Non-germ Cell Research Articles

Teratoma with Malignant Transformation: Experiences of the Cooperative GPOH Protocols MAKEI 83/86/89/96

The designation of a teratoma with malignant transformation (TMT) refers to the occurrence of somatic non-germ cell malignancies within a teratoma. While TMT is a rare but well recognised phenomenon in adult germ cell tumors (GCT), data on TMT in pediatric GCTs are lacking. Between 1982 and 2003, 641 patients with extracranial nontesticular pure teratoma (256 coccygeal, 246 ovarian, 139 other sites) were reported to the MAKEI protocols 83/86/89/96 by various, mainly German centres. Patients with teratoma and somatic malignancy were identified by database queries. Patients with malignant germ cell tumor components were excluded from this analysis. The clinical files were reviewed and re-evaluated centrally. Information was actualized by requisition to the participating hospitals. We identified nine patients (all female, age 0-39 years) meeting the histological criteria of TMT. Two patients had coccygeal teratomas and seven ovarian tumors. Carcinoma was the dominating malignancy (five of nine cases). Tumors with glial differentiation and embryonal tumors occurred in two cases each. Resection was performed in seven patients (including both coccygeal tumors) and adjuvant chemotherapy was administered in one of them. Two patients relapsed after resection, but both were cured with chemotherapy. Two patients suffered from advanced tumors and both were treated with primary chemotherapy. One patient was cured from the malignant component (astrocytoma), but the teratomatous components persisted. The other patient died as a result of progression of her malignant medulloepithelioma. Malignant transformation of pure teratomas constitutes a very rare entity in children and adolescents that is most commonly observed in postpubertal girls with ovarian teratoma. Compared to adult patients, similar malignant entities can be observed in association with teratoma. However, in our series, no sarcoma was diagnosed. In localised tumors, complete resection appears to be adequate, whereas chemotherapy should be considered in patients with R1- or R2-resection. Cisplatinum-based chemotherapy was effective as two of four relapsed patients survived tumor free. However, the ideal regimen has not yet been established and the known sensitivity of the histologic components to cytostatic drugs has to be considered in the choice of treatment. Further molecular biologic studies are necessary to understand the origin of these tumors.

A High-Grade Uterine Leiomyosarcoma With Human Chorionic Gonadotropin Production

Ectopic human chorionic gonadotropin production has been described in a wide variety of non-germ cell tumors, particularly in epithelial tumors, but rarely in sarcomas. In this report, we describe the case of 49-year-old woman with a history of "uterine fibroids," who presented with vaginal bleeding and a positive urine pregnancy test. After pregnancy was ruled out by ultrasound, the patient underwent a laparotomy and hysterectomy for a presumptive diagnosis of "fibroids" and was found to have carcinomatosis at the time of the surgery. Therefore optimal debulking of tumors was performed. Two weeks later, the patient developed a small bowel obstruction, which apparently was due to rapid recurrence of tumors in the abdomen, and soon afterwards she died. Microscopically, the resected pelvic mass was composed of highly atypical and pleomorphic spindle cells admixed with many multinucleated giant cells. The tumor had a high mitotic rate along with areas of hemorrhage and necrosis. Immunohistochemically, the tumor cells were positive for vimentin, desmin, smooth muscle actin, and beta-human chorionic gonadotropin, and were negative for epithelial membrane antigen, keratin AE1/3, S-100, CD31, CD117, Ber-EP4, WT-1, estrogen and progesterone receptors. The majority of cells, including the multinucleated giant cells, were strongly immunoreactive for beta-human chorionic gonadotropin. Only three cases of leiomyosarcomas with beta/human chorionic gonadotropin production have been described in the literature, and all three cases had extrauterine origin. Our case, to the authors' best knowledge, is the first uterine leiomyosarcoma with prominent beta/human chorionic gonadotropin production.

Detection of non-maternal components of gestational choriocarcinoma by PCR-based microsatellite DNA assay

Objective. Gestational and non-gestational choriocarcinomas have distinctly different tissues of origin, parental genotypes, natural histories, and responses to therapy. Our objective was to develop a convenient, fast, and reliable assay that would, using only patient tissue, allow separation of gestational from non-gestational choriocarcinomas. Method. Benign and malignant tissues, preserved in paraffin blocks and separated by microdissection, were examined using a commercial PCR-based tissue identity assay (ABI AmpFlSTR Profiler Plus Kit and ABI 377 DNA sequencer) to detect genetic profiles of 9 microsatellite markers, along with X and Y chromosome markers. Cases included 6 choriocarcinomas. Controls included eight non-germ cell reproductive tract tumors and two hydatidiform moles. Results. The microsatellite markers identified the five choriocarcinomas diagnosed on clinical and histological grounds as gestational, to be of genetically non-maternal (androgenic) origin. The neoplasm previously classified as a non-gestational choriocarcinoma was demonstrated to be of maternal origin, as were the non-germ cell reproductive tract tumors. Samples from hydatidiform moles contained either androgenic markers only or a mix of maternal and androgenic markers, as previously seen in complete and partial moles, respectively. Conclusion. A commercially available microsatellite DNA diagnostic assay is a quick and convenient way to discriminate between gestational and non-gestational choriocarcinoma.

Evidence to Support a Continued Stage Migration and Decrease in Prostate Cancer Specific Mortality

We evaluated whether the proportion of patients with a postoperative PSA-DT less than 3 months, a surrogate for PCSM, decreased significantly during the PSA era. Between July 1988 and July 2002, 3,719 men with clinically localized prostate cancer treated with RP comprised the study cohort. A chi-square metric was used to compare the preoperative and postoperative characteristics, 5-year actual PSA failure rates, and PSA-DTs for patients treated during the 2 equally divided eras of the early PSA era, July 1988 to July 1995 and the late PSA era, August 1995 to July 2002. Patients presenting in the more recent PSA era were of younger age (p < 0.0001), with earlier stage (p < 0.0001) and lower grade disease (p = 0.01). Similarly, patients had lower grade (p < 0.001), stage (p < 0.0001), and positive margin (p < 0.0001) and lymph node rates (p = 0.0002) at RP. The 5-year actual PSA failure rates decreased from 14.3% in the early PSA era to 2.5% in the later PSA era (p < 0.0001). There was a 37% reduction in the proportion of patients with a PSA-DT less than 3 months, corresponding to a decrease in absolute magnitude from 9% to 5.7% between the 2 eras. Absolute reductions of 3.1% and 9% were also noted for the proportion of PSA-DTs of 3 to 5.99 months and 6 to 11.99 months, respectively, whereas PSA-DTs of 12 months or greater increased by 15.3%. During the recent PSA era, postoperative PSA failure has significantly decreased and PSA-DTs have increased, suggesting that PCSM will continue to decrease.

Stem Cell Marker OCT3/4 in Tumor Biology and Germ Cell Tumor Diagnostics: History and Future

The transcription factor OCT3/4 (also known as POU5F1 and Oct4) is regarded as one of the key regulators of pluripotency. Expression in nonmalignant cells is restricted to the pluripotent cells in the embryo and the primordial germ cells that will pass pluripotency to future generations via the gametes. Although major progress has been made in successfully identifying other players in the pluripotency network by using high-throughput screening methods, the exact mechanisms involved in regulation of OCT3/4 in vivo remain largely to be elucidated. In human tumors, OCT3/4 is the most informative marker in germ cell tumors diagnostics and is expressed in the precursor lesions gonadoblastoma and carcinoma in situ, as well as in invasive embryonal carcinoma and seminomatous tumors. Currently, the application of OCT3/4 for screening in high-risk patient populations is the novel focus of study. This article reviews OCT3/4 expression in normal development and germ cell tumors. In addition, expression in adult tissues and nongerm cell tumor malignancies in relation to splice variants and pseudogenes is discussed. An overview of the upstream and downstream factors in the OCT3/4 pathway as well as the epigenetic regulation of the gene is summarized and the possible role in oncogenesis considered.

Chromosome 12p abnormalities in dysgerminoma of the ovary: a FISH analysis

Dysgerminoma is the most common malignant ovarian germ cell tumor and shares histological and immunophenotypical features with its testicular counterpart, seminoma. Chromosome 12p abnormalities are genetic hallmarks of testicular seminomas. Little is known about these genetic changes in dysgerminoma. We performed dual color fluorescence in situ hybridization (FISH) analyses with a centromeric α-satellite probe for chromosome 12 and a subtelomeric probe for 12p on paraffin-embedded tissue sections from 21 dysgerminomas and two gonadoblastomas. Chromosome 12p abnormalities were detected in 81% of dysgerminomas. In all, 57% of cases had only isochromosome 12p and 5% had only 12p overrepresentation. In all, 19% had both isochrome 12p and 12p overrepresentation. Gonadoblastomas were negative for isochromosome 12p or 12p overrepresentation. Chromosome 12p abnormalities are common in dysgerminoma of the ovary. FISH analyses for chromosome 12p abnormalities may be a useful diagnostic adjunct for confirming the diagnosis of dysgerminoma and for distinguishing it from nongerm cell malignancies that enter into the differential diagnosis.

Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis

Bone sarcomas are a clinically and molecularly heterogeneous group of malignancies characterized by varying degrees of mesenchymal differentiation. Despite advances in medical and surgical management, survival rates for high-grade tumors have remained static at 50% to 70%. Tumor stem cells have been recently implicated in the pathogenesis of other heterogeneous, highly malignant tumors. We demonstrate here the existence of a small subpopulation of self-renewing bone sarcoma cells that are capable of forming suspended spherical, clonal colonies, also called “sarcospheres,” in anchorage-independent, serum-starved conditions. These bone sarcoma cells as well as tissue specimens express activated STAT3 and the marker genes of pluripotent embryonic stem (ES) cells, Oct 3/4 and Nanog. Expression levels of Oct 3/4 and Nanog are greater in sarcospheres than in adherent cultures. A subset of bone sarcoma cells displays several surface markers of mesenchymal stem cells (Stro-1, CD105, and CD44) as well as attributes of mesodermal, ectodermal, and endodermal differentiation. Although previously documented in brain and breast tumors, our results support the extension of the cancer stem cell hypothesis to include tumors of mesenchymal lineage. Furthermore, they suggest the participation of ES cell homeobox proteins in non-germ cell tumorigenesis.

547 ORAL Long-term risk of non-germ cell malignancies in 5-year survivors of testicular cancer

547 ORAL Long-term risk of non-germ cell malignancies in 5-year survivors of testicular cancer

Human Embryonic Stem Cell Genes are Expressed in both Human Germ and Non-Germ Cell Cancers

Stem cells have enormous therapeutic potential. However, little is known about the consequences of adult cells expressing genes normally associated with human embryonic stem cells. In particular, human embryonic stem cells (hESC) and cancer share certain properties such as the ability for self-renewal and differentiation. Therefore, it is conceivable that genes associated with undifferentiated hESCs could also be associated with cancer progression. Chromosome 12p is a hot spot for chromosomal abnormalities found in testicular germ cell tumors.

OCT4 Staining in Testicular Tumors. A Sensitive and Specific Marker for Seminoma and Embryonal Carcinoma

OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma. We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool. We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining. Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and “usual,” but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

Surgical salvage therapy for malignant intrathoracic metastases from nonseminomatous germ cell cancer of testicular origin: Analysis of a single-institution experience

Cisplatin-based chemotherapy followed by surgical extirpation of residual benign disease represents the usual sequence of curative therapy for metastatic nonseminomatous germ cell cancer of testicular origin. Occasionally, residual disease is malignant in the form of either a persistent nonseminomatous germ cell cancer tumor or degeneration into non-germ cell cancer. We reviewed our institution's experience with patients undergoing salvage operations to remove malignant intrathoracic metastases. From 1981 through 2001, 438 patients with nonseminomatous germ cell cancer had operations to remove residual intrathoracic disease after cisplatin-based chemotherapy at Indiana University Hospital. A subset of 134 patients who underwent 186 surgical procedures to remove malignant metastases is the basis of this review. Fifty-nine patients had removal of pulmonary metastases, 49 had removal of mediastinal metastases, and 26 had removal of both pulmonary and mediastinal metastases. Surgical pathology demonstrated 84 patients with persistent nonseminomatous germ cell cancer tumors, 38 with degeneration into non-germ cell cancer, and 12 with both malignant pathologic categories. There were 4 (3.7%) operative deaths. The overall median survival was 5.6 years, with 55 (42.3%) patients alive and well after a mean follow-up of 5.1 years. Seventeen variables were analyzed by using Cox regression. Of these, older age, pulmonary metastases (vs mediastinal metastases), and 4 or more (vs 1) total intrathoracic metastases were significantly (P < or = .01) predictive of inferior long-term survival. Salvage thoracic surgery to remove malignant metastases from nonseminomatous germ cell cancer tumors of testicular origin can result in long-term survival in select patients. We identified variables that influence survival in this subset.

Pooled analysis of phase 2 reports of 2 v 1 course of carboplatin as adjuvant for stage 1 seminoma

4572 Introduction: In the last 10 years there has been reports of increased risk of late occurrence of non-germ cell cancers 20 years or more after radiation as adjuvant for stage 1 seminoma. Prompted by a randomised study suggesting that 1 course carboplatin was equally effective but also in the short term(5years) was associated with significantly less tumours in the contrateral testis, this abstract reports 10 and 20 year follow up experience from the phase 2 studies of 1 and 2 course carboplatin that preceeded the randomised trial. Methods: Research of published papers identified 5 publications and 2 abstract with 837 cases followed for a median of 75 months. The data for relapse, germ cell cancer mortality, 2nd GCT and non-GCT causes of death have been pooled and the authors contacted for follow up. Results: 521 patients received 2 courses with 15(2.9%) relapse, 0 GCT deaths 0 second GCT and 7(1.3%) non GCT deaths (p ns). 316 received 1 course with 14(4.4%) relapses, 10/16(8.6%) in those receiving 400...

Pathology of tumours of the male genital tract

The most common neoplasms of the male genital tract are tumours of the testis and prostate. Testicular germ cell tumours are particularly important because they affect young men and even the advanced stages have a high rate of cure. The WHO classification emphasizes the recognition of seminoma and individual non-seminomatous germ cell tumour patterns. Included in this group are the embryonal carcinoma, yolk sac tumour, trophoblastic tumour and teratoma. Many of the tumours are combined, containing more than one tumour component. It is important to differentiate between embryonal carcinoma and a high-grade variant of seminoma or distinguish a malignant change in a teratomatous deposit from one of the patterns of high-grade germ cell tumours. The WHO classification also emphasizes the recognition of various yolk sac tumour patterns. Non-germ cell tumours of testis are uncommon, but it is important to recognise sex cord stromal tumours and differentiate them from germ cell tumours. The sex cord stromal tumours include Leydig cell tumours, Sertoli cell tumours, Granulosa cell tumours and tumours of the thecoma/fibroma group. Malignant lymphoma is the most common amongst haematopoietic tumours occurring in the testis. Prostate cancer the most common malignancy in elderly men in the UK. The use of needle biopsy of prostate has improved early diagnosis, but creates difficulty in interpretation. High-grade prostate intraepithelial neoplasia is a clinically significant finding requiring intervention. Prostate adenocarcinoma is graded by the Gleason scoring system.

OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma: Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.

OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma. We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool. We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining. Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and “usual,” but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Expression and diagnostic significance of OCT4, CD117 and CD30 in germ cell tumors

To study the immunohistochemical expression of OCT4, CD117 and CD30 in germ cell tumors and to assess their diagnostic value. Immunohistochemical study for OCT4 was performed on formalin-fixed, paraffin-embedded tissues of 63 cases of germ cell tumors, including seminoma (21), dysgerminoma (7), germinoma (8), embryonal carcinoma (8), yolk sac tumor (6), mature teratoma (10) and immature teratoma (3), as well as 25 cases of non-germ cell tumors, including granulosa cell tumor (8), clear cell adenocarcinoma (4), Leydig's cell tumor (5), diffuse large B-cell lymphoma (4) and malignant melanoma (4). Besides, the expression of CD117 and CD30 in all germ cell tumors was studied. All cases of seminoma and germinoma, 6/7 cases of dysgerminoma and 7/8 cases of embryonal carcinoma were positive for OCT4, with strong nuclear staining. All other germ cell tumors and non-germ cell tumors were negative for OCT4, except for 1 case of yolk sac tumor and 1 case of clear cell adenocarcinoma which showed weak staining. Positive membranous expression of CD117 was demonstrated in 19/21(90.5%) seminoma, 5/7 dysgerminoma and 7/8 germinoma. Focal weak membranous staining was also noted in 1 case of yolk sac tumor. The melanocytes in teratoma were also positive for CD117. All cases of embryonal carcinoma were negative. On the other hand, positive membranous expression of CD30 were demonstrated in 6/8 embryonal carcinoma. One case of germinoma and 1 case of yolk sac tumor showed weak cytoplasmic positivity. All cases of seminoma and dysgerminoma, 7/8 germinoma and all cases of teratoma were negative for CD30. OCT4 is a sensitive and relatively specific marker for diagnosing seminoma, dysgerminoma, germinoma and embryonal carcinoma. CD117 and CD30 immunostains, when used in combination, represent valuable tools for distinguishing embryonal carcinoma and seminoma, dysgerminoma, germinoma.

Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry.

There are diverse morphologic manifestations of metastatic tumors. The determination of tumor origin is critical for patient management, and it is especially important when the differential diagnosis includes metastatic germ cell tumor, which is a highly treatable condition. OCT4 is a nuclear transcription factor that is expressed in pluripotent embryonic germ cells. In this study, the author sought to determine the usefulness of OCT4 immunohistochemistry in the diagnosis of metastatic germ cell tumors. Sixty-two retroperitoneal lymph node dissection specimens from patients with histories of testicular germ cell tumors were stained using the antibodies against OCT4. In addition, 84 metastatic, nongerm cell lesions from men with known primary tumors were studied in parallel for OCT4 immunohistochemistry. All embryonal carcinoma components (n = 29 specimens) and seminoma components (n = 18 specimens) from retroperitoneal lymph node dissection specimens showed strong, intense, diffuse nuclear staining for OCT4. Yolk sac tumors (n = 12 tumors), choriocarcinomas (n = 4 tumors), mature teratomas (n = 16 tumors), and primitive neuroectodermal tumors (n = 5 tumors) were negative for OCT4 staining. Metastatic, nonsmall cell carcinomas from the lung (n = 14 tumors), colon (n = 12 tumors), stomach (n = 5 tumors), pancreas (n = 7 tumors), prostate (n = 12 tumors), kidney (n = 3 tumors), and urinary bladder (n = 15 tumors) all were found to be negative immunohistochemically for OCT4, as were metastatic small cell carcinomas (n = 4 tumors) and metastatic melanomas (n = 7 tumors). In addition, malignant lymphomas (n = 5 tumors) also were negative for OCT4. Immunohistochemical detection of OCT4 is highly sensitive and specific for the diagnosis of seminoma and embryonal carcinoma metastatic from the testis. Establishing germ cell origin for metastatic tumors has important implications for assessing patient prognosis and treatment options.

A review of genitourinary cancers at the Korle-Bu teaching hospital Accra, Ghana.

To determine the frequency and pattern of genitourinary malignancies seen at the Korle-Bu Teaching Hospital, Accra, Ghana A retrospective review of genitourinary malignancies seen at the Korle-Bu Teaching Hospital from 1980 to 1990 was undertaken. Data was obtained from the operating theatre register, histopathology reports, and patient case notes. Information retrieved included age and sex of patients, organ involved and laterality where appropriate and tumour type. 548 genitourinary malignancies were seen, of which 479 (87.4%) were in males and 69 (12.6%) in females. Adults comprised 93.4% and children 6.6%. The organ-specific distribution was as follows-prostate 349 (63.7%), bladder 117 (21.3%), kidney 57 (10.4%), testis 13 (2.4%), penis 10 (1.8%) and one each of the ureter and urethra. The kidney tumours comprised nephroblatoma (56.1%), adenocarcinoma (35.1%) with the rest being of urothelial origin. Of the bladder tumours, 50.4 % and 44.8 % were transitional cell and squamous cell carcinoma respectively. Virtually all the prostatic cancers (99%) were adenocarcinomas. Of the testicular tumours 8(61.5%) were of germ cell and 5 (38.5%) non-germ cell origin. The penile cancers were all squamous. The ureteric and urethral tumours were due to transitional cell and squamous cell carcinomas respectively. Prostatic carcinoma was the predominant genitourinary tumour, accounting for nearly two-thirds of cases, followed by the bladder and the kidney. Other tumours were relatively uncommon. Transitional cell carcinoma of the bladder was seen a little more commonly than the squamous type.

Surgical “salvage” therapy for intrathoracic chemorefractory metastases from non-seminomatous germ cell cancer of testicular origin: An institutional retrospective review

4528 Background: Cisplatin-based chemotherapy (CTx) followed by surgical extirpation of residual disease represents the usual sequence of curative therapy for metastatic non-seminomatous germ cell cancer of testicular origin (NSGCT). Occasionally residual disease is chemorefractory in the form of either persistent NSGCT or degeneration into non-germ cell cancer (NGCC). This retrospective review evaluated patients (pts) undergoing “salvage” surgery to remove chemorefractory cancer metastatic to the thorax. Methods: From 1981–2001, 438 pts with NSGCT had surgery to remove residual intrathoracic disease after CTx at Indiana University Hospital. A subset of 134 pts who underwent 186 thoracic surgical procedures to remove chemorefractory cancer is the basis of this review. Eighty-one (60.4%) pts underwent second line CTx prior to surgery and 72 (53.7%) had elevated serum tumor markers at the time of surgery. The mean age was 27 yrs. Eighty-four pts had removal of pulmonary metastases, 74 mediastinal metastases, and 26 had removal of both pulmonary and mediastinal metastases. Surgical pathology demonstrated 84 pts with persistent NSGCT, 38 with NGCC, and 12 had both malignant pathologic categories. Sixty-eight pts with persistent NSGCT received CTx after surgery. Results: There were 4 (2.1%) operative deaths. The median survival was 67 months in operative survivors with 55 (41%) pts alive and well after a mean follow-up of 49 months. Twenty-seven variables were analyzed using Cox regression. Of these, older age (p<0.01) and pulmonary (vs. mediastinal) metastases (p=0.01) were significantly predictive of poorer long-term survival. Log rank analysis additionally identified preoperative BHCG≥1,000ng/ml (p<0.04) and ≥ 4 metastases (p<0.01) as negative predictors for survival. Conclusions: Aggressive “salvage” surgical therapy to remove chemorefractory cancer metastatic to the thorax can result in long-term survival. We have identified variables which appear to influence survival for this subset of NSGCT pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline