title: Solid neuroendocrine breast carcinomas: incidence, clinico-pathological features and immunohistochemical profiling.
abstract: Primary pure neuroendocrine breast carcinomas (NEBC) have been considered special features within conventional breast carcinomas until recently. Indeed, the actual incidence of NEBC in BC populations has remained largely unknown due to the lack of unambiguous diagnostic criteria. In 2003, the World Health Organization (WHO) classification of breast tumors definitely established that the immunohistochemical expression of NE markers in more than 50% of the tumor cell population is the unique requisite for NEBC diagnosis. Herein, we sought to determine the incidence, the clinico-pathological features and the immunohistochemical profile of NEBC in a large series of 1368 infiltrating breast tumors collected from 1989 to 2008 in our institution (Dr Josep Trueta University Hospital, Girona, Catalonia). Twelve cases were initially selected to fulfil histopathological patterns compatible with NEBC. Clinical data along with histological and immunohistochemical profiles were collected in all cases. The criterion inclusion was the presence of more than 50% tumor immunoreactivity for one of NE markers including chromogranin, synaptophysin and CD56. Only 7 tumors fully satisfied the NEBC criteria established by the WHO (0.5% prevalence). All the NECB were grade 2 ductal carcinoma infiltrating (DCI) with tumor sizes ranging from 7 to 55 mm. Lymphovascular tumoral emboli was present in 4 cases (57.1% of NEBC) and mucinous features occurred in 2 cases (28.5% of NEBC). Axillary lymph nodes were metastatic in 3 cases (42.8% of NEBC). A positive status for estrogen receptor (ER), progesterone receptor (PR) and synaptophysin was observed in 7 cases (100% of NEBC). None of the NEBC displayed HER2 overexpression. All the patients bearing NECB received hormone therapy and 4 of them underwent radiotherapy and/or chemotherapy. Of note, none of the NEBC patients died from BC-related causes after a median follow-up of 51 months. These findings revealed that: a) Pure solid NEBC do not significantly differ from other breast carcinomas in terms of general clinical features; b) NEBC do not exhibit an aggressive behavior despite the presence of adverse prognostic factors; and c) NEBC immunohistochemical profile mainly corresponds to that of the Luminal A BC subtype. Although it remains to be elucidated whether the good prognosis of NEBC relates to the intrinsic nature of the tumor and/or to a high rate of treatment responses, their immunohistochemical profile strongly suggest that NEBC belong to the Luminal A BC subtype. Forthcoming studies should definitely determine if the clinico-pathological features of NEBC indeed represent an independent good-prognosis subgroup of BC gene signature.
authors.affiliation: Department of Pathology, Dr Josep Trueta University Hospital of Girona, E-17007 Girona, Catalonia, Spain.
authors.forename: Eugeni
authors.initials: E
authors.lastname: López-Bonet
authors.forename: Miguel
authors.initials: M
authors.lastname: Alonso-Ruano
authors.forename: Graciela
authors.initials: G
authors.lastname: Barraza
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Martin
authors.forename: Luis
authors.initials: L
authors.lastname: Bernadó
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D002277:Carcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D002454:Cell Differentiation; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D015994:Incidence; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D011379:Prognosis
chemical_list: D000951:Antigens, Neoplasm