The usefulness of p63 detection for differentiating primary from metastatic skin adenocarcinomas

To the Editor, We would like to thank Drs Kanitakis and Chouvet for their insightful comments regarding our studies on use of p63 as a helpful tool in differentiating adnexal tumors from metastatic adenocarcinomas to skin. (J Cutan Pathol 2008; 35: 692) We appreciate their interest in our work and their shared passion for this subject. We have been given the opportunity to respond to the distinctive points raised in the letter, and we welcome the chance to discuss them. Our initial study assessed the difference in p63 expression in primary cutaneous adnexal neoplasms and metastatic adenocarcinomas to skin, showing that p63 is generally expressed in cutaneous adnexal tumors and is lacking in the metastatic lesions. We would like to stress that it was our intention to especially study p63 expression in metastatic adenocarcinomas to skin (we included tumors with breast or gastrointestinal origin) as we were aware of the p63 positivity in primary and metastatic squamous cell carcinomas (with lung or head and neck origin) or urothelial carcinomas, based on previous studies. In our subsequent paper, we have looked at rare cases of adnexal tumors that metastasized, and we concluded that the majority of them, especially the ones with eccrine differentiation, maintain their p63 expression in their metastatic cognates, while a larger series of metastatic adenocarcinomas to skin were also studied. Based on our findings, we have proposed that p63 can be a helpful (but not the ultimate or the perfect’) marker in distinguishing primary adnexal tumors from metastatic adenocarcinomas to skin. Drs Kanitakis and Chouvet offer in their letter to editor the results of their study, in which they have examined p63 expression in 45 cutaneous metastases and 94 primary epithelial skin tumors. Although they conclude that their findings are at variance with our study, we do believe that actually support our work. In concordance with our findings and reports of others, Drs Kanitakis and Chouvet found that the large majority (88.5%) of primary skin tumors express p63. Of interest is their reported low p63 expression, confined mostly to peripheral (myoepithelial) cells’, in one case of cutaneous mucinous carcinoma. They mention that a previous study of Qureshi et al. supports their findings. However, in the latter paper, three cases of primary mucinous carcinomas were included; two of them were negative for p63 and the third case had focal (11, ,10% of cells) expression of p63 that was considered an in situ component. In one of the largest published case series of mucinous carcinomas of the skin, Kazakov et al. mentioned that an in situ component can be identified in some cases of primary cutaneous mucinous carcinomas; the in situ component will have the surrounding myoepithelial cells that, not surprisingly, will account for the focal p63 positivity. At this point, we would also like to draw the attention that in our studies, we defined the p63 positivity as the expression in at least 25% of the cells. Therefore, we have eliminated the possibility that focal (sometimes non-specific) immunoreactivity will be read as a positive result. Moreover, in metastatic adnexal tumors to skin, sometimes there are entrapped normal adnexal elements (such as eccrine ducts and follicle structures), which will be p63 positive, but most probably these will represent less than 25% of the lesion cells. In Drs Kanitakis and Chouvet’ study, it is reported that 89% of the metastatic tumors to skin are p63 negative, and they found that 5 of 45 (11%) cutaneous metastases have p63 immunoreactivity. However, according to their letter, three of these five cases are not actually adenocarcinomas (two are epidermoid/squamous cell carcinomas from lung