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Year : 2015  |  Volume : 5  |  Issue : 4  |  Page : 224-227

Primary neuroendocrine carcinoma of the breast: A case report and review of literature

Department of Plastic and Reconstructive Surgery, Thanjavur Medical College, Thanjavur, Tamil Nadu, India

Date of Web Publication21-Jan-2016

Correspondence Address:
Dr. Gopalakrishnan Ravikumar
54-Shanthi Nagar, Thanjavur - 613 006, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-9596.174676

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Neuroendocrine tumors of the breast are rare, accounting for less than 0.1% of all breast cancer and less than 1% of all neuroendocrine (NE) tumors. The papillary NE carcinoma of the breast (NECB) with classic morphological and phenotypic features is rare. We describe a case of a 45-year-old woman admitted with a lump in the left breast, initially diagnosed by fine-needle aspiration cytology (FNAC) as intraductal carcinoma. After undergoing modified radical mastectomy, the histopathology showed evidence of alveolar-type primary NECB. A 16-month follow-up of the patient showed no evidence of metastasis. The in situ component of primary NECB may prevail in a core biopsy sample increasing the probability of underdiagnosing this tumor preoperatively. Misdiagnosing primary NECB is detrimental because patients may not receive the optimal adjuvant treatment they need.

Keywords: Breast neoplasm, chromogranin A, neuroendocrine tumor (NE), synaptophysin

How to cite this article:
Ravikumar G, Naveen Prasad GR, Sugapradha GR, Sivakami T. Primary neuroendocrine carcinoma of the breast: A case report and review of literature. Arch Int Surg 2015;5:224-7

How to cite this URL:
Ravikumar G, Naveen Prasad GR, Sugapradha GR, Sivakami T. Primary neuroendocrine carcinoma of the breast: A case report and review of literature. Arch Int Surg [serial online] 2015 [cited 2023 May 30];5:224-7. Available from:

  Introduction Top

Neuroendocrine tumors are rare and slow-growing derived from neuroendocrine (NE) cells, which are present throughout the body; they arise most commonly in the bronchopulmonary system and gastrointestinal tract. Neuroendocrine tumors of the breast are rare, accounting for less than 0.1% [1] of all breast cancer and less than 1% of all NE tumors. [2],[3] Focal NE differentiation can be found in different histological types of breast carcinoma including in situ and invasive ductal, lobular, colloid, or papillary breast cancer. However, the term "neuroendocrine carcinoma" is applied when more than 50% of the tumors show such differentiation. [4]

  Case Report Top

A 45-year-old female patient admitted with a lump in the left breast of 6 months duration. It started as a small swelling in the upper outer quadrant and gradually increased in size. There was a recent rapid increase in size for the past 1 month. There was no history of trauma or pain. There was no discharge from the nipple or previous swelling in the breasts. There was no history of any drug intake. Patient attained menarche at the age of 13. She had regular menstrual flow of 3/30 cycle. She attained menopause at the age of 42. There was no history of pelvic surgery.

The patient was married, with two children; she delivered her first baby at the age of 20. Both the children were breast-fed till the age of 1. No other member in the family suffered from a similar illness. The patient had not received any treatment for the present illness.

Her vital parameters were normal. Local examination of left breast revealed a hard lump of 4 cm × 2 cm in the upper outer quadrant. Skin and deep muscles were free from the tumor. The lump did not have any independent mobility. The nipple and areola were normal in size and position. Three discrete firm, mobile, nontender lymph nodes of 2 cm × 1 cm in the central axillary group were palpable. Examination of the right breast and axilla were normal. Examination of the chest and abdomen were normal. There was no tenderness in the spine and cranium. Rectal and vaginal examination revealed no clinical deposits in the rectovaginal pouch.

Mammography revealed a distinctive mass with microscopic calcifications. Ultrasonogram of the breast showed a solid mass in the upper quadrant. Fine-needle aspiration cytology (FNAC) revealed intraductal carcinoma. Staging workup, which included a chest computed tomography (CT) and a liver ultrasound, was negative for metastatic disease. A clinical diagnosis of cancer of the left breast T2 N1 M0 was made. Modified radical mastectomy of the left breast was done [Figure 1]. The postoperative period was uneventful.
Figure 1: Mastectomy with adequate clearance

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Histopathological Report

Gross examination showed a 4 cm × 3 cm × 2 cm hard, gray-to-white lobulated mass [Figure 2]. Most of the tumors (>50%) were composed of solid tumor nests separated by delicate fibrovascular stroma. The tumor cells were fairly uniform and small in size. They were arranged in solid nests or trabecular fashion [Figure 3]. Glandular spaces were seen in their midst. Vascular invasion was not seen. The tumor cells had finely granular nuclear chromatin with uniform and vesicular nuclei and relatively eosinophilic cytoplasm. Margins were free from infiltration.
Figure 2: Gray-to-white lobulated mass

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Figure 3: Tumor cells arranged in solid nests, glandular spaces in the midst, no vascular invasion

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Immunohistochemistry (IHC) with NE markers was performed. Cancer cells stained positive for both synaptophysin and chromogranin A (individual reactivity rate of 100%) [Figure 4]. Cancer cells were positive for estrogen receptors (ERs) (reactivity rate of 90%) and negative for progesterone receptors (PR) and HER2.
Figure 4: Cancer cells stained positive for synaptophysin

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The examination of 10 left axillary lymph nodes showed reactive hyperplasia and there was no evidence of secondary deposits.

The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatin.

A 16-month follow-up of the patient showed no evidence of metastasis.

  Discussion Top

Although NE tumors may arise anywhere in the body producing well-defined clinical outcomes, primary NE tumors of the breast are rare. They occur in older women and are often positive for ER. [4],[5]

It was only until 2002 when Sapino et al. first suggested a specific definition for NE carcinoma of the breast (NECB), [6] which was subsequently adopted by the World Health Organization (WHO) in 2003 as a means of endorsing it as a unique type of breast cancer. [5]

Theories related to NECB: The histogenesis of NECB has not been fully clarified. An initial theory suggested that NECB cancer cells derived from argyrophilic cells of neural crest origin that migrated to the mammary ducts. [4] Another theory supports in situ development from NE cells naturally found in the breast, but these cells have not been consistently found by other authors. A novel hypothesis suggests that NECB results from an early divergent differentiation event in breast carcinogenesis in which neoplastic stem cells differentiate into both epithelial and endocrine lines.

Classification of NECB

In the WHO classification, NE tumors have been defined as those in which one or more NE markers, such as neuro-specific enolase, chromogranin A, and/or synaptophysin, are expressed in at least 50% of cancer cells. In addition to this, diagnosing primary NECB also requires fulfilling two other criteria:

  1. Other primary sites must be ruled out and
  2. The tumor must show histological evidence of a breast in situ component.

In the 2012 revised WHO classification, three categories of NE carcinoma (NEC) are mentioned:

  1. well-differentiated NEC,
  2. Poorly differentiated NEC, and
  3. Invasive breast carcinoma (IBC) with NE differentiation. [7],[8]


Primary NECB is considered an extremely aggressive tumor for which there is no general agreement about a standardized treatment. [9] The best choice seems to be radical mastectomy with axillary dissection followed by chemotherapy. [10] Radiation therapy appears to be used to a lesser extent than chemotherapy. The current recommendation is for patients with primary NECB to receive hormone therapy based on their hormonal receptor status.

  Conclusion Top

Being aware of the existence of this disease may allow for timely diagnosis. Misdiagnosing primary NECB is detrimental because patients may not receive the optimal adjuvant treatment they need.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Wang J, Wei B, Albarracin CT, Hu J, Abraham SC, Wu Y. Invasive neuroendocrine carcinoma of the breast: A population-based study from the surveillance, epidemiology and end results (SEER) database. BMC Cancer 2014;14:147.  Back to cited text no. 1
Ghanem S, Kabaj H, Naciri S, Glaoui M, Ismaili N, Benjaafar N, et al. Primary neuroendocrine carcinoma of the breast: A rare and distinct entity. J Cancer Res Exp Oncol 2011;3:50-4.  Back to cited text no. 2
Singh S, Aggarwal G, Kataria SP, Kalra R, Duhan A, Sen R. Primary neuroendocrine carcinoma of breast. J Cytol 2011;28:91-2.  Back to cited text no. 3
[PUBMED]  Medknow Journal  
Angarita FA, Rodríguez JL, Meek E, Sánchez JO, Tawil M, Torregrosa L. Locally-advanced primary neuroendocrine carcinoma of the breast: Case report and review of the literature. World J Surg Oncol 2013;11:128.  Back to cited text no. 4
Murthy V, Geethamala K, Kumar B, Sudharao M. Primary neuroendocrine carcinoma of breast: A rare case report. Ann Med Health Sci Res 2013;3 (Suppl 1):S35-7.  Back to cited text no. 5
Sapino A, Righi L, Cassoni P, Papotti M, Pietribiasi F, Bussolati G. Expression of the neuroendocrine phenotype in carcinomas of the breast. Semin Diagn Pathol 2000; 17:127-37.  Back to cited text no. 6
Annaratone L, Medico E, Rangel N, Castellano I, Marchiò C, Sapino A, et al. Search for neuro-endocrine markers (Chromogranin A, Synaptophysin and VGF) in breast cancers an integrated approach using immunohistochemistry and gene expression profilling. Endocr Pathol 2014;25:219-28.  Back to cited text no. 7
Tajima S, Horiuchi H. Neuroendocrine tumour, well differentiated, of the breast: A relatively high-grade case in the histological subtype. Case Rep Pathol 2013;2013:204065.  Back to cited text no. 8
Nicoletti S, Papi M, Drudi F, Fantini M, Canuti D, Tamburini E, et al. Small cell neuroendocrine tumour of the breast in a 40 year-old woman: A case report. J Med Case Rep 2010;4:201.  Back to cited text no. 9
Kinoshita S, Hirano A, Komine K, Kobayashi S, Kyoda S, Takeyama H, et al. Primary small-cell neuroendocrine carcinoma of the breast: Report of a case. Surg Today 2008;38:734-8.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

This article has been cited by
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