Dermatology: Practical and Conceptual Quiz | Dermatol Pract Concept 2016;6(3):3 7 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com The patient A 65-year-old woman presented in our department with a three- year history of a new, slowly growing asymptomatic lesion on her vulva. The physical examination revealed a 10 mm sized, An unusual lesion in the right place Grigorios Theodosiou1, Valeria Zafeiriadou2, Marina Papageorgiou3, Ioanna Mandekou-Lefaki3 1 Department of Dermatology, Skåne University Hospital, Malmö, Sweden 2 First Department of Dermatology-Venereology, Aristotle University Medical School, Hospital for Skin and Venereal Diseases, Thessaloniki, Greece 3 State Clinic of Dermatology, Hospital for Skin and Venereal Diseases, Thessaloniki, Greece Citation: Theodosiou G, Zafeiriadou V, Papageorgiou M, Mandekou-Lefaki I. An unusual lesion in the right place Dermatol Pract Concept 2016;6(3):3. doi: 10.5826/dpc.0603a03 Copyright: ©2016 Theodosiou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Corresponding author: Grigorios Theodosiou, MD, Department of Dermatology, Skåne University Hospital, Jan Waldenströms gata 16, 20502 Malmö, Sweden. Tel. + 0046 040-33 65 16. Email: gregtheodosiou@yahoo.com. Figure 1. A well-circumscribed, flesh-colored, dome- shaped nodule on the left labia majora of the vulva. [Copyright: ©2016 Theodosiou et al.] Figure 2. Cystic tumor with papillary and glandular areas. [Copy- right: ©2016 Theodosiou et al.] well-circumscribed white to skin-colored elevated firm nodule with a smooth surface on the left labia majora of her vulva (Figure 1). There was no family history of similar lesions. The lesion was excised. Histopathologic examination revealed a well-circumscribed tumor located in the dermis with no connection with the overlying epidermis. Within the tumor a complex network with anastomosing papillary struc- tures and tubules as well as glandular areas was observed. The epithelial lining consisted of an inner layer of monomorphic, columnar cells with eosinophilic cytoplasm and nipple-like projections on the surface surrounded by a layer of myoepi- thelial cells (Figure 2). mailto:gregtheodosiou@yahoo.com 8 Quiz | Dermatol Pract Concept 2016;6(3):3 tory epithelium [17]. From its histopathologic similarities to intraductal papilloma of the breast, an accessory mammary- like gland has also been speculated as another candidate source [1,18,19]. The location of the anogenital HP is thought to mirror the distribution of anogenital mammary-like glands [1,18,19]. From this point of view, cases of ectopic HP involving the eyelid and the external auditory canal are viewed as examples of adenomas with papillary architecture arising in Moll’s glands and ceruminous glands, respectively [9,20]. Konstantinova et al have recently conducted a clinico- pathological study of 264 tumors detailing various changes in the tumor and adjacent anogenital mammary-like glands (AGMLG) with emphasis on mammary-type alterations. The study showed that the histopathological changes in HP run a broad spectrum comparable with that in the mammary counterpart and benign breast disease [21]. The presence of HPV DNA in the lesion tissue has been identified in a few cases. However HPV does not appear to play a causative role to the pathogenesis of HP [16,22]. The differential diagnosis of HP includes apocrine hidro- cystoma, Bartholin gland cyst and syringocystadenoma papilliferum. Malignant transformation is extremely rare. There are five documented cases of ductal carcinoma in situ (DCIS) arising within a pre-existing hidradenoma papilliferum in the peer- reviewed literature [23-25]. Another two cases of invasive carcinomas arising from HP (malignant perianal papillary hidradenoma, vulvar adenosquamous carcinoma) have been reported [26,27]. The treatment of choice is total excision. Recurrence is unusual and commonly attributed to incomplete excision of the primary tumor. In conclusion, we present a case of HP, which is a rare tumor of the anogenital region. Diagnosis is based on histo- pathology due to the lack of specific clinical features. Surgical excision is therefore required for definite diagnosis and cure. References 1. Kazakov DV. Site-specific adnexal neoplasms, mimics thereof and related conditions. In: Kazakov DV, McKee P, Michal M, Kac- erovska D. Cutaneous Adnexal Tumors. Philadelphia: Lippincott Williams and Wilkins 2012: 463-9. 2. Patterson J. Sweat gland tumors. In: Weedon D. Weedon´s Skin Pathology. 4th ed. London: Churchill Livingstone Elsevier, 2016; 947-8. 3. Rutten A. Adnexal Tumors. In: Braun-Falco O. Braun-Falco’s Dermatology. 3rd ed. Berlin: Springer-Verlag, 2009:1378. 4. Taylor RS, Perone JB, Kaddu S, Kerl H. Appendage tumors and hamartomas of the skin. In: Wolff K, Goldsmith L, Katz S, et al. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York: McGraw Hill, 2007:1071. What is your diagnosis? Diagnosis Hidradenoma papilliferum Clinical course As HP is considered a benign appendageal tumor and was totally excised, no further diagnostic or therapeutic proce- dures were performed. Answer and explanation Hidradenoma papilliferum (HP) is a rare benign appendageal tumor occurring mainly in the anogenital region of adult women [1,2]. Since Werth first described hidradenoma papilliferum (HP) in 1878, numerous cases have been described, including more than 30 cases of ectopic localization [3]. The most common appearance is that of a solitary, asymp- tomatic, well-circumscribed, skin-colored or pinkish nodule or nodulocystic lesion measuring, in most cases, from 0.5—1 cm. Larger lesions, measuring up to 10 cm, are rare. The tumor is slowly growing. However, rapid growth, possibly accelerated by trauma, has been occasionally described. Rare symptoms include pain and drainage [1-4]. The tumor primarily affects almost exclusively the vulvar and anogenital region of middle-aged women [5]. The labia majora and labia minora are almost equally affected, together accounting for almost 90% of the cases. The rest involve the fourchette, clitoris, perianal area and perineum [1-5]. Ectopic lesions developing on the eyelids, orbit, auditory canal, nose, breast, chest and abdomen have been reported [6-14]. Cases in men have been described [12]. HP can only be diagnosed by histological examination, because the right diagnosis is almost never made clinically. HP is usually partly cystic and has both papillary and glandular areas. Within the tumor, a complex network with anastomosing papillary and tubules as well as glandular structures is observed. The epithelial lining consists of an inner layer of secretory cells and an outer layer of myoepi- thelial cells. The inner layer consists of monomorphic, cuboi- dal or columnar cells with clear or eosinophilic cytoplasm demonstrating focal “decapitation secretion” [1-6]. In some cases, remnants of anogenital mammary-like glands may be seen adjacent to the HP [1]. The mitotic index is variable, but even high mitotic index does not predict a more aggressive behavior [15]. Oxyphilic metaplasia, though rare, can lead to a misdiagnosis of malignancy [16]. The histogenesis of HP remains unclear. Histopathologic and ultrastructural findings have demonstrated that the dif- ferentiation of HP is more closely related to apocrine secre- Quiz | Dermatol Pract Concept 2016;6(3):3 9 17. Hashimoto K. Hidradenoma papilliferum: An electron microscop- ic study. Acta Derm Venereol 1973; 53:22-30. PMID: 4120803. 18. Van der Putte SC. Mammary-like glands of the vulva and their disorders. Int J Gynecol Pathol 1994;13:150-60. PMID: 8005737. 19. Nishie W, Sawamura D, Mayuzumi M, Takahashi S, Shimizu H. Hidradenoma papilliferum with mixed histopathologic features of syringocystadenoma papilliferum and anogenital mammary-like glands. J Cutan Pathol 2004;31:561-4. PMID: 15268713. DOI: 10.1111/j.0303-6987.2004.00176.x. 20. Netland PA, Townsend DJ, Albert DM, Jakobiec FA. Hidrad- enoma papilliferum of the upper eyelid arising from the apocrine gland of Moll. Ophthalmology 1990;97:1593-8. PMID: 1965020. DOI: 10.1016/S0161-6420(90)32373-4. 21. Konstantinova AM, Michal M, Kacerovska D et al. Hidradenoma papilliferum: a clinicopathological study of 264 tumors from 261 patients, with emphasis on mammary-type alterations. Am J Dermatopathol 2016. In press. 22. 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Vulvar adenosquamous carci- noma arising in a hidradenoma papilliferum, with rapidly fatal outcome: case report. Gynecol Oncol 1989;35:395–8. PMID: 2557272. 5. Woodworth H, Dockerty MB, Wilson RB, et al. Papillary hi- dradenoma of the vulva: A clinicopathologic study of 69 cases. Am J Obstet Gynecol 1971;110:501-8. PMID: 4325819. DOI: 10.1016/0002-9378(71)90691-0. 6. Vang R, Cohen PR. Ectopic hidradenoma papilliferum: A case report and review of the literature. J Am Acad Dermatol. 1999; 41:115-8. PMID: 10411423. DOI: 10.1016/S0190-9622(99) 70418-4. 7. Santa Cruz DJ, Prioleau PG, Smith ME. Hidradenoma papil- liferum of the eyelid. Arch Dermatol 1981;117:55-6. PMID: 6257184. DOI: 10.1001/archderm.1981.01650010061028. 8. Katz SE, Collins AB, Peters SB. Hidradenoma papilliferum of the orbit. Orbit. 2013;32:49-50. PMID: 23387456. DOI: 10.3109/01676830.2012.739673. 9. Nissim F, Czemobilsky B, Ostfeld E. Hidradenoma papilliferum of the external auditory canal. J Laryngol Otol 1981;95:843-8. PMID: 6267150. 10. Lee EJ, Shin MK, Haw CR, et al. Two cases of hidradenoma papil- liferum of the nose. Acta Derm Venereol. 2010;90:322-3. PMID: 20526565. DOI: 10.2340/00015555-0845. 11. Kim YJ, Lee JW, Choi SJ, et al. Ectopic hidradenoma papilliferum of the breast: Ultrasound finding. J Breast Cancer 2011;14:153-5. PMID: 21847412. DOI: 10.4048/jbc.2011.14.2.153. 12. Tanaka M, Shimizu S. Hidradenoma papilliferum occurring on the chest of a man. J Am Acad Dermatol 2003;48:S20-1. PMID: 12582377. DOI: 10.1067/mjd.2003.125. 13. Morimura S, Kadono T, Sugaya M, et al. Ectopic hidradenoma papilliferum on the abdomen. Eur J Dermatol. 2011;21:278-9. PMID: 21411413. DOI: 10.1684/ejd.2010.1236. 14. Abudu EK, Umanah IN, Ekpo MD, et al. A giant ectopic hi- dradenoma papilliferum in a Niger delta region of Nigeria. Rare Tumors 2011;3(4):e50. PMID: 22355505. DOI: 10.4081/ rt.2011.e50. 15. Sington J, Chandrapala R, Manek S, Hollowood K. Mitotic count is not predictive of clinical behavior in hidradenoma papilliferum of the vulva: a clinicopathologic study of 19 cases. Am J Derma- topathol 2006;28:322-6. 16. Kazakov DV, Mikyskova I, Kutzner H, et al. Hidradenoma papil- liferum with oxyphilic metaplasia: A clinicopathological study of 18 cases, including detection of human papillomavirus. Am J Dermatopathol 2005; 27:102-10. PMID: 16871035. http://dx.doi.org/10.1016/0002-9378(71)90691-0