Unilateral nevoid hyperkeratosis of the nipple and areola in a Saudi female

Abstract

Nevoid hyperkeratosis of the nipple and areola (NHNA) is a rare, benign condition of unknown origin that is characterized by a hyperpigmented, hyperkeratotic verruca plaque over the nipple and/or areola. NHNA usually occurs bilaterally, but is sometimes present unilaterally. We present a case of a 21-year-old Saudi female who presented at dermatology outpatient clinic with a 3-year history of skin darkening and thickening of the left nipple, associated with moderate itching. The patient was diagnosed with unilateral NHNA on the basis of clinical presentation and skin-punch biopsy findings of epidermal orthokeratotic hyperkeratosis, mild papillomatosis, basal-layer hyperpigmentation and irregular filiform-pattern epidermal acanthosis. To the best of our knowledge, this case represents the first report of NHNA with unilateral presentation in a Saudi female.

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How to cite this article: Mahjoub T. Unilateral nevoid hyperkeratosis of the nipple and areola in a Saudi female. Our Dermatol Online. 2018;9(3):312-315.
Submission: 16.03.2018; Acceptance: 27.04.2018
DOI:10.7241/ourd.20183.23
Unilateral nevoid hyperkeratosis of the nipple and
Unilateral nevoid hyperkeratosis of the nipple and
areola in a Saudi female
areola in a Saudi female
Taghreed Mahjoub
King Abdullah Medical Complex- Jeddah, Saudi Arabia
Corresponding author: Dr. Taghreed Mahjoub, E-mail: dr.taghred@hotmail.com
INTRODUCTION
Nevoid hyperkeratosis of the nipple and areola (NHNA)
was first described by Taber in 1932 [1]. Hyperkeratosis
of the areola and nipple was classified by Levy-Franckel
into three types: type 1 is characterized by an extension
of the epidermal nevus; type 2 occurs secondary
to another form of dermatosis; and type 3 is the
idiopathic, isolated form [2]. However, Pérez-lzquierdo
et al. suggested an alternative classification that
distinguished just two types of nipple hyperkeratosis:
either idiopathic (nevoid) or occurring secondary to
other cutaneous conditions [3].
Nevoid hyperkeratosis of the nipple and areola is
characterized by a hyperpigmented, hyperkeratotic
verruca plaque that involves the nipple and/or
areola [3,4]. This condition is rare, and most frequently
occurs bilaterally, although unilateral cases have also
been reported [5–7].
NHNA is a clinical entity that tends to be diagnosed
on the basis of the exclusion of other conditions.
The patient who presents with hyperkeratosis of the
nipple and/or areola must be examined carefully for
the presence of other underlying cutaneous diseases,
including epidermal nevi, ichthyosis, acanthosis
nigricans, Darier disease, and cutaneous T-cell
lymphoma. If no other diagnosis is suggested by the
clinical findings, then a diagnosis of NHNA can be
made.
Here, we report a case of unilateral NHNA in a 21-year-
old female from Saudi Arabia. The patient presented
with a left-nipple hyperpigmented, hyperkeratotic
verruca plaque with a histopathological finding of
orthokeratotic hyperkeratosis and papillomatosis, with
mild epidermal acanthosis. Diagnosis was made on the
basis of clinical presentation and histopathological
findings, as well as the exclusion of other diagnoses.
CASE REPORT
An otherwise healthy, 21-year-old, single Saudi female
presented to the outpatient dermatology clinic with
a 3-year history of progressive skin thickening and
darkening of the left nipple, associated with moderate
ABSTRACT
Nevoid hyperkeratosis of the nipple and areola (NHNA) is a rare, benign condition of unknown origin that is characterized
by a hyperpigmented, hyperkeratotic verruca plaque over the nipple and/or areola. NHNA usually occurs bilaterally,
but is sometimes present unilaterally. We present a case of a 21-year-old Saudi female who presented at dermatology
outpatient clinic with a 3-year history of skin darkening and thickening of the left nipple, associated with moderate
itching. The patient was diagnosed with unilateral NHNA on the basis of clinical presentation and skin-punch biopsy
findings of epidermal orthokeratotic hyperkeratosis, mild papillomatosis, basal-layer hyperpigmentation and irregular
filiform-pattern epidermal acanthosis. To the best of our knowledge, this case represents the first report of NHNA
with unilateral presentation in a Saudi female.
key words: Nevoid hyperkeratosis; Nipple; Areola
Case Report

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itching. The patient had no history of nipple discharge
or bleeding, breast pain or masses, skin lesions at other
sites of the body, drug use, personal or family history
of atopy or family history of a similar skin condition.
On physical examination, asymmetry was observed
between the patient’s breasts, with normal appearance of
the right breast, but a diffuse, brown, hyperpigmented,
hyperkeratotic verruca plaque over the left nipple and areola
(Figs. 1, 2A and 2B). Bilateral examination of the breasts
found no mass, tenderness or discharge. There was no
evidence of lymphadenopathy. An examination of the skin
of the neck, axillae and other intertriginous areas showed
no increase in pigmentation or thickening. Similarly,
the nails, hair and skin covering other areas of the body
were normal. A 4-mm skin-punch biopsy was performed.
Examination of the skin punch biopsy indicated the
presence of epidermal orthokeratotic hyperkeratosis, mild
papillomatosis, basal-layer hyperpigmentation and an
irregular pattern of epidermal acanthosis with elongated
rete ridges (Figs. 3 and 4).
The diagnosis of unilateral NHNA was made on the basis
of the clinical and the histopathological findings. In
addition, secondary causes of nipple hyperkeratosis, such
as acanthosis nigricans, seborrheic keratosis, mammary
Paget’s disease, atopic dermatitis, superficial basal-
cell carcinoma and mycosis fungoides, were excluded.
Using the Levy-Franckel classification, our patient was
classified as having type III (i.e., idiopathic) NHNA.
The patient was treated with calcipotriol (synthetic
vitamin D3) cream daily for 6 months, at the end
of which she was satisfied with the cosmetic result,
reporting the disappearance of itching and a 50%
decrease in skin thickening of the left nipple and areola.
There was no treatment-related skin irritation.
Prior to the study, patient gave written consent to the
examination and biopsy after having been informed
about the procedure.
DISCUSSION
The present case report identified a Saudi female with
idiopathic hyperkeratosis of the nipple and areola.
Notably, 80% of 45 cases identified in a Review of
NHNA had occurred in female patients [8].
Although the exact cause of NHNA remains unknown,
it has been postulated that some cases could arise from
Figure 1: Photograph of the patient, showing unilateral nevoid
hyperkeratosis of the nipple and areola on the left breast, compared
with the normal tissue of the right breast.
Figure 3: Skin biopsy from the patient’s left breast , stained with
hematoxylin and eosin and, 400x original magnifi cation, showing
orthokeratotic hyperkeratosis, basal-layer hyperpigmentation and
irregular pattern acanthosis with elongated rete ridges.
Figure 4: A skin biopsy from the patient’s left breast , stained with
hematoxylin and eosin and presented at 100x original magnifi cation, to
show irregular fi liform epidermal acanthosis with elongated rete ridges.
Figure 2: A magnifi ed view showing (A) the normal right breast and (B)
the verrucous, hyperpigmented thickening of the left areola and nipple.
A B

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an alteration in estrogen levels [9]. In support of this
hypothesis, two cases of NHNA have been reported
in an elderly male who received estrogen therapy
for prostatic adenocarcinoma [8]. Another patient
developed NHNA during pregnancy [10]. In a study
of female patients with NHNA, six of the seven cases
examined had occurred among women of reproductive
age, who were in the second or third decade of life [3].
Similarly, our patient had started to develop symptoms
3 years before she first presented to the dermatology
clinic at 21 years old.
More than half of the cases of NHNA occur bilaterally,
but unilateral cases have been reported [5–7]. Our
patient presented with the less common unilateral
type of NHNA.
Histopathological findings of NHNA include epidermal
orthokeratotic hyperkeratosis, papillomatosis and
occasional keratin plugging with irregular filiform-
pattern epidermal acanthosis. The basal layer of
epidermis is hyperpigmented, without melanocyte
proliferation, and the dermis may show mild
perivascular lymphocytic infiltration [3,4,6,7,11].
Our case was diagnosed clinically and confirmed with
a left-nipple histopathological finding of epidermal
orthokeratotic hyperkeratosis, mild papillomatosis,
basal-layer hyperpigmentation and an irregular pattern
of epidermal acanthosis with elongated rete ridges.
Different therapeutic options have been used to
manage NHNA, with varying results. The use of
topical calcipotriol (a synthetic form of vitamin D3)
has been reported to be effective and to produce a
rapid outcome [5]. Topical calcipotriol combined
with topical tacrolimus (an immunosuppressant) has
previously been used to treat NHNA in a 19-year-old
female, with improvement noted after 2 months of
treatment [12]. Low-dose oral acitretin (a second-
generation retinoid) has also been combined with
topical calcipotriol for the treatment of NHNA, with
no relapse after 2 years of follow-up [13].
The mechanism of action of topical calcipotriol in
NHNA could involve inhibition of cellular proliferation
and induction of keratinocyte differentiation. Topical
calcipotriol is considered a very safe drug when
used in amounts up to 100 g per week. The most
important adverse effect of topical calcipotriol is
skin irritation, but it also has a potential effect on
calcium hemostasis [14]. Our patient was treated with
topical calcipotriol cream daily for 6 months, and she
experienced disappearance of skin itching, and a 50%
decrease in skin thickening of the left nipple.
Acceptable cosmetic results have been obtained after
the treatment of NHNA with a topical retinoid [15].
Cryotherapy has also been used successfully in the
treatment of NHNA, with improvement noted
after five sessions (with 20 s of cryotherapy per
session) in a female patient who failed to respond to
topical keratolytic agents [16]. In addition, surgical
treatment modalities have been described, including
radiofrequency surgery [17].
To the best of our knowledge, this case provides the first
report of unilateral NHNA in Saudi Arabia. Although
this condition is benign, it is considered distressing for
the patient because of a disfigured appearance and of
concern to doctors because of its similarity to mammary
Paget’s disease.
ACKNOWLEDGEMENTS
I would like to thank Dr. Awadh Al Amri and Dr.Louai
Salah for reviewing the manuscript. Also I would like
to thank King Abdullah International Medical research
center for the article English language editing.
CONSENT
The examination of the patient was conducted
according to the Declaration of Helsinki principles.
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Copyright by Taghreed Mahjoub. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited.
Source of Support: Nil, Confl ict of Interest: None declared.