HJ Byun, et al pISSN 1013-9087ㆍeISSN 2005-3894 Ann Dermatol Vol. 32, No. 6, 2020 https://doi.org/10.5021/ad.2020.32.6.512 CASE REPORT Two Cases of Multiple Epidermolytic Acanthomas Mimicking Verruca Vulgaris Hyun Jeong Byun, Donghwi Jang, Jongeun Lee, Se Jin Oh, Ji-Hye Park, Dong-Youn Lee Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Epidermolytic acanthoma (EA) is a rare benign tumor, which INTRODUCTION usually appears as a solitary small papule. However, there are a few case reports of multiple EA, most of which occurs Epidermolytic acanthoma (EA) is a rare benign acquired on the genital area. Cases of multiple EA may mimic verruca tumor with a wart-shaped surface. It usually appears as an vulgaris, condyloma accuminatum, seborrheic keratosis, asymptomatic brown papule measuring less than 1 cm, and and bowenoid papulosis, and therefore, can be easily is known to occur frequently in middle-aged individuals1. misdiagnosed. A 78-year-old male presented with a 2-week EA can appear as a solitary or multiple papules, or very history of discrete, small skin-colored papules around the rarely as a disseminated form2. According to previous re- anus. The other case involved a 47-year-old male with a ports, 122 out of 131 cases were solitary EAs, and multi- 5-year history of skin-colored papules on the scrotum. Skin ple EAs were much less frequent involving only 7 cases2. biopsy of both cases revealed a well-demarcated papular le- EA is characterized by epidermolytic hyperkeratosis, sion characterized by compact hyperkeratosis, perinuclear which is also observed in bullous ichthyosiform erythro- vacuolization, and reticular degeneration in the granular and derma, Vörner’s palmoplantar keratoderma, and linear ep- upper spinous layer with coarse basophilic keratohyalin idermal nevi variants3. Clinically, it can be misdiagnosed granules. Epidermal invagination was consistent with a as verruca vulgaris, condyloma accuminatum, seborrheic cup-shaped type of EA. Both cases tested negative for human keratosis, and bowenoid papulosis2,4. In a survey of der- papillomavirus. We report typical cases of multiple EA, matopathologists conducted by the American Society of which should be considered as the differential diagnosis of Dermatopathology, only 37% of dermatopathologists cor- small skin-colored papules in the anogenital area, to prevent rectly diagnosed EA, while another 37% misdiagnosed it the misdiagnosis. (Ann Dermatol 32(6) 512∼515, 2020) as verruca vulgaris. Therefore, it is definitely a disease that requires attention for accurate diagnosis2. -Keywords- Epidermolytic hyperkeratosis CASE REPORT A 78-year-old male presented with a 2-week history of Received September 19, 2019, Revised October 17, 2019, Accepted for publi- papular lesions around the anus. Physical examination re- cation October 23, 2019 vealed multiple, flesh-colored papules measuring less than Corresponding author: Dong-Youn Lee, Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, 1 cm, without any symptoms such as pruritus or pain (Fig. Gangnam-gu, Seoul 06351, Korea. Tel: 82-2-3410-3543, Fax: 82-2-3410- 1A). The patient had a history of hypertension, glaucoma 3869, E-mail: [email protected] and urinary tract obstruction. Under polarized contact der- ORCID: https://orcid.org/0000-0003-0765-9812 moscopy, hyperkeratotic callus like structure was ob- This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. served without characteristic features of warts (Fig. 1B). org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, Skin punch biopsy and human papillomavirus (HPV) stain- distribution, and reproduction in any medium, provided the original work ing were performed for accurate diagnosis. Examination is properly cited. under the low-power field revealed compact orthoker- Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology atotic hyperkeratosis. Invagination of the epidermis and fo- 512 Ann Dermatol Epidermolytic Acanthomas Mimicking Verruca Vulgaris Fig. 1. (A) Multiple skin-colored papules located around the anus. (B) Hyperkeratotic callus like struc- ture was observed without charac- teristic features of warts. (C) Epider- mal invagination with compact hy- perkeratosis (H&E, ×40). (D) Reti- cular degeneration and perinuclear vacuolization with coarse basophi- lic keratohyaline granules (H&E, ×200). We received the patient’s consent form about publishing all photographic materials. Fig. 2. (A) Multiple skin-colored papules located on the scrotum. (B) Cup-shaped epidermal invagination with hyperkeratosis (H&E, ×100). (C) Reticular degeneration and perinuclear vacuolization in the granular and upper spinous layers (H&E, ×200). cal papillomatous changes were observed (Fig. 1C). Under of skin lesions on the scrotum. A number of 2 mm-sized high-power field, clear spaces were detected around the flesh-colored papules were detected on the scrotum, and nucleus, along with eosinophilic cytoplasm of keratino- the patient complained of a slight pruritus (Fig. 2A). The cytes in the spinous and granular layers of the epidermis. patient had chronic hepatitis, and presented with onycho- It is also possible to observe larger keratohyaline granules mycosis of toenails, with no significant findings except for and reticular degeneration, which involved intercellular positive test results with rapid plasma reagin (RPR) in se- and intracellular edema in the epidermis (Fig. 1D). The pa- rum tests. Punch biopsy and HPV stain were performed tient tested negative for HPV, and was diagnosed with an for diagnosis. Under a low-power field, the epidermis was EA with typical pathologic findings. The patient was moni- invaginated into a cup-shaped lesion, and hyperkeratosis tored for 6 months without any further treatment after the was observed (Fig. 2B). Under a high power, reticular de- skin biopsy, and no change in the lesion was observed af- generation of epidermis was observed with vacuolar ter 6 months. changes around the nucleus of keratinocytes (Fig. 2C). In Another 47-year-old male presented with a 5-year history addition, perivascular lymphocytic infiltration was seen in Vol. 32, No. 6, 2020 513 HJ Byun, et al the superficial dermis. The patient tested negative for HPV. ided into papillomatous, cup-shaped, and acanthotic types. The second case was also diagnosed with EA based on In papillomatous type, hyperkeratosis and focal parakera- clinical and pathological findings. A number of lesions on tosis are observed along with papillomatous epidermal hy- the scrotum were surgically removed in this patient. perplasia and hypergranulosis3. Cup-shaped lesions can be seen with well-demarcated epidermal invagination, DISCUSSION acanthosis, and hyperkeratosis with focal parakeratosis3. The combination of papillomatous and cup-shaped lesions According to a single institutional study reported previous- of EA have also been reported3. Acanthotic lesion involves ly, the incidence rates of EA were 9.08 per 100,000 speci- only epidermal hyperplasia without papillomatous changes mens per year, with a declining trend2. The incidence rates or epidermal invagination3. Inflammation usually appears of extragenital EA were higher than those of genital lesions, as perivascular lymphocytic infiltration involving the su- although multiple EA predominantly occurred in genital perficial layer3. area2. The pathophysiology of EA is not clear. The possible etio- Since EA is clinically prone to misdiagnosis into other le- logical factors include ultraviolet irradiation, immunosup- sions, further examinations such as dermoscopy or skin bi- pression, trauma, viral infection, and mutations involving opsy are needed for confirmation. In the previous report, keratin 1 and 10 genes2,12. Although a single reported case dermoscopic findings of EA demonstrated pearly white areas, of EA tested positive for HPV13, it is possible that it may a cerebriform pattern, irregular pigmented grooves, and have been discovered accidentally, and many other re- peripheral pigmented radial streak like areas5. However ported EA cases do not appear to be related to HPV14,15. the lesion shown in the previous report clinically ap- Both two cases reported here tested negative for HPV and peared similar to seborrheic keratosis, which resulted in were not in an immunosuppressed state. Also the loca- different dermoscopic features with the present case. tions involved in the present cases were anus and scro- According to the report, “pearly white areas” were the tum, which were not exposed to the ultraviolet radiation. striking feature of the EA, which corresponded to the com- Therefore, the lesions may have been caused by viral in- pact hyperkeratosis above the hypergranulosis and acan- fection, trauma, or mutations in the Keratin 1 and 10 thosis5. This finding was distinguishable with the dermo- genes. Keratin 1 and 10 genes are thought to be asso- scopic findings of seborrheic keratosis which was charac- ciated with EA, because mutations in these genes result in terized by comedo-like opening, milia-like cyst6, and that dermatoses such as epidermolytic ichthyoses associated of verruca vulgaris which showed frogspawn patterns and with hyperkeratosis and a similar histological pattern with lopped or dotted vessels within whitish papillae7. Other EA2. Cohen et al.12 found that immunohistochemical