Ann Thorac Surg 1998;66:547-548
© 1998 The Society of Thoracic Surgeons
Case Reports
Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome
Gregory G. Bebb, MDa,
Frederic W. Grannis, Jr, MDa,
Isaac B. Paz, MDa,
Marilyn L. Slovak, PhDa,
Robert Chilcote, MDa
a Departments of General and Oncologic Surgery, Thoracic Surgery, Cytogenetics, and Pediatric Oncology, City of Hope National Medical Center, Duarte, California, USA
Accepted for publication February 12, 1998.
Address reprint requests to Dr Grannis, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010
e-mail: (fgrannis {at}smtplink.coh.org)
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Abstract
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An 8-year-old boy presented with precocious puberty and a mediastinal mass. A computer search showed that this rare presentation is most common with germ cell tumor of the mediastinum in children with Klinefelter syndrome. The tumor was completely resected after preoperative chemotherapy, and the patient is well 2 years after the operation. In patients with Klinefelter syndrome, germ cell tumors are 50 times more common than in patients without Klinefelter syndrome, usually contain nonseminomatous elements, present at an earlier age, and are seldom testicular in location.
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Introduction
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We present a case report of a primary mixed germ cell tumor (GCT) of the mediastinum (GCT-M) that presented with precocious puberty in an 8-year-old boy. The tumor was successfully treated with chemotherapy and surgical resection.
An 8-year-old white boy presented with precocious puberty. He had no chest symptoms. Findings included a growth spurt of 8.9 cm in 1 year, an enlarged penis, pubic hair, coarsening of facial features, voice changes, and normal testicles.
A chest roentgenogram and computed tomogram (CT) demonstrated a 7.4-cm anterosuperior mediastinal mass (Fig 1). An abdominal CT, testicular magnetic resonance imaging and ultrasound, brain magnetic resonance imaging, bone scan, and echocardiogram were normal. Results of laboratory evaluations included an 
-fetoprotein level of 272 ng/ml and a ß-human chorionic gonadotrophin (ßHCG) level of 125 miU/mL.
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Fig 1. Computed tomogram demonstrates an anterior, superior, mediastinal mass, measuring 7.4 cm in widest diameter, with an irregular border, variegated consistency, and scattered intralesional calcifications.
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A computer search of the National Library of Medicine with Grateful Med software (Grateful Med, Version 1.0 for Windows, © 1996, National Library of Medicine) retrieved journal articles reporting that most cases with this combination of findings are caused by GCT-M in children with Klinefelter syndrome (KS) [1–5]. Peripheral blood cytogenetic studies revealed a 47,XXY karyotype, consistent with KS (Fig 2).
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Fig 2. Peripheral blood cytogenetic studies revealed a 47,XXY karyotype, consistent with Klinefelter syndrome. Flow cytometry demonstrated diploidy and an S-phase of 14.1%. Results of karyotype analysis of the tumor sample were 47,XXY in all 20 metaphases analyzed. There was no evidence for an isochromosome for the short arm of chromosome 12 by either classic cytogenetics of fluorescence in situ hybridization using a chromosome 12 alpha-satellite probe (Oncor D12Z3).
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A left anterior mediastinotomy and biopsy of the mediastinal mass showed seminoma. A clinical diagnosis of a malignant mixed GCT-M was made, based on the presence of elevated levels of serum markers.
The patient was treated with four cycles of etoposide, 100 mg/m2, cis-platinum, 40 mg/m2, and bleomycin, 15 mg/m2 (Pediatric Oncology Group protocol POG 9049). His serum marker levels returned to normal. A repeat CTscan demonstrated a residual 5-cm mediastinal mass. Resection was carried out through a median sternotomy. The final histologic diagnosis was pure mature teratoma with no evidence of residual malignancy.
The patient’s recovery was uneventful. His precocious puberty was reversed. Two years after operation, there is no evidence of recurrent disease; levels of markers and chest CT scan are within normal limits.
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Comment
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Primary mediastinal germ cell tumors
Germ cell tumors of the mediastinum comprise only 1% to 3% of all GCTs [6]. The anterior mediastinum is the second most common site of pediatric extragonadal GCT, and is the most common site in adults. Germ cell tumors comprise 25% of anterior mediastinal masses in children. Germ cell tumors of the mediastinum include a variety of benign and malignant tumors. Any combination of histologies may be included under the designation mixed GCT [7].
Teratoma is the most common GCT-M overall; seminoma the most common malignant variant. Malignant GCT-Ms are uncommon, and most tertiary care centers see only a few cases each year. Benign GCT-Ms are equally distributed among male and female patients; malignant forms have a male preponderance of more than 90% [7].
Precocious puberty, defined as pubertal changes occurring before 8 years of age in girls and 9 years in boys, is thought to be caused by elevated testosterone levels, secondary to stimulation of the testes by ßHCG. Gynecomastia can also be seen secondary to elevated ßHCG. Germ cell tumors are the identified cause of precocious puberty in 21% of cases in boys and 1% in girls [4]. Chest roentgenograms and CT scan delineate the primary tumor. Testicular examination, testicular ultrasound, and abdominal CT scan are needed to rule out a testicular primary cancer. Serum markers include the oncoplacental antigens -fetoprotein and ßHCG. Elevation of -fetoprotein level, in 80%, indicates that a malignant nonseminomatous component is present, and elevation of the ßHCG level, in 30%, suggests a trophoblastic component [7].
Management of benign GCT-Ms is by surgical resection. Malignant GCT-Ms are usually unresectable at presentation and incurable by operation alone [8]. Malignant nonseminomatous and mixed GCT-Ms carry a worse prognosis than other GCT-Ms and primary testicular GCT. Current management involves multidrug, cis-platinum–based chemotherapy, followed by surgical resection of residual masses [7]. Complete remission rates of 58% can be achieved, with 60% of patients maintaining a durable disease-free status.
Klinefelter syndrome
Klinefelter syndrome, the most common sex chromosome abnormality, occurs in 1 in 575 live male births. The diagnosis is rarely suspected before puberty, at which time delayed development of secondary sex characteristics dictates work-up. Small testes, gynecomastia, lack of pubic hair, and phallic underdevelopment are prominent clinical cues.
Germ cell tumors of the mediastinum and klinefelter syndrome
The literature contains reports of more than 40 cases of patients with GCT-M and KS. Klinefelter syndrome is present in 20% of patients with GCT-M [6]. The reported incidence of GCT in KS patients is 1.5/1,000 (a 50-fold increase over the general population).
Klinefelter syndrome may be overlooked in the patient with GCT-M. The GCT-Ms that secrete ßHCG can mimic puberty in the patient with KS, masking the usual clinical signs of KS [6]. Germ cell tumors associated with KS have a number of unusual features. All contain nonseminomatous elements [6]. Pure seminoma is the most common malignant GCT in patients without KS. Patients with KS present with GCTs at a younger age [6] (mean age of presentation, 17 years, compared with 29 years in patients without KS); consequently, precocious puberty is seen more often in GCTs associated with KS. Germ cell tumors in children with KS are almost exclusively extragonadal [6]; with rare testicular GCTs, in striking contrast to GCTs in general, which are extragonadal in only 2% to 5% of cases.
Conclusion
Precocious puberty may represent a marker syndrome for primary malignant GCT-M, and may allow early diagnosis and treatment of this deadly tumor.
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References
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- Konig R., Schonberger W., Grimm W. Mediastinal teratocarcinoma and hypophyseal stalk germinoma in a patient with Klinefelter syndrome. Klin Pediatr 1990;202:53-56.
- Beasley S.W., Tiedemann K., Howat A., et al. Precocious puberty associated with malignant thoracic teratoma and malignant histiocytosis in a child with Klinefelter’s syndrome. Med Pediatr Oncol 1987;15:277-280.[Medline]
- Roger M., Chaussain J.L., Blacker C., Feinstein M.C. Tumors secreting choriogonadotropin in children. Ann Med Interne (Paris) 1984;135:381-384.[Medline]
- Job J.C., Chaussain J.L., Franchimont P., Rolland A. Paraneoplastic precocious puberty in a child. Mediastinal teratoma with chorionic gonadotroopin secretion. Arch Fr Pediatr 1975;332:471-477.
- Hasle H., Jacobsen B.B., Asschenfeldt P., Andersen K. Mediastinal germ cell tumour associated with Kleinfelter syndrome. A report of case and review of the literature. Eur J Pediatr 1992;151:735-739.[Medline]
- Nichols C.R. Mediastinal germ cell tumors: clinical features and biologic correlates. Chest 1991;99:472-479.[Free Full Text]
- Dehner L.P. Germ cell tumors of the mediastinum. Semin Diagn Pathol 1990;7:266-284.[Medline]
- Economou J., Trump D., Holmes E., Eggleston J.J. Management of primary germ cell tumors of the mediastinum. J Thorac Cardiovasc Surg 1982;83:643-669.[Abstract]
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Abstract
Introduction
