Axillary adenopathy as presenting characteristic of diabetic mastopathy Journal: Manuscript ID: Manuscript Type: BMJ Case Reports draft Rare disease Date Submitted by the Author: Complete List of Authors: Keywords: Christiaensen, Els; UZA, ObGyn jacquemyn, yves; UZA, Obstetrics verslegers, inge; uza, radiology van goethem, mireille; uza, radiology Van Marck, Veerle; UZA, Pathology Diabetes 77 < Endocrinology 1325, Breast cancer 282 < Oncology 1333, Obstetrics and gynaecology 1332 Page 1 of 6 TITLE OF CASE Axillary lymphadenopathy as a first symptom of diabetic mastopathy AUTHORS OF CASE Please indicate corresponding author by * Christiaensen E. , Jacquemyn *Y., Verslegers I, Van Goethem M., Van Marck V. SUMMARY Up to 150 words summarising the case presentation and outcome Diabetic mastopathy is an unusual fibro-inflammatory breast lesion that characteristically presents in premenopausal women with long-standing type 1 diabetes mellitus. Patients present with clinically suspicious breast masses or axillary lymph nodes with imaging characteristics indistinguishable from malignancy. Fine needle aspiration is often inadequate and a core biopsy should be performed. Excisional biopsy is not necessary, annual follow-up is recommended. Recognition of diabetic mastopathy should lead to better care of diabetic patients with breast nodules or axillary masses, avoiding surgery for this benign condition. BACKGROUND Why you think this case is important – why you decided to write it up Physicans should be aware of the rare association of long-standing diabetes mellitus with the development of benign fibro-inflammatory breast lesions when managing these in premenopausal women. Although these breast masses may be recurrent, they are not premalignant. The diagnosis can be made by core biopsy, avoiding unnecessary repeated wide excisions in these young patients. CASE PRESENTATION Presenting features, medical/social/family history A 34-year-old caucasian woman presented to the outpatient clinic for evaluation of a palpable, firm gland in her left axilla. She had no family history of breast cancer and no history of previous breast disease. She suffered from type 1 diabetes since the age of 14. In recent years she was treated with one injection of slow-acting insulin and three daily injections of fast-acting insulin. Mean HbA1C value was around 7.2% since more than1 year. She was known with bilateral mild non-proliferative diabetic retinopathy and microproteinuria. Physical examination confirmed the presence of a firm, but freely movable, 1.5cm diameter mass in the left axilla; the contralateral axilla and supraclavicular fossae showed no palpable adenopathy and both breasts were normal. INVESTIGATIONS If relevant An initial mammography showed bilateral dense glandular tissue with no suspect mass lesions. An ultrasound visualised in the left axilla a fusiform lymphatic gland with a diameter of 2.4cm and a thickened cortex of 3.5 mm ( figure 1). Clinical evaluation after 1 month showed na difference. After 4 months, follow-up physical examination revealed, beside the adenopathy, a palpable mass in the superolateral quadrant of the right breast, identified on ultrasound as an inhomogenic hyporeflective zone of 4*3*1.5 cm (figure 2). A fine-needle aspiration (FNA) of the lymphatic gland was inadequate, yielding few red blood cells and lymfocytes, but no atypic cells. A core biopsy from the breast lesion was then performed. Histopathological examination showed no signs of neoplasia. Prominent stromal sclerosis embedding some glandular structures was apparent and in association with a perilobular lymphocytic infiltrate ( including both CD3 positive T cells and CD20 positive B cells) a diagnosis of sclerosing lymphocytic lobulitis or diabetic mastopathy was reached( Page 1 of 3 Page 2 of 6 figure 3). DIFFERENTIAL DIAGNOSIS If relevant Invasive carcinoma Fibroadenoma Mastitis Diabetic mastopathy TREATMENT If relevant No treatment is necessary OUTCOME AND FOLLOW-UP The patient was informed about her benign condition. Clinical breast examination followed by routine mammography and ultrasound as for any nondiabetic woman is recommended. This patient was advised that if there are any changes in size and number of breast/axilla masses, she should consult the breast team again. If the lesions become clinically or radiologically suspicious magnetic resonance imaging of the breast and/or core biopsy can be performed. DISCUSSION including very brief review of similar published cases (how many similar cases have been published?) Diabetic mastopathy or sclerosing lymphocytic lobulitis was first reported as “fibrous disease of the breast” by Soler and Khardori in 1984 (1). Since then less than 200 cases have been reprted in the literature as individual case studies and case series(2). To our knowledge we are the first to report an enlarged palpable lymphatic gland as presenting characteristic of the disease. In order for a diagnosis to be made, the patient must be diabetic. The majority of cases in the literature are found in type 1 diabetes, although some cases are in longstanding type 2 diabetics, insulin therapy is always present. Many cases also report other complications of diabetes mellitus like retinopathy, nephropathy and neuropathy. The majority of cases are reported in premenopausal women, but there are a few cases in men (3,4). Patients present with multiple, sometimes bilateral and recurrent breast masses In ouir case the original presenting symptom was an enlarged contraleteral axillary lymph node a few months before the breast mass became apparent. Mammography usually shows dens breast parenchyma, dense glandular tissue , asymmetric densities and parenchymal deformity. A discrete mass lesion is typically not visualized. So no features conclusive enough to make a diagnosis of diabetic mastopathy nor to exclude malignancy on mammography are present (5). Findings on ultrasound include ill-defined hypoechoic areas with strong acoustic shadowing. This findings are indistinguishable from malignancy (6). Magnetic resonance imaging is unlikely to add any further information in the initial diagnosis, but may demonstrate suspicious areas of focal enhacement wich would require further evaluation and detect malignancy in a diabetic mastopathy patient (7). Because of the fibrosis of the stroma, the characteristic diabetic mastopathy lesion is very resistant to the-in-and-out motion of the fine needle for aspiration biopsy. In 50% of the cases, the aspirate is inadequate for diagnosis (8). A core biopsy should then be performed. The pathophysiology of this condition is unknown, one theory relates to the production of nonenzymatically glycosylated proteins in diabetes. These are often cross-linked and restistant to degradation, and deposited within the matrix of various tissues, including the breast, where they can stimulate an immunogenic response (9). This manifests as a localized autoimmune reaction with perivascular proliferation of lymphocytes. Typical pathologic findings include lymphocytic lobulitis and ductitis, glandular atrophy, Page 2 of 3 Page 3 of 6 lymphocytic/mononuclear perivascular inflammation which is predominantly B-cel type, dense often keloid-like fibrosis and epithelioid-like fibroblasts. LEARNING POINTS/TAKE HOME MESSAGES 3 to 5 bullet points -Consider benign diabetic mastopathy in premenopausal woman with longstanding type 1 diabetes mellitus presenting with a palpable breast mass or lymph node. -When mammographic and ultrasonographic studies do not exclude malignancy, perform core biopsy instead of a fine needle aspiration to avoid unnecessary surgery in young women. -Routine annual follow up is sufficient. REFERENCES Vancouver style (Was the patient involved in a clinical trial? Please reference related articles) 1. Soler 2. 3. 4. 5. 6. 7. 8. 9. Figure captions Figure1: Ultrasound image of lymphatic axillary gland with thickened cortex Figure 2: Ultrasound image og inhomogeneous hyporeflective zone in the right breast Figure 3: Micrograph of a hematoxylin-eosin-stained section of the core biopsy from the lesion Copyright Statement I, [INSERT YOUR NAME IN FULL], The Corresponding Author, has the right to assign on behalf of all authors and does assign on behalf of all authors, a full assignment of all intellectual property rights for all content within the submitted case report (other than as agreed with the BMJ Publishing Group Ltd) (“BMJ Group”)) in any media known now or created in the future, and permits this case report (if accepted) to be published on BMJ Case Reports and to be fully exploited within the remit of the assignment as set out in the assignment which has been read. (http://casereports.bmj.com/instructions-for-authors/copyright.pdf)." Date: PLEASE SAVE YOUR TEMPLATE WITH THE FOLLOWING FORMAT: Corresponding author’s last name and date of submission, eg, Smith_June_2008.doc Page 3 of 3 Page 4 of 6 Page 5 of 6 Page 6 of 6