Brain metastasis from non-seminomatous germ cell tumor of the testis

Brain metastasis occurs rarely in patients with testicular cancer in the modern era where cisplatin-based chemotherapy regimens are used. The occurrence of brain metastasis can be synchronous or metachronous (with or without concurrent systemic disease). Long-term survival can be achieved in some patients. The vast majority of testicular cancer cases with brain metastasis reported in the literature involve nonseminomatous germ cell tumor and this subtype will be the focus of this review. This article reviews the literature of the diagnosis and management of brain metastasis from nonseminomatous germ cell tumor of the testis.     

Gamma knife radiosurgery in brain metastases from testicular tumors

To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8–2.0 Gy. The indications for radiosurgery were tumor volume <20 cm³, microsurgery too risky, refusal of surgery. All the lesions were located in eloquent brain areas. Post-GK high-dose chemotherapy with autologous peripheral-blood stem-cell rescue was administered in two cases due to systemic recurrence of the disease. All patients are still alive with a median and mean follow-up period after radiosurgery of 63 and 68.3 mo, respectively. They had no neurological deficits at the latest examination. Neuroradiological follow-up invariably showed tumor growth control (complete response in two cases and partial response in one) with typically delayed post-radiosurgical imaging changes (transient in two cases and long-lasting in one). In conclusion, GK seems to be highly effective and safe in brain metastases from testicular nonseminomatous germ cell tumor. In cases with diffuse metastatic brain involvement, the whole brain radiotherapy preceding radiosurgery should be delivered with ≤1.8 Gy daily fraction to prevent the risk of long-lasting post-radiosurgical imaging changes.     

Hepatoid pancoast tumor. A case report and review of the literature

A 48-year-old male patient presented with a Pancoast tumor of the right lung and a serum alpha-fetoprotein (αFP) at 39,000 ng/ml. Alpha-fetoprotein is a tumor marker found elevated in patients with hepatocellular carcinoma (HCC), germ cell or stromal tumors of the ovary and nonseminomatous testicular cancer. Occasionally, this tumor marker may rise in non-neoplastic conditions such as cirrhosis and hepatitis and only exceptionally in rare cancers with hepatoid differentiation. We present our case report and review the English literature for αFP-producing lung carcinomas. To the best of our knowledge this is the first report in the literature of an αFP producing Pancoast tumor.     

Comparison of the antitumor activity of cisplatin, carboplatin, and iproplatin against established human testicular cancer cell lines in vivo and in vitro

Cisplatin is a backbone of any combination chemotherapy currently in use for the treatment for nonseminomatous germ cell tumors. Recently new platinum analogs with lower toxicity have been developed. The antitumor activity of two analogs, carboplatin (JM8) and iproplatin (JM9) was compared to cisplatin in vitro and in vivo. The 3thymidine incorporation in three established human testicular cancer cell lines was significantly stronger inhibited by cisplatin than by JM8 or JM9. Cisplatin showed a significantly stronger antitumor activity against heterotransplanted human testicular cancer cell lines in the nude mouse than JM8 or JM9 when given at equitoxic doses. Although both analogs only moderately retarded the tumor growth, cisplatin produced a significant reduction of tumor volume in three of four cell lines. From these data it is concluded that the antitumor activity of cisplatin may be significantly superior to JM8 and JM9, and results of preclinical investigations should be awaited before replacement of cisplatin by JM8 or JM9 in the treatment of nonseminomatous germ cell tumors can be considered.     

Testicular Cancer: When Less is More

Clinical stage I testicular cancer is highly curable. The treatment options include adjuvant chemotherapy or surveillance for most patients, radiotherapy for seminoma, and retroperitoneal lymph node dissection for selected patients with nonseminomatous germ cell tumors. This review discusses the decision points with emphasis on the advantages and disadvantages of each management option.     

Microinvasive germ cell neoplasia of the testis.

BACKGROUND. The term microinvasive germ cell neoplasia denotes the presence of neoplastic germ cells in the tubuli and interstitium of the testis, unaccompanied by clinically detectable tumor. METHODS. Testicular biopsy specimens from three patients (age range, 26-38 years) without clinical evidence of tumor showed microinvasive germ cell neoplasia. The indications for biopsy were gynecomastia and testicular atrophy in Patient 1, infertility in Patient 2, and nonseminomatous cancer in the contralateral testicle in Patient 3. RESULTS. In all three cases, orchiectomy specimens disclosed multifocal intratubular and extratubular growth of neoplastic germ cells, occasionally confluent in seminoma-like infiltrates. In Cases 1 and 2, no malignant cells were found at biopsy of the contralateral testis. CONCLUSIONS. In contrast to intratubular (in situ) germ cell neoplasia, microinvasion constitutes a definitive malignancy and the starting point of differentiation into seminoma or nonseminomatous tumor. Inguinal orchiectomy is recommended as primary therapy. The necessity of complementary therapy is an issue that must be investigated.     

Lung carcinoma with metastasis to testicular seminoma.

Tumor-to-tumor metastases are uncommon. The most frequent donor tumors are the lung, whereas renal cell carcinoma is by far the most common recipient. In this report the authors describe a lung tumor that metastasized to a testicular seminoma. This is the first reported case of tumor-to-tumor metastases in which seminoma of the testis is the recipient. The authors performed mucin and immunohistochemical studies on this case and on ten cases of nonseminomatous germ cell tumors containing embryonal carcinoma and endodermal sinus tumor for comparison. Mucin positivity as well as immunoreactivity for epithelial membrane and carcinoembryonic antigens were confined to metastatic adenocarcinoma in this case, whereas Ki-1 and alpha-fetoprotein immunostaining were restricted to the ten control cases of germ cell tumors. Although the majority of second malignant components found in a seminoma are other nonseminomatous germ cell components, the rare possibility exists that a second malignant component is a metastasis from elsewhere in the body.     

Klinefelter's syndrome associated with mediastinal germ cell neoplasms

Several case reports have suggested an association of primary mediastinal germ cell tumor (PMGCT) and Klinefelter's syndrome (KS). In an effort to confirm this association, 22 patients with mediastinal germ cell tumors had chromosome studies performed in a prospective fashion. Five patients (22%) had karyotypic or pathologic evidence of KS. All of the patients with KS had germ cell tumors of the nonseminomatous subtype and were relatively young (median age, 15 years). The literature confirms the findings of a young median age (18 years), nonseminomatous subtype, and mediastinal location of the germ cell neoplasm. We conclude that patients with KS are predisposed to the development of mediastinal nonseminomatous germ cell cancers.     

Intracaval and intracardiac metastatic nonseminomatous germ cell tumor: a rare cause of hemolytic anemia and thrombocytopenia

Intracaval and intracardiac nonseminomatous germ cell tumor metastases although rare have been previously reported in the literature. Most cases arise as a result of direct hematogenous spread via invasion of the internal spermatic vein, or from lymphatic venous shunting. We report a unique case of disseminated testicular germ cell tumor that presented with extensive intracaval and intracardiac metastatic teratoma and with valvular involvement. These findings were heralded by the presence of a new cardiac murmur, anemia, and severe thrombocytopenia. Resection of the intracardiac mass, prompted by rapid tumor progression despite treatment with systemic chemotherapy, demonstrated mature teratoma and resulted in prompt normalization of the patients hematologic profile.     

Intracaval and Intracardiac Metastatic Nonseminomatous Germ Cell Tumor: A Rare Cause of Hemolytic Anemia and Thrombocytopenia

Intracaval and intracardiac nonseminomatous germ cell tumor metastases although rare have been previously reported in the literature. Most cases arise as a result of direct hematogenous spread via invasion of the internal spermatic vein, or from lymphatic venous shunting. We report a unique case of disseminated testicular germ cell tumor that presented with extensive intracaval and intracardiac metastatic teratoma and with valvular involvement. These findings were heralded by the presence of a new cardiac murmur, anemia, and severe thrombocytopenia. Resection of the intracardiac mass, prompted by rapid tumor progression despite treatment with systemic chemotherapy, demonstrated mature teratoma and resulted in prompt normalization of the patients hematologic profile.     

Postchemotherapy Surgery for Germ Cell Tumors—What Have We Learned in 35 Years?

Postchemotherapy surgery for advanced testicular cancer has evolved over the last couple of decades. Patients with nonseminomatous germ cell tumors and residual retroperitoneal mass ≥1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (RPLND). For seminoma, RPLND is considered in those patients with masses ≥3 cm that are also positron emission tomography positive. Masses that occur outside of the retroperitoneum should be completely resected with the possible exception of bilateral lung masses when resection of the first mass shows necrosis. The role of surgery in patients with extragonadal germ cell tumors is most vital in those with primary mediastinal nonseminomatous germ cell tumors. Importantly, patient selection, surgical planning, and consideration of referral to centers with this expertise are important to optimize success.     

Results of retroperitoneal lymph node dissection and postoperative adjuvant chemotherapy with dactinomycin in the treatment of retroperitoneal metastases of nonseminomatous testicular germ cell tumors

This article discusses 103 patients with a nonseminomatous testicular germ cell tumor. Treatment of 87 patients in clinical Stages I, II-A, and II-B consisted of bilateral retroperitoneal lymph node dissection. In Stage I (54 patients), no further treatment was given. The three-year survival was 96%, while recurrence-free survival was 98%. Of 33 patients in Stages II-A and II-B, 26 received adjuvant chemotherapy with dactinomycin, and ten of these were given radiotherapy (peritoneum/mediastinum) as well. The three-year survival was 88% and recurrence-free survival was 85%. Seven patients in Stages II-A and II-B received no adjuvant chemotherapy; four of them died. Treatment of 14 patients in Stage II-C primarily consisted of dactinomycin therapy, subsequently combined with surgery and radiotherapy. The three-year survival was 28.5%. These findings raise the question whether adjuvant single-agent chemotherapy with dactinomycin for patients with a nonseminomatous testicular germ cell tumor should not be re-evaluated.     

Vascular invasion as a prognosticator of metastatic disease in nonseminomatous germ cell tumors of the testis. Importance in "surveillance only" protocols

Forty-five nonseminomatous germ cell carcinomas of the testis were evaluated retrospectively to define the biologic features associated with the occurrence of metastatic disease. A statistical analysis of several pertinent clinical and pathologic factors was performed. The factors evaluated included: duration of symptoms before diagnosis, serum level of alpha-fetoprotein, serum or urinary level of human chorionic gonadotropin, testicular weight, extent of local tumor (pathologic T stage), and vascular invasion at the primary site. In each case, metastases were documented by a retroperitoneal node dissection, other biopsies, or by chest films. In 29 tumors with vascular invasion, 25 patients were seen with metastatic disease. In 16 tumors without vascular invasion, 3 patients demonstrated metastasis. The presence or absence of vascular invasion was strongly correlated with concomitant lymph node involvement or subsequent appearance of other metastatic disease (chi-square = 17.19). Additionally, vascular invasion in bifactoral++ analysis with tumor size and pathologic T stage proved a significant prognosticator even in low-staged (chi-square = 8.48) and small tumors (chi-square = 8.13). The implications of these findings, both as an adjunct to the staging of nonseminomatous germ cell tumors and in the management of clinical Stage I lesions, are discussed.     

原发纵隔恶性生殖细胞瘤32例临床分析

目的:探讨纵隔恶性生殖细胞瘤(malignant germ cell tumors,MGCT)的临床特点、治疗和预后。方法:32例纵隔MGCT患者,精原细胞瘤18例,非精原细胞瘤14例。所有患者均采用手术和(或)放疗和(或)化疗等多学科综合治疗的方法。结果:非精原细胞瘤患者中位生存期(OS)32.4个月,中位无进展生存期(PFS)18个月,5年无复发生存率和总生存率均为28.6%。精原细胞瘤患者5年无复发生存率和总生存率分别为83.3%和85.6%,中位OS和PFS均未到达。精原细胞瘤患者OS和PFS均明显好于非精原细胞瘤患者,P值分别为0.001 4和0.000 7。结论:纵隔精原细胞瘤采用多学科综合治疗方法能取得较好的治疗效果,本研究的结果与文献报道相符。纵隔非精原细胞瘤的治疗效果有待进一步提高。非精原细胞瘤是影响纵隔恶性生殖细胞瘤预后的重要因素。     

Metastatic carcinoma involving the testis. Clinical and pathologic distinction from primary testicular neoplasms

Metastatic carcinoma to the testis is unusual. There are only seven previously reported cases in which a testicular mass was the first clinical manifestation of an underlying malignancy. The authors review 127 cases in which the testis was involved by metastatic carcinoma, and describe an additional two patients in whom a malignant testicular mass was the presenting sign of an underlying nontesticular carcinoma. The tumors most commonly reported to metastasize to the testis are: prostate (45 cases), lung (25 cases), melanoma (12 cases), colon (11 cases), kidney (10 cases), stomach (6 cases), and pancreas (5 cases). Neuroblastoma, retinoblastoma, carcinoid tumor, and cancers of the bile duct, ureter, bladder, salivary gland, and thyroid have also involved the testis secondarily. Nineteen patients (15%) had bilateral testicular metastases. Patients with secondary testicular neoplasms were older in general than those with germ cell tumors (mean, 55 years; median, 57 years). Histologically, the presence of extensive lymphatic and vascular invasion and an interstitial pattern, in which the seminiferous tubules are spared, is suggestive of a metastasis. In four of the nine cases (44%) in which testicular enlargement was the first manifestation of an underlying carcinoma the correct pathologic diagnosis was initially missed. Serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are occasionally elevated in patients with nontesticular primary tumors, but markedly elevated levels in young patients suggest a nonseminomatous germ cell tumor, as does positive immunoperoxidase staining for AFP and HCG.     

Treatment outcome of patients with extragonadal nonseminomatous germ cell tumors: the Saitama Cancer Center experience

Background

Survival of patients with extragonadal nonseminomatous germ cell tumors remains inferior to that of patients with advanced testicular cancer, although treatment is often the same for both conditions. In addition, the prognosis for nonseminomatous tumors has been shown to be worse than for seminoma.

Methods

Thirteen patients with extragonadal nonseminomatous germ cell tumors were treated between 1998 and 2011; the primary tumors were located in the mediastinum in six and in the retroperitoneum in seven. At initial diagnosis seven patients had distant metastases. According to the IGCCC, eleven patients had poor prognosis and two were intermediate. All 13 patients received cisplatin or carboplatin-based chemotherapy as initial treatment. The patients were further treated by use of a multi-modal strategy which included high-dose chemotherapy, aggressive surgery, and early introduction of salvage regimens.

Results

Complete response was obtained for eight patients. Among these complete responders, one patient remained relapse-free after post-chemotherapy surgical excision of viable cancer tissue. In the course of the chemotherapy, four patients died from cancer progression and one patient died as a result of post-chemotherapeutic sepsis. The other eight patients were alive at the end of the observation period. At the last observation all surviving patients were without evidence of disease. Five-year overall survival for all 13 patients was 62 %, and 5-year cancer-specific survival was 68 %.

Conclusion

Our results indicate that even patients with far-advanced extragonadal nonseminomatous germ cell tumors can be cured by intensive chemotherapy plus surgery.     

Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review.

PURPOSE: Patients with clinical stage I nonseminomatous testicular germ cell tumor should ideally receive adjuvant therapy only when they are at high risk for occult metastasis. We aimed to quantify the importance of predictors for occult metastasis by performing a systematic review of the relevant literature. In addition, we reviewed published multivariable models and risk-adapted treatment policies. PATIENTS AND METHODS: We identified 23 publications between 1979 and 2001, reporting a total of 2,587 patients. Twenty-nine percent of the patients (759 of 2,587 patients) had occult metastases, which was diagnosed either at retroperitoneal lymph node dissection (n = 193) or during follow-up (n = 566). Odds ratios (OR) were pooled using meta-analysis techniques. RESULTS: The presence of vascular invasion of the primary tumor cells had the strongest effect (OR, 5.2; 95% CI, 4.0 to 6.8). Immunohistochemical staining of the primary tumor cells with the MIB-1 monoclonal antibody showing proliferative activity was a promising predictor (OR, 4.7; 95% CI, 2.0 to 11). Intermediate effects were found for embryonal carcinoma in the primary tumor (OR, 2.9; 95% CI, 2.0 to 4.4) and a high pathologic stage of the tumor (OR, 2.6; 95% CI, 1.8 to 3.8). Size of the primary tumor and age of the patient had weaker though also statistically significant associations with occult metastasis. Until now, multivariable models often included vascular invasion and embryonal carcinoma with one or two weaker predictors. None of the published risk-adapted treatment policies included MIB-1 staining. CONCLUSION: Several strong predictors for occult metastasis were identified. A risk-adapted treatment policy should be developed that incorporates all relevant predictors so that adjuvant therapy is targeted better to those with occult metastases.     

Sarcoid reaction mimicking intrathoracic dissemination of testicular cancer

The close observation of patients treated for testicular cancer led to the suspicion of intrathoracic and/or mediastinal metastases on radiologic examination in a number of patients without other evidence of relapse. This report presents two patients with combined seminomatous and nonseminomatous germ cell tumors with isolated sarcoid reactions of hilar and interlobular lymph nodes, detected concomitant with diagnosis and 12 months after diagnosis, respectively. Histologic examination appears to be imperative in these cases to avoid unnecessary chemotherapy.     

Bilateral testicular germ cell tumors: twenty-year experience at M. D. Anderson Cancer Center

BACKGROUND: The incidence of testicular carcinoma in the United States has increased significantly over the last two decades. Germ cell tumors form the majority of malignant testicular tumors. With advances in diagnosis and therapeutic approaches, germ cell tumors are now highly sensitive to treatment, providing long-term survival. It has been speculated that the incidence of bilateral germ cell tumors may increase due to the improved survival of patients with unilateral germ cell tumors. In this report, the authors present a study of bilateral germ cell tumors of the testis in men who were treated at The University of Texas M. D. Anderson Cancer Center over a 20-year period with emphasis on their incidence, histologic features, and clinical features. METHODS: Between 1978 and 1999, 2431 patients with testicular germ cell tumors were treated at The University of Texas M. D. Anderson Cancer Center. Among these, 24 patients with bilateral germ cell tumors were identified. Clinical records and all available pathology slides of the tumors were reviewed. RESULTS: The overall incidence of bilateral germ cell tumors in the patients with testicular germ cell tumors was 1% (24 of 2431 patients). The incidence was 1.8% (14 of 776 patients) in patients with seminoma and 0.6% (10 of 1655 patients) in patients with nonseminomatous germ cell tumors. Patients with seminoma who were age 相似文献   

Inherent sensitivity and induced resistance to chemotherapeutic drugs and irradiation in human cancer cell lines: relationship to mutation frequencies

Metastatic nonseminomatous testicular germ cell tumors are curable using combination chemotherapy in approximately 80% of patients. In contrast, most other patients with other types of cancer either present with or acquire drug-resistant disease following chemotherapy. Cell lines derived from testis tumors retain hypersensitivity to both drugs and radiation in vitro, thus providing a model system with which to investigate the genetic basis of hypersensitivity to these agents. This study compared the spontaneous and both ethyl methanesulfonate- and cisplatin-induced frequencies of mutation of 6-thioguanine resistance in 3 human bladder and 3 testis tumor cell lines and a bladder and a testis cell line with cisplatin resistance induced in vitro. The two tumor types showed similar frequencies of both spontaneous and induced mutation frequencies at this locus. Therefore, we failed to provide evidence for the hypothesis that the curability of testis tumors is associated with a low frequency of mutation to drug resistance.