Discussion:
The primary invasive breast carcinoma with neuroendocrine differentiation is a very rare type of breast tumor. Most commonly the neuroendocrine tumors are found in the gastrointestinal tract, pancreas, and bronchopulmonary system but rarely found in the breast (6). These tumors do not form the specific histopathological category of breast carcinoma but there are groups of breast carcinoma like ductal, lobular carcinoma, mucinous, and solid papillary carcinomas which can produce ectopic hormonal substances (7). There are three categories of neuroendocrine breast tumors as mentioned by the WHO in their 4th revised edition.
There is no specific radiological or clinical sign to diagnose the neuroendocrine tumor. Histopathological examination is the only means of making a definitive diagnosis. Grossly, the tumor is usually yellowish-colored with a firm consistency and multilobulated. (8) In this case, we found the tumor to be a gray-white lobulated structure. Histologically, the tumor usually shows similar features as neuroendocrine tumors of the gastrointestinal tract with nuclear palisading, cellular monotony, loss of cell cohesion, pesudorossete formation, and abundant eosinophilic cytoplasm and nuclei with stippled chromatin(9). Since the microscopic features are inconsistently present, IHC markers like chromatin A or B, synaptophysin, neurospecific enolase (NSE), CD-56, Ki-67, Leu 7(CD-57), INSM-1 are necessary for the diagnosis [12]. INSM and CD-56 were focally positive, and Ki-67 is around 40% with nuclear positivity.
This tumor should be differentiated from metastatic neuroendocrine tumors from extramammary sites. They may show features similar to the other primary tumors of the breast like lobular carcinoma and invasive ductal carcinoma in situ (2). Some markers like CK-7 and caudal-type homeobox-2(CD X-2) are useful to differentiate from GI neuroendocrine tumors. Usually, the neuroendocrine breast tumors are positive for CK-7 and negative for CDX-2 whereas in gastrointestinal neuroendocrine tumors CK-7 is negative and CDX-2 is positive (10).
Invasive breast carcinoma with neuroendocrine features is treated like other invasive carcinoma breast carcinomas. The primary treatment option is surgery depending upon the stage and location of the tumor. (1) The combination of mastectomy, axillary lymph node dissection, and metastasectomy is generally performed for surgical treatment. Like other breast carcinomas, they are treated by chemotherapy and radiotherapy. Immunohistochemistry helps to determine the type of adjuvant therapy (8).
Prognosis in the patient with breast carcinoma with neuroendocrine features generally depends upon the factors like age of the patient, axillary lymph node involvement, clinical-stage, hormonal receptors. (11) Neuroendocrine differentiation was said to be an independent adverse prognostic factor according to the multivariant analysis based on (Surveillance, Epidemiology, and End Results Program) SEER database. (5) In a retrospective comparative study by Zang et al., the breast carcinoma with neuroendocrine features showed a poorer survival rate, lower recurrence-free survival rate, and a high rate of distant metastasis. (12) Some literature reported that these tumors have a similar prognosis with invasive breast carcinoma when the clinical stage and grade of the tumors are compared. (13, 14)