Primary Apocrine Adenocarcinoma of the Axilla
Primary apocrine adenocarcinoma (AA) is a rare malignant cutaneous neoplasm that typically arises in areas of high apocrine gland density such as the axillae and the anogenital region. Due to the nonspecific clinical manifestation of AA, the differential diagnosis may be broad. The rarity of this neoplasm has led to a relative lack of well-established histologic and immunohistochemical diagnostic criteria, further complicating the diagnosis of AA. We report the case of a 49-year-old man with primary AA of the left axilla and provide a review of the clinical and histologic findings, epidemiology, and treatment modalities of this rare cutaneous neoplasm.
Practice Points
- Primary apocrine adenocarcinoma (AA) is a rare cutaneous malignancy with metastatic potential.
It arises in areas of high apocrine gland density including the axillae and anogenital region. - Apocrine adenocarcinoma must be differentiated from various infections and cutaneous metastases from internal malignancies.
- Primary apocrine differentiation with invasion to adjacent tissue is a key histopathologic feature of AA.
Various stains may be used in immunohistochemical analysis to aid in the diagnosis of AA.1,5 Cytokeratin AE1/AE3, CAM5.2, epithelial membrane antigen, smooth muscle antigen, periodic acid–Schiff positivity with diastase resistance, and GCDFP-15 are useful in supporting the diagnosis of AA.2,6,10,17 Cytokeratin AE1/AE3 and CAM5.2 stain various cytokeratins to confirm the epithelial origin of the tissue.2 Epithelial membrane antigen is an antigen present on the apical surface of glandular epithelial cells that also has been used to identify epithelial cells in AA.2 Additionally, smooth muscle actin may be used to detect the myoepithelial layer of cells surrounding the apocrine glands.17 The lack of a continuous layer surrounding the secretory cells suggests invasion into the adjacent tissue.1,9,17 Periodic acid–Schiff staining with diastase resistance can be used to identify the mucin stored in the intracytoplasmic granules of apocrine cells and the lumen.3 Some stains such as GCDFP-15 may highlight cells of multiple origins (eg, apocrine and eccrine).10 However, there is the possibility that poorly differentiated AAs would fail to be identified as such even with well-established apocrine markers, which may explain the differential GCDFP-15 staining patterns in our patient’s skin and lymph node sections.1,5 Therefore, there is not a single perfect set of immunohistological criteria to aid in the diagnosis of AA.6,10,12 Fundamentally, diagnosis requires detection of primary apocrine differentiation with features such as invasion or spread to adjacent tissue to suggest malignancy and rule out an alternate primary malignant process.1,2,9,10,17
Treatment and Prognosis
Primary treatment of AA consists of wide local excision with adjuvant options that include chemotherapy and radiation.2,6 Due to the high rate of lymph node metastases at presentation (40%–50%), SLNB is recommended. A positive SLNB should be followed with complete axillary lymphadenectomy4,6; however, there is a lack of consensus regarding the role of SLNB and lymph node dissection in detecting subclinical lymph node disease, which might improve local recurrence rate and prognosis.6 Similarly, research shows variable results with adjunctive treatment such as chemotherapy or radiation therapy.6,9,13 Adjuvant treatment with chemotherapy or radiation therapy should be considered in cases with large tumor size; perineural, lymphatic, or vascular invasion; or when complete removal of the tumor is not possible due to location or size.2,6 However, neither the role nor the efficacy of such treatments in AA is well established.6,9,13
There is little information in the literature regarding the prognosis of AA. Although no specific or well-documented prognostic criteria exist, it is generally believed that patients with well-differentiated AA will have higher cure rates or lower rates of local recurrence and lymph node metastasis than patients with poorly differentiated neoplasms.3,6,10 A few small case series with long-term follow-up of patients ranging from 2 to 10 years have shown that prognosis may be favorable for AA patients despite local recurrence and regional lymph node metastasis.1,5
Conclusion
Primary AA is a rare cutaneous neoplasm that most commonly occurs in the axillae and the anogenital region. Apocrine adenocarcinoma presents with highly variable clinical and histopathological findings that make diagnosis a challenge. Clinicians should keep this entity in their differential diagnosis for patients who present with nodules arising in apocrine gland–bearing skin. Ultimately, histopathology is critical to diagnosis, and special stains are often required. To make the diagnosis, a tissue biopsy demonstrating apocrine differentiation and anaplastic features to suggest a malignant process are required. Additionally, a careful workup to rule out other diagnoses should be performed. Testing modalities that detect the presence of useful markers such as apocrine or epithelial origin should be used, and the presence of positive findings should support the diagnosis of AA. However, immunohistochemical findings should be used in the context of the patient’s clinical presentation and other available data. Treatment includes wide local excision, and lymphadenectomy is recommended in the setting of nodal spread. For aggressive tumors or metastases, excision may be followed by radiation therapy and chemotherapy.
