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Growing Teratoma Syndrome of the Liver: Treatment with Living Related Donor Liver Transplantation

¹ Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213.
² Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.

Received December 13, 2002; accepted after revision February 4, 2003.

 
Address correspondence to V. Kapoor.

Introduction

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Growing teratoma syndrome is an uncommon entity characterized by the recurrence of mature teratoma lesions in extratesticular sites after orchiectomy of primary nonseminomatous germ cell tumors in young men. Recurrence occurs most commonly in the retroperitoneum. We report a case of extensive growing teratoma syndrome involving retroperitoneal lymph nodes and the liver, successfully treated by debulking surgery and living related donor liver transplantation.

Case Report

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A 24-year-old man with end-stage liver disease caused by extensive testicular metastases was referred to our institution for possible liver transplantation. One year earlier, he had undergone radical orchiectomy, right nephrectomy, and retroperitoneal lymph node resection for a mixed germ cell tumor of testicular origin. The composition of the resected testicular tumor was 50% embryonal, 30% yolk sac, 10% immature teratomatous, and 10% seminomatous at pathology. Serum -fetoprotein levels were initially elevated but normalized after the initial surgery and remain normal at the time of this writing. Sonography (Fig. 1A) and CT (Figs. 1B and 1C) showed marked hepatomegaly from numerous masses with cystic, solid, and calcific components replacing almost the entire liver. Large retroperitoneal lymph nodes had similar components. Sonographically guided core biopsy of a hepatic lesion revealed mature teratoma.

View larger version (121K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —24-year-old man with end-stage liver disease resulting from extensive hepatic metastases from primary nonseminomatous testicular germ cell tumor who had undergone prior radical orchiectomy, right nephrectomy, and retroperitoneal lymph node resection. Sonogram of left hepatic lobe shows multiple cystic masses of varying sizes (arrows) in background of normal liver parenchyma.

View larger version (122K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —24-year-old man with end-stage liver disease resulting from extensive hepatic metastases from primary nonseminomatous testicular germ cell tumor who had undergone prior radical orchiectomy, right nephrectomy, and retroperitoneal lymph node resection. Unenhanced axial CT image of upper abdomen shows large bilobar hepatic masses and retroperitoneal lymph nodes with cystic (solid straight arrows) and solid (arrowheads) components. Coarse amorphous calcification is evident (curved arrow). Left renal vein (open arrows) is displaced anteriorly by large paraaortic lymph node mass.

View larger version (120K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C. —24-year-old man with end-stage liver disease resulting from extensive hepatic metastases from primary nonseminomatous testicular germ cell tumor who had undergone prior radical orchiectomy, right nephrectomy, and retroperitoneal lymph node resection. Contrast-enhanced axial CT image of upper abdomen reveals large discrete and confluent masses in liver with cystic (short straight arrows) and solid components showing heterogeneous enhancement and normal intervening liver parenchyma. Large paraaortic lymph node mass (long straight arrows) shows calcification and is displacing left renal vein (curved arrows) anteriorly.

The patient underwent debulking surgery and living related donor liver transplantation, receiving the right hepatic lobe of a family member because orthotopic transplantation requiring cadaveric livers is generally contraindicated for patients with bilobar hepatic metastases at our institution, given the relative shortage of organ availability and predilection for recurrence. The extirpated liver weighed 6400 g (normal range, 1400-1600 g), with normal hepatic parenchyma intermixed between multiple cystic and solid tumor nodules (Fig. 1D) ranging in size from 1.5 to 20 cm. Histopathology of liver and nodal sections showed mature teratoma elements only, including islands of cartilage and calcification as well as cysts lined by squamous, columnar, glandular, and intestinal epithelium (Fig. 1E). Immature teratoma and other germ cell tumor types, including seminoma, that were present at surgical pathology after initial resection were absent from the reoperative specimens.

View larger version (124K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D. —24-year-old man with end-stage liver disease resulting from extensive hepatic metastases from primary nonseminomatous testicular germ cell tumor who had undergone prior radical orchiectomy, right nephrectomy, and retroperitoneal lymph node resection. Photograph of gross specimen of resected hepatic mass shows mixed morphology of tumor, with cystic component (left) adjacent to more solid component consisting of cluster of grapelike nodules (right).

View larger version (156K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1E. —24-year-old man with end-stage liver disease resulting from extensive hepatic metastases from primary nonseminomatous testicular germ cell tumor who had undergone prior radical orchiectomy, right nephrectomy, and retroperitoneal lymph node resection. Photomicrograph of tumor specimen shows portion of liver (L) with cysts (c) lined by glandular (straight arrows) and squamous (curved arrow) epithelium filled with keratin pearl (arrowhead). (H and E, x 200)

Follow-up CT at 4 months showed regeneration of the transplanted right lobe and resolution of ascites and adenopathy (Fig. 1F); and 1 year after transplantation, follow-up CT revealed no evidence of tumor recurrence in the chest, abdomen, or pelvis.

View larger version (129K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1F. —24-year-old man with end-stage liver disease resulting from extensive hepatic metastases from primary nonseminomatous testicular germ cell tumor who had undergone prior radical orchiectomy, right nephrectomy, and retroperitoneal lymph node resection. Four-month follow-up contrast-enhanced CT image of abdomen shows regeneration of transplanted right hepatic lobe and no evidence of recurrence. Gastrohepatic lymph nodes (arrows) have decreased in size as compared with an early postoperative scan (not shown). These nodes did not show evidence of disease on frozen section during initial transplantation.

Discussion

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Testicular tumors represent 1% of all neoplasms in males and are classified as germ cell or nongerminal tumors. An entity called "growing teratoma syndrome" has been recognized to occur in 1.9-7.6% of all patients with nonseminomatous germ cell tumors that metastasize [1, 2]. The criteria required for the diagnosis of growing teratoma syndrome include [1, 3, 4] nonseminomatous germ cell testicular or extratesticular primary tumor containing mature or immature teratomatous elements; normalization of elevated serum tumor makers such as -fetoprotein, ß-human chorionic gonadotrophin (ß-HCG), and lactate dehydrogenase after therapy; evidence of enlarging metastases, despite chemotherapy and normalization of tumor markers; and exclusively mature teratomatous elements on histopathology of the metastases.

The pathogenesis of growing teratoma syndrome is not precisely known. Two hypotheses have been proposed: selective survival and growth of the mature teratoma component of a nonseminomatous germ cell tumor after chemotherapy; and differentiation of the original nonseminomatous germ cell tumor into a more benign mature teratoma [3]. The first hypothesis is supported by the fact that primary tumors are frequently of mixed germ cell types, with as many as 86% containing mature teratomatous elements [3]. It is believed that these mature teratomatous components resist chemotherapy (whereas other components succumb), metastasize, and, paradoxically, increase in size. This hypothesis would also explain the normalization of the serum tumor markers (-fetoprotein, ß-HCG) that are elaborated by mixed germ cell tumors such as embryonal cell carcinoma and yolk sac tumor. The second hypothesis is supported by documentation of transformation of malignant testicular tumors into benign teratomas [5, 6].

In men who develop growing teratoma syndrome, the testis is the primary site of origin in as many as 93% patients [3], followed by the mediastinum [3, 7] and pineal gland [8]. The most common site of metastases in growing teratoma syndrome is the retroperitoneum, although metastasis has also been reported in the lungs, cervical and mediastinal lymph nodes, pineal gland, and liver [2, 7, 8, 9].

Patients with nonseminomatous germ cell tumors are usually first treated with chemotherapy that invariably leads to normalization of the tumor marker levels and a significant decrease in the size of the primary tumor [8]. After completion of chemotherapy, the residual mass may be resected to improve the prognosis in such patients [9]. Patients suspected of having growing teratoma syndrome should undergo complete resection of the tumor for several reasons. Most important, the diagnosis of growing teratoma syndrome can be made only after complete pathologic examination of the tumor and offers an improved prognosis. Also, mature teratomas do not respond to chemotherapy or radiotherapy, and the only definitive treatment is surgical resection. Malignant transformation and dissemination of growing teratoma syndrome have been described [3, 8]. These tumors may also grow large enough [3, 7, 8] to mechanically compromise vital bodily functions, as they did in our patient. Complete resection of the tumor is possible in as many as 80% of patients [3], with the risk of recurrence of nonseminomatous germ cell tumor being 50% with incomplete resection and 8% with complete resection [3]. Although long-term stability of growing teratoma syndrome has been reported [2], no cases of spontaneous regression have been reported to our knowledge. Because of the resistance to chemotherapy and risk of malignant transformation, patients with suspected or known growing teratoma syndrome tumors should undergo resection with close radiologic follow-up for additional recurrences. This recommendation applies particularly to patients who are undergoing immunosuppressive therapies for organ replacement because of their increased risk for posttransplantation lymphoid and other tumors.

References

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5. Hong WK, Wittes RE, Hajdu ST, et al. The evolu tion of mature teratoma from malignant testicular tumours. Cancer1977; 40:2987 -2992[Medline]
6. Stechmiller B, Wiernich PH, Shin M, Satterfield J. Metastatic teratocarcinoma following chemotherapy: maturation to a mass pathologically in distinguishable from a mediastinal enteric cyst. Chest1976; 69:697 -700[Abstract/Free Full Text]
7. Afifi HY, Bosl GJ, Burt ME. Mediastinal growing ter atoma syndrome. Ann Thorac Surg1997; 64:359 -362[Abstract/Free Full Text]
8. O'Callaghan AM, Katapodis O, Ellison DW, Theaker JM, Mead GM. The growing teratoma syndrome in nonseminomatous germ cell tumor of the pineal gland. Cancer1997; 80:942 -947[Medline]
9. Maroto P, Tabernero JM, Villavicencio H, et al. Growing teratoma syndrome: experience of a sin gle institution. Eur Urol 1997;32:305 -309[Medline]

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