Microcystic Adnexal Carcinoma of the Nipple

Background. Microcystic adnexal carcinoma (MAC) is a rare infiltrative cutaneous tumor, but with its locally aggressive nature, high rate of recurrence, and rare metastatic potential, it is an important clinical entity to consider when faced with a nipple lesion. These tumors are frequently misdiagnosed based on superficial biopsy alone. Case Report. This case of a 15-year-old girl with MAC of the nipple demonstrates the importance of having a high index of suspicion in order to obtain a diagnosis, to determine the extent of disease, and to achieve adequate resection before reconstruction. Close clinical observation is recommended due to the possibility of future recurrences. Conclusions. Between the confusing nomenclature, indolent course, and inadequacy of superficial biopsy to achieve an accurate diagnosis, MAC is a clinical entity that the plastic surgeon must be aware of in order to facilitate proper diagnosis and treatment.

Microcystic adnexal carcinoma (MAC) is a rare infiltrative cutaneous tumor with a confusing historical nomenclature including malignant syringoma, sweat gland carcinoma with syringomatous features, and sclerosing sweat duct carcinoma.^1,2 This tumor frequently manifests as a slow-growing, flesh-colored, yellow or erythematous plaque or papule with or without overlying telangiectasias. White and/or middle-aged or older adults are generally affected, and the risk factors are poorly defined. The vast majority of MACs occur on the head and neck,³ but can be found elsewhere on the body⁴ such as the axilla, buttocks, and scalp,⁵ as well as on the breast in rare cases. The tumor is a locally aggressive neoplasm that leads to high rates of recurrence with both Mohs and conventional surgical excision, with rates from 0% to 47%.^6,7 However, systemic metastasis or death from a MAC is extremely rare.

To complicate matters, MACs are frequently misdiagnosed based on superficial biopsy alone. The initial descriptions of this neoplasm were regarded as other types of skin appendageal tumors or as adenocarcinomas of eccrine sweat glands,^8,9 and its prevalence may be more than reported due to underrecognition.¹⁰ Treatment requires complete surgical excision; Mohs micrographic surgery is recommended to achieve clear margins but is not assured in recurrent neoplasms.^3,9

Between the confusing nomenclature, indolent course, and inadequacy of superficial biopsy to achieve an accurate diagnosis, a MAC is a clinical entity that the plastic surgeon must be aware of in order to facilitate proper diagnosis and treatment.¹ Here, the authors present a unique case of a MAC of the nipple.

A 15-year-old girl presented to a breast surgeon for a 3-year history of worsening right breast pain, increasing nipple size, and discharge. On examination, the nipple was 2 cm in diameter and firm with crusting extending to the areola (Figure 1). No other palpable breast masses or axillary lymph nodes were present on physical examination. Ultrasound was unremarkable and punch biopsy revealed findings suggestive of squamous metaplasia of the lactiferous duct (Figure 2). Given the impact on quality of life and the need for reconstruction after excision, she was referred to plastic surgery.

Initially, the entire nipple-areolar complex was excised but pathology revealed MAC extending to the peripheral and deep margins; a breast pathologist and dermatopathologist confirmed the diagnosis. In order to achieve local control, the patient underwent right skin-sparing mastectomy with immediate placement of a tissue expander. Although sentinel node investigation demonstrated no tumor, pathology revealed extensive perineural invasion (Figure 3) and a positive margin. Due to these factors in addition to the patient’s desire to avoid further surgery, radiation was recommended.

Prior to initiation of radiation, the patient underwent tissue expansion; right silicone implant placement followed at the conclusion of radiation treatment. Four months later, the patient presented to clinic for follow-up with a new area of concern on her left areola, similar to the inciting lesion on the right. Due to her history of MAC in the right breast, the patient elected to undergo a left simple mastectomy with immediate reconstruction with a silicone implant. Pathology revealed focal nonspecific periductal inflammation with no tumor. Seventeen months after surgery, she had no tumor recurrence with an acceptable cosmetic outcome (Figure 4).

She subsequently underwent bilateral nipple areola reconstruction 6 months after the second mastectomy and is followed by plastic surgery and breast oncology.

Plastic surgeons should have a low threshold to biopsy any nonhealing lesion of the breast, even in a young healthy patient. Often times, the plastic surgeon may be the only physician seeing the patient; therefore, a thorough physical exam and knowledge base is imperative in accurate diagnosis and treatment.

Microcystic adnexal carcinoma is a rare, locally aggressive tumor that has been reported to metastasize.² The recurrence rate is nearly 50%, mostly due to inadequate margins. A MAC is most commonly located on the head, but also can be found on the neck, lower extremity, trunk, axilla, and breast on rare occasions.¹ Due to its slow growth, tumors lasting for decades have been reported.^11-13

After a search of the literature, only 1 case of MAC has been reported in the nipple.¹⁴ Several cases of infiltrating syringomatous adenoma of the nipple have been reported,which has been regarded by some authors¹⁵ to be the same entity as MAC. Although they share similar characteristics of numerous keratinized cysts, infiltrating syringomatous adenoma has “small, compressed, duct-like structures surrounded by a fibrotic stromal reaction,” which differentiates them from key histological features of MAC.¹⁶ Immunohistological markers help to differentiate MACs from other tumor types, such as syringomas, desmoplastic trichoepitheliomas, trichoadenomas, and unusual basal cell carcinomas.⁸

Clinically, MAC presents as a slowing-growing, flesh-colored, yellow or erythematous plaque and can be associated with hyperkeratosis.² Histological features of MAC vary at different depths of the tumor. Superficially, there are numerous keratinized cysts of varying sizes, with the deeper component containing smaller nests and strands of cells in a dense, hyalinized stroma. This deeper component also demonstrates a highly infiltrative growth pattern and, often, perineural invasion, which are the key features that help to distinguish this from other similar entities, including syringoma.² Because it is the deeper component that contains the characteristic features of MAC, superficial biopsies can often lead to misdiagnosis, which occurred in the case presented herein.

Treatment of MAC largely consists of wide local excision, sometimes requiring Mohs surgery to achieve clear margins. Data are insufficient to support routine radiation therapy in patients with MAC. Baxi et al¹⁷ recommended surgical excision with radiation therapy could yield success rates similar to those observed with Mohs surgery. Postoperative radiation with a total dose of 60 Gy to 66 Gy should be considered in patients treated with wide local excision alone, perineural invasion demonstrated on histology, or positive surgical margins in patients who do not desire further surgery.¹⁸ All 3 of these features were found in the present patient, supporting the decision to use radiation as an adjunct. As there are no randomized clinical trials for specific radiation doses in MACs, radiation was dosed as if she had a standard breast cancer with a dose of 50 Gy to the breast and a 16 Gy boost to the area of scar, with a total of 66 Gy.

Microcystic adnexal carcinoma is a rare disease, but with its locally aggressive nature and rare metastatic potential, it is an important clinical entity to consider when faced with a nipple lesion. This case demonstrates the importance of having a high index of suspicion in order to obtain a diagnosis, to determine the extent of disease, and to achieve adequate resection before reconstruction. Close clinical observation is recommended due to the possibility of future recurrences.

Affiliations: Division of Plastic Surgery, Department of Surgery, University of Kentucky College of Medicine, Lexington, KY; and Division of Plastic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN

Correspondence: Lesley K. Wong, MD, Division of Plastic Surgery, Department of Surgery, University of Kentucky College of Medicine, 740 South Limestone, Lexington, KY 40536-0284; lesley.wong@uky.edu

Disclosure: The authors disclose no financial or other conflicts of interest.