History

The diagnosis of secondary hyperkeratosis of the nipple and/or areola is usually straightforward because the other cutaneous manifestations of the associated skin diseases that are the cause of the disease are apparent. Secondary hyperkeratosis of the nipple and/or areola associated with an epidermal nevus, organoid nevus, leiomyoma, or verruca usually involves only 1 nipple and/or areola. Secondary hyperkeratosis of the nipple and/or areola is bilateral when this clinical manifestation reflects the more widespread or systemic nature of the underlying disease. Women with unilateral primary hyperkeratosis of the nipple and/or areola lesions may have bilateral disease during pregnancy (secondary hyperkeratosis of the nipple and/or areola) Pregnancy may also produce thicker, darker lesions.

Primary hyperkeratosis of the nipple and/or areola is not associated with any underlying conditions and is an isolated finding. Skin biopsy findings may help confirm the diagnosis if it is unclear from the clinical presentation. Primary hyperkeratosis of the nipple and/or areola can occur unilaterally, but it most frequently affects both sides. In greater than 50% of the cases, primary hyperkeratosis of the nipple and/or areola affects both the nipple and areola. The cutaneous changes of nevoid hyperkeratosis of the nipple and/or areola are generally asymptomatic. Mild pruritus may result from poor hygiene. Most complaints reflect concern about the cosmetic appearance of the thickened hyperpigmented nipples and/or areolas.

Unilateral primary hyperkeratosis of the nipple and/or areola^{[14, 15, 35, 36]}must be distinguished from an underlying breast carcinoma. Pain, bleeding, ulceration, a nipple discharge, or loss of normal anatomy with nipple retraction or loss of nipple should prompt immediate evaluation. Lesions recalcitrant to therapy also warrant investigation (ie, biopsy). The evaluation of these lesions should include complete bilateral breast examination with evaluation of the lymph nodes, mammography, and biopsy of the involved skin. Consultation with a surgical oncologist may be indicated if any of the above occurs.

The American Cancer Society has released 2012 guidelines for early detection of breast cancer.^[37]These guidelines apply to women with the usual (average) risk for breast cancer and no symptoms of breast cancer. Older women or high-risk women (ie, family history of breast cancer) should discuss their risk factors with their doctor for more in-depth guidelines. For average-risk women, the guidelines are as follows:

Early mammograms are recommended starting at age 40 years and continuing for as long as a woman is in good health.
Clinical breast examination (CBE) should be performed about every 3 years for women in their 20s and 30s and every year for women aged 40 years and older.
Women should know how their breasts normally look and feel and report any breast change promptly to their healthcare provider. Breast self-examination (BSE) is an option for women starting in their 20s.
Some womenm because of their family history, a genetic tendency, or certain other factors, should be screened with MRI in addition to mammography.
Women should have the opportunity to become informed about the benefits, limitations, and potential harms associated with regular screening.

Physical Examination

The affected nipple and/or areola are thickened and may be covered with hyperpigmented verrucous or filiform hyperkeratotic plaques (see the images below).

An adult male with bilateral primary hyperkeratosis of the nipple and areola

View Media Gallery

A close-up of the patient's right nipple/areola complex.

View Media Gallery

A close up of the patient's nipple/areola complex.

View Media Gallery

No associated abnormalities of nipple and/or areola anatomy and underlying breast should be present.

Differential Diagnoses

Levy-Franckel A. Les hyperkeratosis de l'areola et du mamelon. Paris Med. 1938. 28:63-6.
Boussofara L, Akkari H, Saidi W, Ghariani N, Sriha B, Denguezli M, et al. Bilateral idiopathic hyperkeratosis of the nipple and areola. Acta Dermatovenerol Alp Panonica Adriat. 2011. 20(1):41-3. [QxMD MEDLINE Link].
Soriano LF, Piansay-Soriano ME. Naevoid hyperkeratosis of the nipple and areola: an extensive form in two adolescent Filipino females. Clin Exp Dermatol. 2015 Jan. 40 (1):23-6. [QxMD MEDLINE Link].
Perez-Izquierdo JM, Vilata JJ, Sanchez JL, Gargallo E, Millan F, Aliaga A. Retinoic acid treatment of nipple hyperkeratosis. Arch Dermatol. 1990 May. 126(5):687-8. [QxMD MEDLINE Link].
Mehanna A, Malak JA, Kibbi AG. Hyperkeratosis of the nipple and areola: report of 3 cases. Arch Dermatol. 2001 Oct. 137(10):1327-8. [QxMD MEDLINE Link].
Chikhalkar SB, Misri R, Kharkar V. Nevoid hyperkeratosis of nipple: nevoid or hormonal?. Indian J Dermatol Venereol Leprol. 2006 Sep-Oct. 72(5):384-6. [QxMD MEDLINE Link].
Kuhlman DS, Hodge SJ, Owen LG. Hyperkeratosis of the nipple and areola. J Am Acad Dermatol. 1985 Oct. 13(4):596-8. [QxMD MEDLINE Link].
Kubota Y, Koga T, Nakayama J, Kiryu H. Naevoid hyperkeratosis of the nipple and areola in a man. Br J Dermatol. 2000 Feb. 142(2):382-4. [QxMD MEDLINE Link].
Bayramgurler D, Bilen N, Apaydin R, Ercin C. Nevoid hyperkeratosis of the nipple and areola: treatment of two patients with topical calcipotriol. J Am Acad Dermatol. 2002 Jan. 46(1):131-3. [QxMD MEDLINE Link].
Baykal C, Buyukbabani N, Kavak A, Alper M. Nevoid hyperkeratosis of the nipple and areola: a distinct entity. J Am Acad Dermatol. 2002 Mar. 46(3):414-8. [QxMD MEDLINE Link].
Aytekin S, Tarlan N, Alp S, Uzunlar AK. Naevoid hyperkeratosis of the nipple and areola. J Eur Acad Dermatol Venereol. 2003 Mar. 17(2):232-3. [QxMD MEDLINE Link].
Baz K, Kokturk A, Kaya TI, Ikizoglu G, Düsmez D, Koca A. A case of hyperkeratosis of the nipple and areola resulting from organoid nevus. Int J Dermatol. 2003 Apr. 42(4):318-20. [QxMD MEDLINE Link].
Samimi M, Maitre F, Esteve E. [Hyperkeratotic lesion of the nipple revealing cutaneous leiomyoma]. Ann Dermatol Venereol. 2008 Aug-Sep. 135(8-9):571-4. [QxMD MEDLINE Link].
D'Souza M, Gharami R, Ratnakar C, Garg BR. Unilateral nevoid hyperkeratosis of the nipple and areola. Int J Dermatol. 1996 Aug. 35(8):602-3. [QxMD MEDLINE Link].
Lee HW, Suh HS, Choi JC, et al. Hyperkeratosis of the nipple and areola as a sign of malignant acanthosis nigricans. Clin Exp Dermatol. 2005 Nov. 30(6):721-2. [QxMD MEDLINE Link].
Fitzgerald DA, Lewis-Jones MS. Darier's disease presenting as isolated hyperkeratosis of the breasts. Br J Dermatol. 1997 Feb. 136(2):290. [QxMD MEDLINE Link].
Ahn SK, Chung J, Soo Lee W, Kim SC, Lee SH. Hyperkeratosis of the nipple and areola simultaneously developing with cutaneous T-cell lymphoma. J Am Acad Dermatol. 1995 Jan. 32(1):124-5. [QxMD MEDLINE Link].
Allegue F, Soria C, Rocamora A, Fraile G, Ledo A. Hyperkeratosis of the nipple and areola in a patient with cutaneous T-cell lymphoma. Int J Dermatol. 1990 Sep. 29(7):519-20. [QxMD MEDLINE Link].
Kavak A, Parlak AH, Aydogan I, Alper M. Hyperkeratosis of the nipple and areola in a patient with chronic mucocutaneous candidiasis. J Dermatol. 2006 Jul. 33(7):510-1. [QxMD MEDLINE Link].
Mold DE, Jegasothy BV. Estrogen-induced hyperkeratosis of the nipple. Cutis. 1980 Jul. 26(1):95-6. [QxMD MEDLINE Link].
Schwartz RA. Hyperkeratosis of nipple and areola. Arch Dermatol. 1978 Dec. 114(12):1844-5. [QxMD MEDLINE Link].
Lambiris AG, McCormick F. Unilateral hyperkeratosis of nipple and areola associated with androgen insensitivity and oestrogen replacement therapy. J Eur Acad Dermatol Venereol. 2001 Jul. 15(4):376-7. [QxMD MEDLINE Link].
Carr ES, Brown SC, Fiala KH. Painful nipple hyperkeratosis secondary to vemurafenib. Dermatol Ther. 2017 Feb 17. [QxMD MEDLINE Link].
Riley CA, Badri T, Hafsi W. Hyperkeratosis Of The Nipple And Areola. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Parimalam K, Chandrakala C, Ananthi M, Karpagam B. Nipple Hyperkeratosis Due to Malassezia Furfur Showing Excellent Response to Itraconazole. Indian J Dermatol. 2015 May-Jun. 60 (3):324. [QxMD MEDLINE Link].
Alenizi DA. Crusted nipple and areola: A new aetiology of secondary hyperkeratosis of the nipple and areola. Indian J Dermatol Venereol Leprol. 2019 Mar-Apr. 85 (2):169-170. [QxMD MEDLINE Link]. [Full Text].
Sengul N, Parlak AH, Oruk S, Boran C. Nevoid hyperkeratosis of the nipple and areola: a diagnosis of exclusion. Breast J. 2006 Jul-Aug. 12(4):383-4. [QxMD MEDLINE Link].
Mazzella C, Costa C, Fabbrocini G, Marangi GF, Russo D, Merolla F, et al. Nevoid hyperkeratosis of the nipple mimicking a pigmented basal cell carcinoma. JAAD Case Rep. 2016 Nov. 2 (6):500-501. [QxMD MEDLINE Link].
Dash S, Behera B, Palit A, Sethy M. Dermoscopy and Histopathology of Darier Disease-Associated Nevoid Hyperkeratosis of Nipple and Areola. Dermatol Pract Concept. 2021 Jul. 11 (3):e2021044. [QxMD MEDLINE Link]. [Full Text].
Claudio C, Arianna D, Roberta G, Iris Z, Nicola DM. Dermoscopic Features of Nevoid Hyperkeratosis of the Nipple and Areola. Dermatol Pract Concept. 2022 Feb. 12 (1):e2022003. [QxMD MEDLINE Link]. [Full Text].
Li L, Xiao M, Huang X, Jin H. Epidermal skin grafts from the scalp for hyperkeratosis of nipple and areola. Indian J Dermatol Venereol Leprol. 2022 Mar-Apr. 88 (2):228-229. [QxMD MEDLINE Link]. [Full Text].
Wei J, Li Q, Wu H, Yin X, Ren G. Severe Bilateral Hyperkeratosis of the Nipples and Areolae: A Case Report and Literature Review. Front Med (Lausanne). 2022. 9:781693. [QxMD MEDLINE Link]. [Full Text].
Foustanos A, Panagiotopoulos K, Ahmad D, Konstantopoulos K. Surgical approach for nevoid hyperkeratosis of the areola. J Cutan Aesthet Surg. 2012 Jan. 5(1):40-2. [QxMD MEDLINE Link]. [Full Text].
Obayashi H, Tsuchida T, Ikeda S. [Hyperkeratosis of the nipple and areola]. Rinsho Dermatol. 1998. 40:147-50.
Vestey JP, Bunney MH. Unilateral hyperkeratosis of the nipple: the response to cryotherapy. Arch Dermatol. 1986 Dec. 122(12):1360-1. [QxMD MEDLINE Link].
Shastry V, Betkerur J, Kushalappa PA. Unilateral nevoid hyperkeratosis of the nipple: a report of two cases. Indian J Dermatol Venereol Leprol. 2006 Jul-Aug. 72(4):303-5. [QxMD MEDLINE Link].
American Cancer Society. Detailed Guide: Breast Cancer. 2012. August 24, 2012. Available at http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/index.
Krishnan RS, Angel TA, Roark TR, Hsu S. Nevoid hyperkeratosis of the nipple and/or areola: a report of two cases and a review of the literature. Int J Dermatol. 2002 Nov. 41(11):775-7. [QxMD MEDLINE Link].
Mehregan AH, Rahbari H. Hyperkeratosis of nipple and areola. Arch Dermatol. 1977 Dec. 113(12):1691-2. [QxMD MEDLINE Link].
Soden CE. Hyperkeratosis of the nipple and areola. Cutis. 1983 Jul. 32(1):69-71, 74. [QxMD MEDLINE Link].
Roustan G, Yus ES, Simon A. Nevoid hyperkeratosis of the areola with histopathological features mimicking mycosis fungoides. Eur J Dermatol. 2002 Jan-Feb. 12(1):79-81. [QxMD MEDLINE Link].
Rosman IS, Hepper DM, Lind AC, Anadkat MJ. Nevoid hyperkeratosis of the areola misinterpreted as mycosis fungoides. J Cutan Pathol. 2012 May. 39(5):545-8. [QxMD MEDLINE Link].
Tocco-Tussardi I, Mobargha N, Bassetto F, Vindigni V. Radical treatment of extensive nevoid hyperkeratosis of the areola and breast with surgical excision after mild response to topical agents: A case report. Int J Surg Case Rep. 2016. 28:117-120. [QxMD MEDLINE Link].
English JC 3rd, Coots NV. A man with nevoid hyperkeratosis of the areola. Cutis. 1996 May. 57(5):354-6. [QxMD MEDLINE Link].
Okan G, Baykal C. Nevoid hyperkeratosis of the nipple and areola: treatment with topical retinoic acid. J Eur Acad Dermatol Venereol. 1999 Nov. 13(3):218-20. [QxMD MEDLINE Link].
Alpsoy E, Yilmaz E, Aykol A. Hyperkeratosis of the nipple: report of two cases. J Dermatol. 1997 Jan. 24(1):43-5. [QxMD MEDLINE Link].
Revert A, Banuls J, Montesinos E, Jorda E, Ramon D, Torres V. Nevoid hyperkeratosis of the areola. Int J Dermatol. 1993 Oct. 32(10):745-6. [QxMD MEDLINE Link].
Guevara-Gutierrez E, Tarango-Martinez VM, Sandoval-Tress C, Hernandez-Torres M. [Unilateral nevoid hyperkeratosis of the nipple and areola treated with topical calcitriol]. Actas Dermosifiliogr. 2008 Jul-Aug. 99(6):500-1. [QxMD MEDLINE Link].
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):337-40. [QxMD MEDLINE Link].
Mitxelena J, Raton JA, Bilbao I, Diaz-Perez JL. Nevoid hyperkeratosis of the areola in men: response to cryotherapy. Dermatology. 1999. 199(1):73-4. [QxMD MEDLINE Link].
Lee HW, Lee MW, Choi JH, Moon KC, Koh JK. To the editor: Unilateral nevoid hyperkeratosis of the nipple and areola: excellent response to cryotherapy. Dermatol Surg. 2005 May. 31(5):611-2. [QxMD MEDLINE Link].
Swan MC, Gwilym SE, Hollowood K, Venning V, Cassell O. Treatment of nevoid hyperkeratosis of the nipple and areola by shave excision. Ann Plast Surg. 2004 Nov. 53(5):510-2. [QxMD MEDLINE Link].
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 Jun. 54(6):667-9. [QxMD MEDLINE Link].
Marin-Bertolin S, Gonzalez-Martinez R, Marquina Vila P. Nevoid hyperkeratosis of the areola. Plast Reconstr Surg. 1998 Jul. 102(1):275-6. [QxMD MEDLINE Link].
Busse A, Peschen M, Schopf E, Vanscheidt W. Treatment of hyperkeratosis areolae mammae naeviformis with the carbon dioxide laser. J Am Acad Dermatol. 1999 Aug. 41(2 Pt 1):274-6. [QxMD MEDLINE Link].
Ozyazgan I, Kontas O, Ferahbas A. Treatment of nevoid hyperkeratosis of the nipple and areola using a radiofrequency surgical unit. Dermatol Surg. 2005 Jun. 31(6):703-5. [QxMD MEDLINE Link].
Verma P, Pandhi D, Yadav P. Unilateral Nevoid/primary Hyperkeratosis of Nipple and Areola Successfully Treated with Radiofrequency Ablation. J Cutan Aesthet Surg. 2011 Sep. 4(3):214-5. [QxMD MEDLINE Link]. [Full Text].
Singh A. Radiofrequency ablation of bilateral nevoid hyperkeratosis of nipple and areola. Indian J Dermatol Venereol Leprol. 2016 Nov-Dec. 82 (6):730-732. [QxMD MEDLINE Link].
Martinez-Garcia E, Taibjee S, Koch D, Osborne R. Vemurafenib-induced hyperkeratosis of the areola treated with topical adapelene. Clin Exp Dermatol. 2015 Feb 22. [QxMD MEDLINE Link].
Burns DA. Breast. Burns T, Breathnach S, Cox N, Griffith C, Eds. Rook's Textbook of Dermatology. 7th ed. New York, NY: Blackwell Science; 2004. 67.8-67.9.

Media Gallery

An adult male with bilateral primary hyperkeratosis of the nipple and areola
A close-up of the patient's right nipple/areola complex.
A close up of the patient's nipple/areola complex.

of 3

Author

Rabindranath Nambi, MD Consulting Staff, Department of Dermatology, Dudley Group of Hospitals, UK

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Edward F Chan, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Kathryn Schwarzenberger, MD Associate Professor of Medicine, Division of Dermatology, University of Vermont College of Medicine; Consulting Staff, Division of Dermatology, Fletcher Allen Health Care

Kathryn Schwarzenberger, MD is a member of the following medical societies: Women's Dermatologic Society, American Contact Dermatitis Society, Medical Dermatology Society, Dermatology Foundation, Alpha Omega Alpha, American Academy of Dermatology

Disclosure: Nothing to disclose.

Ivan D Camacho, MD Dermatologist, Private Practice; Voluntary Assistant Professor of Dermatology, Department of Dermatology and Cutaneous Surgery, University of Miami, Leonard M Miller School of Medicine

Ivan D Camacho, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Florida Medical Association, International Society of Dermatology, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Joshua R Freedman, MD, MS Resident Physician, Department of Dermatology and Cutaneous Surgery, Jackson Memorial Hospital, University of Miami, Leonard M Miller School of Medicine

Joshua R Freedman, MD, MS is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Joseph C English III, MD Clinical Vice-Chairman for Quality and Innovation, Professor of Dermatology, Department of Dermatology, University of Pittsburgh School of Medicine

Joseph C English III, MD is a member of the following medical societies: American Academy of Dermatology and American Medical Association

Disclosure: Nothing to disclose.

Sections Hyperkeratosis of the Nipple and Areola
Overview
Presentation
DDx
Workup
Treatment
Media Gallery
References

Hyperkeratosis of the Nipple and Areola Clinical Presentation

History

Physical Examination

References

Tables

Contributor Information and Disclosures

What would you like to print?