Correspondence

Case 9-2003: Mediastinal Germ-Cell Tumor

N Engl J Med 2003; 348:2469-2470June 12, 2003

Article

To the Editor:

With regard to the discussion by Friedmann et al. (March 20 issue)1 of a mediastinal germ-cell tumor in an 18-year-old man, a malignant mediastinal germ-cell tumor in a young man should raise the suspicion of Klinefelter's syndrome (47,XXY). Patients with Klinefelter's syndrome have a relative risk of 66.7 for the development of a malignant mediastinal germ-cell tumor.2 At least 8 percent of male patients with primary mediastinal tumors have Klinefelter's syndrome — 50 times the expected frequency.3 In a recent study,4 all 10 adolescents with a malignant mediastinal germ-cell tumor were male, and in approximately 50 percent of them, the presence of an additional X chromosome was demonstrated, which is consistent with Klinefelter's syndrome. Therefore, we suggest performing a karyotype analysis in the patient described in the case report, since such a diagnosis is important for his future therapy and counseling.

Daniela Cohen, M.D.
Naomi Weintrob, M.D.
Institute for Endocrinology and Diabetes, Petah Tikva 49202, Israel
cohendaniela@netscape.net

4 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 9-2003). N Engl J Med 2003;348:1150-1158
   Full Text | Web of Science | Medline

2. 2

   Hasle H, Mellemgaard A, Nielsen J, Hansen J. Cancer incidence in men with Klinefelter syndrome. Br J Cancer 1995;71:416-420
   CrossRef | Web of Science | Medline

3. 3

   Hasle H, Jacobsen BB, Asschenfeldt P, Andersen K. Mediastinal germ cell tumour associated with Klinefelter syndrome: a report of case and review of the literature. Eur J Pediatr 1992;151:735-739
   CrossRef | Web of Science | Medline

4. 4

   Schneider DT, Schuster AE, Fritsch MK, et al. Genetic analysis of mediastinal nonseminomatous germ cell tumors in children and adolescents. Genes Chromosomes Cancer 2002;34:115-125
   CrossRef | Web of Science | Medline

Author/Editor Response

We thank Drs. Cohen and Weintrob for pointing out the strong association between Klinefelter's syndrome and mediastinal germ-cell tumors and the need to consider Klinefelter's syndrome as an underlying diagnosis in a male patient with a mediastinal germ-cell tumor. Certainly, Klinefelter's syndrome has a wide clinical spectrum with a variable phenotype and can go undetected into adulthood, with serious consequences for sexual development and function, as well as for mineral density.1 However, all patients with this syndrome have hypogonadism, and presumably, this symptom would have been detected during the careful physical examination indicated in a young man with suspected cancer.2 The patient in this case record was reported to have had a normal karyotype, definitively excluding undiagnosed Klinefelter's syndrome. In addition, the literature indicates that the mediastinal germ-cell tumors seen in adolescents and young adults with Klinefelter's syndrome have nonseminomatous histologic features, and this patient had a germinoma.

Alison M. Friedmann, M.D.
Esther Oliva, M.D.
Massachusetts General Hospital, Boston, MA 02114

2 References

1. 1

   Tyler CV Jr, Kungl PA, Green LA. Genetic diagnosis in adulthood: a case report. J Fam Pract 1998;47:227-230
   Web of Science | Medline

2. 2

   Visootsak J, Aylstock M, Graham JM Jr. Klinefelter syndrome and its variants: an update and review for the primary pediatrician. Clin Pediatr (Phila) 2001;40:639-651
   CrossRef | Web of Science | Medline