A 68-year-old white man presents with 4 weeks of progressively worsening thickening of the skin and plaques on the bilateral nipple and areola. He has no personal or family history of warts or epidermal nevi and has not had hormonal therapy. On examination, he has hyperpigmented, verrucous plaques bilaterally, with no associated erythema or lymphadenopathy. Skin biopsy shows hyperkeratosis with papillomatosis. Corticosteroid treatment failed, but there was some minor improvement with calcipotriol after several weeks of use.
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Nipple hyperkeratosis is an acantholytic disorder of the skin. The condition most commonly presents as diffuse, hyperpigmented, verrucous plaques.1 Pruritis is the most common symptom associated with nipple hyperkeratosis, although the majority of cases are asymptomatic.
Approximately 50 cases of nipple hyperkeratosis have been reported; of these, 80% occurred in women.1,8 The condition mostly occurs in a woman’s second or third decade of life, usually during pregnancy; however, a significant number of cases also occur sporadically. When nipple hyperkeratosis occurs in males, it is usually in those receiving hormone therapy.
In more than 50% of cases, both the nipple and areola are involved.2 Nipple-only involvement is seen in 17% of cases.2 Nipple hyperkeratosis may also be a skin sequela of chronic graft versus host disease.3
Nipple hyperkeratosis can be classified into 3 types: type 1 occurs as an extension of an epidermal nevus; type 2 occurs in association with other dermatoses; and type 3 is idiopathic. In type 2 disease, hyperkeratosis of the nipple occurs as a result of another cutaneous disease process such as atopic dermatitis or acanthosis nigricans.3 Type 3 nipple hyperkeratosis has been associated with puberty, pregnancy, and certain medications used in prostate cancer.4 Most type 3 disease is asymptomatic.
In pregnancy, unilateral disease may become bilateral or there may be increased pigmentation and hyperkeratosis, which often persist postpartum. In addition, hyperkeratosis that occurs during pregnancy is more likely to be symptomatic, with breast tenderness and/or pruritis.
Type 1 nipple hyperkeratosis is usually unilateral and may occur in both men and women. Type 2 disease is bilateral, and type 3 is bilateral and symmetric.5
Diagnosis of the condition is clinical, but biopsy can aid in ruling out other hyperkeratoses. Histologically, in addition to hyperkeratosis, there are nonspecific findings such as acanthosis, papillomatosis, keratin plugging, and dermal lymphocytic infiltration. The immunophenotype of nipple hyperkeratosis shares some features of mycosis fungoides, including a CD3 epidermal infiltrate with a predominance of CD4 cells.6
Clinically, nipple hyperkeratosis can be mistaken for acanthosis nigricans, Darier disease, chronic eczema, epidermal nevus, confluent and reticulated papillomatosis, seborrheic keratosis, Paget disease, basal cell carcinoma, dermatophytosis, or Bowen disease.1 Because nipple hyperkeratosis is generally asymptomatic, features such as nipple discharge or retraction should prompt a search for another etiology. Notably, malignant acanthosis nigricans often presents with hyperkeratosis.7
Nevoid hyperkeratosis of the nipple often presents during or is worsened by pregnancy and estrogen therapy, and therefore, an endocrine association has been postulated. During pregnancy, other physiologic changes of the nipple and areola may occur, including enlargement, hyperpigmentation, secondary areolae, and hypertrophied sebaceous glands. Some argue that pregnancy-associated nipple hyperkeratosis is a distinct clinical entity of hyperkeratosis of the nipple and areola.3
Even when nipple hyperkeratosis is not symptomatic, it can be a cosmetic issue, and hyperkeratosis will not remit unless treated. However, medical treatment alone, including corticosteroids, topical agents (0.025% tretinoin, 12% ammonium lactate, 12% lactic acid),3 or keratolytic agents (6% salicylic acid, urea) are often insufficient.1 One case of remission with acitretin and topical calcipotriol treatment has been reported.7
In many cases, surgery is considered an appropriate initial treatment, even though there may be aesthetic consequences. Ablation with a carbon dioxide laser may offer cosmetically acceptable treatment.8 More invasive approaches include cryotherapy,3 radiofrequency ablation,9 and surgical removal of the nipple,10 with subsequent graft reconstruction. Patients should have follow-up visits in 3 to 6 months after therapy, with instructions to return earlier if they experience nipple discharge, retraction, or mass.
After presentation and discussion of the various treatment options, the patient in our case elected for a trial of 5% salicylic acid. Moderate improvement was noted at 3-month follow-up.
Harina Vin, BS, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston
- Yaghoobi R, Feily A. Bilateral nevoid hyperkeratosis of the nipples and areolae. Int J Dermatol. 2015;54(1):e47-e48.
- Kubota Y, Koga T, Nakayama J, Kiryu H. Naevoid hyperkeratosis of the nipple and areola in a man. Br J Dermatol. 2000;142(2):382-384.
- Higgins HW, Jenkins J, Horn TD, Kroumpouzos G. Pregnancy-associated hyperkeratosis of the nipple: a report of 25 cases. JAMA Dermatol. 2013;149(6):722-726.
- Levy-Franckel A. Les hyperkeratoses de l’areole et du mamelon. Paris Med. 1938;28:63-66.
- Mehregan AH, Rahbari H. Hyperkeratosis of nipple and areola. Arch Dermatol. 1977;113(12):1691-1692.
- Roustan G, Yus ES, Simón A. Nevoid hyperkeratosis of the areola with histopathological features mimicking mycosis fungoides. Eur J Dermatol. 2002;12(1):79-81.
- Kartal Durmazlar SP, Eskioglu F, Bodur Z. Hyperkeratosis of the nipple and areola: 2 years of remission with low-dose acitretin and topical calcipotriol therapy. J Dermatolog Treat. 2008;19(6):337-340.
- Fenniche S, Badri T. Images in clinical medicine. Nevoid hyperkeratosis of the nipple and areola. N Engl J Med. 2010;362(17):1618.
- Ozyazgan I, Kontas¸ O, Ferahbas¸ A. Treatment of nevoid hyperkeratosis of the nipple and areola using a radiofrequency surgical unit. Dermatol Surg. 2005;31(6):703-705.
- Milanovic R, Martic K, Stanec S, Zic R, Vlajcic Z, Stanec Z. Surgical treatment of nevoid hyperkeratosis of the areola by removal of the areola and reconstruction with a skin graft. Ann Plast Surg. 2005;54(6):667-669.