Role of postchemotherapy adjunctive surgery in the management of patients with nonseminoma arising from the mediastinum.

PURPOSE: To evaluate the role of postchemotherapy surgery in patients with nonseminomatous germ cell tumors arising from the anterior mediastinum. PATIENTS AND METHODS: Thirty-two patients with nonseminoma arising from a mediastinal primary site were treated on a clinical trial at our center, and they underwent postchemotherapy surgery. The results of postchemotherapy surgical resection, frequency of viable tumor found during postchemotherapy surgery, and prognostic factors for survival were assessed. RESULTS: Complete resection of all gross residual disease was achieved in 27 patients (84%). Histologic analysis of resected residua postchemotherapy revealed viable tumor in 66%, teratoma in 22%, and necrosis in 12% of the specimens. Viable tumor included embryonal carcinoma, choriocarcinoma, yolk sac carcinoma, seminoma, and teratoma with malignant transformation to nongerm cell histology (eg, sarcoma). Clinical characteristics associated with a shorter survival after surgery included the presence of viable tumor in a resected specimen (P =.003) and more than one site resected during surgery (P =.06). There were no statistically significant differences in survival for patients who underwent surgical resection with normal markers compared with patients with elevated serum tumor markers (P =.33). A trend toward shorter survival was found in patients with increasing tumor markers before surgery compared with patients with normal and declining serum tumor markers (P =.09). CONCLUSION: Surgical resection of residual mass after chemotherapy plays an integral role in the management of patients with primary mediastinal nonseminoma. Teratoma and viable tumor were found in the majority of resected residua after chemotherapy. Because patients who undergo conventional salvage chemotherapy programs rarely achieve long-term disease-free status, selected patients with elevated markers after chemotherapy are considered candidates for surgical resection.     

Primary mediastinal germ cell tumors in children and adolescents: results of the German cooperative protocols MAKEI 83/86, 89, and 96.

PURPOSE: To evaluate children and adolescents with primary mediastinal teratoma and malignant germ cell tumors (GCTs). PATIENTS AND METHODS: Forty-seven patients from the German nontesticular GCT studies were analyzed (median age, 2.5 years; range, neonate to 17 years). Teratoma (n = 21) were resected, and no adjuvant treatment was given. Malignant GCTs (n = 26) were treated with cisplatin-based chemotherapy and resection. Three of 26 patients underwent radiotherapy. RESULTS: In all patients with teratoma, tumor markers were normal. Surgery of teratoma was complete in 17 of 21 patients and microscopically incomplete in four of 21 patients, and we observed no relapse after a median follow-up of 29 months. In 23 of 26 patients with malignant GCTs, alpha-fetoprotein and/or beta-human chorionic gonadotropin were elevated. Twelve of 26 patients received adjuvant chemotherapy after initial resection, which was complete in six of 12 patients, whereas delayed resection after preoperative chemotherapy was complete in 10 of 11 patients (P =.03). Four of six patients underwent second-look thoracotomy after incomplete primary surgery. Three of 26 patients did not undergo tumor resection. The final completeness of resection was the strongest prognostic indicator (event-free survival ?EFS, 0.94 +/- 0.06 v 0.42 +/- 0.33; P <.002). Local stage and distant metastases were not prognostically significant at the.05 level. For all malignant GCTs, the 5-year survival rate was 0.87 +/- 0.05 (median follow-up, 51 months), with an EFS of 0.83 +/- 0.05. CONCLUSION: The prognosis of mediastinal teratoma is excellent after complete or microscopically incomplete resection. In children with malignant GCT, the prognosis is favorable with a therapeutic strategy of delayed resection after preoperative chemotherapy. In most children, the diagnosis can be based on elevated tumor markers and imaging. Biopsy is indicated in nonsecreting GCT.     

Primary Mediastinal Germ Cell Tumors—The University of Western Ontario Experience

Extragonadal germ cell tumors account for 2–5.7% of germ cell tumors (GCTs). Of these, primary mediastinal GCTs (PMGCTs) are responsible for 16–36% of cases. Given the rarity of these tumors, specific treatment strategies have not been well defined. We report our experience in treating these complex patients. In total, 318 men treated at our institution with chemotherapy for GCTs between 1980 and 2016 were reviewed. PMGCT was defined as clinically diagnosed mediastinal GCT with no evidence of testicular GCT (physical exam/ultrasound). We identified nine patients diagnosed with PMGCT. All patients presented with an anterior mediastinal mass and no gonadal lesion; four patients also had metastatic disease. Median age at diagnosis was 30 years (range, 14–56) and median mass size at diagnosis was 9 cm (range, 3.4–19). Eight patients had non-seminoma and one had pure seminoma. All patients received cisplatin-based chemotherapy initially. Surgical resection was performed in four patients; three patients had a complete resection and one patient was found to have an unresectable tumor. At a median follow-up of 2 years (range, 3 months–28 years) six patients had progressed. Progression-free survival was short with a median of 4.1 months from diagnosis (range 1.5–122.2 months). Five patients died at a median of 4.4 months from diagnosis. One and 5-year overall survivals were 50% and 38%, respectively. PMGCT are rare and aggressive. Our real-life Canadian experience is consistent with current literature suggesting that non-seminoma PMGCT has a poor prognosis despite prompt cisplatin-based chemotherapy followed by aggressive thoracic surgery.     

骨巨细胞瘤的诊断与治疗

骨巨细胞瘤是一高侵袭性良性肿瘤,主要发生于年轻人中,骨端发病.典型的影像学表现是骨端完全溶骨的膨胀性改变,多不伴有骨膜反应及软组织包块.CT及MRI可以很好地显示肿瘤的侵及范围,X线平片最具诊断意义.圆形及卵圆形基质细胞及多核巨细胞是骨巨细胞瘤的基本组织构成成分.刮除术是治疗骨巨细胞瘤的基本外科手段,但其复发率较高,应加用物理及化学的方法扩大至边缘或广泛的外科治疗边界.放疗可用于治疗难以手术的病例,但可致肉瘤变.化疗对于骨巨细胞瘤基本无效.骨巨细胞瘤的转移及恶变可能与以往治疗有关.     

Le traitement du cancer du testicule

Germ-cell tumours (GCTs) are the most common type of cancer in young men. Since the late 1970s, disseminated GCT have been a paradigm for curable metastatic cancer and metastatic GCTs are highly curable with cisplatin-based chemotherapy followed by surgical resection of residual masses. Patients’ prognosis is currently assessed using the International Germ-Cell Consensus Classification (IGCCC) and used to adapt the burden of chemotherapy. Approximately 20% of patients still do not achieve cure after first-line cisplatin-based chemotherapy, and need salvage chemotherapy (high dose or standard dose chemotherapy). Clinical stage I testicular cancer is the most common presentation and different strategies are proposed: adjuvant therapies, surgery or surveillance. During the last three decades, clinical trials and strong international collaborations lead to the development of a consensus in the management of GCTs.     

Mediastinal Germ Cell Tumor Exhibiting a Discrepancy between Tumor Markers and Imaging: A Case Study

We report a mediastinal germ cell tumor (GCT) that exhibited a discrepancy between the time course of serum human chorionic gonadotropin (hCG) levels and clinical consequences. An otherwise healthy man, aged 34 years, was diagnosed with a nonseminomatous GCT, most likely embryonal carcinoma (EC), based on a mediastinal tumor biopsy. Standard chemotherapy resulted in an optimal decrease in serum hCG levels. However, multiple lesions in the liver continued to enlarge, which led to his death. Autopsy revealed few viable tumor cells in the liver, with the great majority of the tumor cells appearing to have undergone necrosis, suggesting that they responded to the chemotherapy. The residual tumor cells in the mediastinum and the liver were similar to syncytiotrophoblast cells, suggesting a cho-riocarcinoma (CC). On immunohistochemical analysis, the mediastinal tumor cells in the diagnostic biopsy specimen expressed both CD30 and hCG, whereas residual mediastinal and hepatic tumor cells in the autopsy specimen after chemotherapy also expressed hCG, but not CD30. These findings suggested that the patient suffered from a primary mixed GCT consisting of an EC and a CC. Both pre- and postchemotherapy tumors strongly expressed matrix metalloproteinase-2, supporting the aggressive and invasive features of the tumor phenotype. We speculate that the extremely invasive tumor destroyed normal liver structure, whereas chemotherapy and central necrosis reduced the number of viable cells themselves, causing a discordant decrease in serum hCG levels.Key Words: Nonseminomatous germ cell tumor, Serum human chorionic gonadotropin, Liver metastasis, Matrix metalloproteinase-2     

The role of adjunctive postchemotherapy surgery for nonseminomatous germ-cell tumors: current concepts and controversies

Adjunctive surgical resection of residual disease after chemotherapy is a critical part of the comprehensive management of patients with advanced nonseminomatous germ-cell tumor (NSGCT). Surgical resection is indicated in the presence of residual radiographic abnormalities and normal serum tumor markers. Necrosis, teratoma, and viable carcinoma can be found at any resected site. After induction chemotherapy, necrosis comprises approximately 50% of histologic findings, teratoma 40%, and viable GCT the remaining 10%. A number of investigators have attempted to predict the presence of necrosis in an effort to obviate surgery. A number of variables predictive of necrosis have been identified and tested prospectively, including: degree of tumor shrinkage, size of pre- and posttreatment mass(es), prechemotherapy markers, and teratomatous components in the orchiectomy specimen. However, the risk for a false-negative prediction remains approximately 20%. The most rigorous approach remains a retroperitoneal lymph node dissection (RPLND). Furthermore, the histologic discordance between different sites ranges from 29% to 46%; thus, all sites of residual disease should be resected. The patient's prognosis is influenced by: (1) completeness of resection, and (2) biology of the tumor (histology of residual mass(es), marker status at the time of RPLND, and prior burden of therapy). Surgical boundaries and completeness of dissection should not be compromised in an attempt to preserve ejaculation.     

Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours

We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1-20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31-173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients.     

A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours.

BACKGROUND: The outcome of patients with germ-cell tumours (GCTs), who relapse more than once or relapse with a mediastinal primary is poor. We have shown that topoisomerase 1 may be an attractive target in relapsed GCT. We investigated the role of irinotecan, paclitaxel and oxaliplatin (IPO) followed by topotecan-based high-dose therapy in responding patients, in this patient population. PATIENTS AND METHODS: Twenty-eight patients with multiply relapsed gonadal and mediastinal GCT were recruited to this phase 2 study. All patients received IPO chemotherapy and 12 (43%) went on to receive high-dose therapy. The outcome of these patients was assessed using the Kaplan-Meier method with a median progression-free follow-up of 1 year. RESULTS: Twenty patients (71%) responded to the therapy including five complete remissions (18%), 13 (46%) marker-negative partial responses and two (7%) marker-positive partial responses. Nine (32%) patients continue to be progression free, and the median survival for the whole group currently measures 17 months. Out of 12 individuals who received subsequent high-dose therapy consolidation, seven (58%) remain progression free. The commonest grade III/IV toxicity was infection (68%) and there were no IPO-related toxic deaths; there was one death from high-dose therapy. CONCLUSION: Topoisomerase I-based IPO chemotherapy that lacks etoposide is very active in multiply relapsed GCT. This data merit further investigation.     

Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery?

BACKGROUND: Contemporary therapy for osteosarcoma is comprised of initial treatment with chemotherapy and surgical extirpation of the primary tumor in the affected bone. In view of the major advances forged by chemotherapy in the treatment of the primary tumor, an attempt was made to destroy the tumor exclusively with this therapeutic modality and abrogate surgery. METHODS: Thirty-one consecutive patients were treated. All had localized disease (absence of metastases) at the time of diagnosis. Initial treatment with chemotherapy was comprised of high-dose methotrexate and leucovorin rescue (MTX-LF) in 3 patients and intraarterial cisplatin in 28 patients. Clinical, radiologic, angiographic, radionuclide, and histologic investigations were utilized to assess the efficacy of treatment. After a response at 3 months, entry into the study was permitted and treatment was maintained for a total of 18-21 months with a combination of agents comprised of MTX-LF, intraarterial cisplatin, and doxorubicin. Patients were monitored closely for disease recurrence with the investigations outlined earlier. Two informed consents were required: one at the time of diagnosis and another at 3 months after the initial response had been attained. RESULTS: Only 3 of 31 patients were cured with the administration of chemotherapy alone. Local recurrence and pulmonary metastases were not reported to develop in these 3 patients during a follow-up period of 204+ to 225+ months. Four other patients also possibly were cured with chemotherapy alone. At their request, several months after the cessation of chemotherapy, they underwent surgical extirpation of the tumor. No evidence of viable tumor was found. These patients remained free of disease for 192+ to 216+ months. Thus, only seven patients did not develop local recurrence and/or pulmonary metastases. Among the remaining 24 patients, 9 developed local recurrences without pulmonary metastases 14-74 months (median, 30 months) after the initial response. Eight of the nine patients were rendered tumor free by extirpation of the local recurrence. Two of these eight patients subsequently died, one of the acquired immunodeficiency syndrome (AIDS) and the other of varicella septicemia. The ninth patient refused amputation and died of metabolic complications. Three other patients developed local recurrences 20-69 months and pulmonary metastases 10-98 months after achievement of the initial response. These patients were rendered tumor free by extirpation of the local recurrence and metastasectomy. One of these patients also later died of AIDS. In the remaining 12 patients, local recurrences developed 5-29 months (median, 14 months) after the initial response was achieved. The patients also developed pulmonary metastases 11-60 months after the initial response. In eight patients the local recurrences were extirpated and metastasectomy was performed; however, these patients later died of recurrent pulmonary metastases. The remaining four patients refused to undergo extirpation of the local recurrence. The pulmonary metastases were not resected. They failed to respond to alternate therapy. Thus, the tumor-free survival rate was 23% (7 of 31 patients): 3 patients who were treated with chemotherapy only and 4 patients who were treated with chemotherapy plus surgery. The overall survival rate (patients who remained free of disease and those who underwent resection for local recurrence and metastasectomy) was 48% (15 of 31 patients). Prior to the deaths from AIDS and varicella septicemia, the overall survival was 58% (18 of 31 patients). CONCLUSIONS: Utilizing the regimen employed in the current study, only 3 of 31 patients with osteosarcoma (10%) were cured exclusively with chemotherapy. Four additional patients who underwent extirpation of the primary tumor without disease recurrence and in whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" sin whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" strategies, the results of the current study do not justify the adoption of current forms of chemotherapy as exclusive treatments for osteosarcoma.     

Expression of KIT and epidermal growth factor receptor in chemotherapy refractory non-seminomatous germ-cell tumors.

BACKGROUND: The majority of patients with germ-cell tumors (GCTs) are curable with standard therapy. The molecular differences between curable and incurable disease are unknown. We have studied the expression of KIT and the epidermal growth factor receptor (EGFR) to determine their incidence in chemorefractory disease. PATIENTS AND METHODS: We retrospectively analyzed 23 patients with chemorefractory non-seminomatous GCTs (15 late relapse and eight transformed teratomas). None of these 23 patients were cured by their initial chemotherapy and/or surgery. Immunohistochemical analysis of KIT and EGFR was performed on the most recently available specimen from a metastatic site. PCR amplimers of KIT exon 17 were screened for mutations by a combination of denaturing high-performance liquid chromatography and direct sequencing. RESULTS: KIT was expressed (>/=10% of the tumor displaying membranous or cytoplasmic staining) in 11 of 23 GCT patients [48%; 95% confidence interval (CI) 26% to 68%]. There were no activating KIT mutations in the phosphoryltransferase domain (exon 17) in 21 patients analyzed. EGFR was expressed (1+ to 3+) in 15 of 23 GCT patients (65%; 95% CI 41% to 82%). CONCLUSIONS: KIT and EGFR are expressed in a significant proportion of refractory GCTs. The significance of these findings will be determined by ongoing clinical trials.     

Residual tumor resection after high-dose chemotherapy in patients with relapsed or refractory germ cell cancer.

PURPOSE: To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT). PATIENTS AND METHODS: Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment. RESULTS: Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis. CONCLUSION: Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.     

Alternating cycles of etoposide plus cisplatin and VAB-6 in the treatment of poor-risk patients with germ cell tumors

A phase II trial of 6 months of alternating etoposide plus cisplatin (EP) and cyclophosphamide, vinblastine, actinomycin D, bleomycin, cisplatin (VAB-6) was conducted in 41 evaluable patients in an attempt to improve the treatment results in those patients considered to have "poor-risk" germ cell tumors (GCT). Eight of 14 (57%) patients with mediastinal and retroperitoneal GCTs achieved complete remission (CR), and five (36%) remain alive and free of disease. Fourteen of 27 patients (52%) with poor-risk testicular cancer achieved CR, and ten (37%) remain alive and free of disease. Two patients with seminoma, one each with a testicular and extragonadal primary tumor, achieved durable CRs. Toxicity was tolerable, but greater than that of VAB-6 alone. The response and survival of the 39 patients with nonseminomatous tumors were found to be identical to the results of 29 patients with nonseminomatous GCTs and poor-risk characteristics who were treated with VAB-6 alone. Thus, this 6-month schedule of alternating months of chemotherapy is not recommended for patients with poor-risk GCTs. Patients with such tumors should be referred to centers conducting prospective trials, so that research seeking better therapy may continue.     

The indication for postchemotherapy lymph node dissection in clinical stage IS nonseminomatous germ cell tumor

BACKGROUND: The initial management of patients with clinical stage IS (cIS) nonseminomatous germ cell tumor (NSGCT) has evolved from primary retroperitoneal lymph node dissection (RPLND) to induction chemotherapy. The objectives of the current study were to determine the clinical outcome, patterns of relapse, and incidence of teratoma in the retroperitoneum for men with cIS NSGCT. METHODS: Between 1988 and 2004, 24 patients with cIS stage NSGCT were evaluated and treated at Memorial Sloan-Kettering Cancer Center. Clinical and pathologic data were obtained from the institutional prospective database. Seven patients underwent primary RPLND, and 17 patients received induction chemotherapy as initial management. Clinical outcomes, patterns of relapse, and pathologic findings were reported. RESULTS: Six of the 7 patients who underwent primary RPLND had viable germ cell tumor (GCT) present. Four of those patients did not receive adjuvant chemotherapy, and all experienced systemic relapse. Of the 17 patients who received induction chemotherapy, 3 patients underwent elective postchemotherapy RPLND (PC-RPLND), and 14 patients were followed expectantly. Four patients who were followed expectantly relapsed in the retroperitoneum and underwent PC-RPLND. Of the 7 patients who underwent PC-RPLND, 1 patient had fibrosis (14%), but 6 patients (86%) had teratoma, including 1 patient who also had a viable GCT in the retroperitoneum. Overall, the incidence of teratoma or viable GCT in the retroperitoneum after chemotherapy was 43% (6 of 14 patients). At a median follow-up of 35 months, 23 men remained alive, and 1 man had died of disease. CONCLUSIONS: The current data suggest that patients with cIS stage NSGCT will benefit from adjuvant PC-RPLND.     

Extragonadal seminoma: an international multicenter analysis of prognostic factors and long term treatment outcome

BACKGROUND: The objectives of this study were to evaluate the long term outcome of patients with extragonadal seminomatous germ cell tumors (GCT) so that prognostic variables for disease recurrence and patient survival could be identified and to access the efficacy of different treatment modalities. METHODS: Six hundred thirty-five patients with extragonadal GCT who were treated consecutively at 11 centers in the United States and Europe during the cisplatin-based chemotherapy era between 1975 and 1996 were evaluated retrospectively. RESULTS: Fifty-two patients with primary retroperitoneal GCT (50%) and 51 patients with primary mediastinal GCT (49%) of pure seminomatous histology were identified (n = 1 patient with a primary cervical lymph node) representing 16.4% of 635 patients with extragonadal GCT who were included in the data base. The median age was 37 years (range, 18-70 years). Treatment consisted of platin-based chemotherapy in 77 patients (74%), radiotherapy in 9 patients (9%), and combined modality in 18 patients (17%). Ninety-two percent of patients (95% confidence interval, 87-97%) achieved a favorable response to primary therapy. After a median follow-up of 61 months (range, 1-211 months), 18 patients (17%) have had recurrent disease: 14% of those who received chemotherapy and 67% of those who received radiation therapy. The 5-year progression free survival rate favored the chemotherapy group, with 87% compared with 33% for irradiated patients (P = 0.006), whereas the overall survival rates were equal (90% vs. 67%; P = 0.13). No differences in overall survival or progression free survival were observed among patients with primary retroperitoneal and mediastinal seminoma. Prognostic factors that were identified to influence survival negatively were liver metastases (P = 0.01) and two or more metastatic sites (P = 0.04). CONCLUSIONS: In patients with extragonadal seminoma, a survival rate of > 90% at 5 years is achieved with adequate cisplatin-based chemotherapy. Compared with patients with nonseminomatous extragonadal GCT, no difference in long term survival exists between patients with primary retroperitoneal or mediastinal seminoma location. Primary radiotherapy seems to be associated with a significantly higher rate of disease recurrence, although most patients will be salvaged by subsequent chemotherapy.     

Primary germ cell tumors in the mediastinum: a 50-year experience at a single Japanese institution

BACKGROUND: Primary germ cell tumors (GCT) of the mediastinum share similar clinical and biologic characteristics, which are different from their testicular counterpart. The purpose of the current study was to review the authors' institutional experience of mediastinal GCT, emphasizing the clinical spectrum, time trends of treatment, and recent advances in therapeutic modalities for malignant GCT. METHODS: Between 1951 and 2000, 129 patients (70 males and 59 females) underwent surgical treatment for GCT, which accounted for 16.0% of the mediastinal tumors during the same period. There were 95 patients with mature teratomas, 13 patients with seminomas, and 21 patients with nonseminomatous germ cell tumors (NSGCT) with median ages of 26.4 years, 27.6 years, and 28.5 years, respectively. RESULTS: Adult patients with mature teratomas were less symptomatic (33.3%) than pediatric patients (52.4%). All patients with mature teratoma were cured by resection alone. Eight of the 13 patients (61.5%) with seminoma were symptomatic and 10 of 13 patients (83.3%) survived after surgery and radiation with/without chemotherapy. Nineteen of 21 patients (90.5%) with NSGCT had dyspnea, chest pain, and superior vena cava syndrome. Before 1985, patients received radical resection and/or chemoradiotherapy. However, all patients died due to disease progression, with a median survival period of 7.6 months. After 1986, six of eight patients received cisplatin-based chemotherapy, including three who received additional high-dose chemotherapy with a supporting peripheral blood stem cell transplantation until tumor markers normalized. Five patients who underwent salvage resection are currently disease free with a median survival period of 58.3 months. CONCLUSIONS: The institutional experience indicates the benign nature of mediastinal mature teratomas and the excellent prognosis for patients with seminomas after resection. An improved survival advantage was ensured with cisplatin-based preoperative chemotherapy in patients with NSGCT.     

Results of treatment after relapse from high-dose chemotherapy in germ cell tumors.

PURPOSE: To identify therapy-related or patient-related characteristics that predict response and long-term survival after failure of high-dose chemotherapy (HDCT) for germ cell tumors (GCT). PATIENTS AND METHODS: Between 1986 and 1997, 101 GCT patients relapsed after high-dose carboplatin and etoposide (VP-16) at Indiana University (Indianapolis, IN). Median time to relapse was 10 months (range, 1 to 17 months). HDCT was the first salvage treatment in 29 patients and second or later salvage treatment in 72 patients. RESULTS: Fifty-four of 101 patients received post-HDCT treatment. Of these, 47 received chemotherapy, alone (n = 35) or in combination with surgery (n = 12). Seven patients underwent surgery alone. There were only 12 objective responses (three complete and nine partial responses) for 66 chemotherapy regimens given to 47 patients, for an overall response rate of 18.2%. Fifteen patients received platinum-based chemotherapy, with only one objective response. Chemotherapy was discontinued in 17% of cases because of toxicity. A longer interval between HDCT and post-HDCT treatment was the only variable that was associated with response. Five patients (4.9%) are disease-free at 30, 53, 57, 85, and 93 months after relapse. Of these, three responded to oral VP-16 and underwent resection of residual mediastinal, retroperitoneal, and inguinal cancer, respectively. One had resection of residual mediastinal yolk sac tumor, followed by oral VP-16. One relapsed with teratoma and received thoracoabdominal resection without chemotherapy. CONCLUSION: Patients who experience disease progression after HDCT often receive further chemotherapy and/or surgery. Chemotherapy resulted in a response rate of less than 20%, with only three complete responses. All of the long-term survivors (4.9%) had surgery as a component of their post-HDCT regimen.     

Prognostic Factors and Therapeutic Problems of Primary Intracranial Choriocarcinoma/Germ-Cell Tumors with High Levels of HCG

OBJECTIVE: Primary intracranial choriocarcinoma (PICCC)/germ-cell tumors (GCTs) with high levels of human chorionic gonadotropin (HCG) (PICCC/GCTs with HL-HCG) are rare and malignant. The goal of this study was to report our 3 cases of PICCC/GCTs with HL-HCG and to review the literature to elucidate the clinical problems and prognostic factors and to discuss the therapeutic modalities of this rare tumor. METHODS: Survival was analyzed in 66 previously reported PICCC/GCTs with HL-HCG including our 3 cases, of which the clinical results have been described in the literature since 1975. In the 66 cases (mean age: 12.1 years; male/female: 45/21), 35 were verified histologically as pure choriocarcinoma, 23 were as mixed GCTs with choriocarcinoma element, and 8 were not verified as including choriocarcinoma element histologically but with very high HCG levels. Significance of the differences among survival curves concerning each parameter (age, sex, tumor location, serum HCG/beta-HCG level, precocious puberty, extent of surgery, radiotherapy, chemotherapy, mixture of other non-germinomatous GCT elements and extraneural metastasis) was tested using univariate and multivariate analyses. RESULTS: The median survival time and the 1- and 2-year survival rates were 22 months, 61.2% and 49.8%, respectively. In univariate analysis, male, subtotal removal or more, radiotherapy and chemotherapy were revealed to be significantly good prognostic factors. However, suprasellar region and tumor hemorrhage were poor prognostic factors. Multivariate analysis showed that extent of surgery, radiotherapy and chemotherapy were independent prognostic factors. CONCLUSIONS: Although, we should mind the limitations of this study design because of case selection bias, different treatment protocols and incomplete follow-up of patients, this study led the following results and suggestive conclusions. Tumor hemorrhage and progressive extraneural and cerebrospinal fluid metastasis were characteristic clinical problems of PICCC/GCTs with HL-HCG. In the cases with extremely elevated levels of HCG, biopsy for histological diagnosis may be no longer needed. Initial biopsy and radiotherapy may lead to tumor hemorrhage. To prevent tumor hemorrhage, gross tumor removal followed by radiotherapy and chemotherapy should be aimed for. A few courses of chemotherapy before surgery may prevent metastasis. Stereotactic radiotherapy and high dose chemotherapy may be promising options for treatment.     

23例软组织颗粒细胞瘤临床病理学特征

目的:探讨软组织颗粒细胞瘤(GCT)的临床病理学特征，以提高对该肿瘤的诊断水平。方法:收集23例存档GCT标本，对其进行免疫组化染色及分子病理学检测，并结合文献对其临床病理学特征进行综合分析。结果:23例GCT患者平均年龄47.9岁（范围为16~70岁），其中女性16例（69.6%），男性7例（30.4%）。21例（91.3%）为良性，2例（8.7%）为恶性。显微镜下，良性GCT肿瘤细胞呈圆形、卵圆形或多角形，细胞质嗜伊红颗粒明显。21例（91.3%）良性病例均未见核分裂象及坏死。2例恶性GCT细胞异型性明显，核分裂象分别为7个和4个/10HPF，其中1例可见坏死。免疫组化染色S-100、CD68、Vimentin在良性中阳性率分别是100%（21/21）、90.5%（19/21）、100%（21/21），恶性中均为100%（2/2）；良性Ki-67增殖指数平均2.1%（范围0%~10%），恶性Ki-67增殖指数平均22.5%（范围15%~30%）。1例足部恶性GCT行荧光原位杂交检测，未检测到EWSR1重排，进一步除外透明细胞肉瘤。良性GCT随访19例（14个月至8年）无复发，2例复发均为恶性GCT。结论:GCT是一种少见的外周神经组织肿瘤，免疫组化是GCT诊断的常规手段，分子遗传学还有待于深入研究。GCT注意应与多种病变鉴别，特别是冰冻病理学检查容易误诊。     

Late relapse in testicular germ cell tumors

AIMS AND BACKGROUND: Analysis of patients with late relapse of testicular germ cell tumors (GCTs) with reports on clinicopathological features and outcomes. METHODS: We identified all patients diagnosed with testicular GCTs at our Institute between 1988 and 2004 who developed relapse > or = 24 months after completion of primary therapy. A retrospective case-note review was performed to extract clinical, pathological, treatment and outcome data. RESULTS: Six patients (1.25%) developed late relapse. All patients presented with stage I disease and were classified as "good risk" according to the International Germ Cell Consensus Classification. Mean time to late relapse was 48 months. Markers at late relapse were normal in all patients. Relapse was confined to retroperitoneal sites in five patients and located in the mediastinum in one patient. Five patients were managed by chemotherapy alone while one underwent combined treatment with surgery followed by chemotherapy. All patients obtained a complete response and all remained free from recurrence with a mean follow-up of 115 months. CONCLUSIONS: The incidence of late relapse in this small series is low. Chemonaive patients with late relapse were successfully salvaged with chemotherapy alone or surgical excision followed by cisplatin-based chemotherapy. The optimal duration of follow-up in patients with testicular GCTs is not known and practice varies widely. At our Institute we advise lifelong follow-up of all patients with malignant GCTs of the testis.