microglandular adenosis ( mga ) is a rare benign disease that causes proliferative glandular lesions in the breast .
these benign lesions may progress to a wide spectrum of disease , from atypical microglandular adenosis ( amga ) to carcinoma arising in microglandular adenosis ( camga ) .
although mga itself is benign , it can cause carcinoma , which can lead to problems if not excised completely . in this study
case 1 was a 44-year - old woman with a previous history of breast - conserving surgery because of ductal carcinoma in situ ( dcis ) in her right breast 4 years ago . after breast - conserving surgery
, she received radiotherapy on her right breast but no hormonal therapy or chemotherapy . during a regular follow - up
she had no symptoms or signs associated with a breast mass . on physical examination ,
mammography showed heterogeneously dense breast tissue and a newly developed small nodular density at the left upper outer quadrant of the breast ( figure 1a ) .
ultrasound examination revealed an ill - defined irregular hypoechoic nodule measuring approximately 8 mm and an ill - defined hypoechoic nodule measuring approximately 7 mm ( bi - rads category 4b ) at the 1 to 2 o'clock region and 5 cm from the left nipple . both nodules were adjoining ( figure 1b ) .
ultrasound guided localization excisional biopsy and frozen section revealed that the lesion was invasive carcinoma .
she underwent modified radical mastectomy ( mrm ) with sentinel lymph node biopsy ( slnb ) .
no definite mass - like lesion was found on gross examination ( figure 2 ) . microscopic examination revealed widely spread round proliferative glands lined by a single layer of flat to cuboidal epithelial cells and lacking a myoepithelial layer , indicating typical mga . in part of the lesion
, the glandular lumen was obliterated by proliferation of monotonous , atypical small cells with frequent mitotic figures , indicating carcinoma in situ . a cord - like arrangement and irregular aggregates of highly atypical cells
were scattered in the stroma and extended into the adipose tissue ( figure 3 ) .
immunohistochemical ( ihc ) staining revealed the following : s-100 protein ( + ) , estrogen receptor ( er ) ( - ) , progesterone receptor ( pr ) ( + , allred score 3 ) , human epidermal growth factor receptor 2 ( her2 ) ( - ) , lysozyme ( + ) , 1-antitrpysin ( + ) , calponin ( - ) , and p63 ( - ) . the slnb showed no evidence of metastasis .
the final diagnosis was multifocal invasive carcinoma associated with dcis ( grade 3 ) arising in mga with stage 1a , t1 ( < 1 cm , in the largest one ) , n0 ( 0/1 ) , m0 , and lymphovascular invasion ( - ) .
after 14 months of medical follow - up , no evidence of recurrence has been found .
case 2 was a 57-year - old woman with a palpable mass in her right breast .
a firm , movable mass measuring approximately 3 cm was palpable at the right upper outer quadrant of the breast .
mammography revealed a huge mass - like lesion at the right upper breast and ultrasound revealed a lobulating heterogeneous hypoechoic mass measuring 2.62.2 cm at the 11 o'clock region of the right breast ( figure 4 ) .
positron emission tomography revealed fluorodeoxyglucose ( fdg ) uptake at a 2.7 cm hypermetabolic mass in the upper outer quadrant of the right breast ( suvmax : 15.4 ) and fdg uptake in lymph nodes of the right axilla ( level 1 ) .
microscopic examination revealed encapsulated papillary carcinoma arising in mga , which exhibited atypia and variable proliferation ( approximately 5.2 cm in the largest dimension ) .
most areas of the mga were atypical and were lined by large pleomorphic cells with nuclear hyperchromasia and prominent nucleoli . a 0.30.25 cm focus of invasion
typical mga tubules with intraluminal colloid - like secretory material were found at the more peripheral area of the lesion ( figure 6 ) .
ihc staining revealed the followings : s-100 protein ( + ) , smooth muscle myosin - heavy chain ( - ) , er ( - ) , and pr ( - ) . no metastasis was observed in the sentinel lymph nodes .
the final diagnosis was invasive ductal carcinoma ( grade 2 ) associated with encapsulated papillary carcinoma arising in mga with stage ia , t1 ( 0.30.25 cm ) , n0 ( 0/5 ) , m0 , and lymphovascular invasion ( - ) .
the patient showed no evidence of recurrence on medical follow - up at 19 months .
fattaneh tavassoli , a breast pathologist at the yale school of medicine , usa , about these two cases .
case 1 was a 44-year - old woman with a previous history of breast - conserving surgery because of ductal carcinoma in situ ( dcis ) in her right breast 4 years ago . after breast - conserving surgery
, she received radiotherapy on her right breast but no hormonal therapy or chemotherapy . during a regular follow - up
she had no symptoms or signs associated with a breast mass . on physical examination ,
mammography showed heterogeneously dense breast tissue and a newly developed small nodular density at the left upper outer quadrant of the breast ( figure 1a ) .
ultrasound examination revealed an ill - defined irregular hypoechoic nodule measuring approximately 8 mm and an ill - defined hypoechoic nodule measuring approximately 7 mm ( bi - rads category 4b ) at the 1 to 2 o'clock region and 5 cm from the left nipple . both nodules were adjoining ( figure 1b ) .
ultrasound guided localization excisional biopsy and frozen section revealed that the lesion was invasive carcinoma .
she underwent modified radical mastectomy ( mrm ) with sentinel lymph node biopsy ( slnb ) .
no definite mass - like lesion was found on gross examination ( figure 2 ) . microscopic examination revealed widely spread round proliferative glands lined by a single layer of flat to cuboidal epithelial cells and lacking a myoepithelial layer , indicating typical mga . in part of the lesion
, the glandular lumen was obliterated by proliferation of monotonous , atypical small cells with frequent mitotic figures , indicating carcinoma in situ . a cord - like arrangement and irregular aggregates of highly atypical cells
were scattered in the stroma and extended into the adipose tissue ( figure 3 ) .
immunohistochemical ( ihc ) staining revealed the following : s-100 protein ( + ) , estrogen receptor ( er ) ( - ) , progesterone receptor ( pr ) ( + , allred score 3 ) , human epidermal growth factor receptor 2 ( her2 ) ( - ) , lysozyme ( + ) , 1-antitrpysin ( + ) , calponin ( - ) , and p63 ( - ) . the slnb showed no evidence of metastasis .
the final diagnosis was multifocal invasive carcinoma associated with dcis ( grade 3 ) arising in mga with stage 1a , t1 ( < 1 cm , in the largest one ) , n0 ( 0/1 ) , m0 , and lymphovascular invasion ( - ) .
after 14 months of medical follow - up , no evidence of recurrence has been found .
case 2 was a 57-year - old woman with a palpable mass in her right breast .
a firm , movable mass measuring approximately 3 cm was palpable at the right upper outer quadrant of the breast .
mammography revealed a huge mass - like lesion at the right upper breast and ultrasound revealed a lobulating heterogeneous hypoechoic mass measuring 2.62.2 cm at the 11 o'clock region of the right breast ( figure 4 ) .
positron emission tomography revealed fluorodeoxyglucose ( fdg ) uptake at a 2.7 cm hypermetabolic mass in the upper outer quadrant of the right breast ( suvmax : 15.4 ) and fdg uptake in lymph nodes of the right axilla ( level 1 ) .
the patient underwent right mrm with slnb . a well - demarcated solid mass measuring 2.82.4 cm
microscopic examination revealed encapsulated papillary carcinoma arising in mga , which exhibited atypia and variable proliferation ( approximately 5.2 cm in the largest dimension ) .
most areas of the mga were atypical and were lined by large pleomorphic cells with nuclear hyperchromasia and prominent nucleoli
. a 0.30.25 cm focus of invasion was associated with an altered chondromyxoid stroma adjacent to the encapsulated papillary carcinoma .
typical mga tubules with intraluminal colloid - like secretory material were found at the more peripheral area of the lesion ( figure 6 ) .
ihc staining revealed the followings : s-100 protein ( + ) , smooth muscle myosin - heavy chain ( - ) , er ( - ) , and pr ( - ) .
the final diagnosis was invasive ductal carcinoma ( grade 2 ) associated with encapsulated papillary carcinoma arising in mga with stage ia , t1 ( 0.30.25 cm ) , n0 ( 0/5 ) , m0 , and lymphovascular invasion ( - ) .
the patient showed no evidence of recurrence on medical follow - up at 19 months .
fattaneh tavassoli , a breast pathologist at the yale school of medicine , usa , about these two cases .
since mga was first described in 1968 , by mcdivitt et al . , several studies have reported cases of amga and camga [ 2 - 7 ] .
to the best of our knowledge , the present cases are the first cases of invasive carcinoma arising in mga to be reported in korea .
although one report suggested that the incidence of carcinoma could be as high as 64% , it appears to have been affected by bias .
results of ihc staining of carcinoma arising in mga did not differ significantly from those of mga . in most cases ,
results of ihc staining showed positivity for cytokeratin , e - cadherin , and s-100 and negatively for er , pr , her2 , cystic disease fluid protein ( gcdfp)-15 , epithelial membrane antigen , smooth muscle actin , cd10 , calponin , and p63 .
one of the major differences in ihc staining of mga from invasive carcinoma is that mga stains basement membranes with laminin and collagen iv . in mga and carcinoma in situ , in contrast to invasive carcinoma
the preliminary pathologic diagnosis was acinic cell carcinoma ( acca ) , and it was revised to camga after consultation with dr .
some camga cells are immunoreactive for amylase , lysozyme , and 1-antichymotrypsin , which are found in acca , indicating acinic cell differentiation . in addition to this , both exhibit glandular structures and granularity as well as stain positively for s-100 and antitrypsin , and negatively for er and pr .
signs of mga include regular nuclei , a single layer of cuboidal cells , basal lamina , eosinophilic luminal content , and empty cytoplasm on electron microscopy .
. however , acca does not show regular nuclei and basal lamina , but shows granular cytoplasm and dense core granules on electron microscopy .
it may or may not reveal a single layer of cells , cuboidal cells , luminal content , and gcdfp-15 in ihc staining .
if mga is accompanied by amga or camga , it must be completely excised with a negative surgical margin .
incomplete excision of a primary benign mga lesion can cause recurrence of mga with development of carcinoma .
it is difficult to secure a safety margin because of the insidiously invasive character of mga , and cases of axillary lymph node metastasis and distant metastasis have been reported .
in addition to surgery , radiation therapy should be considered in patients with breast - conserving surgery , and adjuvant chemotherapy should be considered in patients with axillary metastasis or with invasive tumors larger than 1 cm in the absence of nodal metastasis . despite histopathological and ihc features indicating poor prognoses ,
most studies have reported relatively favorable prognoses . however , longer follow - up periods are needed to determine the exact prognosis of camga .
 microglandular adenosis ( mga ) is a rare benign disease that shows an infiltrative growth pattern of small glands , and it may progress to include atypia and carcinoma . here 
 we report two cases of breast carcinoma arising in mga . 
 case 1 was a 44-year - old woman with a previous history of ductal carcinoma in situ in her right breast . during a follow - up , a 1.8 cm mass - like lesion 
 was found in her left breast . 
 an excisional biopsy suggested that the lesion was breast carcinoma . 
 case 2 was a 57-year - old woman with a 2.9 cm mass in her right breast . 
 a core needle biopsy of the lesion suggested invasive carcinoma . 
 both patients underwent modified radical mastectomy with sentinel lymph node biopsy . 
 both tumors lacked a myoepithelial cell layer and stained positively for s-100 , lysozyme , and 1-antitrypsin , which is typical of mga . 
 both cases showed invasive carcinoma arising in mga . 