Nevoid Hyperkeratosis of the Nipple and Areola

Background

This rare hyperkeratotic lesion of the nipples areola is a recently described benign disease.

OUTLINE

Epidemiology

Disease Associations

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Differential Diagnosis

Prognosis and Treatment

Commonly Used Terms

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Hyperkeratosis of the nipple

INCIDENCE Rare

SEX (M:F)
Usually women, rare male cases

AGE 2-3rd decades

DISEASE ASSOCIATIONS CHARACTERIZATION

EPIDERMAL NEVUS

ESTROGEN THERAPY

Estrogen-induced hyperkeratosis of the nipple.

Mold DE, Jegasothy BV.
Cutis 1980 Jul;26(1):95-6 Abstract quote
Hyperkeratosis of the nipple and areola has been classically divided into three categories: a part of an epidermal nevus, a type associated with ichthyosis, and a nevoid form seen in young women.

A case of hyperkeratosis of the nipples in a patient with adenocarcinoma of the prostate treated with diethylstilbestrol is described herein. A possible correlation between estrogens and an acquired form of this rare skin disorder is suggested.

ICHTHYOSIS

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Hyperkeratosis of nipple and areola.

Mehregan AH, Rahbari H.
Arch Dermatol 1977 Dec;113(12):1691-2 Abstract quote
Hyperkeratosis of the nipple and areola is a rare condition that may occur in association with various forms of ichthyosis or as the result of extension of an epidermal nevus. The nevoid form is extremely rare and appears most commonly in women in their second or third decade of life. It is characterized by verrucous thickening and brownish discoloration of both nipples and areolae. Thirteen cases of this type have been reported.

We are describing two additional cases to bring the total to 15 instances.

Hyperkeratosis of the nipple and areola.

Kuhlman DS, Hodge SJ, Owen LG.
J Am Acad Dermatol 1985 Oct;13(4):596-8 Abstract quote
Hyperkeratosis of the nipple and areola is a rare condition. We report two cases of hyperkeratosis of the nipple and areola occurring in men with no underlying endocrinopathy or synthetic estrogenic drug therapy. Both patients demonstrated prompt resolution of the hyperkeratosis of the nipples with a keratolytic gel.

Because our cases were not associated with ichthyosis or epidermal nevus, they best fit into the category of nevoid hyperkeratosis of the nipples.

Hyperkeratosis of the nipple: report of two cases.

Alpsoy E, Yilmaz E, Aykol A.

Department of Dermatology, Akdeniz University Medical Faculty, Antalya, Turkey.
J Dermatol 1997 Jan;24(1):43-5 Abstract quote
Hyperkeratosis of the nipple and areola is a rare condition; its characteristic properties are verrucous thickening and brownish discoloration of the nipples and areola. The nevoid form of the disease is extremely rare, usually seen in women in the second or third decade of life. The nipple is seldom affected alone.

We report two cases of the nevoid form of hyperkeratosis of the nipple. In both female patients, lesions developed after puberty and were confined to both nipples alone. One of the patients' lesions became darker and more verrucous during pregnancy, making breast feeding impossible.

Nevoid hyperkeratosis of the nipple and areola: A distinct entity

Can Baykal, MD
Nesimi Büyükbabani, MD
Ayse Kavak, MD
Murat Alper, MD

Istanbul and Düzce, Turkey

J Am Acad Dermatol 2002;46:414-8 Abstract quote

Although nevoid hyperkeratosis of the nipple and areola was initially described in 1923, there are only case reports or reviews about it; no large series have been documented to date.

The clinical features of the reported cases in the literature are not uniform, and it is questioned whether nevoid hyperkeratosis of the nipple and areola is a distinct clinicopathologic entity or a clinical presentation of various dermatoses. We describe 7 cases with hyperkeratotic nevoid lesions localized on the nipple and areola with different clinical features. None of them had any other associated dermatologic or systemic disease. Histopathologic examination was performed in 6 patients. Four of them had common histopathologic features suggesting a distinct entity, namely, nevoid hyperkeratosis of the nipple and areola; 2 of them had histopathologic features consistent with seborrheic keratosis.

Seborrheic keratosis presents as sharply demarcated papules or plaques, whereas nevoid hyperkeratosis of the nipple or areola presents as a plaque diffusely involving the nipple or the areola.

VARIANTS

MALE

A man with nevoid hyperkeratosis of the areola.

English JC 3rd, Coots NV.

Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200, USA.
Cutis 1996 May;57(5):354-6 Abstract quote
Nevoid hyperkeratosis of the nipple and areola is a unique clinical entity and a diagnosis of exclusion. The patient presenting with nipple/areolar hyperkeratosis must be examined carefully for other underlying cutaneous diseases such as epidermal nevi, ichthyosis, acanthosis nigricans, Darier's disease, cutaneous T-cell lymphoma, and other chronic skin dermatitides that may be responsible for the changes. If no other clinical findings are evident, the diagnosis can be made. Although the disorder is more common in women of childbearing age, men may show nevoid changes after estrogen therapy or idiopathically.

The use of topical 12 percent lactic acid lotion (Lac-Hydrin) resolves the skin changes over a six-month period.

Naevoid hyperkeratosis of the nipple and areola in a man.

Kubota Y, Koga T, Nakayama J, Kiryu H.
Br J Dermatol 2000 Feb;142(2):382-4

UNILATERAL

Unilateral nevoid hyperkeratosis of the nipple and areola.

D'Souza M, Gharami R, Ratnakar C, Garg BR.
Int J Dermatol 1996 Aug;35(8):602-3 Abstract quote

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

VARIANTS

MYCOSIS FUNGOIDES LIKE CHANGES

Nevoid hyperkeratosis of the areola with histopathological features mimicking mycosis fungoides.

Roustan G, Yus ES, Simon A.

Department of Dermatology, Clinica Universitaria Puerta de Hierro, Madrid, Spain.
Eur J Dermatol 2002 Jan-Feb;12(1):79-81 Abstract quote
Hyperkeratosis of the areola is a rare benign condition of unknown etiology characterized by slowly growing verrucous thickening and brown pigmentation of the areola or/and the nipple. It may be presented as isolated nevoid form or associated with other skin diseases.

We described a 21-year-old woman with characteristic lesions of nevoid hyperkeratosis in both areolas but with histopathological findings resembling mycosis fungoides. Cutaneous lesions have remained unchanged after two years of follow-up.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

SEBORRHEIC KERATOSIS

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

TREATMENT

CALCIPOTRIOL

Nevoid hyperkeratosis of the nipple and areola: treatment of two patients with topical calcipotriol.

Bayramgurler D, Bilen N, Apaydin R, Ercin C.

Department of Dermatology, Kocaeli University School of Medicine, Izmit, Turkey.
J Am Acad Dermatol 2002 Jan;46(1):131-3 Abstract quote
Nevoid hyperkeratosis of the nipple and areola, which is characterized by verrucous thickening and pigmentation of the nipple or areola, is a rare condition. Different therapeutic options have been used with varying results, but there is no uniformly effective treatment. |

We describe two patients with hyperkeratosis of the nipple and areola who responded well to topical calcipotriol ointment.

CRYOTHERAPY

Unilateral hyperkeratosis of the nipple: the response to cryotherapy.

Vestey JP, Bunney MH.
Arch Dermatol 1986 Dec;122(12):1360-1

LASER

Treatment of hyperkeratosis areolae mammae naeviformis with the carbon dioxide laser.

Busse A, Peschen M, Schopf E, Vanscheidt W.

Department of Dermatology, University of Freiburg, Germany.
J Am Acad Dermatol 1999 Aug;41(2 Pt 1):274-6 Abstract quote
Hyperkeratosis of the nipple and areola is a rare mamma condition. Typical lesions are characterized by persistent verrucous thickening and dark pigmentation of the nipple or areola (or both) and may occur unilaterally or bilaterally in both sexes.

We report what we believe to be the first therapeutic trial with carbon dioxide laser in a patient with hyperkeratosis areolae mammae naeviformis.

RETINOIC ACID

Retinoic acid treatment of nipple hyperkeratosis.

Perez-Izquierdo JM, Vilata JJ, Sanchez JL, Gargallo E, Millan F, Aliaga A.
Arch Dermatol 1990 May;126(5):687-8

Nevoid hyperkeratosis of the nipple and areola: treatment with topical retinoic acid.

Okan G, Baykal C.

Department of Dermatology, Istanbul Medical Faculty, Istanbul University, Turkey.
J Eur Acad Dermatol Venereol 1999 Nov;13(3):218-20 Abstract quote
The disease has a benign course and may only be a cosmetic problem. Different modalities have been used in the treatment of NHNA. In our case treatment with topical retinoic acid induced an acceptable response.

Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.

Commonly Used Terms

Keratoses

Last Updated 3/28/2002

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Hyperkeratosis of nipple and areola. Mehregan AH, Rahbari H.	Arch Dermatol 1977 Dec;113(12):1691-2 Abstract quote Hyperkeratosis of the nipple and areola is a rare condition that may occur in association with various forms of ichthyosis or as the result of extension of an epidermal nevus. The nevoid form is extremely rare and appears most commonly in women in their second or third decade of life. It is characterized by verrucous thickening and brownish discoloration of both nipples and areolae. Thirteen cases of this type have been reported. We are describing two additional cases to bring the total to 15 instances.
Hyperkeratosis of the nipple and areola. Kuhlman DS, Hodge SJ, Owen LG.	J Am Acad Dermatol 1985 Oct;13(4):596-8 Abstract quote Hyperkeratosis of the nipple and areola is a rare condition. We report two cases of hyperkeratosis of the nipple and areola occurring in men with no underlying endocrinopathy or synthetic estrogenic drug therapy. Both patients demonstrated prompt resolution of the hyperkeratosis of the nipples with a keratolytic gel. Because our cases were not associated with ichthyosis or epidermal nevus, they best fit into the category of nevoid hyperkeratosis of the nipples.
Hyperkeratosis of the nipple: report of two cases. Alpsoy E, Yilmaz E, Aykol A. Department of Dermatology, Akdeniz University Medical Faculty, Antalya, Turkey.	J Dermatol 1997 Jan;24(1):43-5 Abstract quote Hyperkeratosis of the nipple and areola is a rare condition; its characteristic properties are verrucous thickening and brownish discoloration of the nipples and areola. The nevoid form of the disease is extremely rare, usually seen in women in the second or third decade of life. The nipple is seldom affected alone. We report two cases of the nevoid form of hyperkeratosis of the nipple. In both female patients, lesions developed after puberty and were confined to both nipples alone. One of the patients' lesions became darker and more verrucous during pregnancy, making breast feeding impossible.
Nevoid hyperkeratosis of the nipple and areola: A distinct entity Can Baykal, MD Nesimi Büyükbabani, MD Ayse Kavak, MD Murat Alper, MD Istanbul and Düzce, Turkey	J Am Acad Dermatol 2002;46:414-8 Abstract quote Although nevoid hyperkeratosis of the nipple and areola was initially described in 1923, there are only case reports or reviews about it; no large series have been documented to date. The clinical features of the reported cases in the literature are not uniform, and it is questioned whether nevoid hyperkeratosis of the nipple and areola is a distinct clinicopathologic entity or a clinical presentation of various dermatoses. We describe 7 cases with hyperkeratotic nevoid lesions localized on the nipple and areola with different clinical features. None of them had any other associated dermatologic or systemic disease. Histopathologic examination was performed in 6 patients. Four of them had common histopathologic features suggesting a distinct entity, namely, nevoid hyperkeratosis of the nipple and areola; 2 of them had histopathologic features consistent with seborrheic keratosis. Seborrheic keratosis presents as sharply demarcated papules or plaques, whereas nevoid hyperkeratosis of the nipple or areola presents as a plaque diffusely involving the nipple or the areola.
VARIANTS
MALE
A man with nevoid hyperkeratosis of the areola. English JC 3rd, Coots NV. Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200, USA.	Cutis 1996 May;57(5):354-6 Abstract quote Nevoid hyperkeratosis of the nipple and areola is a unique clinical entity and a diagnosis of exclusion. The patient presenting with nipple/areolar hyperkeratosis must be examined carefully for other underlying cutaneous diseases such as epidermal nevi, ichthyosis, acanthosis nigricans, Darier's disease, cutaneous T-cell lymphoma, and other chronic skin dermatitides that may be responsible for the changes. If no other clinical findings are evident, the diagnosis can be made. Although the disorder is more common in women of childbearing age, men may show nevoid changes after estrogen therapy or idiopathically. The use of topical 12 percent lactic acid lotion (Lac-Hydrin) resolves the skin changes over a six-month period.
Naevoid hyperkeratosis of the nipple and areola in a man. Kubota Y, Koga T, Nakayama J, Kiryu H.	Br J Dermatol 2000 Feb;142(2):382-4
UNILATERAL
Unilateral nevoid hyperkeratosis of the nipple and areola. D'Souza M, Gharami R, Ratnakar C, Garg BR.	Int J Dermatol 1996 Aug;35(8):602-3 Abstract quote

Epidemiology
Disease Associations
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Hyperkeratosis of the nipple
INCIDENCE	Rare
SEX (M:F)	Usually women, rare male cases
AGE	2-3rd decades

DISEASE ASSOCIATIONS	CHARACTERIZATION
EPIDERMAL NEVUS
ESTROGEN THERAPY
Estrogen-induced hyperkeratosis of the nipple. Mold DE, Jegasothy BV.	Cutis 1980 Jul;26(1):95-6 Abstract quote Hyperkeratosis of the nipple and areola has been classically divided into three categories: a part of an epidermal nevus, a type associated with ichthyosis, and a nevoid form seen in young women. A case of hyperkeratosis of the nipples in a patient with adenocarcinoma of the prostate treated with diethylstilbestrol is described herein. A possible correlation between estrogens and an acquired form of this rare skin disorder is suggested.
ICHTHYOSIS

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
VARIANTS
MYCOSIS FUNGOIDES LIKE CHANGES
Nevoid hyperkeratosis of the areola with histopathological features mimicking mycosis fungoides. Roustan G, Yus ES, Simon A. Department of Dermatology, Clinica Universitaria Puerta de Hierro, Madrid, Spain.	Eur J Dermatol 2002 Jan-Feb;12(1):79-81 Abstract quote Hyperkeratosis of the areola is a rare benign condition of unknown etiology characterized by slowly growing verrucous thickening and brown pigmentation of the areola or/and the nipple. It may be presented as isolated nevoid form or associated with other skin diseases. We described a 21-year-old woman with characteristic lesions of nevoid hyperkeratosis in both areolas but with histopathological findings resembling mycosis fungoides. Cutaneous lesions have remained unchanged after two years of follow-up.

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
SEBORRHEIC KERATOSIS

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT
CALCIPOTRIOL
Nevoid hyperkeratosis of the nipple and areola: treatment of two patients with topical calcipotriol. Bayramgurler D, Bilen N, Apaydin R, Ercin C. Department of Dermatology, Kocaeli University School of Medicine, Izmit, Turkey.	J Am Acad Dermatol 2002 Jan;46(1):131-3 Abstract quote Nevoid hyperkeratosis of the nipple and areola, which is characterized by verrucous thickening and pigmentation of the nipple or areola, is a rare condition. Different therapeutic options have been used with varying results, but there is no uniformly effective treatment. \| We describe two patients with hyperkeratosis of the nipple and areola who responded well to topical calcipotriol ointment.
CRYOTHERAPY
Unilateral hyperkeratosis of the nipple: the response to cryotherapy. Vestey JP, Bunney MH.	Arch Dermatol 1986 Dec;122(12):1360-1
LASER
Treatment of hyperkeratosis areolae mammae naeviformis with the carbon dioxide laser. Busse A, Peschen M, Schopf E, Vanscheidt W. Department of Dermatology, University of Freiburg, Germany.	J Am Acad Dermatol 1999 Aug;41(2 Pt 1):274-6 Abstract quote Hyperkeratosis of the nipple and areola is a rare mamma condition. Typical lesions are characterized by persistent verrucous thickening and dark pigmentation of the nipple or areola (or both) and may occur unilaterally or bilaterally in both sexes. We report what we believe to be the first therapeutic trial with carbon dioxide laser in a patient with hyperkeratosis areolae mammae naeviformis.
RETINOIC ACID
Retinoic acid treatment of nipple hyperkeratosis. Perez-Izquierdo JM, Vilata JJ, Sanchez JL, Gargallo E, Millan F, Aliaga A.	Arch Dermatol 1990 May;126(5):687-8
Nevoid hyperkeratosis of the nipple and areola: treatment with topical retinoic acid. Okan G, Baykal C. Department of Dermatology, Istanbul Medical Faculty, Istanbul University, Turkey.	J Eur Acad Dermatol Venereol 1999 Nov;13(3):218-20 Abstract quote The disease has a benign course and may only be a cosmetic problem. Different modalities have been used in the treatment of NHNA. In our case treatment with topical retinoic acid induced an acceptable response.