lipid - rich carcinoma is a very rare histological variant of breast cancer that accounts for less than 1% of all breast cancers . it is composed of clear to vacuolated cytoplasm with abundant neutral lipid present within 90% of the tumor cells . lipid - rich carcinomas are considered to behave aggressively and have a worse prognosis than other types of breast cancer . gene expression profiling studies have refined breast cancer classification and identified distinct subgroups that have an independent association with patient outcome [ 3 , 4 ] , and findings can be surrogated by immunohistochemical markers that match the gene expression patterns [ 5 , 6 , 7 ] . here , a case of lipid - rich carcinoma previously included as case 1 in a series of 13 breast cancer patients who received long - term treatment with neuroleptics   was re - evaluated to determine the intrinsic immunohistochemical ( ihc ) subtype . the present report describes the histological characteristics and intrinsic subtype profile of this case of lipid - rich carcinoma of the breast . a 57-year - old japanese woman who had received long - term neuroleptic treatment for schizophrenia noticed a painless , pea - sized lump in her right breast , and she was admitted to our hospital . the tumor size was 2.5  1.5 cm in diameter , and an excisional biopsy confirmed malignancy ( t1n0m0 ) . the excised tissue specimens were routinely processed for histological , histochemical , and ihc examinations . briefly , formalin - fixed , paraffin - embedded tissues were deparaffinized and stained with hematoxylin and eosin ( he ) and periodic acid - schiff ( pas ) with or without diastase digestion . immunohistochemistry was performed with the primary antibodies listed in table 1 and a labeled streptavidin biotin staining kit ( dako , carpinteria , calif . , frozen sections cut on a cryostat were prepared from the formalin - fixed wet tissues and stained with oil red o. macroscopically , the excised tumor measured 2.0  1.2  1.1 cm in diameter , and its cut surface was grayish - white . histologically , tumor cells were large with clear to foamy cytoplasm , accompanied by cellular pleomorphism and nuclear atypia . 1a ) or formed atypical epithelial tufts that protruded into the lumen with desquamated cells within the lumen ( fig . 2a ) but the tumor cell cytoplasm was negative for basal cytokeratins ( ck5 , ck6 , and ck14 ) . however , basal ( myoepithelial ) cells surrounding the glandular lumen composed of apocrine extrusion of the nuclei were positive for ck5 ( fig . cancer cells were prolactin ( prl)-negative , whereas the prolactin receptor ( prlr ) showed cytoplasmic staining ( fig . 2c ) . cancer cells were invariably negative for estrogen receptor ( er ) , progesterone receptor ( pgr ) , epidermal growth factor receptor 1 ( her1 ) , and her2 . cancer cell invasion was seen in the mammary fat pad , but vessel invasion was not seen . all 16 right axillary lymph nodes were free of metastasis . the patient has remained cancer - free for 20 years without any evidence of recurrence . long - term neuroleptic usage produces a persistent and marked elevation of serum prl levels , which results in secretory activity in the breast . prlr is a transmembrane protein that consists of extracellular , transmembrane , and intracellular domains , and prl acts through the prlr . monoclonal antibody b6.2 is directed against the extracellular domain of human prlr . although cancer cells were prl - negative , they were positive for prlr , which indicates that prl might have played an important role in the development of the lipid - rich carcinoma of the breast mediated through the prlr pathway . the lipid - rich carcinoma contained a large amount of neutral lipid but did not contain glycogen or mucin . secretory carcinomas , apocrine carcinomas and glycogen - rich carcinomas are also composed of clear to vacuolated cancer cells . a pas - negative reaction can differentiate lipid - rich carcinomas from these other histological types of carcinomas . additionally , in the present case , -lactalbumin was diffusely positive in the cytoplasm of cancer cells lining the glandular lumina . histologically , lipid - rich carcinomas contain in situ areas and invasive areas . in situ areas contain cells arranged in an alveolar pattern with a hobnail appearance , in which the luminal borders exhibit apocrine - type cytoplasmic blebs and extrusion of hyperchromatic pleomorphic nuclei . invasive areas contain cells with clear and foamy cytoplasm arranged in sheets , nests , and cords [ 1 , 10 , 11 ] . basal cells in the breast express high - molecular - weight basal cks including ck5/6 and ck14 [ 12 , 13 ] , and -sma is a marker of myoepithelial differentiation . foci surrounded by basal ( myoepithelial ) cells indicate an in situ portion , while the lack of these cells indicates an invasive portion . breast cancer can be distinguished as ductal or lobular in nature , and lipid - rich carcinoma can be associated with either ductal or lobular carcinoma in situ . e - cadherin , a transmembrane glycoprotein that binds similar types of cells together , exists in the membranes of cells in ductal lesions while it is lacking in lobular lesions . in the present case , the tumor was e - cadherin positive , which suggests that the carcinoma is ductal in nature . lipid - rich carcinomas in the form of ductal carcinoma in situ ( dcis )   or in the form of an invasive component accompanied with dcis   have been reported . ihc intrinsic subtypes can be defined by using markers as follows : luminal a ( er+ and/or pgr+ , her2 ) , luminal b ( er+ and/or pgr+ , her2 + ) , her2-enriched ( er , pgr , her2 + ) , and triple negative ( er , pgr , her2 ) . the triple - negative subtype can be further divided into basal - like ( er , pgr , her2 , ck5/6 + , and/or her1 + ) and unclassified ( negative for all five markers ) [ 5 , 6 , 7 ] . according to this system , the present case is the unclassified subtype . due to the rarity of lipid - rich carcinomas , the association between intrinsic subtypes and aggressiveness has not been extensively studied . in one study , 5 of 6 ( 83.3% ) lipid - rich carcinomas were er+ and/or pgr+ , while 3 of 6 ( 50% ) lipid - rich carcinomas were her2 + . in a study of 17 lipid - rich carcinomas , 1 tumor was er+ and/or pgr+ , and all 17 carcinomas were her2 + . in a third study , 5 of 49 ( 10.2% ) lipid - rich carcinomas were er+ and/or pgr+ and 35 of 49 ( 71.4% ) lipid - rich carcinomas were her2 + . thus , the positive rate of er and/or pgr tended to be low , and her2 expression tended to be high in these studies of lipid - rich carcinomas . according to ihc intrinsic subtype analysis , patients who have her2-enriched and triple - negative subtype cancers have a significantly shorter disease - free survival period than patients with other subtypes . the poor prognosis among triple - negative cases is conferred almost entirely in basal - like breast cancer . breast carcinoma with basal differentiation can be defined based on the expression of basal ck , such as ck5 , ck6 , and ck14 , and lipid - rich carcinoma with a basal cell phenotype ( er , pgr , her2 , high molecular weight ck+ , her1 + ) has been reported . although the lipid - rich carcinoma in the present case report was er- and pgr - negative , it was also negative for her2 and basal cell cks , and the patient remains disease - free 20 years after the surgery . therefore , in lipid - rich carcinoma , like in other histologic types of breast carcinomas , her2 and basal - like subtypes may indicate the aggressive behavior of the neoplasm .