Fernandez-Flores, Angel MD, PhD
doi: 10.1097/DAD.0b013e3181bbd430
Letter to the Editor
To the Editor:
It was a pleasure to learn that Dr. Resnik and Dr. Kutzner took an interest in reading my reports, as they kindly acknowledge in their letter to this journal.1 I sent those reports2,3 to Dr. Resnik, because they were published in journals with a low impact index. I also thought he might be interested in them, because of his publication with Dr. Kutzner on CD30+ infiltrates.4
One of the reports2 was previously sent to a well-known journal of pathology, but the article was rejected. One of the reviewers repeatedly claimed that “the authors should make sure they understand that a diagnosis of lymphomatopid papulosis requires staining of >75% of the larger atypical cells in an infiltrate.” This made me think that the reviewer himself did not clearly understand the concepts on lymphomatoid papulosis (LyP). He had misunderstood the requisite to diagnose an anaplastic large cell lymphoma (ALCL; over 75% of the larger atypical cells) with the requisite for the diagnosis of LyP. This also made me wonder if there was really a requisite on such a matter, regarding LyP. In literature, the number of CD30+ cells in the infiltrate of LyP ranges from5 25% to more than 90%, but in some cases seem to have only scattered CD30+ cells.6 Others simply do not mention the percentage of CD30+ cells.7
Some reports have focused on the subject of keratoacanthomatous changes related to LyP.7,8 But there is some conflicting information in these reports. For instance, some have described cases with an infiltrate composed of large and pleomorphic lymphocytes (although no image of the CD30 immunostaining is shown) without describing the percentage of CD30+ cells.8 Despite describing the infiltrate as “large and pleomorphic,” the authors conclude that the infiltrate was part of the keratoacanthoma (KA) and not of the LyP. Others authors (again, with no description of the CD30+ cell percentage), interpret their results as LyP with keratoacanthomatous changes, in spite of their description: “in biopsy specimens from some of the lesions only occasional CD30+ cells were identified”.9 These examples lend support to their assertion made by Drs. Resnik and Kutzner that there is an overlap between KA with reactive CD30+ cells and LyP with reactive KA-like changes.
In one of our reports,3 we took a step further, and postulated that CD30+ cells play a role in KA “persistence” since these cells tend to disappear when the KA started to regress (but not totally regressed). This parallelism with LyP, is intriguing, since both entities require the presence of CD30+ cells: in LyP, as a condition for diagnose and in KA, as a stimulus to persist. The connection brought on by Dr. Resnik and Dr. Kutzner on the possibility of a viral infection in CD30+ cells, brings a nice and simple possible explanation for all these phenomenona.
It might be hypothesized that the persistence of CD30+ cells might determine the progression of a KA into a deeply infiltrating squamous cell carcinoma. On the other hand, there is already some proof suggesting that CD30 plays a crucial role in the progression from LyP to cutaneous ALCL. The latter phenomenon occurs in around 10% of patients with LyP.10 Some have demonstrated how a CD30 ligand agonist antibody can cause proliferation of clonal cell lines derived from LyP.10 Moreover, some studies suggest that while CD30 activation induce regression of LyP lesions, but it can also induce progression in cutaneous ALCL cells.11 This latter phenomenon implies a functional change at some point of the CD30 regression route. Needless to say that in modern times of antibody therapeutics, CD30 might play a crucial role as a target in the close future. The question is if it will be a target only regarding lymphomas, or and squamous carcinomas with CD30+ accompanying cells.
Angel Fernandez-Flores, MD, PhD
Service of Cellular Pathology, Clinica Ponferrada, Ponferrada, Spain
REFERENCES
1. Resnik KS, Kutzner H. Of lymphocytes and cutaneous epithelium: keratoacanthomatous hyperplasia in CD30+ lymphoproliferative disorders and CD30+ cells associated with keratoacanthoma.
Am J Dermatopathol. 2010;32:314-315.
2. Fernandez-Flores A. CD30+ cell population in common keratoacanthomas: a study of 21 cases.
Rom J Morphol Embryol. 2008;49:159-162.
3. Fernandez-Flores A. CD30+ cells in regressing keratoacanthoma and in nonkeratoacanthomatous squamous-cell carcinoma.
Bratisl Lek Listy. 2008;109:508-512.
4. Resnik KS, Kutzner H. Mimicry illuminating pitfalls in histopathologic diagnosis: nutritional deficiency-like dermatitis secondary to topical tazarotene and keratoacanthomatous pseudocarcinomatous hyperplasia in CD30+ lymphoproliferative disorder as illustrative.
Am J Dermatopathol. 2009;31:22-25.
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Mod Pathol. 2000;13:446-451.
6. Paulli M, Berti E. Cutaneous T-cell lymphomas (including rare subtypes). Current concepts. II.
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7. Cespedes YP, Rockley PF, Flores F, et al. Is there a special relationship between CD30-positive lymphoproliferative disorders and epidermal proliferation?
J Cutan Pathol. 2000;27:271-275.
8. Guitart J, Gordon K. Keratoacanthomas and lymphomatoid papulosis.
Am J Dermatopathol. 1998;20:430-433.
9. Scarisbrick JJ, Calonje E, Orchard G, et al. Pseudocarcinomatous change in lymphomatoid papulosis and primary cutaneous CD30+ lymphoma: a clinicopathologic and immunohistochemical study of 6 patients.
J Am Acad Dermatol. 2001;44:239-247.
10. Kadin ME, Levi E, Kempf W. Progression of lymphomatoid papulosis to systemic lymphoma is associated with escape from growth inhibition by transforming growth factor-beta and CD30 ligand.
Ann N Y Acad Sci. 2001;941:59-68.
11. Levi E, Wang Z, Petrogiannis-Haliotis T, et al. Distinct effects of CD30 and Fas signaling in cutaneous anaplastic lymphomas: a possible mechanism for disease progression.
J Invest Dermatol. 2000;115:1034-1040.
