Primary Apocrine Adenocarcinoma of the Axilla

Figure 2. A lesional punch biopsy revealed normal apocrine glands adjacent to poorly differentiated glandular and cordlike structures (A)(H&E, original magnification ×10). The neoplastic cells were cuboidal to angulated in appearance with prominent nuclei and abundant cytoplasm demonstrating poorly differentiated apocrine glands (B)(H&E, original magnification ×40).

Immunohistochemically, tumor cells reacted strongly to cytokeratin AE1/AE3 and CAM5.², stains used to identify various cytokeratins present in epithelial tissue. Staining for epithelial membrane antigen and carcinoembryonic antigen revealed focal glandular differentiation, which further supported the epithelial origin of the neoplastic cells. Gross cystic disease fluid protein 15 (GCDFP-15) is a marker of apocrine differentiation and may indicate a carcinoma of apocrine or eccrine origin. In our case, staining for GCDFP-15 was negative in the cutaneous sections but highlighted tumor cells in 6 of 13 ipsilateral lymph nodes from locoregional metastasis. The cellular and structural morphology, immunohistochemistry, and absence of an alternative primary visceral malignancy supported the diagnosis of primary AA.

Initially the patient was not considered to be a candidate for surgery due to the rapid growth of the tumor with metastases, fatigue, weight loss, and pain. Therefore, radiation therapy was started. The patient responded well to treatment with controlled pain and resolution of the palpable mass of the left axilla. Moreover, a follow-up PET scan revealed no residual tumor and persistent, albeit decreased, axillary lymphadenopathy. As the patient’s clinical status had improved, excision of the left axillary tumor with lymph node dissection was performed 10 months after initial presentation.

In this case, the differential diagnosis consisted of various cutaneous neoplasms, primary mammary carcinoma, cutaneous metastasis, and infection. Diagnostic imaging and laboratory testing failed to identify any primary internal malignancies. Similarly, the negative cultures ruled out an infectious process. Furthermore, the axillary mass was noted to be separate from the breast tissue on physical examination and mammography. Histologically, the tumor showed features that were suggestive of an anaplastic process as well as decapitation secretion and glandular formation that clearly resembled apocrine differentiation.

Comment

Apocrine adenocarcinoma arises from apocrine sweat glands and therefore is mostly reported in areas of high apocrine gland density such as the axillae and the anogenital region.^2,4,6 However, AA also has been reported in unusual locations,^1,5,10,14-16 and they may arise from a pre-existing nevus sebaceous or from supernumerary nipples, which can occur anywhere along the milk lines.^4,15 Apocrine adenocarcinoma most commonly arises in individuals aged 40 to 50 years.^3,17 A slight male predominance has been reported but no racial predilection.^1,4-6 Although a few reports have described the development of AAs within pre-existing benign tumors such as apocrine adenomas, apocrine hyperplasias, cylindromas, and nevi sebaceous, they usually are thought to arise de novo.^4-6

Clinical Presentation

Apocrine adenocarcinoma is highly variable in its clinical manifestation.^1,6 Most cases arise as erythematous to violaceous, firm, solitary nodules. Nonetheless, AA also can present as erythematous patches of skin resembling erysipelas and ulcerated nodules with overlying granulation tissue and purulent exudate.^4,6,9,11 Although AA typically is slow growing and indolent, the time frame reported from onset to diagnosis ranges from weeks to decades.^1,6,7 Most cases present asymptomatically; when symptoms do occur, the most common ones are tenderness, purulent discharge, and restricted range of motion from extremely large tumors.^3,9 Incidence of lymph node metastasis is reported at 40% to 50% at the time of presentation.^4,6 Additionally, AA has a high rate of local recurrence, but extranodal metastasis rarely is seen.^2,6 When metastasis does occur, it is via lymphatic and hematogenous spread.^6,9 Metastatic dissemination of AA may occur in the liver, lungs, bone, brain, and parotid glands, as well as the skin via intraepidermal pagetoid spread.^4,6,9,13

Histopathology

The histologic characteristics essential to the diagnosis of primary AA are anaplastic differentiation and apocrine origin.^1,2,9,10,17 Apocrine units include coiled secretory glands that reside in the deep dermis connecting to a straight duct that empties into the isthmus of the hair follicle.^9,13 These secretory glands have a single row of cuboidal secretory cells lining the tubular component and stratified squamous epithelium lining the straight intradermal component that opens onto the hair follicle.⁹ Contractile myoepithelial cells surround the secretory cell layer of the gland.^9,13

The cuboidal secretory cells of the apocrine gland have abundant eosinophilic cytoplasm^1,4,9 and are further characterized by glandular arrangement and decapitation secretion, 2 features that are strongly suggestive of apocrine differentiation.^4-6 In contrast, the tumor cells of AA can be characterized by hyperchromatic nuclei, nuclear pleomorphism, mitotic figures, and a lack of decapitation secretion.^1,2,6 In malignancy, erratic or poorly differentiated ductal structures may be seen,^1,3-6 including papillary, cordlike, solid, or complex glandular patterns that can potentially invade the adjacent tissue without a clearly recognizable myoepithelial layer that contains them.^1,3,4,6 Moreover, AA may progress with lymphatic, vascular, or neural invasion.^1,13