A 62-year-old Chinese woman presented with a painless pigmented lesion on the right nipple-areola complex (NAC). The lesion began as a small asymptomatic black spot on the base of nipple five years ago and had gradually increased in size. Physical examination revealed an irregular pigmented macular lesion, about 4×3 cm, on the right NAC (fig 1). The borders of the lesion were darkly pigmented, with scales on the surface. The lesion was painless and moveable from the underlying structures. The woman denied any discharge, pruritus, or history of carcinogen exposure; and her family history was unremarkable.
On palpation, no breast masses or lymphadenopathy were found.
What are the differential diagnoses for a pigmented skin lesion with colour variegation on the NAC?
Differential diagnoses include: eczematous breast conditions, seborrheic keratosis, pigmented Bowen’s disease, pigmented mammary Paget’s disease, and superficial spreading melanoma. In contact dermatitis and eczema, hyperpigmentation appears in the chronic phase.1 In seborrheic keratosis, hyperkeratosis and horn cysts are present. In pigmented mammary Paget’s disease, the lesion occurs on the surrounding skin as well as on the NAC. In BCC-NAC there is usually erythema, scaling, ulceration, subareolar nodules, plaques, papules, eczematous lesions, and/or crusty ulcers on the NAC.
Generally, these diseases have similar pigmented manifestations, but in eczematous conditions, such as contact dermatitis and eczema, hyperpigmentation appears in the chronic phase.1 The hypertrophic scaly dark red patches with lichenification and pigmentation are the typical manifestations, and history for allergic reaction is helpful for diagnosis. Pigmented seborrheic keratosis usually shows seborrheic and verrucous lesions with a well demarcated border.2 Pigmented Bowen's disease presents with a well defined black plaque with crusting or scaling surface, and the colour varying from brown to black.3 In pigmented mammary Paget’s disease, the lesion occurs on the NAC and surrounding skin. It is always associated with underlying intraductal mammary carcinoma and presents as a black plaque with variable colour and irregular borders.4 Superficial spreading melanoma frequently exhibits as a slightly raised macule or plaque in the non-exposed areas characterised by asymmetry, border irregularity, and colour variegation.5 Superficial pigmented BCC-NAC usually presents as irregular pigmented macula with erythema and scale on the NAC.678
What investigations are required?
Diagnosis is made through histopathological evaluation of the skin biopsy. Immunohistochemistry for HMB45 and S100 of tissue sections is required to diagnose melanoma.5
Sonography, mammography, and magnetic resonance imaging are required to investigate for potential metastases to the breast tissue and lymph nodes of malignant lesions. Imaging is not essential if benign lesions have been diagnosed.
Histopathological features of eczematous conditions include hyperkeratosis, parakeratosis, acanthosis, and increased melanin in the epidermis basal layer.1 In pigmented seborrheic keratosis, hyperkeratosis and horn cysts are present, which are clearly demarcated from adjacent skin.2 In pigmented Bowen’s disease, histological examination shows hyperkeratosis, acanthosis, melanophages, and atypical keratinocytes with pigmented cytoplasm.3 Pigmented mammary Paget’s disease is characterised by the Paget cells, the large cytoplasm and mucin rich adenocarcinoma cells, as well as a large amount of melanin in the cytoplasm of tumour cells.4 Superficial spreading melanoma is characterised by atypical epithelioid melanocytes with abundant cytoplasm, prominent nucleoli, and nuclei that scatter throughout the epidermis. Immunostaining studies of superficial spreading malignant melanoma are positive for HMB45 and S100 antibodies.5
Irregular proliferation of basaloid cells attached to the epidermis and peritumoral retraction clefts are the typical features for BCC-NAC, but not for other differential diseases including breast eczematous conditions, seborrheic keratosis, pigmented Bowen’s disease, pigmented mammary Paget’s disease, and superficial spreading melanoma.6910
Investigation results guide management, eg, the treatment of malignant pigmented NAC lesions depends on the extent of the tumour and the possible involvement of mammary tissue or lymph nodes.
When would a patient with a pigmented skin lesion on the NAC be referred for specialist input?
Consider non-urgent referral to dermatology if a malignant skin lesion is suspected. Generally, benign lesions are symmetrical and uniform in colour, and malignant lesions are asymmetrical with colour variegation.
ABCDE is an acronym to predict melanoma: asymmetry, border irregularity, colour variegation, diameter >5mm, and evolution rapidly.
Other features of malignancy include breast mass, lymphadenopathy, and/or refractory eczema.
For superficial pigmented BCC, pigmented Bowen's disease, and pigmented mammary Paget's disease, features of asymmetry and colour variegation are likely to be observed. Superficial spreading melanoma and pigmented mammary Paget's disease are invasive. Therefore, palpation for breast and lymph nodes is important. Consider pigmented mammary Paget’s disease in a patient with refractory eczema, as the lesions are similarly erosive and eczematous.
Perform routine tests (in preparation for tentative surgery) and comprehensive imaging while awaiting specialist input.
Treatment for all malignant pigmented lesions involve selective surgery. However, treatment for superficial spreading melanoma and mammary Paget's disease should be performed more promptly due to their invasive nature. Pigmented Bowen's disease and superficial pigmented BCC are less invasive, and surgery is less urgent. However, observe the rate of any change in these lesions, and request imaging of the underlying tissue and adjacent superficial lymph nodes.
Findings on sonography, mammography, and magnetic resonance imaging of the breast and lymph nodes were normal. Skin biopsy showed aggregates of basaloid cells emanating from the under surface of the epidermis, with peripheral palisading (fig 2). The adjacent stroma was mucinous and fibrotic. Sparse melanophages near aggregates of basaloid cells were found. A peritumour cleft was identified. Immunohistochemistry of tissue sections was negative for HMB45 and S100. Superficial pigmented BCC-NAC was diagnosed. The patient was treated with simple excision with a 1 cm safe margin under local anaesthesia. No recurrence or metastasis was observed during 12 months of follow-up.
- We have read and understood The BMJ policy on declaration of interests and declare no competing financial interests. We declare the following non-financial interests:
- Xing-Hua Gao is a board member for the International Society of Dermatology which is involved in not for profit dermatology research and education.
- Patient consent obtained.
- Provenance and peer review: not commissioned; externally peer reviewed.
- ME BarrettMM HellerH Fullerton StoneJE Murase. Dermatoses of the breast in lactation. Dermatol Ther2013;26:331-6. 10.1111/dth.12071 23914890
- A MinagawaM TanakaH KogaR Okuyama. Pigmented seborrheic keratosis showing starburst pattern. J Am Acad Dermatol2016;75:e11-3. 10.1016/j.jaad.2015.12.048 27317533
- AN MotaJ Piñeiro-MaceiraMdeF AlvesMJ Tarazona. Pigmented Bowen’s disease. An Bras Dermatol2014;89:825-7. 10.1590/abd1806-4841.20142725 25184929
- WI Al-DarajiAM O’SheaLM LooiCH YipI Ellis. Pigmented mammary Paget’s disease: not a melanoma. Histopathology2009;54:614-7. 10.1111/j.1365-2559.2009.03267.x 19413640
- SS FernandoS JohnsonJ Bäte. Immunohistochemical analysis of cutaneous malignant melanoma: comparison of S-100 protein, HMB-45 monoclonal antibody and NKI/C3 monoclonal antibody. Pathology1994;26:16-9. 10.1080/00313029400169021 8165017
- R KalyaniBR VaniMV SrinivasP Veda. Pigmented Basal cell carcinoma of nipple and areola in a male breast - a case report with review of literature. Int J Biomed Sci2014;10:69-72.24711752
- KA ChunPR Cohen. Basal cell carcinoma of the nipple-areola complex: a comprehensive review of the world literature. Dermatol Ther (Heidelb)2016;6:379-95. 10.1007/s13555-016-0128-3 27363851
- MA MinaA PicarielloJL Fewkes. Superficial basal cell carcinomas of the head and neck. Dermatol Surg2013;39:1003-8. 10.1111/dsu.12178 23465089
- Y OramC DemirkesenAD AkkayaE Koyuncu. Basal cell carcinoma of the nipple: an uncommon but ever-increasing location. Case Rep Dermatol Med2011;2011:818291. 10.1155/2011/818291 23259074
- YI ZhuD Ratner. Basal cell carcinoma of the nipple: a case report and review of the literature. Dermatol Surg2001;27:971-4.11737135
MEDICAL DISCLAIMER NOTICE: To the fullest extent permitted by law, the material and information displayed in The BMJ is provided "as is" without any guarantees, conditions or warranties as to accuracy. We rely on our authors of articles, contractors and third party data providers to confirm the accuracy of information and advertisements presented and to describe generally accepted practices and therefore we as the publisher and editors cannot warrant its accuracy. Differences may occur also between the print and online text of articles and advertisements. Readers should be aware that professionals in the field may have different opinions. Because of this fact and also because of regular advances in medical research we strongly recommend that readers independently verify any information that they chose to rely upon. Ultimately it is the reader's responsibility to make their own professional judgements. Opinions posted on Rapid Responses, the Advice Zone, International Experience and any other parts of the sites are those of the individuals posting them and not the views of BMJ.