions that displayed features of HPV infection and epithelial dysplasia”), lesions such as generic epithelial dysplasia with occasional cells exhibiting nuclear hyperchromasia with peri-nuclear vacuolization in the superficial layers and even some cases of verrucous carcinoma would be diagnosed as koilocytic dysplasia (KD). That is a broader spectrum than the bowenoid lesions that exhibit atypical—and even bizarre—mitosis, apoptotic fragments or cells, karyomegally without hyperchromasia or cytoplasmic clearing, multinucleation, and dyskeratosis, all of which are randomly distributed throughout the epithelial layers. Consequently, we believe that their term koilocytic dysplasia is not discrete enough for the microscopically unique bowenoid lesions, and therefore we chose to maintain the bowenoid terminology to emphasize the potential for significantly different biological behavior of these lesions when they involve the oral mucosa. We do not share Fornatora et al’s concerns with the terms Bowen’s disease (BD) and bowenoid papulosis (BP). For those who may be uncertain about these terms, we carefully describe what is meant in the first 2 paragraphs of the introduction in our paper. Trying to sort out oral lesions that exhibit bowenoid features microscopically is the intent of our paper, because clinical features alone are obviously inadequate. Furthermore, the value of a term should not be based on how long it has existed, but on whether it is still relevant. We believe that the terms BD and BP are still applicable to oral lesions, and we recommend their continued use unless, or until, evidence shows otherwise. 2.Biological behavior: The bottom line is biological behavior and the ability of diagnosticians to predict it so that patients can receive appropriate treatment. It is clear from our data and from the as-yet unpublished findings of Fornatora et al that 3 of their 100-plus cases had become malignant and that the present level of knowledge is insufficient. In our opinion, placing all lesions that exhibit bowenoid microscopic features into one group, along with other HPV-containing dysplasias not exhibiting bowenoid features, under the term KD does not help. We must try to find a means of differentiating these lesions, as we have attempted to do in our article. In their letter, Fornatora et al suggest that we “modernize” by assessing HPV status and host response. They seem somehow oblivious to the fact that we did assess HPV status—by in situ hybridization with probe cocktails and confirmation of expression of the HPV16 E6 gene by in situ rtPCR—and host response at the morphologic level by assessing lymphocyte infiltration, and at the molecular level with our attempts to determine the apoptotic and cell-cycling molecules involved. 3.Other comments: Bowen’s disease may be a carcinoma in situ, but it is a very special subset with unique histologic features. The relationship of BD to other oral dysplasias has yet to be determined. To include it with carcinomas in situ without bowenoid features is, in our opinion, premature and probably inappropriate. To consider bowenoid papulosis a carcinoma in situ is also inappropriate, because its biological behavior is benign and the affected patient is likely to be overtreated. This is why we must strive to determine ways of differentiating these lesions. When they complete their study of 100-plus cases, which will be a welcome addition to the oral pathology literature, we anticipate that Fornatora et al will find a spectrum of biological behavior. We hope that they will try to identify clues that will allow us to predict the aggressive lesions from the indolent ones; histologic clues (although oldfashioned) would be very helpful to the practicing pathologist. They can call these different groups BP and BD , or perhaps they’ll prefer KD type 1 and KD type 2 . But that, again, is a matter of semantics.