neuroendocrine tumors are derived from neuroendocrine cells and the most common site is the bronchopulmonary system . theoretically , primary neuroendocrine tumors do not occur in the breast due to the lack of endocrine cells .
although there are many published studies regarding this rare pathological entity , there are a few reports that also include radiology findings . however , most of the published studies of patients with radiology findings are of the small cell type of tumor , and the characteristic imaging features are not described well ( 1 - 7 ) .
we report the imaging findings in a case of primary neuroendocrine tumor ( large cell neuroendocrine carcinoma with atypical carcinoid features ) found in the breast .
a 42-year - old female was presented with a lump in her right breast , which she had been aware of for several weeks . on physical examination ,
an approximately 5-cm , firm , movable lump was palpated in the upper outer subareolar region of her right breast .
mammography revealed a high - density mass with an ill defined margin in the 11 o'clock direction of the right breast subareolar area .
targeted sonography of the right breast revealed an irregularly shaped , lobulated marginated , heterogeneous echotextured mass with posterior enhancement .
heterogeneous echotexture was noted , especially in the center of the mass , and increased vascular flow was noted in the mass on color doppler scanning .
there was also lymphadenopathy in the right axilla with cortical thickening and loss of fatty hilum ( fig .
the mass was categorized as breast imaging reporting and data system category 5 , highly suggestive of malignancy .
fine needle aspiration cytology revealed highly cellular smears with monotonous hyperchromatic atypical small cells , suggesting high - grade invasive ductal carcinoma .
the mass appeared to be of heterogeneously low signal intensity on t1 weighted images and a few parts of the mass showed intermediate to high signal intensity on t2 weighted images .
the t2 non - high signal area showed rapid enhancement within the first two minutes of gadolinium injection , and washout was noted ( fig .
the patient underwent a modified radical mastectomy and axillary dissection of the right breast . on the cut surface , the tumor appeared as a fairly well - defined but partially infiltrative , gray - white , solid mass with morphology similar to that of commonly seen , invasive ductal carcinoma .
histopathologically , several , large , mucoid , necrotic areas with foamy macrophages were surrounded by dark , solid , and trabecular pattern tumor cells .
the tumor was composed of a mostly solid growth of large to intermediate , polygonal or occasionally spindle cells , which showed organoid , nesting , trabecular , rosette - like , and palisading patterns .
immunohistochemically , the tumor cells were diffusely positive for synaptophysin and were focally positive for chromograin a , although they were negative for cd 56 .
, we considered this tumor to be a large cell neuroendocrine carcinoma with atypical carcinoid features ( histologic grade 3 , t2n1m0 , estrogen receptor [ er ] [ + ] , progesterone receptor [ pr ] [ + ] , human epidermal growth factor receptor 2 [ - ] ) .
positron emission tomography - computed tomography after surgery showed an absence of abnormal uptake , suggesting that the breast was the only primary site .
neuroendocrine tumors are derived from the neuroendocrine cells and the most common site is the bronchopulmonary system , where the endocrine cells are constantly present . in the breast ,
hyperplastic or benign neoplastic neuroendocrine lesions have never been reported , and this lead to the hypothesis that neuroendocrine differentiated breast tumors probably do not arise from the pre - existing endocrine cells , but are rather the result of the differentiation process within breast carcinoma ( 8) .
focal neuroendocrine differentiation can be found in diverse histological types of breast carcinoma . in one case series , most neuroendocrine cells were found with invasive ductal carcinoma or with mixed carcinoma showing mucinous differentiation or signet - ring cells ( 9 ) . however , the term , neuroendocrine tumor , is defined by the diffuse expression of neuroendocrine markers , such as chromogranin - a , neuron - specific enolase , synaptophysin , and cd56 , in more than 50% of the cell population .
neuroendocrine breast tumors are very rare , comprising of approximately 2 - 5% of all breast cancers , and most of these patients are in the sixth or seventh decade of life ( 10 ) . different classifications , according to the morphological features of histopathology , have been proposed for neuroendocrine tumors , arising within the breast .
perhaps the most pragmatic is the who classification , which defines three principle tumors , i.e. , solid neuroendocrine carcinoma , small cell / oat cell carcinoma , and large cell neuroendocrine carcinoma ( 10 ) .
it should be noted , however , that not all breast tumors that exhibit neuroendocrine features completely fit into the who classification categories .
there are no specific differences in the clinical features of neuroendocrine tumors from those of the other breast malignancy , and endocrine hormone - related syndromes are extremely rare .
of interest is the increase in neuroendocrine markers , such as chromogranin a , in the blood ( 10 ) .
as metastatic neuroendocrine tumors of the breast are more common than that of primary neuroendocrine tumors of the breast , it is , therefore , important to differentiate primary breast neuroendocrine tumor from metastatic disease to the breast because of the differences in treatment focus .
primary neuroendocrine tumor of the breast can be diagnosed if the presence of a non - mammary primary site can be clinically ruled out or if an in situ component is histologically detected , or both .
the treatment of primary neuroendocrine tumors is highly variable , although surgery should always be considered as the first line of treatment .
recent reports , which only deal with small cell neuroendocrine carcinoma , indicate that the size , stage of disease at the time of diagnosis , expression of the er and pr , and the ki-67 index are important determinants of the prognosis ( 11 - 13 ) .
there is no relevant report about the prognosis of primary large cell neuroendocrine carcinoma seen in our case .
however , the prognosis of our case would be poor , considering tumor size , axillary metastasis , and histologic grade .
previously published case reports with radiology findings ( 1 - 7 ) have also described the imaging features of neuroendocrine tumors .
( 1 ) described that the common radiological features of breast neuroendocrine tumor include , a high - density mass with predominantly spiculated or lobulated margins on mammography and mostly irregular or microlobulated , homogeneously hypoechoic masses with normal sound transmission on sonography .
, the number of cases with radiology findings has been too small to allow generalization of the imaging features , and there is no case report with radiology and pathology findings similar to ours . in this report
we present a case of primary neuroendocrine tumor ( large cell neuroendocrine carcinoma with atypical carcinoid features ) of the breast , together with its mammographic , sonographic , and mri features . however , the radiologic findings are hard to differentiate from those of much more commonly seen invasive ductal carcinoma
. reports of new cases will be necessary in order to determine the radiologic presentation of primary neuroendocrine tumor of the breast .
 focal neuroendocrine differentiation can be found in diverse histological types of breast tumors . 
 however , the term , neuroendocrine breast tumor , indicates the diffuse expression of neuroendocrine markers in more than 50% of the tumor cell population . 
 the imaging features of neuroendocrine breast tumor have not been accurately described due to extreme rarity of this tumor type . 
 we present a case of a pathologically confirmed , primary neuroendocrine breast tumor in a 42-year - old woman , with imaging findings difficult to be differentiated from that of invasive ductal carcinoma . 
INTRODUCTION
CASE REPORT
DISCUSSION