Malignant Non-seminomatous Germ Cell Tumors Research Articles

Ectopic activation of WNT signaling in human embryonal carcinoma cells and its effects in short- and long-term in vitro culture

Human embryonal carcinoma (EC) cells comprise the pluripotent stem cells of malignant non-seminomatous germ cell tumors (GCTs) and represent the malignant counterpart of embryonic stem cells (ESCs). WNT/β-catenin signaling has been implicated in regulating adult and embryonic stem cells although its role in EC cells is less investigated. Here, we studied WNT signaling in a panel of representative pluripotent and nullipotent human EC cell lines. We found that EC cell lines show distinct levels of intrinsic WNT signaling and respond differently to ectopic WNT activation. Short-term activation of WNT signaling induced a differentiation-response in the pluripotent EC cells (NT2 and NCCIT) whereas the nullipotent EC cells (TERA1 and 2102Ep) were refractory and maintained high levels of OCT4 and SSEA4 expression. Long-term activation of WNT signaling in NCCIT and, to a lesser extent, TERA1 cells led to (re)gain of OCT4 expression and a switch from SSEA4 to SSEA1 surface antigens ultimately resulting in OCT4+/SSEA4−/SSEA1+ profile. Cisplatin treatment indicated that the OCT4+/SSEA4−/SSEA1+ NCCIT cells became more resistant to chemotherapy treatment. Our findings are of particular interest for the GCT and ES cell biology and shed light on the role of WNT signaling in human EC cells.

Long-term outcomes of pediatric and adolescent mediastinal germ cell tumors: a single pediatric oncology institutional experience.

To evaluate the epidemiologic, demographic, and clinical characteristics, as well as prognostic factors and long-term outcomes of mediastinal germ cell tumors (MGCT) in children. A retrospective study of pediatric patients diagnosed with a primary MGCT between January 1963 and August of 2014 was performed. Twenty-five patients were identified. Six children with teratomas were treated with resection alone (median age 7.8years, range newborn to 15years) and were cured without recurrence or progression. Nineteen children were treated for a malignant MGCT (median age 11.7years, range 7months-18years); 5year overall survival (OS) was 0.39±0.12. For malignant non-seminomatous mediastinal germ cell tumors, platinum-based chemotherapy regimen (OS 0.56 vs 0.14, p=0.03), complete surgical resection with negative margins (OS 0.73 vs 0.11, p=0.03); and localized disease (OS 0.76 vs 0.0, p=0.004) demonstrated a survival advantage. Initial surgical resection is appropriate for teratomas. Localized disease, complete resection, and platinum-based chemotherapy are associated with improved survival in malignant non-seminomatous mediastinal germ cell tumors. Neoadjuvant, platinum-based three drug regimens followed by delayed surgical resection is the appropriate treatment modality for malignant mediastinal germ cell tumors.

Role of SOX2 in the Etiology of Embryonal Carcinoma, Based on Analysis of the NCCIT and NT2 Cell Lines

The transcription factor SOX2, associated with amongst others OCT3/4, is essential for maintenance of pluripotency and self-renewal of embryonic stem cells. SOX2 is highly expressed in embryonal carcinoma (EC), the stem cell component of malignant nonseminomatous germ cell tumors, referred to as germ cell cancer (GCC). In fact, OCT3/4 together with SOX2 is an informative diagnostic tool for EC in a clinical setting. Several studies support the hypothesis that SOX2 is a relevant oncogenic factor in various cancers and recently, SOX2 has been suggested as a putative therapeutic target for early stage EC. We demonstrate the presence of genomic amplification of SOX2 in an EC cell line, NCCIT, using array comparative genome hybridization and fluorescence in situ hybridization. Down-regulation of SOX2 by targeted siRNA provokes NCCIT cells towards apoptosis, while inhibition of OCT3/4 expression induced differentiation, with retained SOX2 levels. Mice pluripotent xenografts from NCCIT (N-NCCIT and N2-NCCIT) show a consistent SOX2 expression, in spite of loss of the expression of OCT3/4, and differentiation, with retained presence of genomic amplification. No SOX2 amplification has been identified in primary pure and mixed EC in vivo patient samples so far. The data presented in this study are based on a single EC cell line with a SOX2 amplification, with NT2 as control EC cell line, showing no profound induction of apoptosis upon SOX2 downregulation. The findings are of relevance to identify mechanisms involved in the pathogenesis of EC tumors, and support the model of SOX2-oncogene dependency of EC, which however, does not exclude induction of differentiation. This finding is likely related to the presence of wild type p53 in GCC, resulting in expression of downstream target genes, amongst others miR-34a, miR-145 and SOX2, associated to the unique sensitivity of GCC to DNA damaging agents.

Cutaneous metastasis from testicular germ cell tumour

The skin is an unusual site of metastases from solid organ malignancies. We report the case of a patient with a malignant mixed non-seminomatous germ cell tumor of the testis, presenting with cutaneous metastasis, which was treated with salvage chemotherapy.

Computed tomography and magnetic resonance imaging of mediastinal tumors

We describe the clinical, pathological, and imaging findings of mediastinal tumors with focus on thymic hyperplasia, thymic epithelial tumors, and germ cell tumors, malignant lymphoma, and various cystic masses. Chemical shift magnetic resonance imaging (MRI) is useful in characterization of the normal thymus and differentiation of hyperplastic thymus and thymic tumors. In contrast to noninvasive thymomas, invasive thymomas and thymic carcinomas show a more aggressive growth pattern. Local invasion and pleural spread are characteristic of invasive thymoma and mediastinal lymphadenopathy and distant metastasis suggest thymic carcinomas. Mature teratoma typically shows various computed tomography (CT) attenuation, and MR signal intensity depending on its contents and fat tissue and bone within the lesions are its characteristic findings. Seminomas typically have homogenous internal CT attenuation and MR signal intensity with minimal contrast enhancement. Nonseminomatous malignant germ cell tumors characteristically show prominent internal degenerative changes and invasion to the adjacent structures. In mediastinal lymphomas, a residual mass is common after treatment and MRI provides important information in distinguishing viable tumors from residual benign masses. Some mediastinal cysts may reveal high attenuation similar to solid lesions on CT depending on their contents and MRI can be useful in the differentiation of cystic masses from solid lesions.

Rete testis invasion by malignant germ cell tumor and/or intratubular germ cell neoplasia: what is the significance of this finding?

Pathologic stage and postsurgical treatment guidelines of malignant germ cell tumors, currently take into account angiolymphatic invasion, degree of extra testicular invasion, and serum tumor marker levels. The significance of rete testis invasion by malignant germ cell tumors or intratubular germ cell neoplasia however remains controversial. A search through the surgical pathology and expert consultation files at our institution from 2002 to 2009 was made for malignant germ cell tumors and intratubular germ cell neoplasia in orchiectomy specimens. Clinicopathologic data including rete testis status were obtained. Two hundred ninety-two orchiectomy specimens were identified. One hundred thirty-six were associated with malignant germ cell tumors. Mean patient age was 33 years (range, 14-67 years). The mean greatest tumor dimension was 4.1 cm (range, 0.8-18 cm). Fifty-six were pure seminoma (40%), 50 were nonseminomatous malignant germ cell tumors (35%), and 35 were mixed malignant germ cell tumors including a seminoma component (25%). Intratubular germ cell neoplasia was identified in 99 cases (70%). Pathologic stage at presentation was as follows: stage 1, 71 patients (50%); stage 2, 62 patients (45%); stage 3, 2 patients (1%); and indeterminate, 6 patients (4%). Seventy-eight patients had documented rete testis status: rete testis invasion, 41 (53%); no rete testis invasion, 37 (47%). Angiolymphatic invasion was present in 62 cases (44%). Follow-up information was available in 43 patients with known rete testis status. Mean follow-up duration was 43 months (range, 3-65 months). Twenty patients had rete testis invasion, and 23 patients had no rete testis invasion. Intratubular germ cell neoplasia was present in patients with rete testis invasion in 18 cases (90%), compared to only 13 cases (57%) in patients without rete testis invasion, P = .02. Serum markers were elevated in 10 patients (50%) with rete testis invasion compared to only 6 patients (26%) without rete testis invasion, P = .05. The combination of rete testis invasion and angiolymphatic invasion were present in 8 cases and were found to be associated with elevated serum tumor markers in 7 (88%) of the 8 cases, compared to the combination of no invasion of the rete testis and angiolymphatic invasion showing elevated serum tumor markers in 3 (38%) of 8 cases. However, 7 patients (35%) with rete testis invasion developed metastatic disease, and 11 patients (48%) without rete testis invasion developed metastatic disease. Rete testis status should be documented in orchiectomy specimens with malignant germ cell tumors. Intratubular germ cell neoplasia may be the only component of a malignant germ cell tumor involving the rete testis. In this series, elevated tumor markers were more likely associated with angiolymphatic invasion and positive rete testis status. Positive rete testis status does not appear to be an independent predictor of patient outcome.

Cisplatin-based chemotherapy followed by surgery for malignant nonseminomatous germ cell tumor of mediastinum: one institution’s experience

The objective of this study was to evaluate the efficacy and safety of cisplatin-based chemotherapy followed by surgery for patients with a malignant nonseminomatous germ cell tumor (NSGCT) of the mediastinum. Ten patients with malignant NSGCTs received cisplatin-based induction chemotherapy and then underwent surgery. The clinicopathological characteristics of these 10 patients were examined retrospectively. A partial response to induction chemotherapy was noted in eight patients and no response in two. The induction chemotherapy was tolerated well by all the patients. Each patient underwent complete surgical resection of the residual tumor following chemotherapy. A yolk sac tumor was detected in one patient and malignant teratoma along with a yolk sac tumor in one patient postoperatively. The overall survival of the 10 patients was 67% at 60 months of follow-up. The survival rate at 60 months was poorer for the patients whose resected specimens exhibited the presence of viable cells than for those whose specimens were free of viable cells. Postchemotherapy surgical resection of the residual tumor plays an integral role in the management of patients with NSGCT. The presence of viable tumor cells in the resected specimens is associated with poor survival.

Risk factors in germ cell tumour patients with relapse or progressive disease after first-line chemotherapy: Evaluation of a prognostic score for survival after high-dose chemotherapy

Purpose To retrospectively re-evaluate a published prognostic score for response to salvage treatment in patients with germ-cell tumours relapsing or progressing after cisplatin-based first-line chemotherapy. Patients and methods From a database of 257 germ cell tumour (GCT) patients treated with salvage high-dose chemotherapy (HDCT) we identified 176 patients (67%) with relapse or progression after first-line conventional-dose chemotherapy (CDCT). Patients were retrospectively grouped according to a published prognostic score defined by Fossa and colleagues [Fossa SD, Stenning SP, Gerl A, et al. Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumors. Br J Cancer 1999; 80:1392–9]. Overall survival (OS) and event free survival (EFS) after HDCT were retrospectively evaluated in each prognostic group. Results After a median follow-up of 9 years the OS probability for all 176 patients was 38% and the EFS probability was 35%. The respective survival probability at 5 years in 100/176 (57%) good prognosis patients and 76/176 (43%) poor prognosis patients were 47% versus 28% for OS ( p < 0.001) and 41% versus 26% for EFS ( p < 0.005). Whereas survival probabilities did not differ in good prognosis patients, OS and EFS in poor prognosis patients were substantially better in the current series of patients treated with HDCT compared to the ones reported by Fossa treated with CDCT. Conclusion This retrospective analysis confirms the impact of prognostic factors on the results of salvage treatment in patients with GCT and suggests a clinical benefit for patients with poor prognosis features receiving a single course of HDCT.

Primary Germ Cell Tumors of the Mediastinum: 10 Years of Experience in a Tertiary Teaching Hospital

Germ cell tumors occur mostly in the gonad. Extragonadal germ cell tumors are rare, and most occur in the retroperitoneum and mediastinum. Primary mediastinal germ cell tumors are often found in the anterior portion of the mediastinum and include teratomas and non-teratomatous tumors. Non-teratomatous tumors include seminomas and malignant non-seminomatous germ cell tumors (MNSGCTs). MNSGCTs include yolk sac tumors, choriocarcinomas, embryonal carcinomas, and mixed type germ cell tumors. Teratomas are the most common germ cell tumors of the mediastinum, and seminomas are the most common non-teratomatous germ cell tumors of the mediastinum. Cases of primary mediastinal MNSGCT reported in the literature are rare. In this report, we review all primary mediastinal germ cell tumors from a 10-year period at the Chung-Ho Memorial Hospital of Kaohsiung Medical University. A total of 14 cases were reviewed, including 11 patients with mature teratomas, two with yolk sac tumors, and one with seminoma. We discuss the differences in clinical presentation, histopathologic characteristics, treatment, and prognosis.

Beneficial Impact of a Clinical Care Pathway in Patients with Testicular Cancer Undergoing Retroperitoneal Lymph Node Dissection

Since 1997, we have used a clinical collaborative care pathway for patients undergoing retroperitoneal lymph node dissection. We examined its impact on perioperative care and outcome. We examined the records of all patients with germ cell carcinoma who underwent retroperitoneal lymph node dissection from July 1990 to July 2001. Variables examined included clinical/pathological stage, hospital stay, postoperative care and the complication rate. A total of 118 patients underwent retroperitoneal lymph node dissection for germ cell carcinoma during this period, including 46 (39%) before pathway implementation in 1997 and 72 patients (61%) after pathway implementation. Of the 118 patients 40 (34%) underwent the procedure after chemotherapy. This rate remained fairly constant in the period before and after pathway initiation (31% and 36%, respectively). After pathway implementation fewer patients received a nasogastric tube (94% versus 5%, p <0.001) and had complications (26% versus 16%, p = 0.036). Mean hospital stay decreased after pathway implementation in all primary and post-chemotherapy retroperitoneal lymph node dissection cases (4.2 versus 6.4 days, p <0.005). Although patients who underwent the procedure after chemotherapy were more likely to have complications than those who underwent a primary procedure, the difference was not statistically significant (p = 0.09). Our collaborative clinical care pathway safely and efficiently outlines routine postoperative care and significantly decreased hospital stay.

Mediastinal germ cell tumors: a radiologic-pathologic review.

Germ cell tumors of the mediastinum are histologically identical to those found in the testes and ovaries. Early diagnosis and treatment improve the survival rate. Imaging studies of teratoma demonstrate a rounded, often lobulated heterogeneous mass containing soft tissue elements with fluid and fat attenuation. Calcification is present in 20-43% of cases. Seminomas are large masses of homogeneous soft tissue attenuation. Malignant nonseminomatous germ cell tumors are heterogeneous tumors with irregular borders due to invasion of adjacent structures. CT shows the location and extent of the tumors as well as intrinsic elements including soft tissue, fat, fluid, and calcification. CT is the modality of choice for the diagnostic evaluation of these tumors. MRI reveals masses of heterogeneous signal intensity, is more sensitive in depicting infiltration of the adjacent structures by fat plane obliteration, and is performed as an ancillary study.

Mediastinal germ cell tumors.

Mediastinal germ cell tumors are uncommon tumors that occur predominantly within the anterior mediastinum and frequently present as a very large mass with local compression. Symptoms are typically vague and represent the local mass effects of the tumor. Chest computed tomography and examination of serum tumor markers provide the critical workup before a tissue diagnosis is obtained. Seminomas are extremely sensitive to both chemotherapy and radiation and are primarily treated nonsurgically. Benign teratomas without malignant elements are extremely resistant to both chemotherapy and radiation and are treated exclusively with surgical resection with excellent outcomes. Malignant nonseminomatous germ cell tumors are primarily treated with chemotherapy, with adjuvant surgery reserved for patients with residual mediastinal masses after systemic therapy.

RISK ADAPTED MANAGEMENT WITH ADJUVANT CHEMOTHERAPY IN PATIENTS WITH HIGH RISK CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TUMOR

We propose that patients with high risk, clinical stage I nonseminomatous germ cell tumors receive 2 cycles of chemotherapy initially, instead of undergoing surgery or observation. A total of 59 patients with high risk, clinical stage I nonseminomatous germ cell tumor received risk adapted adjuvant chemotherapy. Until June 1987, 20 patients were treated with 2 courses of adjuvant cisplatin, vinblastine and bleomycin at 3-week intervals. After June 1987 another 39 patients were treated with 2 cycles of bleomycin, etoposide and cisplatin. Long-term results with this treatment strategy have been excellent with limited morbidity. Adjuvant chemotherapy may be of particular value in patients with compromised followup.

RETROPERITONEAL LYMPH NODE DISSECTION FOR THE MANAGEMENT OF CLINICAL STAGE I NONSEMINOMA

We review the rationale for the use of retroperitoneal lymph node dissection for clinical stage I nonseminomatous testis cancer. The published literature regarding the alternative treatments for clinical stage I nonseminoma was reviewed as well as the personal experience of the authors to define the role of retroperitoneal lymph node dissection. Retroperitoneal lymph node dissection alone is curative in 50% to 75% of patients with pathological stage II disease. The only significant long-term morbidity is a 1% chance of small bowel obstruction. If recurrence develops after retroperitoneal lymph node dissection, it is virtually always curable with cisplatin based chemotherapy. Retroperitoneal lymph node dissection retains a therapeutic and staging capability in these patients. The probability for cure, short and long-term morbidity, and minimal need for long-term followup in these patients indicates that retroperitoneal lymph node dissection continues to be standard therapy for clinical stage I nonseminoma.

Tumors of the thymus.

Thymic neoplasms are a common cause of an anterior mediastinal mass and may be benign or malignant. Thymic cysts are congenital or acquired and may be associated with a thymic malignancy. True thymic hyperplasia and thymic lymphoid hyperplasia may enlarge the thymus and simulate a neoplasm. Thymoma and thymic carcinoma are epithelial malignancies with distinct clinicopathologic features. Thymic carcinoid is a rare aggressive neuroendocrine malignancy associated with multiple endocrine neoplasia 1. Thymolipoma is a benign neoplasm. Hodgkin and non-Hodgkin lymphoma may primarily or secondarily involve the thymus. Primary mediastinal germ cell tumors may arise primarily within the thymus and include mature teratoma, seminoma, and non-seminomatous malignant germ cell tumors.

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. ‘Progressive disease’ included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of ‘conventional’ platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0–99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23–38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a ‘small’ centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l−1 or hCG >100 IU l−1) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37–56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60–88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated ‘conventional’ platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l−1 and AFP < 100 kU l−1). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors. © 1999 Cancer Research Campaign

Prognostic factors in children with localized malignant nonseminomatous germ cell tumors.

Prognostic factors were studied in children older than 1 year who were treated with chemotherapy for extracranial localized malignant non seminomatous germ cell tumors. Data from two consecutive protocols were pooled. The TGM 85 (1985-1989) protocol consisted of alternating courses of cyclophosphamide, dactinomycin and vinblastine, bleomycin, and cisplatin at a dose of 100 mg/m(2) per course. The TGM 90 (1990-1994) protocol was initiated with carboplatin 400 mg/m(2) substituted for cisplatin as the only modification to the previous protocol. We examined alpha-fetoprotein (AFP) levels, disease stage, and primary site and identified three prognostic groups. Patients with a poor prognosis had either an AFP level >/= 10,000 ng/mL or stage III disease and a sacrococcygeal or mediastinal primary site; such patients represented 46% of the patient population and experienced a 43% 3-year failure-free survival rate and a 77% overall survival rate. Patients with a good prognosis had an AFP level less than 10,000 ng/mL, stage I or II disease, and a testicular, ovarian, perineal, or retroperitoneal primary site; such patients represented 22% of the patient population and experienced no treatment failures. The other patients were classified in the intermediate prognosis group and represented 37% of the patient population, with an 81% 3-year failure-free survival rate and a 92% overall survival rate. Initial AFP level, disease stage, and primary site are the most important prognostic factors in this analysis. Prognostic models for pediatric germ cell tumors should allow the stratification of patients for a risk-adapted approach to treatment.

Survival of patients with viable malignant non-seminomatous germ cell tumour persistent after cisplatin-based induction chemotherapy.

Review of the outcome in patients with viable residual postchemotherapy malignant germ cell tumour treated at the Norwegian Radium Hospital from 1980 to 1993 and to establish prognostic factors. During the years 1980-1993, about 270 patients with malignant non-seminomatous germ cell tumours underwent postchemotherapy surgery at the Norwegian Radium Hospital. In 27 of these patients, residual viable malignant germ cell tumour was found in the operation specimen. These patients were scheduled to receive 3 adjuvant cisplatin-based chemotherapy cycles after surgery, if possible, containing cytostatic agents not given during induction chemotherapy. All patients were followed up until death or January 1st, 1995 (median observation time in surviving patients: 51 months; range: 9-166 months). Sixteen patients developed a relapse after surgery after a median time of 4 weeks (range 1-19 weeks), 12 of them before any adjuvant chemotherapy could be started. Only 2 of these relapsing patients could be salvaged. At the last follow-up, 13 patients were alive, and a 43% 5-year survival was obtained. All deaths occurred within 3 years after surgery. The 9 patients with elevated alpha-fetoprotein and/or human chorionic gonadotropin before surgery have a particularly low survival rate (11%), as compared to the 18 patients with normal markers (62%). The most important prognostic parameter for the postoperative survival was, however, the initial tumour burden: the 14 patients with initially large or very large tumour volume (MRC criteria) had a 9% 5-year survival, whereas the percentage was 84% for the 13 patients with small volume disease. Prognosis is poor in patients in whom residual malignant germ cell tumour persists in spite of conventional cisplatin-based induction chemotherapy, especially in patients who initially present with large or very large volume disease and/or pre-operatively elevated tumour markers. More effective treatment modalities have to be developed for these patients. The role of high-dose chemotherapy with stem cell support should be investigated in future trials, especially in the subgroup of patients with poor prognosis.

Germ cell tumors of the mediastinum. A 30-year experience.

The records of 98 consecutive patients (58 males and 40 females; median age, 27 years; age range, 2-64 years) who presented with a primary germ cell tumor (GCT) of the mediastinum between January 1960 and December 1990 were reviewed. There were 45 mature teratomas, 8 immature teratomas, 16 pure seminomas, and 24 malignant nonseminomatous GCT (MNSGCT). All patients with mature teratomas were cured by radical resection alone, except one patient who died intraoperatively. Among the eight patients with immature teratomas, five were treated before the advent of cisplatin treatment (two children younger than 15 years were cured by surgery alone and three adults died within 7 months after operation). Three patients underwent surgery followed by cisplatin-based chemotherapy (two are still alive and one died of an associated rhabdomyosarcoma). Thirteen of 16 patients with seminomas (81%) were cured by surgery either alone (5 patients) or with adjuvant radiation therapy (8 patients). Among the 24 MNSGCT, 10 were treated before 1980 without cisplatin and all but 1 died of disease progression. Fourteen patients were treated by initial high-dose cisplatin combination chemotherapy and 8 (57%) achieved complete remission (2 died of systemic mastocytosis development). Results indicate the benignity of mature teratomas of the mediastinum, the age-dependent clinical course of immature teratomas, and the excellent prognosis of seminomas. The improved survival advantage resulting from cisplatin-based chemotherapy in MNSGCT is impaired by the propensity to nongerminal solid tumor development and hematologic malignancies.

From the archives of the AFIP. Mediastinal germ cell tumors: radiologic and pathologic correlation.

Germ cell tumors occur most frequently in the gonad but can rarely occur in extragonadal locations, usually in or near the midline. The most common extragonadal site of primary germ cell tumors is the anterior mediastinum. The most common histologic type of mediastinal germ cell tumor is mature teratoma, which is typically asymptomatic and incidentally discovered. Radiographically, these tumors appear as rounded, often lobulated masses; calcification may be seen. Imaging studies of mature teratoma frequently demonstrate cystic components and may demonstrate fat or calcium. Malignant germ cell tumors usually occur as large masses in symptomatic young male patients. Seminomas are typically of homogeneous soft-tissue attenuation, and nonseminomatous malignant germ cell tumors are typically of heterogeneous attenuation on computed tomographic scans. Therapy varies according to cell type and may include surgery, radiation therapy, or chemotherapy. Prognosis is excellent for patients with mature teratoma, good for patients with pure seminoma, and poor for patients with nonseminomatous malignant germ cell tumors and mixed germ cell tumors.