Elsevier

Human Pathology

Volume 37, Issue 4, April 2006, Pages 477-480
Human Pathology

Case report
Extragonadal germ cell tumors are often associated with Klinefelter syndrome

https://doi.org/10.1016/j.humpath.2006.01.029Get rights and content

Summary

Klinefelter syndrome is a well documented abnormality of sex differentiation, with an incidence of 1 in 600 newborn males. It is characterized by a 47,XXY or a mosaic karyotype and clinical findings of hypergonadotrophic hypogonadism, small testes, infertility, reduced body hair, gynecomastia, and tall stature. Other conditions like venous disease, autoimmune disorders, mild neurobehavioral deficit, diabetes mellitus, sexual precocity, and osteoporosis may also affect these patients. Different malignancies such as breast cancer, testicular tumors, leukemia, and lymphomas occur in 1%-2% of the cases. Klinefelter syndrome has been associated with other malignancies such as extragonadal germ cell tumors; however, some authors consider this association an unusual finding. We report the molecular cytogenetic studies performed in 4 young males with mediastinal germ cell tumors. In 2 cases, a 47,XXY karyotype was recognized in different tissues by fluorescent in situ hybridization, whereas the other 2 had a normal XY karyotype. We propose that in young patients with mediastinal teratoma, a cytogenetic analysis must always be performed.

Introduction

Klinefelter syndrome (KS) is a well documented abnormality of sex differentiation occurring in 1 in 600 new born males. Patients with KS also have a higher risk of developing malignant mediastinal germ cell tumors [1], [2], and at least 8% of male patients with primary mediastinal tumors have KS [3]. The incidence of this syndrome among patients with mediastinal germ cell neoplasms is 50 times higher than in the general population. Because of the broad clinical spectrum of KS, some cases lack the classical phenotype, and the diagnosis is made until a complication is present [4]. We studied 4 cases of mediastinal tumors, and in 2 of them, a 47,XXY karyotype was recognized, whereas in the other 2, a normal XY karyotype was observed.

Section snippets

Case 1

A 16-year-old male patient was admitted with a history of progressive dyspnea, nausea, and vomiting 1 month before admission. Physical examination revealed respiratory distress that required mechanical ventilation. The chest x-ray showed an anterior mediastinal tumor expanding into the right hemithorax (Fig. 1A, B). The day after, he developed hemodynamic complications and had an irreversible cardiorespiratory arrest. Autopsy disclosed a large infiltrating tumor, involving the anterior and

Discussion

KS has been associated with several malignancies including extragonadal germ cell tumors mainly in the mediastinum. Nevertheless, some authors consider this association as an unusual finding [7], [8], [9], [10], [11], [12]. This report describes the molecular cytogenetic studies performed in 4 young males with mediastinal germ cell tumors, none was previously diagnosed as having KS. FISH analysis revealed a 47,XXY karyotype in cases 1 and 2 and a normal karyotype in patients 3 and 4. Although

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This work was supported by DGAPA Grant number IN206902-3, Research Department of the Hospital General de Mexico, and CONACYT grant number 45208M.

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