Practice Essentials
Hyperkeratosis of the nipple and/or areola (HNA) is defined as excessive keratinization of the nipple and/or areola. Hyperkeratosis of the nipple and/or areola is characterized by hyperpigmented, verrucous or filiform, keratotic thickening of the nipple and/or areola, with a papillomatosis or velvety sensation to touch. Hyperkeratosis of the nipple and/or areola has classically been classified into the following 3 subsets [1, 2, 3] :
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Type I - hyperkeratosis of the nipple and/or areola due to the extension of an epidermal nevus
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Type II - hyperkeratosis of the nipple and/or areola in conjunction with disseminated dermatoses
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Type III - nevoid hyperkeratosis of the nipple and/or areola
Perez-Izquierdo et al suggested an alternative classification, distinguishing 2 types: (1) those that are idiopathic or nevoid and (2) those that are secondary to other conditions. [4] Others have advocated that the term “nevoid” be replaced by “idiopathic”. [5, 6] Upon review of the literature, a recommended classification is into (1) primary hyperkeratosis of the nipple and/or areola, which is idiopathic, [7, 8, 9, 10, 11] and (2) secondary hyperkeratosis of the nipple and/or areola, which is associated with the following:
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Epidermal nevus
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Organoid nevus [12]
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Leiomyomas [13]
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Verruca [14]
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Malignant acanthosis nigricans [15]
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Chronic eczema such as atopic dermatitis
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Pregnant females
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Estrogen therapy for androgen insensitivity syndrome [22]
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Vemurafenib treatment [23]
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Spironolactone treatment [24]
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Malassezia furfur infection [25]
Furthermore, there has been a recorded case of secondary hyperkeratosis of the nipple and areola associated with failure to clean the breast and nipple area due to mental distress. [26]
Causes
The etiology of primary hyperkeratosis of the nipple and/or areola is unknown. The etiology of secondary hyperkeratosis of the nipple and/or areola is related to the underlying disorder.
Diagnostics
No blood or urine laboratory tests aid in the diagnosis of primary hyperkeratosis of the nipple and/or areola (HNA). Imaging studies must be performed if any concern about underlying breast disease exists. Mammography should be performed, with or without ultrasonography. Ultrasonography of the nipple may demonstrate skin thickening. [27]
In cases of secondary HNA, additional testing may be required. Malignant acanthosis nigricans-associated HNA requires possible endoscopy and/or colonoscopy and computed tomography scanning. Cutaneous T-cell lymphoma–associated blood testing for clonality and CT scanning for staging may need to be performed.
Dermoscopy findings have mimicked a pigmented basal cell carcinoma in 1 case, with multiple blue-gray globules and leaflike areas. [28] In a case of HNA secondary to Darier disease, dermoscopy revealed a crater containing a yellow to yellowish-brown keratotic plug surrounded concentrically by white radial streaks. The outermost area was a uniform brown with a pigment network. [29] There were similar dermoscopic findings in a case of idiopathic primary HNA. [30]
Skin biopsy may be indicated. See Procedures.
Treatment
The clinical course of primary hyperkeratosis of the nipple and/or areola (HNA) is variable and often unpredictable. Many treatment modalities for primary HNA have been used; however, the results of most are anecdotal and not verified in randomized, placebo-controlled clinical trials. In addition, reported results vary among individual patients and with various medications.
Li et al reported treatment of a single case of severe bilateral idiopathic HNA with epidermal skin grafts from the scalp. There were no recurrence and good cosmetic results at 6 months postprocedure. [31]
In a single case of idiopathic bilateral HNA, clinicians discovered differing molecular expression in the patient's HNA versus a normal nipple areolar complex through RNA sequencing. Furthermore, there was overactivation of signaling pathways in immune-related cells in the patient's specimens. These findings raise the question of whether anti-autoimmune therapy would be beneficial in certain HNA cases. [32]
Consultations
In some cases, consultation with a plastic surgeon may be appropriate. [33]
Epidemiology
Hyperkeratosis of the nipple and/or areola is rare, and currently no domestic or international incidence rates have been documented in the literature.
Hyperkeratosis of the nipple and/or areola has no reported racial predilection. Hyperkeratosis of the nipple and/or areola is more common in females than in males. In a study of 45 primary hyperkeratosis of the nipple and/or areola patients 80% were females. [34]
In females, hyperkeratosis of the nipple and/or areola most commonly occurs in those aged 10-40 years. Males with nevoid hyperkeratosis of the nipple and/or areola are often older than females, but no specific age distribution is reported.
Prognosis
Primary hyperkeratosis of the nipple and/or areola is not associated with mortality. The morbidity rate is low, and morbidity is primarily limited to the undesirable cosmetic results of the abnormal nipple and/or areola. The morbidity and mortality rates of secondary hyperkeratosis of the nipple and/or areola are those of the underlying diseases; thus, the rates with secondary hyperkeratosis of the nipple and/or areola may be greater than those with other types of hyperkeratosis of the nipple and/or areola.
Patient Education
Patient education of nevoid hyperkeratosis of the nipple and/or areola is important to help individuals understand their condition and to allow them to form realistic expectations regarding treatment. Patients should be warned that with topical preparations, a long period may pass before clinical improvement occurs. Treatment with an individual medication should be continued for at least 6 months before it is deemed a failure.
Lesions may recur after therapy is discontinued. In some patients, hyperkeratosis of the nipple and/or areola does not respond to any treatment.
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An adult male with bilateral primary hyperkeratosis of the nipple and areola
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A close-up of the patient's right nipple/areola complex.
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A close up of the patient's nipple/areola complex.
