the differential diagnosis between breast lymphoma and breast adenocarcinoma is difficult clinically and radiologically as these diseases share common characteristics , and the diagnosis is usually confirmed postoperatively .
diagnosis of the two conditions in a single patient is often thought to be coincidental , but there is evidence supporting a possible pathophysiological connection involving a common genetic background or etiologic factor , or possibly , one disease causes the other . in this case , the presentation of multifocal bilateral epithelial breast cancer with three primary tumors suggests that tumorigenesis was not coincidental .
it has also been suggested that breast lymphoma can change the behavior of concomitant breast cancer either by altering the axillary lymphatic vessels , which aids breast cancer dissemination , or by changing the lymph node microenvironment .
distinct treatment strategies are required for these two diseases including surgery , radiotherapy , hormonal therapy , chemotherapy , and immune therapy , depending on the disease type and patient characteristics such as stage of disease , aggressiveness , histological subtype , and estrogen receptor ( er)/human epidermal growth factor receptor 2 ( her2 ) status . here , we report the unique case of a patient with ductal carcinoma in situ ( dcis ) and follicular lymphoma of the breast , who also presented with second primary contralateral multifocal breast cancer at a later date .
a 55-year - old caucasian woman presented in april 2011 to the hospital with a painless lump in the upper outer quadrant of the left breast , discovered during a breast self - examination .
the patient had a 20 - 30 pack - year smoking history and had one full - term pregnancy previously .
her medical history was significant for a swelling of the left parotid gland 6 months before her current presentation .
this was investigated by ultrasonography and fine - needle aspiration ( fna ) , which revealed an enlarged benign intraparotid lymph node .
a clinical examination revealed a small , firm , painless , ill - defined nodule in the upper outer quadrant of the left breast with no associated lymphadenopathy .
an enlarged lymph node was found in the right inguinal area , which corresponded to the nodule detected by the patient .
the examination of the right breast and axilla , neck , abdomen , and left inguinal area was unremarkable .
a bilateral mammography and breast ultrasound revealed a single lesion in the upper outer quadrant of each breast with characteristics suspect of malignancy , but a tissue diagnosis was warranted ( figure 1 ) .
a histological examination of the left breast specimen revealed the presence of a lymph node with complete coagulative necrosis .
the necrotic area contained some medium - sized shadow cells , which were immunohistochemically positive for cluster of differentiation 20 ( cd20 ) and cd10 , and were admixed with some small b - cells .
immunohistochemical analysis showed b- and t - cells , and scattered cells positive for cd10 , cd23 , and b - cell cll / lymphoma 6 ( bcl-6 ) ( figure 2 ) .
a histological examination of the right breast specimen revealed a typical dcis , which followed an ethmoid pattern with intermediate nuclear - grade and comedo - type necrosis ( figure 3 ) .
accordingly , histological analysis showed that the inguinal lymph node was infiltrated by a follicular b - cell lymphoma grade 1/2 ( figure 4 ) .
immunohistochemical analysis showed that the cells were positive for cd10 , bcl-6 , and bcl-2 , and partly for cd23 .
the tumor ki-67 proliferative index was low at approximately 10% . cells positive for cd10 and bcl-6 were found in the interfollicular area , and monoclonality for the kappa light chain was also noted .
the neoplastic cells had infiltrated the nodal capsule and spread to the perinodal adipose tissue .
the patient underwent computed tomography of the cervix , thorax , and abdomen , which was normal .
the final diagnosis was simultaneous dcis of the right breast and non - hodgkin b - cell follicular lymphoma , stage iiiea .
right breast irradiation was administered for dcis postoperatively . as the follicular lymphoma was disseminated , but did not fulfill the criteria for treatment initiation , a watch and wait strategy was adopted . in december 2013 , a routine follow - up mammography showed two speculated lesions in the left breast .
one was retroareolar and measured < 1 cm in maximum diameter , while the other lay deeper and measured approximately 1.5 cm in diameter .
ultrasonography and magnetic resonance imaging confirmed the suspicious findings , and an ultrasound - guided core biopsy was taken from the largest lesion .
this revealed a grade ii invasive ductal carcinoma ( idc ) , positive for the er/ progesterone receptor ( pr ) and her2 ( 2 + ) .
new staging investigations revealed no evidence of lymphoma and no metastases from the breast disease .
after several consultations with the patient , a bilateral routine skin - reducing mastectomy with an inferior dermal flap and silicon - based reconstruction , together with a left sentinel node biopsy was performed .
the breast histopathologic examination revealed 2 grade ii idcs , measuring 0.9 cm and 1.4 cm with surrounding dcis .
er and pr were strongly positive , and fluorescence in situ hybridization analysis confirmed her2 amplification .
the sentinel lymph nodes were free of breast cancer deposits . however , immunohistochemical analysis for cd20 , cd3 , cd10 , bc1 - 2 , and ki-67 was indicative of in situ follicular lymphoma as shown by the presence of lymphoma cells bcl-2 ( + ) , bcl-6 ( + ) , cd10 ( + ) confined into the germinal center ( figure 5 ) .
subsequently , the patient completed four cycles each of anthracycline and taxane - based chemotherapy in september 2014 , and was prescribed trastuzumab in combination with an aromatase inhibitor .
synchronous breast cancer and follicular lymphoma is a rare clinical condition , and has been described only a few times in the literature .
our case describes the synchronous presentation of dcis and secondary breast lymphoma ( according to the wiseman and liao criteria ) , further complicated by metachronous contralateral infiltrating breast carcinoma .
primary or secondary breast lymphoma may have a clinical presentation indistinguishable from breast cancer as it usually manifests as a breast lump or axillary lymphadenopathy .
generally , the diagnosis of lymphoma is made postoperatively after the histological examination , but occasionally , analysis of the preoperative fna or core biopsy can lead to a diagnosis .
breast cancer patients have been found to have an increased incidence of non - hodgkin lymphoma because of treatment with radiotherapy and chemotherapy ; however , this does not explain cases with synchronous disease .
there are several hypotheses regarding the connection between these two entities , including the role of epidemiologic factors , such as age or gender , or a common genetic background , or possibly that one disease causes the other . with regard to the common genetic background
, mutations in the ataxia telangiectasia mutated gene have been found in both lymphoid neoplasia and breast cancer .
furthermore , the mouse mammary tumor virus is strongly suspected to play an etiologic role in both tumors , as its genetic sequence or similar sequences have been discovered in both breast cancer and lymphoma cells , but not in nonneoplastic cells .
finally , results from rare cases of collision tumors support the hypothesis that breast cancer may act as an antigenic stimulus and cause non - hodgkin lymphoma , analogous to cases where helicobacter pylori inflammation of the stomach may cause mucosa - associated lymphoid tissue lymphoma .
furthermore , it seems that the connection between these two diseases may not just be etiologic and there may be synergism between the two cancers after tumorigenesis has occurred .
one important theory is that the lymphoma could obliterate the lymphatic channels , thus altering the predominant mode of breast cancer metastasis .
there are also clinical data suggesting that lymphomas can change the course of a radioactive tracker , diminishing the utility of a sentinel lymph node biopsy to indicate breast cancer lymphatic dissemination
. moreover , neoplastic lymphoid cells could reduce tissue necrosis factor or interleukin - induced adhesion of breast cancer cells to the endothelial layer of the axillary lymph nodes , thus facilitating lymphatic dissemination to certain lymph nodes .
however , since some lymphomas develop outside of the nodal sinuses , these theories are not universally accepted , and any interaction between breast cancer and breast lymphoma may be overestimated .
described a case of t1n0 idc coexisting with lymphoma in the ipsilateral axillary lymph nodes .
cox et al .   described two cases , one with t1n0 idc coexisting with disseminated follicular lymphoma ( stage iii ) and one with dcis coexisting with lymphoma in the ipsilateral axillary lymph nodes .
reported a case of synchronous invasive lobular carcinoma and follicular lymphoma discovered during sentinel lymph node dissection .
describe a case of t3n0m0 idc coexisting with follicular lymphoma in the ipsilateral lymph nodes .
finally , tamaoki et al .   described dcis of the breast coexisting with lymphoma in the para - aortic lymph nodes . in all of these reports
, lymphoma was discovered incidentally during the histologic examination of the specimen ; however , in our case , a palpable inguinal lymph node was present .
the occurrence of metachronous breast tumor after the synchronous diagnosis of dcis and lymphoma is unique . while lymphoma patients have a higher risk for second tumor development due to the therapy they have received , this does not apply to our patient as she did not receive any treatment .
to our knowledge , only two similar cases involving three primary malignancies have been described in the literature .
the coexistence of dcis in the right breast and diffuse large b - cell lymphoma in the right axilla , and invasive ductal carcinoma in the left breast has been described by miles and jacimore , while synchronous bilateral invasive ductal carcinoma and primary breast lymphoma has been described by garg et al . .
in conclusion , the coexistence of breast cancer and follicular breast lymphoma , complicated by contralateral metachronous multifocal mammary carcinoma has not been described before now in the literature .
there appears to be a pathophysiol ogical connection between the two diseases , involving cancer pathogenesis and behavior , although this may be due to circumstantial evidence .
management of coexisting breast lymphoma and breast cancer may be a challenge , requiring input from surgeons , medical and clinical oncologists , radiologists , and pathologists . a multidisciplinary approach ,
a high level of clinical vigilance , and teamwork are required to avoid an undesirable outcome .
 breast cancer coexisting with lymphoma is a rare condition with various diagnostic and therapeutic implications . in this report 
 , we describe the case of a 55-year - old caucasian woman who presented with simultaneous ductal carcinoma in situ of the right breast , and follicular lymphoma involving an inguinal lymph node and the left breast . 
 the patient underwent local excision and radiotherapy for the ductal carcinoma in situ , while a watch and wait strategy was adopted for the lymphoma . 
 two years later , the patient presented with multifocal ductal carcinoma of the left breast and reappearance of the lymphoma in the left axillary lymph nodes . 
 she underwent bilateral mastectomy , left sentinel node biopsy , and chemotherapy . 
 synchronous follicular lymphoma and bilateral metachronous breast carcinoma has not been described previously . 
 diagnosis is based on tissue histology after excision or a needle biopsy . 
 treatment for these two diseases is distinct , and a multidisciplinary approach should be adopted . 