although any organ may be infiltrated by leukemic cells , breast infiltration is extremely rare .
breast infiltration as the initial presentation or relapse of leukemia can be mistaken for a benign breast mass or primary breast cancer . to my knowledge , there has been no previous case report of leukemic infiltration of the breast by biphenotypic acute leukemia ( bal ) .
most case reports have described extramedullary leukemic infiltration by acute myeloid leukemia ( aml ) and acute lymphoblastic leukemia ( all ) . here
i present the case of a patient with extramedullary infiltration of the breast as a presentation of bal relapse and review the literature .
in march 2014 , a 28-year - old korean woman , at 24 weeks of gestation , presented with easy fatigue and an abnormal blood test .
a complete blood count revealed a total white blood cell ( wbc ) count of 2.6910/l with 12% immature cells , a hemoglobin level of 6.8 mg / dl , and a platelet count of 8110/l . a bone marrow biopsy showed 78% blasts with various size nucleoli , fine chromatin , and basophilic cytoplasm .
immunophenotyping of the bone marrow revealed that the patient was positive for the following : cd7 , cd13 , cd19 , cd33 , cd117 , ccd79a , hla - dr , and terminal deoxynucleotidyl transferase ( tdt ) ; and negative for the following : cd2 , cd3 , cd5 , cd20 , ccd22 , cd10 , cd14 , cd61 , and myeloperoxidase .
this result showed coexpression of markers for b lymphoid ( cd19 and ccd79a ) and myeloid lineage ( cd117 , cd13 , and cd33 ) , based on which a diagnosis of bal was confirmed .
after a cesarean delivery at 28 weeks of gestation , the patient was treated with induction and consolidation therapy from may 2014 to september 2014 .
the induction regimen included daunorubicin 90 mg / m on days 1 to 3 , vincristine 2 mg / m on days 1 and 8 , prednisolone 60 mg / m on days 1 to 14 , l - asparaginase 4,000 units /
m on days 17 to 28 , and intrathecal methotrexate 15 mg on days 2 and .
for the first and third cycles , she was treated with daunorubicin 45 mg / m on days 1 and 2 , vincristine 1.4 mg / m on days 1 and 8 , prednisolone 60 mg / m on days 1 to 14 , and l - asparaginase 4,000 units / m on days 1 to 7 . for the second cycle , she received cytarabine 2,000 mg / m on days 1 to 4 and etoposide 150 mg / m on days 1 to 4 .
m on days 1 and 15 ; 720 mg / m on days 2 and 16 ) . in november 2014
there was no evidence of relapse for 23 months after the stem cell transplantation . in september 2016 , the patient presented with easy fatigue , a palpable right breast mass , and nipple discharge , which had developed 4 months prior .
she had no history of bleeding , weight loss , or dizziness over the previous few months . on physical examination ,
a 6 cm6 cm firm , irregular , nontender mass was palpated in the upper inner area of her right breast .
mammography showed extremely dense breast tissue but no well - defined mass ( figure 1a ) .
however , breast ultrasonography revealed 5.72.15.9 cm and 3.01.42.5 cm masses with partly indistinct margins and a heterogeneous echoic pattern in her right breast ( figure 1b ) .
a complete blood count showed a total wbc count of 7.4110/l , a hemoglobin level of 14.3 mg / dl , and a platelet count of 15110/l .
a core needle biopsy ( cnb ) was performed on the 2 oclock direction mass in the right breast .
microscopic examination revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin ( figure 2a ) .
the immunohistochemical ( ihc ) staining showed that the majority of blast cells were positive for cd34 and cd117 ( figure 2b and c ) .
a bone marrow karyotyping demonstrated 46 , xy and no recipient xx cells , which suggested complete engraftment of transplanted donor cells .
bone marrow differential counting showed 3.8% blasts and a 2.1:1 ratio of myeloid to erythroid precursors , which were within normal ranges .
however , a bone marrow biopsy showed diffuse infiltration of immature cells with irregular nucleoli and a markedly decreased number of normal hematopoietic cells .
infiltration of the breast by acute leukemia is rare , regardless of whether it is found at initial presentation or at relapse after treatment .
of 235 patients with aml , only four had involvement of the breast ( 1.7% ) .
although few cases have been described , breast infiltration seems more likely to occur in patients with aml rather than those with all .
the expression of adhesion molecules such as cd56 was associated with extramedullary granulocytic sarcoma , which occurred in 3% to 7% of aml cases .
patients with leukemic infiltration of the breast usually present with a palpable breast mass that mimics a benign breast lesion , such as a fibroadenoma . mammography and breast ultrasonography
findings are variable and can be unremarkable with diffusely dense breast parenchyma . on ultrasonography , no definitive imaging pattern suggesting leukemic infiltration of the breast has been described because sonographic features of tumors vary from hypoechoic to hyperechoic masses .
magnetic resonance imaging ( mri ) may be another diagnostic tool , especially in patients with dense glandular tissue , breast implants , or pregnancy .
mri features include t2 hyperintensity and rapid ring - enhancement of the lesions . for a final diagnosis of leukemic infiltration of the breast
a cnb under ultrasono - graphy guidance is an acceptable and safe method to establish the diagnosis and avoid unnecessary surgical biopsy .
the cytologic features of breast infiltration of all include dispersed monomorphic blastic cells with variable size , high ratio of nuclear to cytoplasmic , round or convoluted nuclei with dispersed chromatin , and scanty cytoplasm .
in the initial bone marrow biopsy of our case , cd7 , cd13 , cd19 , cd33 , cd117 , ccd79a , hla - dr , and tdt were positive , indicating expression of both myeloid cell and lymphoid cell markers . in the biopsy of breast
based on literature reviews , leukemic infiltration of the breast by acute leukemia has occurred in patients with aml and all . however , to the best of our knowledge , this is the first report of leukemic infiltration of the breast by bal .
most experts believe that there is no role of surgery for breast leukemic infiltration because there is no evidence of a clinical benefit of surgery for breast lesions , and surgery may delay the initiation of systemic therapy . in conclusion ,
it should be considered in the differential diagnosis of breast masses , especially when there is a history of acute leukemia .
mammography and breast ultrasonography may be useful to detect breast nodules . with cnb and ihc staining for leukemia markers ,
a definitive diagnosis can be established while avoiding unnecessary breast surgery , thus enabling early initiation of systemic therapy .
 in acute leukemia , leukemic infiltration of the breast is extremely rare . 
 we report a case of biphenotypic acute leukemia ( bal ) that presented as a breast mass . a 30-year - old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue . 
 she had received chemotherapy and peripheral blood stem cell transplantation for bal and had been in complete remission for the last 2 years . 
 core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin , consistent with leukemic infiltration . 
 subsequent bone marrow biopsy showed diffuse infiltration of immature cells . 
 however , bone marrow karyotyping showed 46 , xy , suggesting complete engraftment of transplanted donor cells . 
 this is the report of bal recurring as a breast mass . in the differential diagnosis of a breast mass , 
 extramedullary relapse should be considered when the patient has a history of leukemia . 
INTRODUCTION
CASE REPORT
DISCUSSION