We would like to thank Dr. Goto for his comments on our recent publication, “Polymorphous sweat gland carcinoma: An immunohistochemical and molecular study.”1 Dr. Goto expresses the opinion that our cases represent basal cell carcinomas (BCCs) of “adenoid-cystic type with focal carcinoid pattern.” He supports this opinion with a variety of arguments, mainly his interpretation of the illustrations provided in our article. We take it for granted that in the marketplace of ideas in academic medicine, everyone is entitled to their opinion and all opinions have merit and deserve to be heard. For this reason, we welcome Dr. Goto's opinions; however, we believe his comments deserve a response.
Dr. Goto states in his letter that “it has been indicated that the histopathologic features of these tumors are very similar to, and possibly in a similar or same spectrum as, adenoid cystic carcinoma,” and he quotes 2 books, the first one authored by Kazakov et al2 and the second one authored by himself.3 It was precisely because Dr. Kazakov, in his chapter on polymorphous sweat gland carcinoma (PSGC), stated his opinion that these tumors can manifest areas resembling adenoid cystic carcinoma that we decided to share our cases with him before publication and requested to have the molecular study for the detection of the MYB-NFIB fusion performed in his laboratory so that there would be no doubt or bias regarding the results. The molecular study performed in his laboratory clearly demonstrated that our 3 cases did not harbor this translocation, thus providing support for our contention that these tumors are unrelated to adenoid cystic carcinoma.
Dr. Goto then goes on to interpret the images in our publication. He claims that the images in Figures 2, 3A, B, and 4F of the article show a definite palisaded cell arrangement at the periphery of the tumor nests. The dominant growth pattern in these images, however, is a cribriform and ribbon-like pattern of growth. Although peripheral palisading of nuclei is a frequent feature in a broad variety of skin adnexal tumors other than BCC, in BCC, the central portions of the palisaded cell islands are most often solid and composed of a monotonous population of primitive “basaloid” cells rather than the ribbons and cribriform structures seen in our cases, which contain large round to oval cells with ample cytoplasm and minimal pleomorphism. Dr. Goto states that images 3A–E and 4A–F in our article show “prominent mucin deposition in and around the tumor nests.” The images clearly show no mucin deposition around the tumor cell nests (where it would be normally expected for BCC) but rather within the lumens of ductular or luminal structures, as would be expected of any other adnexal tumor of the skin. Dr. Goto further indicates that Figures 3D, 4A and F show “cleft-like spaces between the tumor nests and the surrounding stroma due to stromal retraction.” We see no such clefts and fear this may be an overinterpretation; clefting in BCC is readily apparent on scanning magnification and does not require higher magnification to identify. Dr. Goto further claims that the “pseudoglandular” structures shown in Figures 3A, B, E, 4A, C, F “exactly match” BCC. Although BCC with eccrine differentiation have been reported in the literature,4 they are extremely rare and, in the opinion of a prominent expert, they shade into lesions best classified with eccrine carcinoma.5 Dr. Goto's opinion that such structures are distinctive of BCC may, thus, be overstated.
Dr. Goto also argues that the immunoprofile of these tumors supports a diagnosis of BCC rather than PSGC. To the best of our knowledge, a distinctive or specific immunohistochemical pattern of staining for BCC has not yet been identified. All the markers so far identified in BCC are nonspecific and expressed in a variety of other adnexal and metastatic tumors. In fact, the pattern of staining of skin adnexal tumors shows considerable overlap to the point of making immunohistochemistry a useless exercise in most cases for separating these tumors.6
Although we appreciate the arguments that have led Dr. Goto to interpret our cases as examples of a rare variant of BCC, we do not believe these arguments are sufficiently convincing. What was described in our initial publication7 was a tumor of the skin that was characterized by large dermal nodules that were unconnected to the epidermis and displayed a variegation of growth patterns within the same lesion, showed morphologic features of adnexal differentiation commonly associated with eccrine/apocrine units, and had a definite, albeit low-grade, potential for aggressive behavior. The presence of stromal sclerosis and hyalinization surrounding the epithelial elements, the variegation of growth patterns within the same lesion, the foci of glandular or ductular differentiation, the focal papillary architecture, and their large size and deep location in the dermis without connection to the epidermis were emphasized as distinctive features that pointed toward these tumors representing a type of lesion showing features that were clearly not reproduced by any other of the commonly described skin adnexal neoplasms. Our recent article was an attempt to further characterize the immunophenotype of this tumor and determine whether it shared the specific translocation of adenoid cystic carcinoma. As stated in our current article, despite the superficial resemblance of PSGC to adenoid BCC, these tumors can be easily distinguished because adenoid BCCs will retain their peripheral nuclear palisading and show stromal retraction, which is not seen in our cases, in addition to showing a clear connection to the overlying epidermis. In other words, we recognize the adenoid cystic variant as BCC because the tumors retain, at least focally, the characteristic features of BCC, which include solid islands of tumor cells showing a proliferation of primitive, poorly differentiated “basaloid” cells that usually show brisk mitotic and apoptotic activity. Despite Dr. Goto's personal interpretation of the illustrations provided in our article, we simply did not see any such features in our cases, nor were they present in any of the cases previously described in the literature.7–10
So, clearly, we have here a practical and philosophical difference of approach to these tumors. It would seem that Dr. Goto is objecting to the use of the particular term, “polymorphous sweat gland carcinoma,” and he is certainly entitled to his opinion. We respect Dr. Goto's preference for regarding these tumors as a variant of BCC, but we prefer to consider them as a separate and distinct process. From our experience, these tumors are sufficiently distinctive and different from BCC and adenoid cystic carcinoma that they deserve to be recognized as a distinct and separate morphologic entity. Academic pathologists have traditionally been engaged in reinterpreting, rediscovering, and renaming previously described pathologic processes; so, Dr. Goto's reinterpretation of the images in our article is understandable. The one thing that we can be all in agreement with is Dr. Goto's suggestion that additional studies may be of help to clarify the exact nosologic position of these tumors. Rather than dismiss further inquiry by declaring that the concept of PSGC is invalid or that the cases have been incorrectly diagnosed, we would encourage identification of more cases with similar morphologic features to help us gain more clarity on the subject.
1. Ronen S, Giorgadze T, Aguilera-Barrantes I, et al. Polymorphous sweat gland carcinoma—an immunohistochemical and molecular study. Am J Dermatopathol. 2018 [epub ahead of print].
2. Kazakov DV, Michal M, Kacerovska D, et al. Cutaneous Adnexal Tumors. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2012:145.
3. Goto K. Other rare malignant sweat gland tumors. In: Anasi SI, Goto K, eds. Atlas of Cutaneous Adnexal Tumors [in Japanese]. Tokyo, Japan: Igaku-shoin; 2018:88–93.
4. Heenan PJ, Bogle MS. Eccrine differentiation in basal cell carcinoma. J Invest Dermatol. 1993;100:2955–2995.
5. Weedon D. Tumors of the epidermis, chapter 31. In: Skin Pathology. London, United Kingdom: Churchill Livingston; 2002:770.
6. Plaza JA, Froehlich H. Immunohistology and molecular studies of epithelial tumors, chapter 1, In: Plaza JA, Prieto VG, eds. Applied Immunohistochemistry in the Evaluation of Skin Neoplasms. Switzerland: Springer International; 2016:4–8.
7. Suster S, Wong TY. Polymorphous sweat gland carcinoma. Histopathology. 1994;25:31–39.
8. Ronnen M, Ben-Dor D, Huszar M. Recurrent polymorphous sweat gland carcinoma of the skin. J Am Acad Dermatol. 2002;46:914–916.
9. Walker A, Mesinkovska NA, Emanuel PO, et al. Polymorphous sweat gland carcinoma: a report of two cases. J Cutan Pathol. 2016;43:594–601.
10. Gourget B, Duga I, Lamant L. L'adenocarcinome sudoripare polymorphe. Ann Pathol. 1996;16:442.