Fine needle aspiration cytology of primary neuroendocrine tumor of the breast and it's differential diagnosis

The neuroendocrine tumors (NETs) originate from the neuroendocrine (NE) cells that produce various types of amines and peptides. NETs of the breast are rare slow-growing tumors and accounts for less than 1% of all NETs and less than 0.1% of all breast cancer. Focal NE differentiation can be associated with different histologic subtypes of breast carcinomas like in situ carcinoma and invasive ductal, lobular, colloid, or papillary carcinoma. Sapino et al proposed the first diagnostic criteria in 2001 according to which the term Neuroendocrine Carcinoma of Breast (NECB) was entitled to those tumors expressing NE markers—Synaptophysin and/or Chromogranin in more than 50% of the tumor. However, in the 2012 World Health Organization (WHO) classification, it was concluded that a 50% threshold for NE marker expression was arbitrary, hence it was removed. Diagnostic requirements for primary NECB includes the histological presence of an in situ component and exclusion of any evidence of metastatic NEC. According to WHO classification 2012, NECs were subdivided into three categories—well-differentiated NET, poorly differentiated NE carcinoma/small cell carcinoma, and invasive breast carcinoma with NE differentiation. However, in a recently proposed consensus statement by the WHO and International Agency for Research on Cancer (IARC), the term “neuroendocrine neoplasm (NEN)” was adopted harmonizing with those of other organ systems to provide a uniform classification framework. NENs encompasses both welldifferentiated NETs corresponding to Grade 1 (carcinoid-like) and Grade 2 (atypical carcinoid-like) tumors (regarded as carcinomas in the breast) and poorly differentiated NECs, represented by small-cell and large-cell carcinoma. A 78-year-old female presented to the Surgery Outpatient Department with the complaint of a left-sided breast lump for 2 months. On examination, a hard, tender, 3 × 3 cm size lump was palpated above the nipple and areola of the left breast. There was no history of nipple discharge or nipple retraction. No history of breast trauma or any other significant family history was elicited. Ultrasound showed a tumor measuring 22 × 18 mm, located in the upper medial quadrant, left breast. The patient was referred for FNAC. FNA smears stained with Giemsa showed moderately cellular smears with a monomorphic population of plasmacytoid cells arranged singly or in a loose cohesive manner. The tumor cells displayed a mild to moderate degree of nuclear anisokaryosis with fine, salt-pepper type chromatin. The tumor cells showed abundant eosinophilic cytoplasm with discrete cell borders with reddish, fine to coarse cytoplasmic granules (Figure 1A,B). Occasional binucleated cells, multinucleated cells, histiocytic giant cells, and stromal fragments were also seen. No evidence of necrosis or mitotic figure was seen. Based on cytomorphology, a differential diagnosis of NE carcinoma of the breast, lobular carcinoma, granular cell tumor, and plasmacytoma (Table 1) was considered and subsequently, a modified radical mastectomy was planned. Grossly, the cut section revealed a grayish white irregular mass measuring 3 cm × 2.5 cm × 2.0 cm in the upper medial quadrant. A total of 11 lymph nodes were isolated. Hematoxylin and Eosin (H&E) stained sections revealed tumor cells arranged as nests, cords, and at places as trabeculae separated by thin fibrous septae. Individual tumor cells were small, monomorphic predominantly plasmacytoid, spindleshaped, with salt and pepper chromatin, and abundant finely granular eosinophilic cytoplasm (Figure 2). The foci of in situ components with