A 30-year-old man comes to the office due to a 3-month history of progressive left breast enlargement. He has had no breast pain or nipple discharge. The patient has a history of Klinefelter syndrome and takes testosterone replacement therapy. Vital signs are within normal limits. BMI is 30 kg/m². Physical examination shows a 2.5-cm, nontender, firm subareolar mass on the left side. Right breast examination is normal. The testes are atrophic and body hair is sparse. Which of the following is the best next step in management of this patient?

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Explanation: 11ec25c8_d21f_346f_bc81_5d7f51ff917a_MD0003_00 This patient has a firm, unilateral breast mass concerning for breast cancer. Klinefelter syndrome (KS) (47,XXY) is associated with testicular fibrosis and is a common cause of primary hypogonadism. Testosterone production is reduced, and the compensatory increase in gonadotropins causes increased expression of aromatase, leading to increased conversion of testosterone to estradiol and an elevated estrogen/androgen ratio. In the breast, this causes gynecomastia and an elevated risk of breast cancer. Initial evaluation of suspected breast cancer in men is similar to that for women and should include mammography, which has a sensitivity and specificity of ≥90%. Characteristic features that can distinguish benign gynecomastia from malignancy include: Gynecomastia can have variable density but is typically symmetric, is centrally located with respect to the nipple, and may have an indistinct margin with surrounding fat. Breast cancer is more likely eccentric to the nipple, has well-defined or spiculated margins, and may contain calcifications. The diagnosis can be confirmed with biopsy (eg, fine-needle aspiration, core-needle biopsy). As in women, invasive ductal carcinoma is the most common histologic type, and most tumors are hormone receptor-positive. (Choice A) Selective estrogen receptor modulators (eg, tamoxifen) are commonly used as adjuvant therapy for estrogen receptor-positive breast cancer and are occasionally given to adolescents with KS to prevent gynecomastia. They have limited use for established gynecomastia and would not be given to this patient unless the diagnosis of breast cancer is confirmed. (Choice B) Gonadotropin (ie, FSH, LH) measurement is used to differentiate primary from secondary/central hypogonadism and is elevated in most patients with KS. Measurement is not needed for this patient with an established KS diagnosis. (Choice C) Androgen therapy can alleviate the symptoms of hypogonadism (eg, decreased libido) but has minimal benefit for established gynecomastia. Malignancy should be ruled out first in this patient. (Choice E) Weight loss can be helpful for patients with pseudogynecomastia due to excessive breast fat. However, this patient has a firm breast mass suspicious for cancer and requires additional evaluation. Educational objective: Klinefelter syndrome is a common cause of primary hypogonadism and is associated with an elevated estrogen/androgen ratio. This causes gynecomastia and an increased risk of breast cancer. Invasive ductal carcinoma is the most common histologic type, and most tumors are hormone receptor-positive. The initial evaluation of suspected breast cancer should include mammography. References: The endocrinology of male breast cancer. (http://www.ncbi.nlm.nih.gov/pubmed/29752333)

A 30-Year-Old Man Comes to the Office Due to a 3-Month