Tyrosinase Expression in Malignant Melanoma, Desmoplastic Melanoma, and Peripheral Nerve Tumors

To the Editor—We read with interest the article “Tyrosinase Expression in Malignant Melanoma, Desmoplastic Melanoma, and Peripheral Nerve Tumors” by Boyle et al.1 In the article, Boyle et al reported that 100% (5/5) of their desmoplastic melanomas stained with antibodies to tyrosinase and HMB-45 using a microwave-based antigen-retrieval immunohistochemical technique. This result surprised us because our immunohistochemical laboratory has been using microwave-based antigen-retrieval techniques for many years and we have never seen consistent staining of desmoplastic melanoma with tyrosinase and HMB-45, except focally in superficially located or in situ epithelioid or nevoid components of the lesions. In fact, our previous study and many others in the literature demonstrated rare if any staining of the spindle cell component of desmoplastic melanoma with tyrosinase and HMB-45.23Most desmoplastic melanomas are positive for S100, but frequently lack the melanocytic differentiation markers such as tyrosinase, gp100 (HMB-45), melan-A, and MITF. In an effort to resolve the difference, we performed tyrosinase immunostaining on 5 well-characterized desmoplastic melanomas using microwave-based antigen-retrieval techniques and the same tyrosinase antibody (T311) as was used in the mentioned article. In 4 of 5 cases (80%), the tumor cells were completely negative; in 1 case (20%), only superficial more epithelioid tumor cells were positive; however, the deeper more spindled cells were negative for tyrosinase. In all of these cases, internal positive controls stained properly.We disagree with the conclusion of Boyle et al and would also like to raise 3 questions. First, a conventional microwave oven has no device to control the buffer temperature and can only be estimated at about 100°C when the buffer is boiling; however, the authors stated that their antigen-retrieval technique was performed at 121°C, a temperature that likely required a pressure cooker or specially designed microwave oven. In the article, there was no detail about how 121°C was achieved in a microwave oven. Second, the antigen retrieval condition used in the paper (121°C, 20 minutes) is very harsh to the tissue. In our experience, heating tissue sections in a pressure cooker more than 5 minutes will often result in dissolution of the tissue section. In addition, we wonder whether the authors used other means to validate their findings so as to exclude the possibility that the staining was due to cross-binding of the antibody to some unrelated epitopes generated by the harsh antigen-retrieval technique? Third, because the photomicrographs of the desmoplastic melanoma showed aggregates of epithelioid to spindled tumor cells, unlike typical desmoplastic melanoma, in which individual tumor cells are embedded in a fibrotic stroma, we question whether these tumors may represent nondesmoplastic spindle cell melanomas, which might account for the discrepancy in the reported findings.We believe it is misleading to represent desmoplastic melanomas, at least in their predominant spindle cell components, as reacting with HMB-45 and tyrosinase. It is well known that desmoplastic melanoma can mimic scar and benign neural lesions because of its bland spindle cell morphology; and it is dangerous to assume that negative HMB-45 and tyrosinase stains are sufficient to rule out desmoplastic melanoma.