In this report, we present a case of a BNET arising in the axilla of a man. Male accessory breast cancer in the axilla is rare, but BNETs like this case are even rarer. Although the tumor is relatively small (15 mm in size), it already has had the axillary lymph nodes metastasis. Therefore, systemic treatment is considered necessary, but because the disease is rare, the diagnosis and treatment plan is interesting but confusing.
Male breast cancer is comprising approximately 1% of all breast cancer cases [5]. It is often detected as an accessory breast cancer, which usually presents as an axillary tumor [6, 7]. The accessory breast cancer must be pathologically proven to be a solitary lesion adjacent to a normal breast duct or lobule. Additionally, the possibility of metastatic disease from another primary cancer must be excluded [8].
During the diagnosis of our case, it was difficult to differentiate the cutaneous adnexal tumor or metastatic lesion from another primary cancer. Histopathological and immunohistochemistry (IHC) findings revealed features of endocrine mucin-producing sweat gland carcinoma (EMPSGC) that were compatible with the tumor in this case. However, the possibility of EMPSGC was excluded because these tumors are usually found in the head and neck, and they are commonly observed on the eyelids of older women [9]. To rule out a metastatic lesion from another primary cancer, imaging studies, including CT, ultrasonography, and FDG-PET/CT, were performed and revealed no evidence of primary malignancy. However, NETs, especially low-grade NETs, often do not have FDG accumulation, and the use of OctreoScan is recommended to exclude primary NETs at other sites [10]. The pathological examination showed no evidence of normal breast ducts or lobules around the primary lesion; therefore, an examination to determine the presence of NETs at other sites using OctreoScan was considered. However, the immunohistochemical features of the tumor (positive for ER, PR, and GATA3) suggested that this tumor was derived from the mammary gland. Therefore, we diagnosed this axillary tumor as a BNET.
Neuroendocrine neoplasms (NENs) arise from neuroendocrine cells and can occur anywhere in the body. The most common sites include the gut, lungs, and bronchi; however, the soft tissue is an uncommon site [4] and is classified as NETs and neuroendocrine carcinomas (NECs) according to the latest World Health Organization (WHO) edition published in 2019 [11]. Dholaria et al. [12] reported a case of NEC in the axilla of a man. IHC of this tumor showed positive Syp, and negative for CK7 and CK20, with a high Ki-67 index (80%). Therefore, he was diagnosed with NEC and axillary metastasis from an unknown primary or de novo [12].
Primary breast NEN (BNEN) is rare, accounting for less than 1% of all NENs, and its definition is confusing [13]. A BNEN is classified breast NEC (BNEC) and BNET by the most recent WHO classification [11]. BNEC is reported to be small cell type and morphologically similar to NEC of other organs [14]. According to the current WHO classification, BNET is considered a mixed neuroendocrine and non-neuroendocrine breast neoplasms with a non-neuroendocrine component of less than 10% [11]. BNEN has a higher expression of ER and PR than other breast cancers and is usually categorized as a luminal A or luminal B HRE2-negative breast cancer [15, 16]. NETs affecting other organs are classified as G1, G2, or G3 based on the mitotic count, Ki-67 proliferation index, and presence of necrosis, whereas BNETs are classified in the same way as nonspecific types of breast cancer [17]. BNETs typically have IHC markers such as CK7, ER, PR, and GATA3 [18]. Our tumor was positive for CAM 5.2, Syp, ER, PR, and GATA3, and it was negative for HER2, with a Ki-67 index of 21%; therefore, we believe that it was a BNET in the luminal A breast carcinoma category.
There are no specific guidelines for the treatment of BNENs; therefore, they are managed with conventional breast cancer treatment. Endocrine therapy has proven effective as an adjuvant therapy for some cases of hormone receptor-positive BNENs, and chemotherapy is widely used for patients at high risk for recurrence [19, 20]. In our case, we diagnosed BNET with three axillary lymph node metastases in a man. The Ki-67 index was 21%, which is equivalent to G3 NET of other organs. The need for postoperative adjuvant treatment is controversial; however, as mentioned, the use of the same treatment used for conventional breast cancer is recommended. Therefore, we administered TC chemotherapy, endocrine therapy, and radiotherapy after surgery.