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Table of Contents
Year : 2021  |  Volume : 39  |  Issue : 4  |  Page : 226-227

Bacteria-related pigmented clear cell acanthosis of the nipple and areola

1 Department of Dermatology, Skin Institute, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan
2 Department of Dermatology, Skin Institute, Buddhist Tzu-Chi General Hospital; Doctoral Degree Program in Translational Medicine, Tzu Chi University and Academia Sinica, College of Medicine; Institute of Medical Sciences, College of Medicine, Tzu Chi University, Hualien, Taiwan

Date of Submission18-May-2021
Date of Decision21-Oct-2021
Date of Acceptance18-Nov-2021
Date of Web Publication29-Dec-2021

Correspondence Address:
Dr. Chung-Hsing Chang
Department of Dermatology, Skin Institute, Buddhist Tzu-Chi General Hospital, Hualien
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ds.ds_53_21

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How to cite this article:
Lin CS, Wu RW, Chang CH. Bacteria-related pigmented clear cell acanthosis of the nipple and areola. Dermatol Sin 2021;39:226-7

How to cite this URL:
Lin CS, Wu RW, Chang CH. Bacteria-related pigmented clear cell acanthosis of the nipple and areola. Dermatol Sin [serial online] 2021 [cited 2022 Dec 3];39:226-7. Available from: https://www.dermsinica.org/text.asp?2021/39/4/226/334170

Dear Editor,

Clear cell acanthoma (CCA) on the nipple and areola was first reported by Kim et al. in 1999, while CCA was previously reported on the legs.[1] Kuo et al. had presented 12 cases of CCA of the nipple and areola and proposed to rename CCA to “CCA-like eczematous dermatitis” of the nipple and areola.[2] The normal epidermis of the nipple and areola contains keratinocytes with prominent glycogenated cytoplasm, which contributes to the histology of “clear cells.” Herein, we present a case with chronic inflammatory nature and nonclonal proliferation of keratinocytes of the nipple and areola and rename it “clear cell acanthosis.”

An 85-year-old female presented with a moist pigmented plaque on her left nipple and areola for more than 1 year without any treatment [Figure 1]a and [Figure 1]b. Biopsy was conducted and histopathology showed nonclonal epidermal hyperplasia, defined as acanthosis and increased basal melanin and melanin incontinence in the dermis [Figure 2]a. HMB45 staining revealed activated melanocytes with branching dendrites [Figure 2]b. The epidermal cells contained abundant cytoplasmic glycogen (periodic Acid–Schiff-positive [PAS+] and diastase PAS [D-PAS-]), fulfilling the character of clear cell [Figure 2]c and [Figure 2]d. Inflammatory cell infiltration was found in the dermis, including CD3+ T cells [Figure 2]e, CD68+ histiocytes [Figure 2]f, CD117+ mast cells [Figure 2]g, and few eosinophils and CD138+ plasma cells [Figure 2]h, indicating chronic inflammation may play a role in inducing the pigmented clear cell acanthosis (PCCA). Due to some discharge of the skin lesion, we performed the bacterial culture, which revealed a significant amount of Staphylococcus aureus (++) and Corynebacterium striatum (++). The sensitivity test of antibiotics demonstrated a sensitive response to fucidin and several other antibiotics. Therefore, topical fusidic acid (antibacterial) was prescribed first for 1 week and followed by desoximetasone (anti-inflammation), and an improvement was observed 2 months later. Total remission of the skin lesion on the left nipple and areola was noted at the 1-year follow-up [Figure 1]c and [Figure 1]d.
Figure 1: The clinical appearances of the uninvolved right nipple and areola (a) and a brownish, pigmented, and well-demarcated plaque with a moist surface over the left nipple and areola (b). The uninvolved right nipple and areola (c) and remission of the skin lesion over the left nipple and areola at the 1-year follow-up (d).

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Figure 2: Histopathology of the skin lesion. With hematoxylin-eosin staining, the skin lesion shows epidermal hyperplasia with acanthosis and increased basal melanin and melanin incontinence in the dermis (a, ×100). HMB45 staining revealed activated melanocytes with branching dendrites (b, ×200). The clear epidermal cells with cytoplasmic glycogen stain positively with periodic Acid-Schiff stain (c, ×200). They are removed by digestion with diastase (d, ×200). The inflammatory infiltrate in the dermis mainly shows CD3+ T cells (e, ×200), CD68+ histiocytes (f, ×200), CD117+ mast cells (g, ×200), and CD138+ plasma cells (h, ×200).

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During reviewing 24 reported cases of CCA on the nipple or areola, we found that most of the patients were Asians, mainly Koreans (5) and Taiwanese (12), and some were Europeans and Americans (7). Female has a predilection, with a female-to-male ratio of 7.3. Including our case (n = 25), the mean age of disease onset is 30.4 years old, and one-third (32%) of patients have atopic diathesis.[2] The inflammatory nature of CCA reported by previous studies is mainly exocytosis of neutrophils and eosinophils in the epidermis and dermal eosinophilic infiltration.[2],[3] Here, we further demonstrate remarkable exocytosis and perivascular infiltration of inflammatory cells in the dermis of CCA including T cells, histiocytes, mast cells, and plasma cells, indicating a more chronic immune reaction. The chronic inflammation may lead to activated melanocytes and melanin incontinence, causing a PCCA. Dean et al. found that the amount of melanin presented per length of basement membrane was 2.14 times higher in areolar skin than breast skin. The ratio of melanocytes to keratinocytes was 1:9.7 in areolar skin and 1:14.7 in the breast skin.[4] Thus, we put forward to name such skin lesions on the nipple and areola “pigmented” clear cell “acanthosis.” In contrast to “hyperkeratosis of the nipple and areola,” PCCA has no orthokeratotic hyperkeratosis or keratotic plugging and has more obvious dermal inflammation.

We have identified the infection of S. aureus and C. striatum on PCCA, which may trigger the inflammation. The breasts themselves harbor significant concentrations of endogenous bacteria. In one study of 150 breast tissue samples, Staphylococcus species presented in 23%, Propionibacterium acnes presented in 11%, and Corynebacterium species presented in 2% of all tissues sampled.[5] Higher surface lipid levels and hydration states on the areola than on adjacent breast skin results in differences in the microbiome, barrier function, and type of cellular immune response.[6] Balato et al. suggested that microbiome dysbiosis could contribute to chronic inflammatory skin diseases. Corynebacterium and Staphylococcus were also noted to have a significant increase in lesional skin compared with healthy skin in psoriasis patient.[7] In previous reports, only 40% of cases improved by steroids alone.[2],[3],[8] However, 24% of cases were treated with topical or oral antibiotics since steroids alone with little improvement, indicating that dysbiosis during steroids treatment should be considered.

In conclusion, we report a case of bacteria-related PCCA of the nipple and areola, which was successfully treated with topical antibiotics and steroids. Because of the unique nature of the nipple and areola skin, we hypothesize that PCCA is a chronic inflammatory skin disease, possibly triggered by dysbiosis of the skin microbiome. Therefore, we suggest that the evaluation of skin infection is essential for the therapeutic strategy of chronic nipple eczema, which may appear before the development of PCCA. Skin culture should be conducted, and if pathogens are present, topical antibiotics should be applied before steroids.


We are grateful to Prof. Yung-Hsiang Hsu, Department of Pathology, Buddhist Tzu-Chi General Hospital and Tzu-Chi University, Hualien, Taiwan, for his valuable comments.

Financial support and sponsorship


Conflicts of interest

Prof. Chung-Hsing Chang, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.

  References Top

Kim DH, Kim CW, Kang SJ, Kim TY. A case of clear cell acanthoma presenting as nipple eczema. Br J Dermatol 1999;141:950-1.  Back to cited text no. 1
Kuo KL, Lo CS, Lee LY, Yang CH, Kuo TT. Clear cell acanthoma (CCA)-like lesions of the nipple/areola: A clinicopathological study of 12 cases supporting a nonneoplastic eczematous disease. J Am Acad Dermatol 2019;80:749-55.  Back to cited text no. 2
Park SY, Jung JY, Na JI, Byun HJ, Cho KH. A case of polypoid clear cell acanthoma on the nipple. Ann Dermatol 2010;22:337-40.  Back to cited text no. 3
Dean N, Haynes J, Brennan J, Neild T, Goddard C, Dearman B, et al. Nipple-areolar pigmentation: Histology and potential for reconstitution in breast reconstruction. Br J Plast Surg 2005;58:202-8.  Back to cited text no. 4
Bartsich S, Ascherman JA, Whittier S, Yao CA, Rohde C. The breast: A clean-contaminated surgical site. Aesthet Surg J 2011;31:802-6.  Back to cited text no. 5
Peters MS, Lehman JS, Comfere NI. Dermatopathology of the female breast. Am J Dermatopathol 2013;35:289-304.  Back to cited text no. 6
Balato A, Cacciapuoti S, Di Caprio R, Marasca C, Masarà A, Raimondo A, et al. Human microbiome: Composition and role in inflammatory skin diseases. Arch Immunol Ther Exp (Warsz) 2019;67:1-18.  Back to cited text no. 7
González-Guerra E, Rodriguez JR, Casado AF, Taboada AC, Toro JA, Bran EL. Bilateral clear cell acanthoma of the areola and nipple: Good response to topical corticosteroids. An Bras Dermatol 2017;92:27-9.  Back to cited text no. 8


  [Figure 1], [Figure 2]


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