703 CIRCULATING TUMOR CELLS CAN BE DETECTED IN PATIENTS WITH TESTICULAR GERM CELL TUMORS

Vol. 189, No. 4S, Supplement, Sunday, May 5, 2013

reduced over time. Furthermoe, this risk was independent of both primary and lymph node stage suggesting that it related more directly to the surgery itself that the extent of disease. Source of Funding: None

702 CLINICAL FEATURES AND TESTICULAR MORPHOLOGY IN INFANTILE PATIENTS WITH KALLMANN SYNDROME Hidenori Nishio*, Kentaro Mizuno, Satoshi Kurokawa, Hideyuki Kamisawa, Makoto Imura, Yoshinobu Moritoki, Yasuhiro Shibata, Akihiro Nakane, Toshiki Kato, Tetsuji Maruyama, Yoshiyuki Kojima, Yutaro Hayashi, Kenjiro Kohri, Nagoya, Japan INTRODUCTION AND OBJECTIVES: Kallmann syndrome (KS) is a genetic disorder characterized by the simultaneous occurrence of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Although there have been some reports about genes responsible for KS, their impact on the testicular tissue of KS during infantile periods remains unclear. We retrospectively reviewed the patients clinically diagnosed KS, and evaluated the testicular morphology of KS these patients by performing testicular biopsies during orchiopexy. METHODS: A retrospective assessment was conducted of 4 cryptorchid patients diagnosed with KS. The assessment included a determination of the chief complaints of the patients upon presentation, the age at which the orchiopexy was performed, and the results of hormone tests, including tests for luteinizing hormone-releasing hormone and human chorionic gonadotropin (hCG). In addition, testicular morphology was assessed during testicular biopsy, and histrogical examinations were performed. Especially the presence of Leydig cells was examined by immunohistochemistry using antibodies against Ad4BP/SF1. RESULTS: Laboratory testing showed low values of LH, FSH, and testosterone, confirming hypogonadotropic hypogonadism. LH and FSH did not increase in response to intravenous gonadotropin-releasing hormone treatment; hCG tests also failed to show changes in testosterone levels. Head magnetic resonance imaging scans failed to show evidence of pituitary tumors but showed deficiencies in the olfactory bulbs and grooves. Histologic examinations of the testes showed immature seminiferous tubules with mild interstitial fibrosis and edema; spermatogonia were not detected. Leydig cells were detectable in the testis of the interstitium and Sertoli cells in the seminiferous tubules by immunohistochemistry using antibodies against Ad4BP/SF1 in the testes of one patient. CONCLUSIONS: Although the diagnosis of KS before puberty is difficult, LH-RH and hCG tests were useful for the differential diagnosis. The present study showed the presence of Leydig cells in the testis of one patient with IHH using immunohistochemistry for Ad4BP/ SF1, even though Leydig cells were reportedly absent. Testicular morphology in the patients with KS is more varied than expected, and further investigations are required to elucidate the hormonal effects on normal testicular development. Source of Funding: None

703 CIRCULATING TUMOR CELLS CAN BE DETECTED IN PATIENTS WITH TESTICULAR GERM CELL TUMORS Christian Ruf*, Paulina Nastaly, Pascal Becker, Hendrik Isbarn, Friedemann Honecker, Klaus Pantel, Sabine Riethdorf, Hamburg, Germany; Dirk Hoeppner, Berlin, Germany; Margit Fisch, Walter Wagner, Sascha Ahyai, Hamburg, Germany INTRODUCTION AND OBJECTIVES: The available serum tumor markers (AFP, ␤-HCG, LDH) are increased in only approximately 60% of testicular germ cell tumors (TGCT) patients. Therefore, additional markers would facilitate clinical diagnosis, staging and treatment of these patients. Detection of circulating tumor cells (CTC) has been

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associated with poor prognosis in other malignancies (e.g. Prostate-, Colon- and Breastcancer), however, little is known about the presence of CTC in blood of TGCT patients. METHODS: In order to select the most appropriate markers for CTCs detection, the expression of different epithelial and germ cellspecific markers was examined in 4 different TGCT cell lines (TCam2/2102Ep/NCCIT/NT2) as well as 12 histologically different primary testicular tumors. Peripheral and testicular vein blood samples from 73 and 12 patients, respectively, were collected and examined for CTCs. All samples were enriched for mononuclear cells using Ficoll density gradient centrifugation and CTCs were detected by alkaline phosphatase (AP) enzymatic activity and immunocytochemistry using antikeratin, anti-EpCAM and anti-SALL4-antibodies. Additionally, peripheral blood samples were tested for the presence of CTCs by the automated CellSearch® system. Patients with ⱖ1 CTC/sample were classified as CTC-positive. To compare results for testicular and peripheral blood, CTC yields were calculated as number of CTC per 1 ml of blood. RESULTS: Based on the previous analyses, double immunofluorescent staining for SALL4 and keratin, as well as analysis of AP activity were performed to detect CTCs. According to both detection systems uˆ the one based on selected markers and automated CellSearch®, 7 (58.3%) testicular vein and 13 (17.8%) peripheral blood samples showed presence of at least one CTC. The CTC number ranged from 5 to 108/ml and 0.13 to 2.18/ml of testicular vein and peripheral blood, respectively. CTC were detected in seminoma and non-seminoma, in clinically metastasized and non-metastasized stages. CONCLUSIONS: This is the first study to demonstrate CTC detection in TGCT patients. The proposed detection systems seem to be specific and sensitive for the identification of CTC. An association between CTC and histological subtype as well as metastatic stage is under investigation and will be presented at the meeting. Source of Funding: None

704 MULTI-FOCALITY OF TESTICULAR GERM CELL TUMOURS ⴚ SINGLE INSTITUTION REVIEW OF 100 UK CASES James Douglas*, Sam Dockree, Jeffery Theaker, Matthew Hayes, Southampton, United Kingdom INTRODUCTION AND OBJECTIVES: There is an increasing recognition of the importance of organ preserving surgery for numerous tumour types including testis tumours. Currently, guidelines suggest consideration of partial orchidectomy in testis tumours that are solitary and less than 2cm in maximum diameter. The objective of this study was to assess tumour focality in the last 100 cases of testicular germ cell tumours undergoing radical orchidectomy to determine what proportion of patients might have been potential candidates for partial orchidectomy using these criteria. METHODS: The pathology departmentÆs database was interrogated to ascertain the last 100 cases of germ cell testicular tumours that met the study criteria. Patients, who were referred from external hospitals, had previous chemotherapy, radiotherapy, history of undescended testis or pure CIS were excluded from the study. The original pathology blocks were retrieved and reviewed by a single pathologist with a special interest in testis tumours. The size and number of tumours were re-assessed. The tumour type was recorded and the subtypes grouped into seminoma, pure or mixed non-seminomatous germ cell tumour (NSGCT) or NSGCT ⫹ seminoma. The tumour was described as uni-focal, multi-focal or total involvement. RESULTS: 67% of case were seminomas, 25% pure or mixed NSGCT and 8% NSGCT ⫹ seminoma. Mean tumour size was 40.8mm (4-110 mm). Overall 46% of tumours were multi-focal and 85% were multi-focal or total involvement. 84% of cases had concurrent carcinoma in situ. 16.4 % of the seminomas were uni-focal, 16% of the pure or mixed NSGCT uni-focal and none of the NSGCT ⫹ seminoma group were uni-focal. All tumours that were greater than 70mm were either