INTRODUCTION
Diabetic mastopathy has been described as a clinicopathologic entity based on the presence of a benign fibrous disease in breast tissue in patients with type I diabetes (1, 2). However, recent cases of diabetic mastopathy in type II diabetes mellitus have been reported (3, 4). Diabetic mastopathy represents less than 1% of benign breast lesions (2, Patient with diabetic mastopathy present with hard, painless and irregular mass 5-7). of the breast, which clinically simulates breast cancer, and misinterpretation of these masses as breast cancer has resulted in unnecessary mastectomy (5, 8). Here we report an uncommon case of diabetic mastopathy in type II diabetes.
CASE REPORT
The patient was a 66-year-old postmenopausal woman, who was diagnosed with type II diabetes in 2004. She has been treated with  α -glucosidase inhibitor for 6 years and also suffered from ureterolithiasis for 5 years. However, she had no microvascular and macrovascular diabetic complications. She noticed a lump in her right breast two examination  revealed previously. weeks Physical a hard, movable, and well-circumscribed mass in the upper outer quadrant of the right breast. The size was approximately 14x20 mm in diameter.   No axillary lymph node swelling was noted and there was no nipple discharge. Blood sugar was 162 mg/dl and HbA1c was 6.6%. Thyroid function tests were all within normal limits thyroid stimulating hormone(TSH), 1.7 μ U/ml; free triiodothyronine(fT 3 ), 3.2 pg/ml; and free thyroxine(fT 4 ), 1.2 ng/dl. Mammography breast showed localized of the increased    density without microcalcification or architectural distortion (Fig. 1).  Ultrasonography of the lesion revealed a hypoechoic mass with a distinct margin, containing high echo in the cavity and measured 20x8 mm in diameter (Fig. 2).  Fine needle aspiration cytology was performed but sufficient tissue was not obtained.    A cluster of small epithelial cells with nucleus swelling and increased chromatin was demonstrated. A core needle biopsy was advised but the patients requested resection of the mass. In November 2009, removal of the tumor was performed under local anesthesia, and the procedure was completed successfully.   An impression of benign tumor was gained from the cut surface of the resected specimen.   Pathological findings showed that the lesion consisted of massive collagen fibers with keloid-like fibrosis and lymphatic infiltration around the lobules and ducts (Fig. 3, 4). These lymphocytes were composed predominantly of B-cells since they were immunohistochemically positive for CD20 (Fig 5). A diagnosis of diabetic mastopathy was determined.
DISCUSSION
Soler and Khardori (1) first reported 12 cases of fibrous disease of the breast in association with type I diabetes mellitus of long duration in 1984.    Diabetic mastopathy is considered as an uncommon tumor of fibrous tissue of the breast mimicking breast cancer.  In addition, diabetic mastopathy has also been observed in type II diabetes mellitus, and until 2006 twenty-five cases of diabetic mastopathy have been reported in This condition is also found in patients with type II diabetes mellitus patients(9). other endocrine disorders, especially thyroid diseases (2, 6, 8). Honda et al. (10) reported differences of diabetic mastopathy between Japan and Western countries, showing that most cases in Western countries are in premenopausal women with type I diabetes, while in Japan, most cases are in postmenopausal women with type II diabetes. They speculated that differences of genetic factors, including HLA type, between Japan and the Western countries were the source of this finding. nontender, single or Diabetic mastopathy involves a hard, irregular, movable, multiple, unilateral or bilateral mass(4, 7, 11).  Seidman  et al.(6) reported a mean duration of longer than 13 years (range 4-27 years) for diabetic mastopathy to develop. Mammographic appearances show the presence of a dense parenchymal structure with no distortions or microcalcifications (7, 12).  Ultrasound findings vary from irregular hypoechoic mass with marked acoustic shadowing to a vague hypoechoic area without shadowing (7, 12).    However no discrete solid or cystic masses were identified. specific mastopathy is a distinct clinicopathologic entity Diabetic with histopathologic characteristics, which include keloidal fibrosis, epithelioid fibroblasts, wide spread perivascular/lobular lymphocytic infiltration, and widespread perivascular lymphocytic infiltration (2).  The frequency of the four features is approximately 60-70% (4, 6, 13) and these cases are relatively specific for insulin-requiring diabetes mellitus. The lesion we studied is characterized by the presence of dense keloid-like fibrosis and perivascular lymphocytic infiltration, but lacks epithelioid fibroblasts. Epithelioid fibroblasts, although they may be an integral component of the lesion (6), are not necessary for the diagnosis of diabetic mastopathy (2) and they were also seen in patients without a diabetic history(3, 4). Thus, it seems that the proposed features are not as specific as previously maintained, or the appearance of diabetic mastopathy in the breast may precede the onset of clinical diabetes or another autoimmune process (4). Lymphatic infiltration in diabetic mastopathy consists predominantly of B-cells, in contrast to non-diabetic mastitis in which lymphocytic infiltration consists mostly of T-cells (2, 14). This B-cell predominance is similar to the lymphocytic infiltrate seen in other disorders, Hashimoto’s benign autoimmune such thyroiditis and as lymphoepithelial lesion of salivary gland (6).  The present case also showed B-cell lymphatic infiltration in immunohistochemical findings, but we have not had the opportunity to examine our patient for autoimmune disorders. Although the pathogenesis is still obscure and could be multifactorial, it is generally believed that these lesions are attributable to extracellular matrix expansion secondary to increased collagen production and decreased degradation, in part related to the hyperglycemic state(2). Another reason is autoimmune reaction, showing lymphocytic infiltration for B cells (1, 2, 4, 7). The role of autoimmunity in the case of diabetic mastopathy was first suggested by Soler and Khardori (1).   Type II diabetes often have endogenous hyperinsulinemia and only patients on exogenous insulin developed diabetic mastopathy, suggesting that exogenous insulin use may be related to diabetic In type I diabetes, Kudva et al. (15) reported that diabetic mastopathy mastopathy. development is not associated with the use of insulin or degree of glycemic control and patients with sclerosing lymphocytic lobulitis show significantly higher prevalence of retinopathy and neuropathy.  On the contrary, Tomaszewski et al.(2) described that diabetic mastopathy without epithelioid fibroblasts showed no secondary diabetic changes. Histologic findings are necessary for the diagnosis of diabetic mastopathy, but fine needle aspiration cytology cannot obtain sufficient material for a diagnosis because of Core needle biopsy is recommended to avoid unnecessary surgical the hard tumor. procedure because surgery may exacerbates the condition.  Additional data in the literature shows that approximately over half of lesions are bilateral or recurrent or both (4, 11).  With reference to recurrence Camuto et al. (11) reported that about 60% of diabetic mastopathy tends to recur after surgical excision in the same location and involves more breast tissue than the preceding lesion, and surgical biopsy should not be This suggests that the natural history of diabetic mastopathy involves a considered. multicentric field effect of diabetes on breast tissue.  Recognition of this capacity for disease recurrence is considered to be important as it might help to avoid repeated In our case, a correct diagnosis was not obtained using fine needle biopsy  (4). aspiration cytology, and an excisional biopsy was performed by the patient's request. We were aware of the disease of diabetic mastopathy, but it was not included in If we had recognized the entity of diabetic differential diagnosis in this case. mastopathy, we might have taken core needle biopsy in consideration of the possibility of recurrence of this disease. Fibrous 1. Soler Khardori R. the thyroiditis NG, disease breast, and of cheiroarthropathy in type I diabetes mellitus. Lancet, 1:193-195, 1984. 2. Tomaszewski JE, Brooks JSJ, Hicks D, Livolsi VA. Diabetic mastopathy. A distinctive clinicopathologic entity. Human Pathol, 23:780-786, 1992. 3. Morgan MC, Meaver MG, Crowe JP, Abdul-Karim FW. Diabetic mastopathy a clinicopathologic study in palpable and nonpalpable breast lesions. Mod Pathol, 8:349-354, 1995. 4. Ely KA, Tse G, Simpson JF, Clarfeld R, Page DL. Diabetic masthopathy. A clinicopathogic review. Am, J Clin Pathol, 113:541-545, 2000. 5. 6. Foschini MP, Cavazza A, Macedo Pinto IM, Eusebi V.   Diabetic fibrous mastopathy. Report of two cases. Virchows Arch A Pathol Anat Histopathol, 417:529-532, 1990. Seidman JD, Schnaper LA, Phillips LE. Mastopathy in insulin-requring diabetes mellitus. Hum Pathol, 25:819-824, 1994. 7. Logan WW, Hoffman NY.   Diabetic fibrous breast disease. Radiology, 172:667-670, 1989. 8.   Rode S, Favre C, Hivolet C. Diabetic mastopathy: a frequent source of confusion with lobular breast carcinoma.   Diabetes Care, 21:322, 1998. 9.   Sotome K, Ohnishi T, Miyoshi R, Nakamaru M, Furukawa A, Miyazaki H, Morozumi K, Tanaka Y, Iri H. An uncommon case of diabetic mastopathy in type II non insulin dependent diabetes mellitus. Breast cancer, 13:205-209, 2006. 10. Honda M, Mori Y, Nishi T, Mizuguchi K, Ishibashi M. Diabetic mastopathy of bilateral breasts in an elderly Japanese woman with type 2 diabetes: A case report and a review of the literature in Japan. Internal Medicine, 46:1573-1576, 2007 11. Camuto PM, Zetrenne E, Ponn T. Diabetic mastopathy a report of 5 cases and a review of literature. Arch Surg 135:1190-1193, 2000 12. Byrd BF, Hartman WH, Graham LS, Hogle HH. Mastopathy in insulin dependent diabetes. Ann Surg, 205:529-532, 1987. 13. Sternberg M, Cohen-Fortere L, Peyroux J. Connective tissue in diabetes mellitus: biochemical alterations of the extracellular matrix with special reference to proteoglycans, collagens and basement membranes. Diabetes Metab, 11;27-50, 1985 14. Lammie GA, Bobrow LG, Staunton MDM, Levison DA, Page G, Millis RR. Sclerosing lymphocytic lobulitis of the breast ---Evidence for an autoimmune pathogenesis. Histopathol, 19:13-20,1991 15. Kudva  YC,  Reynolds  C,  O’Brien  T,  Powell  C,  Oberg  AL,  Crotty  TB.  "Diabetic Mastopathy", or Sclerosing Lymphocytic Lobulitis, is strongly associated with type 1 diabetes. Diabetes Care, 25:121-126, 2002. Fig. 1 Mammography demonstrated localized increased density. Fig. 2   Ultrasound showed hypoechoic mass with distinct margin, containing high echo. Fig. 3 Bands of dense collagen with keloid-like features.( HE stain   x4) Fig. 4 Lymphocytic infiltration around the lobules and ducts.(HE stain   x10) Fig. 5. Immunohistochemical stain for CD-20 antibody( x4). Infiltrative lymphocytes with predominant B-cell were positively stained.