An 18-year-old man comes to the physician with bilateral breast enlargement. He has not seen a physician for the past 6 years. He says that his puberty was "somewhat delayed." The patient has no past medical problems and takes no medications. He does not use tobacco, alcohol, or illicit drugs. He has not used any "steroids" to build muscle.
The patient is 6' 2" (188 cm) tall and weighs 187 lbs (85 kg). He has sparse facial hair. His axillary and pubic hair is normal. He has Stage 3 bilateral gynecomastia without any mass or nipple discharge. Visual fields are normal on confrontation. The testes are firm and small (8 mL).
Laboratory evaluation shows normal hematocrit and basic metabolic profile. Serum luteinizing and follicle-stimulating hormones are elevated and testosterone is low. Serum prolactin and thyroid-stimulating hormone are normal.
The patient is at highest risk for a malignancy at which of the following sites?

Question

An 18-year-old man comes to the physician with bilateral breast enlargement.  He has not seen a physician for the past 6 years.  He says that his puberty was "somewhat delayed."  The patient has no past medical problems and takes no medications.  He does not use tobacco, alcohol, or illicit drugs.  He has not used any "steroids" to build muscle.
The patient is 6' 2" (188 cm) tall and weighs 187 lbs (85 kg).  He has sparse facial hair.  His axillary and pubic hair is normal.  He has Stage 3 bilateral gynecomastia without any mass or nipple discharge.  Visual fields are normal on confrontation.  The testes are firm and small (8 mL).
Laboratory evaluation shows normal hematocrit and basic metabolic profile.  Serum luteinizing and follicle-stimulating hormones are elevated and testosterone is low.  Serum prolactin and thyroid-stimulating hormone are normal.
The patient is at highest risk for a malignancy at which of the following sites?

Quizplus · Accepted Answer

This patient has characteristic features of Klinefelter's syndrome, which include delayed puberty; tall stature; gynecomastia; small, firm testes; testosterone deficiency; and elevated gonadotrophins. The testes are small (normal, 18-25 mL) and firm due to severely damaged seminiferous tubules. In contrast, patients with gonadotrophin deficiency have small and soft testes. Karyotype of peripheral leukocytes confirms the diagnosis. The most common genotype is 47,XXY and is due to an extra X chromosome. Treatment involves testosterone replacement. Patients with Klinefelter's syndrome are at increased risk of breast cancer. When breast cancer develops, the mortality is high compared to that for the general population. Although there is no consensus, some clinicians order periodic mammograms after age 45. Careful palpation of breast tissue is of utmost importance. Patients with Klinefelter's syndrome also have a higher risk of developing extra-gonadal germ cell tumors, non-Hodgkin's lymphoma, and lung disease (eg, COPD and bronchiectasis). (Choices A and D) Klinefelter's syndrome is rarely associated with adrenal or prostate cancer. (Choice C) The risk of pancreatic cancer is higher with positive family history, tobacco use, and chronic pancreatitis. (Choice E) Thyroid cancer risk is higher with positive family history, childhood head and neck radiation exposure, and some familial cancer syndromes (eg, MEN2). Educational objective: Klinefelter's syndrome is the most common genetic cause of primary hypogonadism. Patients typically present with gynecomastia and hypogonadism. Karyotype of peripheral leukocytes confirms the diagnosis. Patients with Klinefelter's syndrome are at increased risk of breast cancer. __________ References: Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. (http://www.ncbi.nlm.nih.gov/pubmed/16106025) Prevalence of Klinefelter's syndrome in male breast cancer patients. (http://www.ncbi.nlm.nih.gov/pubmed/9494523)

An 18-Year-Old Man Comes to the Physician with Bilateral Breast