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Ann Thorac Surg 1997;64:359-362
© 1997 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Mediastinal Growing Teratoma Syndrome

Thoracic Service, Department of Surgery, and Solid Tumor Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York

Accepted for publication March 8, 1997.

	Abstract

Top Footnotes Abstract Introduction Case Presentations Comment References

 
Background. The growing teratoma syndrome refers to the phenomenon whereby germ cell tumors enlarge after chemotherapy despite complete eradication of malignant cells and normalization of serum tumor markers. This clinical scenario must be differentiated from that in which germ cell tumors maintain their malignant characteristics with elevated levels of serum tumor markers.

Methods. Hospital record review was conducted of 2 cases.

Results. Two male patients are presented, 1 with a metastatic germ cell tumor of both the retroperitoneum and mediastinum (with elevated -fetoprotein level) and 1 with a primary germ cell tumor of the mediastinum (with elevated -fetoprotein and ß-human chorionic gonadotropin levels). After completion of chemotherapy and normalization of tumor markers, both patients presented with pulmonary symptoms attributable to their massively enlarging mediastinal teratomas. The clinical and roentgenographic features of patients with thoracic manifestations of the growing teratoma syndrome, as well as its management, are reviewed.

Conclusions. After chemotherapy in patients with primary or metastatic mediastinal germ cell tumors whose tumor markers normalize, a growing mass in the mediastinum may represent the growing teratoma syndrome.

	Introduction

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The evolution in the treatment of nonseminomatous germ cell tumors (NSGCTs) over the past 15 years has resulted in substantial improvement in "cure," from less than 10% to approximately 80%. Since the advent of cisplatin-based chemotherapeutic regimens, germ cell carcinomas have demonstrated dramatic responses and normalization of serum tumor markers, with surgical resection reserved for radiologic evidence of one or more persistent masses. However, a small proportion of patients during follow-up or treatment demonstrate tumor growth, typically in the retroperitoneum or lung, with normal tumor marker values. The growing teratoma syndrome refers to the enlargement of mixed NSGCT after chemotherapy with normalization of tumor marker values. In the mediastinum, these tumors are similar to other teratomas of the mediastinum, in that they present with significant morbidity and possible mortality secondary to their encroachment on adjacent structures, despite their benign histology. Thus far, discussions of this syndrome have referred primarily to retroperitoneal tumors [1–6]. In this report, 2 patients are described with rapidly growing masses of the mediastinum after chemotherapy for NSGCT, metastatic in 1 and primary in the other, both of whom underwent successful complete resection. The literature on the growing teratoma syndrome manifesting in the chest is reviewed.

	Case Presentations

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Patient 1
A 28-year-old man initially presented with a left testicular mass, which was slowly enlarging over 4 months. At presentation, serum tumor markers were quantitated: serum -fetoprotein (AFP) level was 1384 ng/mL (normal = 0 to 5 ng/mL), ß-human chorionic gonadotropin (ß-HCG) level was normal, and lactate dehydrogenase level was 1,264 IU/mL (normal = 91 to 181 IU/mL). He subsequently underwent a radical left orchiectomy for a mixed NSGCT. Pathologic examination demonstrated predominantly embryonal cell carcinoma, with elements of choriocarcinoma and teratocarcinoma. He underwent an extent of disease workup, which included a chest and abdominal computed tomographic scan revealing both a large retroperitoneal mass as well as a superior mediastinal mass. He subsequently received four courses of bleomycin, etoposide, and cisplatin. After chemotherapy the levels of serum tumor markers were normal. Three months after chemotherapy, a retroperitoneal lymph node dissection was performed with removal of a 15 x 11 x 12-cm mature teratoma. A computed tomographic scan of his chest at that time revealed a residual superior mediastinal mass (Fig 1). He was subsequently lost to follow-up for 4 months. He presented afterward with chest pain, and repeat computed tomography demonstrated the superior mediastinal mass enlarged by a factor of 3, with extension beneath the aortic arch to involve the aorticopulmonary window and anterior mediastinum (Fig 2). He underwent a bilateral anterolateral thoracotomy with transverse sternotomy ("clamshell thoracotomy") [7] with resection of a bilobed superior and anterior mediastinal tumor measuring 11 x 8 cm and 5 x 6 cm, respectively, as well as a right upper lobe pulmonary parenchymal nodule removed by wedge excision. Pathologic examination of all masses demonstrated mature teratoma. He is currently alive and well 4 years after resection of his mediastinal and pulmonary masses with normal tumor markers.

View larger version (100K): [in this window] [in a new window]   Fig 1. . Computed tomogram of the chest demonstrating 4.5 x 2.5-cm superior mediastinal mass in a 28-year-old man (patient 1).

View larger version (107K): [in this window] [in a new window]   Fig 2. . Computed tomographic scan of the chest demonstrating marked growth of the superior mediastinal mass in patient 1, with the mass now growing beneath the arch of the aorta to involve the aorticopulmonary window.

View larger version (113K): [in this window] [in a new window]   Fig 3. . Computed tomograms of the chest in a 20-year-old man (patient 2) demonstrating a large anterior mediastinal mass compressing the great vessels (A) and the heart (B).

View larger version (110K): [in this window] [in a new window]   Fig 4. . Computed tomograms of the chest in patient 2 two months after Figure 3 was taken, with massive enlargement of the anterior mediastinal mass with almost complete compression of both lungs (A) and marked displacement of the heart into the left hemithorax (B).

	Comment

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Operation is usually reserved after chemotherapy for the resection of residual masses once levels of serum tumor markers normalize to document the presence or absence of viable tumor. Resected surgical specimens have been shown to contain mature teratoma (40%), fibrotic and necrotic tissue (45%), or residual viable tumor (15%). Growth or persistence of a mass in the presence of elevated levels of serum tumor markers represents persistent disease or recurrence. This must be differentiated, however, from growth in the presence of normal levels of serum tumor markers, described as growing teratoma syndrome. This distinction is extremely important. Although the latter refers to a histologically benign tumor, it can be clinically aggressive with morbidity secondary to encroachment upon nearby structures. Prompt resection is indicated, because teratomas are unresponsive to chemotherapy.

The growing teratoma syndrome was first described in 1981 by Carr and associates [11] and later given its current name in 1982 by Logothesis and colleagues [1] when they reported 6 cases of enlarging metastatic NSGCTs. Of the patients reported, 4 had pulmonary metastases. Requirements for the growing teratoma syndrome include (1) radiographic evidence of enlarging masses after chemotherapy for NSGCT, (2) normal levels of serum tumor markers, and (3) histologic confirmation of mature teratoma without malignant elements.

Jeffrey and associates [2] reviewed 131 patients with metastatic NSGCT over 13 years and found that 7.6% (10 patients) fulfilled criteria for growing teratoma syndrome, but only 1.7% (3) had thoracic involvement (all 3 had pulmonary metastases). Gelderman and coworkers [12] described this phenomenon in 3 of 86 patients (3.5%) with malignant germ cell tumors. All 3 had enlarging masses in their retroperitoneum a mean of 30 months after chemotherapy, despite normal serum markers, and underwent resection of mature teratoma. The majority of cases of the growing teratoma syndrome reported in the literature have been retroperitoneal tumors [1–6]. The greater frequency of retroperitoneal lesions is, in all likelihood, secondary to the greater propensity of testicular tumors to metastasize via the lymphatic route preferentially to the retroperitoneum, as opposed to the mediastinum.

Of the 15 cases of intrathoracic growing teratoma syndrome reported in the literature [1–3, 5, 11, 13–15], 14 (93%) occurred in pulmonary metastases, and only 1 (7%) occurred in the mediastinum [14] (Table 1). Table 1 summarizes the literature concerning intrathoracic growing teratoma after chemotherapy for NSGCT. Chen and associates [14] described a primary 4 x 10 x 10-cm NSGCT of the mediastinum with an AFP level of 14,500 ng/mL and ß-HCG level of 196 MIU/mL. Open biopsy revealed immature teratoma, and the patient was treated with four cycles of cisplatin, etoposide, and bleomycin for a mixed NSGCT. The AFP level decreased to 93 ng/mL and the mediastinum was treated with 4,000 cGy of radiotherapy. The AFP level decreased further to 64 ng/mL, but the tumor increased in size (10 x 12 x 15 cm). The mediastinal tumor was resected, and pathologic examination again revealed immature teratoma. Although this patient probably had a component of benign teratoma, this report does not fulfill all requirements to be classified as a growing teratoma syndrome, because the AFP level did not normalize and mature teratoma was not documented after resection. Both of our 2 cases fulfill all criteria to be classified as growing teratoma syndrome.

The treatment is complete surgical resection, because this represents the only hope for "cure." One anecdotal case described the use of interferon after a second relapse as treatment for a growing retroperitoneal lesion that was deemed unresectable [17]. However, therapy was instituted for 2 years with less than 50% regression reported and minimal stabilization at best. Such medical therapy leading to a minimal response would appear to be an unpredictable and unsatisfactory alternative to definitive surgical resection.

Growing teratoma syndrome is an uncommon phenomenon in the setting of NSGCTs, occurring in 3% to 8% of patients treated with effective chemotherapy. Its recognition is critical, because resection is the only "curative" option.

	Footnotes

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Address reprint requests to Dr Burt, Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021 (e-mail: burtm{at}mskcc.org).

	References

Top Footnotes Abstract Introduction Case Presentations Comment References

 

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Hazem Y. Afifi Michael E. Burt Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Afifi, H. Y. Articles by Burt, M. E. Search for Related Content PubMed PubMed Citation Articles by Afifi, H. Y. Articles by Burt, M. E.