Neuroendocrine Breast Carcinoma
Neuroendocrine breast cancer is a name frequently given to a generic ductal carcinoma (NOS or ‘not otherwise specified’) with a predominant neuroendocrine differentiation. In order to be diagnosed as neuroendocrine carcinoma, at least 50% of tumor cells must test positive for neuroendocrine markers. Other common and historical names for this type of breast cancer include spindle cell endocrine breast carcinoma, carcinoid endocrine breast carcinoma, breast carcinoma with endocrine differentiation, and argyrophilic carcinoma of the breast.
I just want to let you know that I have decided to create a newer version of this page with more up-to-date information on rare breast cancer types, including Neuroendocrine Breast Cancer.
What does neuroendocrine mean?
The ‘endocrine system‘ concerns all aspects of the human biological system associated with the production and regulation of hormones. Hormones typically function as ‘growth-signals‘ for cells, but at other times they may inhibit or simply maintain the function of their target cells. ‘Neuroendocrine‘ refers to those particular cells which release hormones into the circulating blood stream in response to a ‘neural‘ (brain or nervous system) stimulus.
Neuroendocrine breast cancer. therefore describes a tumor in which at least 50% of the malignant cells are, or were, neuro-endocrine cells.
Statistical prevalence of neuroendocrine breast carcinoma
Neuroendocrine breast carcinoma is thought to account for about 5% of all breast cancers. This type of breast malignancy is most common in older women, increasing in frequency with age. Neuroendocrine carcinoma also tends to present as a low-grade, slow-growing cancer, although higher grades of the disease are most likely referred to by different names, such as small-cell carcinoma.
Statistics on neuroendocrine carcinoma tend to be a little vague, as the name is often associated with other common breast carcinomas like papillary carcinoma, micropapillary carcinoma, and mucinous or colloid carcinoma. Neuroendocrine cells are common in these and other cancer variants but not in sufficient quantities for a differentiated identification. There is some speculation that where there is neuroendocrine differentiation in a mucinous breast carcinoma, histological features tend to be more favorable and prognosis is improved. But, little is known about potential advantages of high neuroendocrine involvement in other breast cancers.
One particular strain of neuroendocrine breast carcinoma is referred to as the ‘Apocrine phenotype‘ (with postie androgen receptor status in at least 50% of cells) which is only associated with elderly women. In fact, one of the reasons statistics surrounding neuroendocrine breast cancer are somewhat ambiguous is that, given it’s slow-growing nature its tendency to develop in older women, cause of death is often due to other factors related to ‘old age‘ and not directly linked to the breast cancer.
However, with increased research specifically on differentiated neuroendocrine breast carcinoma the statistical occurrence is bound to decrease. Some studies suggest the actually rate neuroendocrine breast cancer to be less than 2% of all breast carcinomas.
Neuroendocrine tumors in general
Neuroendocrine cells occur occur throughout the body and therefore cancer can occur at many sites. For any endocrine-related carcinoma, there is an increased tendency to metastasize to the lymph nodes, and the liver. Almost all neuroendocrine cancers care considered malignant and treated aggressively, usually with surgical removal. However, neuro-endocrine cancers including neuroendocrine breast cancer, tend to be very slow growing.
Neuroendocrine markers used to differentiate neuroendocrine breast cancer
The use of ‘marker‘ is a kind of diagnostic checklist indicating the positive presence of a variety or cell types, hormones, proteins, and other biological agents. Test results may be obtained through staining of tissue samples, blood-serum levels, and in some cases electron-microscope images. The most definitive markers for positive neuroendocrine carcinoma indicate the presence of chromogranin, synaptophysin, or neuron-specific enolase, occurring in at least 50% of malignant tumor cells. Identification of neuroendocrine markers seems simple enough, but it is actually a highly complex and remarkable bio-chemical study.
Other cytological (microscopic) features of neuroendocrine breast carcinoma
There is considerable variety in the patterns of neuroendocrine breast tumors. Often malignant neuroendocrine cells will cluster in ‘nests‘ separated by strands of fibrous tissue. Neuroendocrine carcinoma may also form into solid sheets or other insular pattern, with peripheral palisading (like a ‘fence‘ of of malignant cells around the tumor margin). Many times a ‘rosette’ formation (small rose-like shape) is reported. Extra cellular mucin is also common (neuroendocrine and mucinous carcinoma can sometimes ‘merge‘).
With the ‘spindle-cell‘ variant of neuroendocrine carcinoma the tumor is primarily composed of spindle cells, with occasional cuboidal (square-block) and gland (clustered) formations. Mitosis (evidence of cell division) tends to be rare in neuroendocrine breast carcinoma. Comedo necrosis (duct ‘plugged‘ with debris) is very uncommon in neuroendocrine carcinoma.
Chromatin often appears in a stippled formation with neuroendocrine breast carcinomas
Malignant nuclei tend to be round and regular to mildly-irregular, and about three times the size of a red blood cell. Malignant cells in neuroendocrine breast cancer tend to be medium to large, sometimes describes as similar in appearance to plasmacytoid cells (which is a kind of red blood cell) Chromatin is often revealed in a kind of ‘stippled‘ formation (as granules or ‘salt and pepper‘ specs on and around the nucleus), and this is in fact highly characteristic of endocrine and neuroendocrine tumors.
Mixed formations versus ‘pleomorphism’ in neuroendocrine carcinoma the breast
Some studies suggest that neuroendocrine breast tumors tend not to demonstrate pleomorphism (cell clusters forming into many different shapes), which may sound a bit contradictory. While there are many different presentations and formations for neuroendocrine breast cancer generally, cell formations within a given tumor will tend to be quite consistent. Neuroendocrine breast cancer is not pleomorphic; it just presents in a wide assortment of consistent patterns.
Neuroendocrine breast cancer is diagnosed histologically
Due to the varied presentations and contexts of neuroendocrine carcinoma, a diagnosis may only be confirmed through histological means. Specifically, by testing for the pretense and frequency of neuroendocrine markers.
Neuroendocrine breast carcinoma no longer associated with other carcinoid cancers
Neuroendocrine breast tumors are sometimes described as having ‘carcinoid-like‘ features, and it is in fact relatively recently that neuroendocrine cancers were made as a separate category from carcinoid tumors. Carcinoid cancers most frequently develop in the gut wall or the appendix, but almost always metastasize to the lymph nodes.
Carcinoid cells are of neuroendocrine origin but derive from very primitive stem cells, so they can evolve into many different forms. The histological patterns of carcinoid tumors are very similar to neuroendocrine tumors, forming into ribbons, glands or rosette-like patterns, various solid and nodular cords, or they may be poorly differentiated or mixed. Like neuroendocrine cancers, carcinoid tumors have a strong positive reaction to neuroendocrine markers such as chromogranin and synaptophysin.
However, neuroendocrine cancer of the breast has a distinct morphology and unique growth characteristics and is no longer treated as a sub-class of carcinoid tumors, though one still finds the term ‘carcinoid tumor of the breast‘ in use.
For further reading, I suggest you visit this page that has a bunch of information on hormone receptor status of breast cancers, and go to this page for an overview of breast cancer treatments.
References
- Lee,Yu-Chen., ChenYao-Li.,Chan, Szu-Erh.,Tseng,Hsin-Shun., Chen,Dar-Ren., Neuroendocrine Carcinoma of the Breast: Case Report and Literature Review. Breast Care 2009;4:324-327.
- Sapino A, Papotti M, Righi L, Cassoni P, Chiusa L, Bussolati G. Clinical significance of neuroendocrine carcinoma of the breast. Ann Oncol. 2001;12 Suppl 2:S115-7.
- Tse GM, Ma TK, Chu WC, Lam WW, Poon CS, Chan WC. Neuroendocrine differentiation in pure type mammary mucinous carcinoma is associated with favorable histologic and immunohistochemical parameters. Mod Pathol. 2004 May;17(5):568-72.
- Sapino A, Bussolati G. Is detection of endocrine cells in breast adenocarcinoma of diagnostic and clinical significance? Histopathology. 2002 Mar;40(3):211-4.
- Rouse, Robert V.(editor) Surgical Pathology Criteria: Stanford School of Medicine. Located at http://surgpathcriteria.stanford.edu. (2006)
- Das, Dilip K.,Sheikh, Zaffar A.,Breast Carcinoma with Neuroendocrine Differentiation: Diagnosis of a Case by Fine Needle Aspiration Cytology and Immunocytochemistry.Acta Cytologica. Volume 48, 2. March-April 2004. p 292.
- Sapino A, Righi L, Cassoni P, Papotti M, Gugliotta P, Bussolati G. Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women. Mod Pathol. 2001 Aug;14(8):768-76.
- Mardi K, Sharma J. Fine needle aspiration cytology of breast carcinoma with neuroendocrine features–a case report with histopathological and immunohistochemical correlation. Indian J Pathol Microbiol. 2007 Jan;50(1):65-8.
- Maluf HM, Koerner FC. Carcinomas of the breast with endocrine differentiation: a review. Virchows Arch 1994;425:449–457.
- Broaddus RR, Herzog CE, Hicks MJ. Neuroendocrine tumors (carcinoid and neuroendocrine carcinoma) presenting at extra-appendiceal sites in childhood and adolescence. Arch Pathol Lab Med. Sep 2003;127(9):1200-3.
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