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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 517-519
Ciclosporin-induced accessory breast tissue: Dramatic improvement after dose adjustment


Department of Internal Medicine, Dr. Salma Center for Kidney Disease and Transplantation, Faculty of Medicine, University of Khartoum, Khartoum, Sudan

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Date of Submission15-Dec-2018
Date of Acceptance15-Jan-2019
Date of Web Publication23-Apr-2019
 

   Abstract 


Accessory breast tissue is a relatively common congenital condition in which abnormal accessory breast tissue is seen as a mass anywhere along the course of embryologic mammary streak in addition to the presence of normal breast tissue. Ciclosporin therapy has been associated with benign breast disease in women. However, to the best of our knowledge, there are no reported cases of accessory breast tissue growth associated with ciclosporin therapy and regression after adjusting the dose. A 48-year-old woman had renal transplantation in 2009 with her brother as the donor. Her transplant follow-up over eight years had been unremarkable. She presented to our transplant follow-up clinic with bilateral painful axillary masses approximately 3 cm × 3 cm in diameter, not attached to the skin or underlying structures with no skin changes and no lymphadenopathy. Breast examination did not reveal any abnormalities. Her ciclosporin levels over the previous three years ranged between 130 and 150 ng/mL. These levels were within the acceptable recommended level of 100–150 ng/mL at that time (currently reduced to 80–120 ng/ml). Ultrasound of both axilla showed well-defined hypoechoic smooth outline masses in both axillary regions 3 cm × 4 cm. Fine-needle aspiration showed lesions consisting of cohesive ductal cells. The findings were consistent with accessory breast tissue with no evidence of inflammatory infiltrate or malignant changes. Her ciclosporin dose was reduced with the subsequent follow-up visits levels ranging between 90 and 110 ng/mL. Clinical examination four months later showed dramatic reduction in the axillary masses on both sides. Ultrasound confirmed the regression in the size of both masses. We conclude that ciclosporin was probably responsible for the formation of accessory breast tissue and reduction in the dose of ciclosporin resulted in substantial reduction in the tissue size.

How to cite this article:
Mahmoud Karrar WN, Elsafi AA, Abboud OI. Ciclosporin-induced accessory breast tissue: Dramatic improvement after dose adjustment. Saudi J Kidney Dis Transpl 2019;30:517-9

How to cite this URL:
Mahmoud Karrar WN, Elsafi AA, Abboud OI. Ciclosporin-induced accessory breast tissue: Dramatic improvement after dose adjustment. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 21];30:517-9. Available from: http://www.sjkdt.org/text.asp?2019/30/2/517/256860



   Introduction Top


Accessory breast tissue is a relatively common congenital condition in which abnormal accessory breast tissue is seen in addition to the presence of normal breast tissue.[1] This normal variant can present as a mass anywhere along the course of the embryologic mammary streak (axilla to the inguinal region), but masses are most frequently found in the axilla and may occur bilaterally. They are rarely seen in the face, back, and thigh. Supernumerary nipples may be seen. The condition is found in 2%–6% of women and 1%–3% of men.[2] It responds to hormonal stimulation and may become more evident during menarche, pregnancy, or lactation.[1] Discomfort, pain, milk secretion, axillary thickening, and local skin irritation are the presenting symptoms.

No treatment is required in the vast majority of cases. The treatment of choice for symptomatic accessory axillary breast tissue is surgical excision as removal of the tissue will relieve physical or mechanical discomfort in case of large volume accessory tissue.[3]

In common with regular breast tissue, accessory mammary tissue may exhibit malignancy, fibroadenoma, mastitis, and fibrocystic change. The ectopic breast tissue has been found to have a higher propensity to develop malignancy that tend to occur at an earlier age.[3]

Recently, an association between ciclosporin therapy and the development of benign breast disease in women has been described,[4],[5] but to the best of our knowledge, there are no reported cases of ciclosporin-induced accessory breast tissue growth and no reported cases of reduction in the size of ciclosporin-induced accessory breast tissue after dose adjustment.


   Case Report Top


A 48-year-old Sudanese single woman presented to our transplant clinic for regular follow-up. She complained of bilateral axillary masses which she noticed over the past two months. The patient was diagnosed with having end-stage renal failure requiring dialysis in the year 2004. The cause of her renal failure was not known. She was successfully maintained on hemodialysis for four years. In May 2009, she received a kidney transplant from her brother with uneventful postoperative period. She was maintained on immuno-suppressive drugs in the form of ciclosporin, mycophenolate mofetil and prednisolone. She had stable kidney function over the whole period of follow-up, but her ciclosporin level had a tendency to be at a higher level in the past three years.

There was no family history of renal disease or genetic disorders. She did not have any other medical or surgical history. She neither had any breast disease nor did she notice any breast or axillary masses before. Her menarche was around the age of 14 years and her menstrual cycle was regular except over the previous two years when it started to occur every three to five months.

Examination showed that the patient, of average weight and height, had bilateral axilla masses approximately 3 cm × 3 cm in diameter, not attached to the skin or underlying structures, no skin changes and no lymphadenopathy. Breast examination did not reveal any abnormalities. The transplanted kidney felt normal, and systemic examination was otherwise unremarkable. Laboratory tests were within acceptable limits. The ciclosporin level was 130 ng/mL. Review of the ciclosporin levels over the previous three years showed levels consistently being between 130 and 150 ng/mL. These levels were within the acceptable recommended level of 100–150 ng/mL at that time. Recently, however, the recommended acceptable therapeutic range has been reduced to 80–120 ng/mL, after adverse side effects of the higher level were noted.[6]

Ultrasound of both axillae showed well-defined hypoechoic smooth outline masses in both axillary regions 3 cm × 4 cm suggestive of accessory breast tissues. Fine-needle aspiration was done and showed lesions consisted of cohesive ductal cells, myoepithelial cells and stromal fragments in a clear background with no evidence of inflammatory infiltrate or malignancy.

Her ciclosporin dose was adjusted with a range between 90 and 110 ng/mL, and the patient was reassured that there were no malignant changes in the axillary masses and no evidence of bacterial infection. In a follow-up visit after two months, she reported relief of the discomfort and reduction in the size of the axillary masses. On examination, the masses were indeed substantially less in size on both axilla compared to the previous reported sizes. A further follow-up ultrasound confirmed the regression in the size of both masses to 1.7 cm × 0.9 cm × 1.8 cm on the right and 2.5 cm × 2.9 cm × 1.6 cm on the left in comparison with 3 cm × 4 cm in the first ultrasound. Further, follow-up (up to 12 months) showed more reduction in size.


   Discussion Top


In 1980, Rolles and Calne first highlighted the association between ciclosporin therapy and the development of benign breast disease in women.[4] The incidence of fibroadenoma among kidney transplanted patients receiving ciclosporin was estimated to be one in 9.4 patients.[4] The mechanisms involved remain unclear. Proposed mechanism includes: (a) direct effect of the drug on breast fibroblast as several ciclosporin-binding proteins have now been identified in lymphoid and non-lymphoid cells; (b) an endocrine pathway mediated by hypothalamus-pituitary axis;[5] (c) increased synthesis and expression of transforming growth factor B, also believed to be the cause of gingival hypertrophy.[5]

In the general population, about 2%–6% of the females and 1%–3% of males have accessory breast tissue, which is usually found (67%) along the thoraco-abdominal region of the milk line.[2] Occasionally, it is found in unusual locations such as the face, scapula, and thigh. Usually, it starts to be symptomatic by the onset of puberty or pregnancy. However, in most cases, it may pass unnoticed. Our patient was not diagnosed previously with accessory breast tissue nor did she experience any symptoms (such as tenderness, swelling in the axilla or difficulty with shoulder movement) before the use of ciclosporin. There are no clear estimations about the incidence of bilateral axillary breast tissue among the general population in Sudan. There is no available data in the literature about ciclosporin-induced accessory breast tissue. A few cases reported unilateral fibroadenoma in the axillary area on top of accessory breast tissue or giant fibroadenoma presented as an axillary mass as reported by Sitt et al.[5]


   Conclusion Top


Ciclosporin therapy post renal transplantation is associated with an increased incidence of benign breast changes. Fibroadenomas are the most frequently reported ones, while accessory breast tissues are the least if any. Awareness of the association between ciclosporin and benign breast conditions should help to achieve the correct diagnosis without subjecting these patients to unnecessary procedures. Regular follow-up and appropriate selection of immunosuppressant therapy are essential in the management of these patients.

Conflict of interest: None declared.



 
   References Top

1.
Knipe H. Accessory Breast Tissue. Electronic Article. Available from: https://www. radiopaedia.org/articles/accessory-breast-tissue. Last accessed on 2 March 2018.  Back to cited text no. 1
    
2.
Patel PP, Ibrahim AM, Zhang J, Nguyen JT, Lin SJ, Lee BT. Accessory breast tissue. Eplasty 2012;12:ic5.  Back to cited text no. 2
    
3.
Eardley KS, Wan DI, Thomas ME, Banerjee AK, Radojkovic M, Taylor JL. Transplant-associated inflammatory breast disease. Nephrol Dial Transplant 2002;17:512-5.  Back to cited text no. 3
    
4.
Rolles K, Calne RY. Two cases of benign lumps after treatment with cyclosporin A. Lancet 1980;2:795.  Back to cited text no. 4
    
5.
Sitt JC, Ni SY, Tosi VY, Chan WC, Chau HH. Giant fibroadenoma presenting as an axillary mass in a young renal transplanted recipient on long term ciclosporin therapy. Hong Kong J Radiol 2017;19:300-2.  Back to cited text no. 5
    
6.
Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4:481.  Back to cited text no. 6
    

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Correspondence Address:
Wieam Nabil Mahmoud Karrar
Department of Internal Medicine, Dr. Salma Canter for Kidney Disease and Transplantation, Faculty of Medicine, University of Khartoum, Khartoum
Sudan
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DOI: 10.4103/1319-2442.256860

PMID: 31031389

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    Abstract
   Introduction
   Case Report
   Discussion
   Conclusion
    References
 

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