methylene blue dye ( mbd ) has been successfully used worldwide with few complications in patients undergoing breast surgery . we herein describe 2 different complications in 2 patients : 1 ) skin and parenchymal necrosis when mbd was injected subdermally and 2 ) mycoplasma infection caused by contaminated mbd in breast reduction surgery . several publications advocate the use of subdermal mbd injections for sln mapping without complications 1 - 3 ; however , several publications report complications ranging from blue staining of the skin and fat necrosis 4 - 6 . the american society of clinical oncology ( asco ) guidelines advocate the use of blue dye in conjunction with radioisotope for sln mapping as this combined strategy yields the highest rates of successful sln mapping 7 . some surgeons prefer mbd over lymphazurin ( isosulphan blue dye ) because lymphazurin is more expensive , sometimes unavailable due to national shortages , and may rarely cause anaphylaxis 3 , 8 . our objective is to bring to light the fact that although mbd is relatively safe , it is not without potential for serious complications . the 2 patients described in these case reports were seen at the university of arizona cancer center during 2008 and referred to a breast surgical oncologist for further care . we evaluated and managed complications of mbd injected by 2 referring surgeons for different indications . a 67-year - old woman with a t1b n0 m0 infiltrating ductal carcinoma of the left breast was treated by a surgeon at the referring institution : she underwent a left segmental mastectomy and sentinel lymph node ( sln ) biopsy for a 10 mm primary tumor located at the 9 o'clock position . the initial operating surgeon injected mbd in a subareolar subdermal fashion , complicated by mbd skin necrosis . the patient initially presented describing pain and tenderness of her left breast that persisted for two months following her first surgery . we noted a sinus in the 8 o'clock position , draining purulent fluid ; erythema surrounding the areola , extending toward the axilla ; and fluctuance in the central breast . on breast ultrasound examination , an area of loculated fluid culture results of this fluid showed corynebacteria and anaerobic gram negative rods , which was clinically believed to be due to infection of the chronic open wound secondary to mbd necrosis . we subsequently admitted the patient to the hospital to perform an incision and drainage ( i&d ) of her left breast unresolving abscess cavity . we made an incision in the area of maximal fluctuance in the left breast in the periareolar region at 5 o'clock . to explore the borders of the cavity , we used a lacrimal probe ; we noted that the cavity was connected to the sinus in the 8 o'clock position . the cavity measured approximately 8 cm x 7 cm x 2.5 cm and contained necrotic tissue . then , we made a separate incision over the sinus in the 8 o'clock position and completely excised the tract . once we debrided the cavity , we placed a wound vacuum - assisted closure ( vac ) device for negative pressure treatment with suction drainage 9 , 10 through 2 separate incisions ( figures 1 - 4 ) . a 45-year - old pre - menopausal woman underwent bilateral breast reductions performed by the referring surgeon in 2007 . centers for disease control and prevention ( cdc ) have reported contamination of mbd with mycobacteria chelonae in facelift patients in 200311 . however , to our knowledge , infectious contamination of mbd has not been previously reported in any breast surgery patients . the patient 's plastic surgeon that had previously performed her breast reductions cultured mycobacteria chelonae directly from a contaminated bottle of mbd ( personal correspondence , microbiology reports ) . this plastic surgeon had a series of 24 mycoplasma chelonae infections secondary to mbd on several of his cosmetic surgery patients during a period of 3 months in 2007 ( personal correspondence , microbiology reports ) . this was never reported to the cdc or elsewhere in the medical literature to date . our patient 's follow - up mammogram showed distortion of the right breast in the upper quadrant , which was thought to be scarring from prior surgery , along with a separate mass , located in the 8 o'clock position , reported with the dimensions of 1.2 cm . we performed an ultrasound - guided core biopsy of that mass and identified nottingham grade 2 infiltrating lobular carcinoma with associated lobular carcinoma in situ . a bilateral breast magnetic resonance imaging ( mri ) showed a broad region ( 6.2 x 2.7 cm ) of abnormal enhancement in the right breast , which was suspicious for lobular carcinoma ( figures 6 - 7 ) . to evaluate the extent of disease , we performed 3 mri - guided core biopsies : 2 were negative for malignancy , and 1 revealed lobular carcinoma in situ . thus , mri was proven to overestimate her extent of disease secondary to her breast infections due to breast reduction . the patient elected to undergo bilateral total skin - sparing mastectomies and right axillary sln dissection . final pathology of the right breast revealed a 1.8-cm , multifocal , grade 2 , invasive lobular carcinoma with associated lobular carcinoma in situ . margins were 2 cm from the tumor , with none of the 4 slns involved . she enrolled in the trial assigning individualized options for treatment ( tailor rx ) and was randomized to undergo chemotherapy . her chronic lingering infection was an important factor in the decision to use systemic therapy with cyclophosphamide , methotrexate , and 5-fluorouracil ( cmf ) , to avoid neutropenia . her history of bilateral breast infections requiring numerous debridements also factored into her decision making to select bilateral mastectomies . she has completed chemotherapy , underwent breast reconstruction and is maintained on tamoxifen hormonal therapy . a 67-year - old woman with a t1b n0 m0 infiltrating ductal carcinoma of the left breast was treated by a surgeon at the referring institution : she underwent a left segmental mastectomy and sentinel lymph node ( sln ) biopsy for a 10 mm primary tumor located at the 9 o'clock position . the initial operating surgeon injected mbd in a subareolar subdermal fashion , complicated by mbd skin necrosis . the patient initially presented describing pain and tenderness of her left breast that persisted for two months following her first surgery . we noted a sinus in the 8 o'clock position , draining purulent fluid ; erythema surrounding the areola , extending toward the axilla ; and fluctuance in the central breast . on breast ultrasound examination , an area of loculated fluid culture results of this fluid showed corynebacteria and anaerobic gram negative rods , which was clinically believed to be due to infection of the chronic open wound secondary to mbd necrosis . we subsequently admitted the patient to the hospital to perform an incision and drainage ( i&d ) of her left breast unresolving abscess cavity . we made an incision in the area of maximal fluctuance in the left breast in the periareolar region at 5 o'clock . to explore the borders of the cavity , we used a lacrimal probe ; we noted that the cavity was connected to the sinus in the 8 o'clock position . the cavity measured approximately 8 cm x 7 cm x 2.5 cm and contained necrotic tissue . then , we made a separate incision over the sinus in the 8 o'clock position and completely excised the tract . once we debrided the cavity , we placed a wound vacuum - assisted closure ( vac ) device for negative pressure treatment with suction drainage 9 , 10 through 2 separate incisions ( figures 1 - 4 ) . a 45-year - old pre - menopausal woman underwent bilateral breast reductions performed by the referring surgeon in 2007 . she required multiple debridements , which resulted in extensive scar tissue and granuloma formation . the u.s . centers for disease control and prevention ( cdc ) have reported contamination of mbd with mycobacteria chelonae in facelift patients in 200311 . however , to our knowledge , infectious contamination of mbd has not been previously reported in any breast surgery patients . the patient 's plastic surgeon that had previously performed her breast reductions cultured mycobacteria chelonae directly from a contaminated bottle of mbd ( personal correspondence , microbiology reports ) . this plastic surgeon had a series of 24 mycoplasma chelonae infections secondary to mbd on several of his cosmetic surgery patients during a period of 3 months in 2007 ( personal correspondence , microbiology reports ) . this was never reported to the cdc or elsewhere in the medical literature to date . our patient 's follow - up mammogram showed distortion of the right breast in the upper quadrant , which was thought to be scarring from prior surgery , along with a separate mass , located in the 8 o'clock position , reported with the dimensions of 1.2 cm . we performed an ultrasound - guided core biopsy of that mass and identified nottingham grade 2 infiltrating lobular carcinoma with associated lobular carcinoma in situ . a bilateral breast magnetic resonance imaging ( mri ) showed a broad region ( 6.2 x 2.7 cm ) of abnormal enhancement in the right breast , which was suspicious for lobular carcinoma ( figures 6 - 7 ) . to evaluate the extent of disease , we performed 3 mri - guided core biopsies : 2 were negative for malignancy , and 1 revealed lobular carcinoma in situ . thus , mri was proven to overestimate her extent of disease secondary to her breast infections due to breast reduction . the patient elected to undergo bilateral total skin - sparing mastectomies and right axillary sln dissection . final pathology of the right breast revealed a 1.8-cm , multifocal , grade 2 , invasive lobular carcinoma with associated lobular carcinoma in situ . margins were 2 cm from the tumor , with none of the 4 slns involved . she enrolled in the trial assigning individualized options for treatment ( tailor rx ) and was randomized to undergo chemotherapy . her chronic lingering infection was an important factor in the decision to use systemic therapy with cyclophosphamide , methotrexate , and 5-fluorouracil ( cmf ) , to avoid neutropenia . her history of bilateral breast infections requiring numerous debridements also factored into her decision making to select bilateral mastectomies . she has completed chemotherapy , underwent breast reconstruction and is maintained on tamoxifen hormonal therapy . we are aware of only a few published complications of mbd in breast surgery patients ( table 1 ) . varghese et al 1 , described safely injecting mbd in the subdermal plane in the subareolar region with 97.6% identification rate . their only reported complication was temporary tattooing from mbd , which was also seen on goavert et al series 12 . mathelin et al 2 and soni et al 3 both used mbd safely without adverse reactions in sln mapping . stradling et al 5 was the first to describe local skin reactions to mbd injection for sln mapping , including skin necrosis in 5 of 24 patients . zakaria et al 4 and salhab et al 6 both reported skin and fat necrosis in a small percentage of patients who received mbd injections for sln mapping . komenaka et al 13 described a palpable mass at the site of injection of mbd . nearly all of the masses resolved by one year , however , one resolved after 18 months . they reported capsular contraction associated with mbd , after immediate reconstruction using breast prosthesis . in their case they attributed local inflammatory reaction from the mbd as the main cause of the capsular contraction . one of our patients ( case 1 ) presented with a well - developed region of fat necrosis with cavity formation . fat necrosis is an important diagnostic consideration as it may persist and can clinically mimic carcinoma . early in its development , fat necrosis is composed of disrupted fat cells and hemorrhage with an influx of histiocytes , some becoming multinucleate as they ingest debris . after several weeks the affected area develops peripheral fibrosis , often with calcification and forming a tumor - like lesion which may clinically mimic carcinoma 15 . electrocautery has evident thermal effect around the edges and involved areas and does not cause such extensive destruction beyond the local tissue perimeter , with several centimeters of fat necrosis , as in the case of our patient . we are aware of 1 report of mbd contamination with mycobacteria chelonae that caused infections in patients who had undergone facelifts 11 . to our knowledge , our case represents the initial report of contaminated mbd in breast surgery patients . this is of particular concern due to the impact that contaminated mbd had on the surgical and adjuvant management of breast cancer for our patients . our 2 case reports confirm the findings of previous publications that complications of mbd are capable of causing tissue necrosis . of note , both of our patients required extensive surgical debridements , revealing that mbd does indeed have side effects not considered in the previously published literature . in our case report # 2 , the discovery of a complicating mycobacterial infection led to delayed adjuvant treatment and had a significant impact on our choice for systemic treatment . historically , giuliano et al 16 , described using blue dye as peritumoral injection with good results ; peritumoral injection of blue dye is the most common approach to lymphatic mapping with vital blue dyes . there are a limited number of studies indicating high success rates of identifying slns using subareolar injection of blue dye 20 - 22 . rodier et al 23 , using both blue dye and radiolabelled isotope , found that using periareolar injection was equivalent to using peritumoral injection in identifying sln . there are several studies supporting the different sites of injection for blue dye , but subareolar and dermal injections have been proven to cause more local side effects , like discoloration of the breast , that can last several months 24 . in our case it caused more than just discoloration but led to substantial tissue loss due to necrosis . lymphazurin had long been held as the standard for sentinel lymph node mapping in breast cancer25 . however , mbd has demonstrated equivalent efficacy in lymphatic mapping compared to lymphazurin 3 , 26 - 28 , is less expensive , more readily available and is not associated with the potentially deleterious side effects of severe allergic reaction , including anaphylaxis 3 , 8 , 29 as has been reported with lymphazurin . raut et al reported an incidence of severe anaphylactoid reaction to lymphazurin of 1.1 % ; preoperative prophylaxis reduced the severity , but not the overall incidence ( 0.5% ) of adverse reactions to lymphazurin blue dye 30 . blue urticaria and facial edema were the reactions observed after preoperative prophylaxis in that study . as described in the above cases and table , mbd is not without its own potential for complications . the risk for complications of mbd should be taken into consideration when selecting a blue dye for lymphatic mapping . either may be used in combination with radioactive colloid and a gamma probe for sentinel lymph node mapping . according to the asco guidelines , the greatest proportion of successful mappings and the lowest false negative rates are associated with the use of blue dye and radiolabelled colloid used in conjunction 7 . however , golshan and colleagues 31 have recently published data to show that sentinel nodes can be successfully identified with mbd only . additionally , they recommend the use of mbd over lymphazurin , due to the latter 's known potentially deleterious side effects of severe allergic reaction , anaphylaxis or even death . the dosing and concentration of mbd , in successful identification of sln , has been described as 1 - 5 milliliters ( ml ) of 1% methylene blue 3 , 5 , 31 or 1.25mg / ml 2 , 4 . mbd may indeed become the most prevalent vital blue dye for these reasons and due to intermittent national shortages of lymphazurin blue dye 3 . the importance of understanding its proper usage and potential complications , therefore , can not be understated . we are aware of only a few published complications of mbd in breast surgery patients ( table 1 ) . varghese et al 1 , described safely injecting mbd in the subdermal plane in the subareolar region with 97.6% identification rate . their only reported complication was temporary tattooing from mbd , which was also seen on goavert et al series 12 . mathelin et al 2 and soni et al 3 both used mbd safely without adverse reactions in sln mapping . stradling et al 5 was the first to describe local skin reactions to mbd injection for sln mapping , including skin necrosis in 5 of 24 patients . zakaria et al 4 and salhab et al 6 both reported skin and fat necrosis in a small percentage of patients who received mbd injections for sln mapping . komenaka et al 13 described a palpable mass at the site of injection of mbd . nearly all of the masses resolved by one year , however , one resolved after 18 months . they reported capsular contraction associated with mbd , after immediate reconstruction using breast prosthesis . in their case they attributed local inflammatory reaction from the mbd as the main cause of the capsular contraction . one of our patients ( case 1 ) presented with a well - developed region of fat necrosis with cavity formation . fat necrosis is an important diagnostic consideration as it may persist and can clinically mimic carcinoma . early in its development , fat necrosis is composed of disrupted fat cells and hemorrhage with an influx of histiocytes , some becoming multinucleate as they ingest debris . after several weeks the affected area develops peripheral fibrosis , often with calcification and forming a tumor - like lesion which may clinically mimic carcinoma 15 . electrocautery has evident thermal effect around the edges and involved areas and does not cause such extensive destruction beyond the local tissue perimeter , with several centimeters of fat necrosis , as in the case of our patient . we are aware of 1 report of mbd contamination with mycobacteria chelonae that caused infections in patients who had undergone facelifts 11 . to our knowledge this is of particular concern due to the impact that contaminated mbd had on the surgical and adjuvant management of breast cancer for our patients . our 2 case reports confirm the findings of previous publications that complications of mbd are capable of causing tissue necrosis . of note , both of our patients required extensive surgical debridements , revealing that mbd does indeed have side effects not considered in the previously published literature . in our case report # 2 , the discovery of a complicating mycobacterial infection led to delayed adjuvant treatment and had a significant impact on our choice for systemic treatment . the site of injection of blue dyes is still controversial . historically , giuliano et al 16 , described using blue dye as peritumoral injection with good results ; peritumoral injection of blue dye is the most common approach to lymphatic mapping with vital blue dyes . there are a limited number of studies indicating high success rates of identifying slns using subareolar injection of blue dye 20 - 22 . rodier et al 23 , using both blue dye and radiolabelled isotope , found that using periareolar injection was equivalent to using peritumoral injection in identifying sln . there are several studies supporting the different sites of injection for blue dye , but subareolar and dermal injections have been proven to cause more local side effects , like discoloration of the breast , that can last several months 24 . in our case it caused more than just discoloration but led to substantial tissue loss due to necrosis . lymphazurin had long been held as the standard for sentinel lymph node mapping in breast cancer25 . however , mbd has demonstrated equivalent efficacy in lymphatic mapping compared to lymphazurin 3 , 26 - 28 , is less expensive , more readily available and is not associated with the potentially deleterious side effects of severe allergic reaction , including anaphylaxis 3 , 8 , 29 as has been reported with lymphazurin . raut et al reported an incidence of severe anaphylactoid reaction to lymphazurin of 1.1 % ; preoperative prophylaxis reduced the severity , but not the overall incidence ( 0.5% ) of adverse reactions to lymphazurin blue dye 30 . blue urticaria and facial edema were the reactions observed after preoperative prophylaxis in that study . as described in the above cases and table , mbd is not without its own potential for complications . the risk for complications of mbd should be taken into consideration when selecting a blue dye for lymphatic mapping . both mbd and lymphazurin are vital blue dyes . either may be used in combination with radioactive colloid and a gamma probe for sentinel lymph node mapping . according to the asco guidelines , the greatest proportion of successful mappings and the lowest false negative rates are associated with the use of blue dye and radiolabelled colloid used in conjunction 7 . however , golshan and colleagues 31 have recently published data to show that sentinel nodes can be successfully identified with mbd only . additionally , they recommend the use of mbd over lymphazurin , due to the latter 's known potentially deleterious side effects of severe allergic reaction , anaphylaxis or even death . the dosing and concentration of mbd , in successful identification of sln , has been described as 1 - 5 milliliters ( ml ) of 1% methylene blue 3 , 5 , 31 or 1.25mg / ml 2 , 4 . mbd may indeed become the most prevalent vital blue dye for these reasons and due to intermittent national shortages of lymphazurin blue dye 3 . the importance of understanding its proper usage and potential complications , therefore , can not be understated . the use of mbd in breast surgery patients is not without risk . in both of these patients , mbd was integral to complications requiring surgical debridements for local wound problems . in each patient 's case , awareness should be raised regarding mbd 's potential to elicit tissue necrosis resulting in significant morbidity , cosmetically unsatisfactory results and even delayed cancer treatment .