1Department of Pneumology; 2Unit of Medical Oncology; 3Unity of Pathological Anatomy, Centre Hospitalier Lyon-Sud, Pierre-Benite Cedex and 4Centre Leon Berard, Lyon, France
Received 12 February 2001; revised 18 April 2001; accepted 3 May 2001.
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Abstract |
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Key words: embryonal rhabdomyosarcoma, mediastinal germ-cell tumour, teratoma, yolk sac tumour
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Introduction |
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Moreover, mediastinal germ-cell tumours are often associated with haematological malignancies that develop from yolk sac elements [8]. The prognosis of mediastinal germ-cell tumours is poor: only 30% of patients are cured [3].
We report on a case of mediastinal germ-cell tumour associated with embryonal rhabdomyosarcoma. Such an association is rare in adult patients.
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Case report |
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The patient received three cycles of the standard BEP regimen of chemotherapy (30 mg bleomycin 1 day every week, 100 mg/m2/day etoposide and 20 mg/m2/day cisplatin from day 1 to day 5 every 3 weeks). He experienced a partial response on the CT scan with normalization of the serum AFP level after the first cycle of chemotherapy. The tolerance of chemotherapy was fair. After three cycles of chemotherapy, the patient had a surgical resection of the residual tumour that was adherent to the mediastinal vessels (right and left brachioencephalic vessels) and to the trachea. The resection was incomplete. The histological pattern was a mature teratoma with nervous and chondroid elements and presence of viable embryonal rhabdomyosarcoma.
It was decided to switch to a salvage chemotherapy regimen that aimed to treat the sarcomatous part of the tumour. The patient received alternating cycles of chemotherapy: carboplatin, epirubicin, vincristine (CEV), ifosfamide, vincristine, actinomycin (IVA) and ifosfamide, vincristine, etoposide (IVE). This treatment was poorly tolerated. The patient received three cycles but the tumour progressed in the medi-astinum (occurrence of a vena cava syndrome) with pleural effusion and lung metastasis.
Radiotherapy to the mediastinum had a palliative effect on the local compression. The serum AFP level remained within normal limits. However, proof of progression of the embryonal rhabdomyosarcoma component was obtained by bone marrow aspiration, which was indicated by the occurrence of anaemia and thrombocytopenia. The patient died of disease progression and cranial haemorrhage 8 months after diagnosis.
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Discussion |
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Using cytogenetic arguments, the relationship between the germ-cell tumour and the embryonal rhabdomyosarcoma has been established. Germ-cell tumours have a common specific cytogenetic marker: the presence of the isochromosome [i(12p)] [12, 13]. This marker is also observed within the embryonal rhabdomyosarcoma component [14]. Moreover, the same chromosomal marker has been described in leukaemia associated with germ-cell tumours [14, 15]. It is derived from teratomatous elements of the germ-cell tumours. It also has been shown that haematopoetic stem cells may derive from yolk sac elements in mediastinal germ-cell tumours [16]. As malignant transformation of teratoma may occur both before and after chemotherapy, it seems very unlikely that chemotherapy might induce such a transformation. Conversely, it is probable that non-germ-cell elements derive from germinal stem cells. The mechanism of action of this transformation is unknown.
Occurrence of the sarcomatous component in a mediastinal teratoma has no specific initial clinical feature. Teratomas that are likely to progress to such an outcome can not be differentiated from others on the basis of clinical or radiological criteria [6]. Diagnosis can be fortuitous at the time of histopathological examination of a tumour biopsy or after tumour resection or, more frequently, as a result of an unusual outcome with chemotherapy of a presumed non-teratomatous germ-cell tumour [3, 5].
Sarcomatous components of germ-cell tumours, especially rhabdomyosarcoma, have a proper metastatic potential and a poor prognosis, particularly in adults and if the primary site is mediastinal [11]. This prognosis can be influenced by many factors such as resectability of the tumour and histopatho- logical subtype of the malignant component, its occurrence in a metastatic site and its sensitivity to chemotherapy [1, 6].
Embryonal rhabdomyosarcomas in adult patients are rare, mostly in the paratesticular area [10]. The prognosis is generally worse than that of their paediatric counterpart. Mediastinal rhabdomyosarcomas are most often resistant to chemotherapy. They have a poor prognosis, worse than their gonadal counterpart [10, 17], with a short survival of <2 years. Patients die mostly by regional involvement and multiple metastasis [5, 10]. At present, there is no standard schedule of chemotherapy in adult embryonal rhabdomyosarcoma and the paediatric protocols are often not effective in adults, and no chemotherapy is effective on both the germinal and non-germinal components. The most important prognostic factors in adult rhabdomyosarcomas are age, tumour size, extent of disease and complete resection [17]. The median survival in a population of 84 adult patients was 22 months, despite aggressive multimodality management (associated chemotherapy and surgery).
It is noteworthy that in our case, as in others, the germ-cell component of the tumour was very chemosensitive. However, the embryonal rhabdomyosarcoma was refractory to a chemotherapy regimen which is generally considered as effective in this tumour type. A review of the literature [1, 5, 6, 10, 1922] shown in Table 1 demonstrates that the prognosis of this disease is poor (only one out of 16 patients is cured). Of the 15 patients with mediastinal germ-cell tumours, reported by Gonzalez-Vela [19], four with sarcoma components died of disease, but six of 11 without sarcoma components lived. Experience proves that surgery is a very important part of treatment, and as is the case in active germ-cell residual tumours, complete surgical resection appears to be the most important prognostic factor of survival [23]. At present, little information concerning the diseases behaviour and treatment modalities is available.
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Footnotes |
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References |
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