Concurrent Diagnosis and Management of Primary Mediastinal Germ Cell Tumor and Klinefelter Syndrome.

Primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) stands out among other germ cell tumors not only because of its mediastinal site of origin, but by its aggressive behavior, need for maximal multidisciplinary therapy, and relatively poor prognosis. We present a case of a 22-year-old man who was evaluated for chest-related and systemic symptoms and found to have a large mediastinal mass compressing the pulmonary artery with no apparent disease outside the mediastinum. Physical exam at presentation to medical oncology revealed gynecomastia and small testicles, suspicious for sex hormone dysregulation. Workup revealed the diagnosis of PMNSGCT as well as Klinefelter syndrome (KS), a sex chromosome abnormality condition in males caused by an extra copy of the X chromosome. The association between these two conditions is reported but not well known, given the uncommon incidence of both and the lack of an obvious connection. Pre-treatment management included referral to multidisciplinary specialties and assessment for fertility preservation. The patient was treated with a curative intent with etoposide, ifosfamide, and cisplatin (VIP) chemotherapy for four cycles at full doses despite various side effects. He underwent surgical resection of his residual mediastinal mass, with pathology revealing a complete pathologic response, which is considered a good prognostic indicator for survival. Therefore, he did not require adjuvant chemotherapy. He was started on testosterone replacement therapy for KS-related hypogonadism with improvement in his testosterone level and quality of life. To date, he has not had evidence of recurrence. We discuss the evaluation and management of PMNSGCT and KS, as well as the evidence for their association reported in the literature.