G. Mazzoleni

Complete response after treatment with imatinib in pretreated disseminated testicular seminoma with overexpression of c-KIT

We describe the case of a 39-year-old man with disseminated testicular seminoma that was refractory to salvage chemotherapy, and who had complete remission after imatinib administration. In September, 1999, the patient underwent a right orchifunicolectomy for a classical seminomatous tumour. A CT scan of the chest and abdomen showed retroperitoneal bulky disease (massive enlargement of right periaortic, paracaval, and interaortocaval lymph nodes of at least 4·3 cm in diameter). Baseline alpha-fetoprotein and human chorionic gonadotropin were within the normal ranges of 0·5–9·0 ng/ml and 0–2 mUI/ml, respectively, whereas lactate dehydrogenase concentration was increased at 722 UI/L (normal range 200–479 UI/L). The tumour was staged as pT1 N2. A classic chemotherapy regimen of cisplatin, etoposide, and bleomicin was given for three cycles, after which the patient’s concentrations of lactate de hydrogenase normalised and he had a complete response. The patient had standard follow-up according to the European Society for Medical Oncology recommendations. His fi rst relapse occurred in October, 2000, when retroperitoneal lymph-node involvement (right paracaval lymph nodes at least 5 cm in diameter that involved the right ureter and needed a pielostomy) and an increase in lactate dehydrogenase concentration to 1342 UI/L was noted. The patient underwent a classic second-line chemotherapy regimen with cisplatin, ifosfamide, and etoposide. A CT scan showed a reduction of the mean diameter of lymph nodes to 1 cm after two cycles, a complete response in all disease sites after four cycles, and normalisation of lactate de hydrogenase concentration to 293 UI/L after four cycles. At the end of chemotherapy, the patient received consolidation radiotherapy (2400 cGy in 12 fractions). A second relapse occurred 3 months later, with a CT scan showing lung metastases and supradiaphragmatic and infra diaphragmatic enlarged lymph-nodes. Tumour markers, including lactate dehydrogenase (326 UI/L), were normal. Between June, 2001, and November, 2001, after mobilisation and collection of peripheral-blood stem cells, the patient received two cycles of induction chemotherapy with gemcitabine and paclitaxel, followed by intensifi cation with high-dose chemotherapy (CARBOPEC—carboplatin, etoposide, and cyclophosphamide—with reinfusion of peripheral stem cells), and had a complete response in the thorax and a partial response in the abdomen with a residual mass of 1·5 cm disappearing 3 months later. In March, 2004, after 28 months of sustained complete remission, further restaging showed multiple bilateral metastases in the lung parenchyma (fi gures 1A and 1B). The CT scan did not show any infradiaphragmatic or supradiaphragmatic nodal metastases, unlike at the time of high-dose chemotherapy. Tumour markers were negative. A biopsy of the lung metastases was not done because CT images were indicative for secondary tumours. Because several investigators have reported KIT expression in a wide variety of human malignancies, and have shown that the kinase activity of KIT might be involved in the pathophysiology of some of these tumours—including germ-cell tumours and, more frequently, seminomas—we assessed KIT expression in the orchiectomy specimen by immunohistochemistry. Staining for KIT was strongly positive (fi gure 2). A standard avidin-biotin staining protocol was used with a polyclonal rabbit antibody for KIT (Dako A4502; Dako Corp, Carpinteria, CA, USA). The patient started receiving imatinib at the dose recommended for the treatment of gastrointestinal stromal tumours (400 mg/day). Treatment was well-tolerated, with Lancet Oncol 2007; 8: 1039–40