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In my article I gave unequivocal historical credit and precedence to Coupland and Damato’s (C&D) cogent work on developing an alternative diagnostic pathologic approach to primary acquired melanosis in the face of its well-established ascendancy. Despite the citations of their initial paper, their classification and nomenclature have not gained widespread use in the United States. Folberg’s go-with editorial appearing with my piece totally overlooks their classification system, and the most recent edition (2015) of a standard American ophthalmic pathology textbook does not describe or discuss it. Owing to the word limit of the letter format, I will have to restrict the remainder of my comments to the salient scientific points they raise about my own terminology.


First, the main reason why I used “proliferation” rather than “neoplasia” is that the former encompasses both neoplastic (clonal) and hyperplastic (nonclonal) lesions. In my review I define hyperplasia just as C&D do. C&D dismiss hyperplasia completely as a diagnostic challenge even though it is a term not infrequently invoked by dermatopathologists, but at this moment we do not know its precise role in the melanocytic spectrum owing to the limitations of morphology. In other contexts it has been shown that hyperplasia can be an antecedent lesion that progresses to neoplasia. We have not identified which molecular events promote a melanocytic transition, nor have we any markers that would allow us to identify it. Examples in other systems are reactive lymphoid hyperplasia (polyclonal) evolving into lymphoma (monoclonal), especially in Sjögren syndrome; Helicobacter -induced MALT hyperplasia of the stomach culminating in marginal zone lymphoma; parathyroid C-cell hyperplasia transforming into medullary carcinoma ; and hyperplastic polyps of the stomach eventuating in carcinomas. Ultraviolet radiation, viruses, bacteria, Chlamydia , and ingested or external chemicals are all putative agents indicted for transforming hyperplasia into more serious conditions. As an ironic and somewhat irreverent aside, I would also draw attention to the infelicitous quirk that the term “conjunctival melanocytic intraepithelial neoplasia,” which when abbreviated as C-MIN and then pronounced, results in an unfortunate urologic conjuring.


Second, my gentle criticism of the term “hypermelanosis” used by C&D was resolved in my own mind by the descriptor of “nonproliferative melanocytic pigmentation,” which C&D believe is inaccurate. I am definitely aware that melanocytes synthesize melanin and also transfer it to surrounding keratinocytes, particularly the basal keratinocytes among which the melanocytes are lodged. I deal with this aspect of the functioning of melanocytes and illustrate it in my paper under the subheading of “Melanocytic Origins and Biology,” and have also studied the subject in depth by electron microscopy in my American Ophthalmological Society thesis. I suppose a more biologically refined but awkward term might be “melanocytogenic” pigmentation. In any case, it is the nonproliferative nature of the condition which is paramount; of secondary importance is distinguishing melanin-related pigmentation from other conjunctival/scleral deposits like ochronosis, drug by-products, silver (argyrosis), etc.


C&D are a team of productive and biologically oriented clinical investigators who have made substantive contributions to the analysis and treatment of conjunctival melanocytic lesions. I thank them for engaging with my work. Whatever the differences between us that may exist, in my opinion we are in fundamental agreement on the central issues, with only a few cavils at the periphery. I look forward to the publication of the results of their multicenter study that applies their grading system to conjunctival melanocytic lesions.

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Jan 6, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Reply

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