Becker Nevus Syndrome Presented with Ipsilateral Breast Hypoplasia

Abstract

Becker nevus syndrome (BNS) is a rare epidermal nevus syndrome characterized with Becker nevus and ipsilateral breast gland hypoplasia or other skin, skeletal and/or muscle tissue disorders. A 24-year-old woman presented with brown, irregular bordered patch with a diameter of approximately 10 cm which consisted of several small macules on the left breast skin. The ultrasonography and magnetic resonance imaging revealed left breast hypoplasia. Histopathological examination demonstrated minimal acanthosis, papillomatosis, increase in basal layer melanin and hypertrophy of the erector pili muscle. Immunohistochemical staining was positive for androgen in the epidermis, dermal stromal cells and skin appendages. Depending on the clinical and histopathological findings, the patient was diagnosed as BNS. Diagnosis of BNS needs careful examination of pigmented macules and patches since non-hairy BN may be easily overlooked. Patients with BN should be evaluated for associated abnormalities of BNS, in which the severity and extend of ectodermal involvement may differ from patient to other.

Introduction

What was known?

Becker nevus syndrome (BNS) is a rare epidermal nevus syndrome characterized with Becker nevus and ipsilateral breast gland hypoplasia or other skin, skeletal and/or muscle tissue disorders.

Becker nevus (BN) is an epidermal cutaneous hamartoma which is characterized with hypertrichosis and hyperpigmentation. Becker nevus usually presents as numerous macules especially located unilaterally on the trunk and shoulders. It mostly appears in the adolescent period, being five times more frequent in men than in women.[1] Histopathological evaluation of BN shows acanthosis, papillomatosis and hyperpigmentation in the epidermis, hyperplasia of the erector pili muscle, and melanophages in the dermis.[2]

Becker nevus syndrome (BNS) is a rare epidermal nevus syndrome consisting of Becker nevus and ipsilateral breast gland hypoplasia or other skin, skeletal and/or muscle tissue disorders.[1] The etiopathogenesis of BNS is unclear. Although BNS frequently occurs sporadically, familial involvement may seldom occur due to the incomplete penetrance of autosomal dominant inheritance. The frequent onset of BN during the peripubertal period, presence of hypertrichosis, acne and associated scrotum anomalies with BN in some patients suggested that androgens may involve in the pathogenesis of BNS.[1,3] Since androgens participate in the development of bones, muscles and hair, they may also play a role in the clinical manifestations of diseases that affect the skin and the locomotor system.[1]

Herein, we report a 24-year-old woman with BNS which was presented with ipsilateral breast hypoplasia.

Case Report

A 24-year-old woman was presented to our out-patient clinic with a brown discoloration which initially appeared as a little spot on her left breast 11 years ago and then expanded with time. In addition, the underlying left breast tissue had not grown during the peripubertal period. The patient did not have any systemic disease and drug intake. Her family history was unremarkable.

Dermatological examination revealed brown, irregular bordered patch with a diameter of approximately 10 cm which consisted of several smaller macules on the left breast skin [Figure 1a and b]. In physical examination, the underlying left breast tissue was remarkably hypoplastic when compared with the right breast tissue. In addition, the patient had also congenital hypoplastic right breast. Ultrasonography and magnetic resonance imaging of the left breast showed hypoplasia.

Figure 1.

(a and b) A large, non-hairy Becker nevus on the skin of the hypoplastic left breast of the patient

Histopathological examination of the brown patch demonstrated minimal acanthosis, papillomatosis, increase in basal layer melanin, minimal dermal fibrosis and mononuclear cell infiltration around vessels, and hypertrophy of the erector pili muscle [Figure 2a and b]. Immunohistochemical stains for estrogen and progesterone were negative. Positive staining with androgen was noticed in epidermis, skin appendages and stromal cells of the dermis [Figure 3]. Depending on the clinical and histopathological findings, the patient was diagnosed as BNS.

Figure 2.

Histopathological examination showed (a) Minimal acanthosis, papillomatosis, increase in basal layer melanin, minimal dermal fibrosis and mononuclear cell infiltration around vessels (H and E, ×40)and (b) Hypertrophy of the errector pili muscle (H and E, ×200)

Figure 3.

Immunohistochemical examinations demonstrated positive staining with androgen in (a) Control tissue for androgen staining, and (b) The epidermis (×400), (c) Dermal stromal cells (arrows) (×400), and (d) Skin appendages (×400) of the patient with BNS

Laboratory and imaging studies were performed to investigate additional disorders that could accompany this syndrome. Complete blood count, liver, kidney and thyroid function tests, follicular stimulating hormone, luteinizing hormone, 17-OH-progesteron, and prolactin levels of the patient were all within normal limits. Chest x-ray and abdominal ultrasonography did not reveal abnormalities. Since the patient requested cosmetic correction for breast hypoplasia, a mammoplasty operation was performed.

Discussion

Becker nevus usually develops on the trunk of the patients in their adolescence period. At initial, the color of BN may not be prominent to be noticed by the patient or physicians. The color of BN can get darken after puberty and hair or acneiform lesions may develop over BN.[1] Permanent hypertrichosis may become prominent after the formation of pigmentation. Besides this typical clinical presentation of BN, non-hairy BN, as observed in our case, may also exist.[4]

Despite the fact that hyperchromia exists in Becker nevus, this nevus in not regarded as a melanocytic lesion. It is rather accepted as a special epidermal nevus form such as verrucous epidermal nevus, sebaceous nevus, Jadassohn's sebaceous nevus, nevus comedonicus, ecrine nevus, apocrine nevus, and white sponge nevus.[1] Epidermal nevi occurs as a result of hamartomatous proliferation within the embryological ectoderm layer. Therefore, they consist of hyperplastic ectodermal structures such as keratinocytes, hair follicles, ecrine, apocrine, and sebaceous glands. Epidermal nevus syndrome usually involves the tissues originating from ectoderm and rarely effect the mesodermal tissues. In parallel to the structure and development of this entity, BNS can be accepted as a variant of epidermal nevus syndrome.[5,6]

Various disorders including adrenal hyperplasia, hypoplasia of bone, muscle, breast and fat tissue (mostly ipsilateral, rarely bilateral), hemivertabrae, spina bifida, pectus carinatum, pectus excavatum, scoliosis, localized lipodistrophy, accessory nipple, facial dysplasia or asymmetry, accessory scrotum, umbilical hernia, loose axillary hair, contralateral hypoplasia of labium minus can accompany Becker nevus and then this clinical syndrome is named BNS. Becker nevus syndrome may sometimes remain unnoticed since it usually proceeds with non-specific clinical findings.[1] In female patients, the presence of breast hypoplasia together with hyperpigmented patch may facilitate the diagnosis.[6] In the present case, co-existence of breast hypoplasia and ipsilateral brown discoloration of BN over the breast made the diagnosis of BNS. Since the patient was in adulthood and had normal levels of sexual hormones, the insufficient development of the right breast was considered as congenital hypoplasia. No other clinical pathology was detected associated with BNS.

The underlying mechanism for breast hypoplasia accompanying BNS may be the unresponsiveness of the tissue to estrogen or the excessive androgen sensitivity of the breast tissue. While estrogens provide ductal growth in breast tissue, the increase in the number of androgen receptors may suppress the estrogenic activity, resulting in breast hypoplasia. Although we could not perform immunohistochemical staining for androgen receptors in the breast tissue, the positive stain in the BN of the patient suggested that BN may be an androgen-dependent nevus and these androgen receptors may present in the breast tissue of our patient, resulting in hypoplasia.

Recent genetic studies have shown that a somatic recombination occurring in early embryogenesis may result in the emergence of nevi and nevus related disorders. When ectoderm is somehow disturbed during embryological development, disorders in tissue and organ groups evolving from ectoderm become prominent.[1] The severity and extend of the ectodermal involvement may be the reason for the variability of the clinical signs and symptoms associated with BNS. The differences in androgen receptors and ectoderm involvement may lead to the alterations in the clinical course of BNS within a long period of time. Therefore, patients should be recommended to come for regular clinical follow-ups to examine whether any associated abnormalities are developed in time.

There is no effective treatment for BNS. Since BN usually has a large size on the skin, treatment with surgical excision is usually limited. Satisfying results were achieved with Q-switched ruby (694 nm) and Erbium: YAG lasers.[7] Various successful epilation techniques can be used for cases with hypertrichosis.[8]

Conclusion

The diagnosis of BNS needs careful examination of pigmented macules and patches since non-hairy BN may be easily overlooked. The patients with BN should be evaluated for associated abnormalities of BNS, in which the severity and extend of ectodermal involvement may differ from one patient to the other.

What is new?

Careful examination of pigmented macules and patches and underlying tissues is important since non-hairy BN may be easily overlooked. The positive stain for androgen receptors in macule suggested that BN may be an androgen-dependent nevus.