Journal of Cytology
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Year : 2011  |  Volume : 28  |  Issue : 2  |  Page : 91-92
Primary neuroendocrine carcinoma of breast


Department of Pathology, Pt. B.D. Sharma, PGIMS, Rohtak, Haryana, India

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Date of Web Publication12-May-2011
 

How to cite this article:
Singh S, Aggarwal G, Kataria SP, Kalra R, Duhan A, Sen R. Primary neuroendocrine carcinoma of breast. J Cytol 2011;28:91-2

How to cite this URL:
Singh S, Aggarwal G, Kataria SP, Kalra R, Duhan A, Sen R. Primary neuroendocrine carcinoma of breast. J Cytol [serial online] 2011 [cited 2018 Sep 21];28:91-2. Available from: http://www.jcytol.org/text.asp?2011/28/2/91/80755


Sir,

Neuroendocrine tumors are rare, slow-growing tumors derived from neuroendocrine 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% of all breast cancer and less than 1% of all neuroendocrine tumors. [1] Focal neuroendocrine 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 tumor shows such differentiation. The papillary neuroendocrine carcinoma of breast with classic morphological and phenotypic features is rare. We report a case of primary neuroendocrine breast carcinoma that was diagnosed preoperatively by fine needle aspiration cytology (FNAC) and subsequently confirmed by histology and immunohistochemistry. Only about 30 cases of primary neuroendocrine carcinoma of breast have been reported in the literature. [2]

A 60-year-old woman, a known case of ischemic heart disease presented with bloody discharge from nipple in surgery outpatients department (OPD). There was no palpable lump. Ultrasonography (USG) showed dilated ducts in right breast. Mammography was suggestive of ductal malignancy. Patient was referred for stereotactic FNAC. FNA smears stained with May-Grünwald-Giemsa (MGG) showed moderate cellularity. The dyscohesive cells were arranged in acinar structures and loose clusters with many dissociated cells. The cells were moderately pleomorphic, polygonal and plasmacytoid with abundant cytoplasm containing fine to coarse azurophilic granules particularly evident at cell borders and poles [Figure 1], occasional cells with prominent nucleoli were also seen. There were no areas of necrosis or mucoid degeneration. Mitotic figures were also not evident. Based on cytomorphology, a diagnosis of neuroendocrine carcinoma of breast was suggested and mastectomy was performed.
Figure 1: Moderately pleomorphic, polygonal and plasmacytoid cells with abundant cytoplasm containing fine to coarse azurophilic granules, particularly at cell borders and poles(MGG, ×400)

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Grossly, tumor measured 1.2 cm in diameter with well-defined lobulated margins and grey white homogenous cut surface. Light microscopy revealed a tumor predominantly (more than 50%) composed of solid nests and trabeculae without tubule formation and focal rosette-like structures. The tumor cells ranged from oval to spindle and plasmacytoid, separated by delicate fibrous stroma. They had mildly pleomorphic nuclei with fine pepper chromatin [Figure 2]. The cytoplasm was eosinophilic and had fine granules. Immunohisto-chemistry revealed positive staining for cytokeratin (CK), estrogen receptor (ER), progesterone receptor (PR) non-specific esterase(NSE), chromogranin and synaptophysin [Figure 3]. The case was signed out as neuroendocrine carcinoma. Thorough examination and investigations including computed tomography (CT) scan and magnetic resonance imaging (MRI) did not disclose any primary tumor. A final diagnosis of primary neuroendocrine carcinoma of the breast was made.
Figure 2: Tumor composed of solid nests and trabeculae without tubule formation(H and E, ×100)

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Figure 3: Tumor cells positive for synaptophysin (a) and chromogranin (b) (IHC, ×400)

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Although neuroendocrine tumors may arise anywhere in the body producing well-defined clinical outcomes, primary neuroendocrine tumors of the breast are rare. They occur in older women and are often positive for estrogen receptor. [3] Clinically, there are no notable or specific differences in presentation from other type of breast tumors. [4] Strict histological criteria have been defined for the diagnosis of the primary neuroendocrine carcinoma of the breast that includes demonstration of in situ component histologically and/or absence of non-mammary site clinically. Three histological characteristics that suggest endocrine differentiation in a breast carcinoma include low nuclear grade, palisading of nuclei at the periphery of tumor islands and dense sparsely cellular collagenous stroma surrounding it. [5] Sapino et al., [6] in one of the largest series of these tumors have described five subtypes; solid cohesive, alveolar, small cell, solid papillary and cellular mucinous. In our case, the predominant pattern was solid, but at places, alveolar arrangement was also identified.

Cytomorphology of neuroendocrine tumors consists of hypercellular smears with monotonous population of round to polyhedral cells, both singly and in clusters, with delicate cyanophillic cytoplasm within a relatively clean background. These cells have high nucleo-cytoplasmic ratio, round to ovoid nuclei with granular chromatin and small nucleoli. There is little variation in size and shape from cell to cell yielding a uniform homogenous smear pattern. [7] In FNA smears the most important feature to recognize in these tumors is the presence of cytoplasmic granules. These granules are particularly evident in Romanowasky-stained smears and are located at the apex of the plasmacytoid cells. Many theories have been proposed regarding the histogenesis of these tumors. It is likely that neuroendocrine mammary carcinomas derive from progressive neuroendocrine differentiation are subset of cancerous cells rather than pre-existent endocrine cells. [6]

As of now, the treatment modalities are not different from those for the other conventional types and prognostic significance also cannot be commented upon due to only a small number of cases being reported till date. However, chromogranin production in neuroendocrine breast carcinoma has clinical and genetic implications owing to the biochemical analogy between granin and breast cancer (BRCA) protein. Hence, therapy targeted against these genetic markers may be a future treatment strategy.

 
   References Top

1.Ogawa H, Nishio A, Satake H, Naganawa S, Imai T, Sawaki M, et al. Neuroendocrine tumor in the breast. Radiat Med 2008;26:28-32.  Back to cited text no. 1
    
2.Akhtar K, Zaheer S, Ahmad SS, Hassan MJ. Primary neuroendocrine carcinoma of the breast. Indian J Pathol Microbiol 2009;52:71-3.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.Maluf HM, Koerner FC. Carcinoma of the breast with endocrine differentiation: a review. Virchows Arch 1994;425:449-57.  Back to cited text no. 3
    
4.Ellis IO, Schmitt SJ, Sastre-Garau X. Invasive breast carcinoma. In: Tavassoli FA, Deville P, editors. World Health Organization classification of tumors. Pathology and genetics of the tumors of breast and female genital organs. Lyon: IARC press; 2003. p. 13-59.  Back to cited text no. 4
    
5.Rosen PP. Mammary carcinoma with endocrine features. In: Rosen PP, editor. Rosen's Breast Pathology. 2nd ed. Philadelphia: Lippincott William and Wilkins; 2001. p. 503-8.  Back to cited text no. 5
    
6.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
    
7.Mills AS, Contos MJ, Goel R. The stomach. In: Silverberg SG, editor. Silverberg's principles and practice of surgical pathology and cytopathology. 6th ed. Philadelphia: Churchill Livingstone; 2006. p.1350.  Back to cited text no. 7
    

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Correspondence Address:
Garima Aggarwal
107, Bank Enclave, Laxmi Nagar, Delhi - 110 092
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.80755

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