Nevoid Hyperkeratosis of the Nipple and/or Areola: Treatment with Topical Steroid.

Nevoid hyperkeratosis of the nipple and/or areola (NHNA) is a rare and benign disease, with poorly understood etiology and no definite therapeutic plan. Hereby, we report another case of NHNA, discuss about its clinical and histopathological features, differential diagnosis, and responsiveness to topical steroid.

What was known?

Nevoid hyperkeratosis of the nipple and/or areola is a rare and benign disease, with poorly understood etiology and no definite therapeutic plan.

Introduction

Nevoid hyperkeratosis of the nipple and/or areola (NHNA) is an uncommon skin disease with an unknown etiology, initially reported in 1923.[1] Despite its benign nature, it is a distressing condition for patients because of its disfigured appearance, and for clinicians, due to its similarity to Paget's disease.

Like other rare diseases, our knowledge is based on case reports. Herein, we report clinical presentation and histopathological findings of NHNA in a 20-year-old female and discuss about its differential diagnosis. To our knowledge, it is the first case report of NHNA from Iran.

Case Presentation

A 20-year-old female was referred to the dermatology outpatient clinic of Razi hospital, Tehran, Iran in August 2010. She suffered from a 2-year history of asymptomatic discoloration and thickening of the both areolas [Figure 1]. It initiated with a pink, scaly, and eczematous plaque of areola, which gradually became darker. Worsening during the past 2 months, disturbed and encouraged her to seek medical care. There was no history of atopy, bloody discharge, breast malignancy, or drug intake.

Figure 1

Diffuse verrucous thickening of areolas

On examination, there was a diffuse brownish pigmentation and verrucous thickening of the whole right and upper part of the left areola with overlying scale-crust. No abnormal findings including palpable mass, lymphadenopathies, nipple retraction, or discharge were encountered.

Other dermatologic examination was unremarkable. She was not obese at all. Routine laboratory tests were within normal limits.

A skin biopsy specimen showed marked thickening of the epidermis with slight papillomatosis and downward filiform rete ridges, anastomizing to each other. The basal layer of the epidermis was hyper pigmented without associated melanocytic proliferation. Slight fibrosis of upper dermis was identified [Figure 2].

Figure 2

Photomicrograph of the areola biopsy. Note the diagnostic filiform downward acanthosis and anastomizing rete ridges (H and E, magnification ×10)

Considering clinical and histopathological findings, our patient highly probable, had NHNA.

She was reassured about the benign nature of the disease and was advised to use topical Mometasone furoate cream 0.1% (Elocom®) and emollient. One month later, she responded to therapy partially, with an acceptable cosmetic result [Figure 3]. In a period of 8 months follow-up, she experienced several recurrences and benefited from the prescribed topical steroid and emollient. However, she never had a complete clearance.

Figure 3

Acceptable improvement, 1 month after topical steroid therapy

Discussion

NHNA is a rare and benign skin disease, which occurs predominantly in females of child-bearing age, especially during 2nd and 3rd decade of life.[1] Despite more than 50 reported cases during 7 decade from the first description, its etiology remains poorly understood and thus its treatment is empirical with an unpredictable therapeutic outcome. It characterized by brown and verrucous thickening of the nipple and/or areola unilaterally or bilaterally, which was classified to 3 types by Levy-Frenckel in 1938:[1]

Type 1: Associated with epidermal nevus.

Type 2: Associated with various dermatoses such as acanthosis nigricans, Darier's disease, chronic eczema, cutaneous T-cell lymphoma,

Type 3: Isolated form with an unknown etiology.

Other than the noted associated skin diseases, malignant condition, especially Paget's disease, is the most important differential diagnosis for the clinicians and is disturbing concern for the patients which should be dismissed by a thorough physical examination of the involved breast and histological studies.

Base on the antecedent reports, its occurrence and aggravation around puberty and pregnancy support the theory that NHNA might be a hormonal hyperkeratosis. The reported affected men undergoing hormonal therapy for other diseases enhance the likelihood of the hormonal etiology, again.[234]

The eruption of unsightly lesions over areola and/or nipple cause extreme distress in some patients, thus effective treatment with an acceptable cosmetic outcome is mandatory.

As noted before, there is no consensus about the guideline of treatment, but using topical agents (keratolytics, steroid, retinoic acid, calcipotriol), first and ablative modalities (cryotherapy, carbon dioxide laser, radiofrequency surgical unit and shave excision) in the next step is popular among dermatologists.[5678]

Based on the clinical and histopathological findings, our patient was typical for NHNA type 3; however, the main differential diagnosis of NHNA include: Acanthosis Nigricans, in which involvement of other flexoral areas and associated endocrinopathies or obesity differ from the isolated form of NHNA; epidermal nevus characterized by onset in early infancy or childhood; seborrheic dermatitis characterized with sharply demarcated velvety plaque in areola instead diffuse pattern of involvement in NHNA. Although the above-mentioned conditions can mimic NHNA histopathologically, some diagnostic histopathological clues in NHNA such as striking filiform downward acanthosis and anastomizing rete ridges can be used for differentiation [Figure 2].[1]

Erosive adenomatosis of nipple is another differential diagnosis, which is a benign neoplasm of nipple-areola complex, with a peak incidence around fifth decade of life, itchy or burning sub-areolar ulcerated or crusted nodule and in histologic studies, dermal tubular structure proliferation.

Finally, after ruling out malignancy by history, physical examination, and histopathology of the taken skin biopsy, we reassured our patient about the benign behavior of such a bad-looking disorder. Interestingly, it improved with Mometasone furoate cream 0.1%. However, Shastry et al. reported no beneficial therapeutic effect of topical steroid on their two patients with NHNA.[9]

In conclusion, we report NHNA, its histopathologic studies, and its good therapeutic response to topical steroid.

What is new?

Good response to topical steroid plus emollient and recurrent character of NHNA in our patient that is the first report from Iran, may pose nipple dermatitis as an etiologic factor of NHNA.