Modified grading system for clinical outcome of intracranial non-germinomatous malignant germ cell tumors

This study investigated the clinical outcome of intracranial non-germinomatous malignant germ cell tumors (NGMGCTs). All histologically proven cases of NGMGCTs treated in Shanghai Huashan Hospital, Fudan University were reviewed. A total of 39 cases were analyzed. There were 15 mixed germ cell tumors, 15 immature teratomas, 7 embryonal carcinomas and 2 yolk sac tumors. Patients were treated surgically first, followed by radiotherapy and/or chemotherapy. Some patients also received gamma knife surgery. The common 5-year survival rate was 36.8%. According to Matsutani's grading system, the 5-year actuarial survival rate for patients in the intermediate and poor prognosis groups were 45.8 and 14.3%, respectively. Individual analysis of each type of tumor showed that the median survival time of embryonal carcinoma was 27 months, which is very close to that of the intermediate group (28 months). We therefore classified embryonal carcinoma into the intermediate group where the 5-year actuarial survival rate for patients in the new intermediate prognosis group was 42.6%. Further analysis of immature teratoma cases found that the 5-year survival rate of patients with immature teratoma who received gamma knife surgery is 100%. This rate exhibited a significant difference (P=0.0049) compared to that of patients who did not undergo gamma knife surgery. In conclusion, we consider surgery as the first choice of treatment although for different histologis, the type of the tumor should be treated separately.     

Proliferative characteristics of intracranial and spinal tumors of developmental origin

The proliferative potential of 17 intracranial and spinal tumors (six craniopharyngiomas, four chordomas, three mature teratomas, one immature teratoma, one embryonal carcinoma, one choriocarcinoma, and one dermoid tumor) was assessed. The patients received a 30-minute to 60-minute infusion of bromodeoxyuridine (BUdR) (200 mg/m2 intravenously [IV]) at the time of surgery but before a biopsy of the tumor was performed, to label cells in the DNA synthesis phase. The labeling index (LI) was calculated by determining the percentage of BUdR-labeled cells. The mean LI of the squamous epithelial elements of mature teratomas, craniopharyngiomas, and the dermoid tumor were 3.1 +/- 1.2%, 1.9 +/- 0.9%, and 2.9 +/- 1.9%, respectively. As in normal epithelium, the labeled cells were located in the basal layer. These results and the clinical findings suggest that the proliferation kinetics of these tumors are similar to those of normal skin and differ from those of rapidly growing malignant neoplasms. The other tissue elements (i.e., respiratory epithelium and cartilage) also demonstrated "organized" proliferation patterns similar to those of the corresponding normal tissues. An immature teratoma, an embryonal carcinoma, and a choriocarcinoma each had a high LI (24.6 +/- 5.3%, 32.3 +/- 3.8%, and 17.0 +/- 4.6%, respectively), and no organized pattern of proliferation was observed. In contrast, the mean LI of the four chordomas varied from 1.5% to 5.8%, and there was an even larger variation in the LI of different areas in individual tumors (from less than 1% to 7.5%). This finding suggests that even "slow-growing" chordomas sometimes can be locally aggressive and show a high incidence of recurrence, regardless of morphologic similarities.     

Transvaginal color Doppler ultrasonic characterization of benign and malignant ovarian cystic teratomas and comparison with serum squamous cell carcinoma antigen

BACKGROUND: The preoperative diagnosis of squamous cell carcinoma (SCC) arising in mature cystic teratoma of the ovary remains difficult. The purpose of this study is to examine the usefulness of transvaginal color Doppler ultrasound (TV-CDU) in differentiating malignant (SCC) from benign cystic teratoma of the ovary. METHODS: Eighty-eight patients with an ovarian tumor showing gray scale sonographic appearances of mature cystic teratoma were preoperatively evaluated for the presence or absence of intratumoral blood flow by TV-CDU. The blood flow characteristics of the tumor vessels were analyzed using the resistance index (RI), pulsatility index (PI), and peak systolic velocity (PSV). The serum levels of SCC antigen were also randomly examined preoperatively in 50 patients. RESULTS: Intratumoral blood flow was significantly detected in malignant teratomas (SCCs) (80.0%; 4 of 5) compared with benign teratomas (20.5%; 17 of 83) (P < 0.01). All malignant teratomas with intratumoral blood flow showed both RI less than 0.4 and PI less than 0.6, whereas no benign teratomas showed any such value except for 1 case with struma ovarii. In addition, both the mean RI and the mean PI values in the tumor vessels were significantly lower in the malignant teratomas (RI: 0.31 +/- 0.07; PI: 0.40 +/- 0.16) than in the benign teratomas (RI: 0.62 +/- 0.13; PI: 1.06 +/- 0.44) (P < 0.001). However, the mean PSV value of the malignant teratomas (PSV: 20.6 +/- 8.33) was not significantly different from the benign teratomas (PSV: 18.1 +/- 9.9). Elevation of serum SCC was found in 4 of 5 patients (80%) with malignant teratomas, whereas the elevation was found in 11 of 45 patients (24.4%) with benign teratomas (P < 0.05). The diagnostic accuracy using the RI (cutoff value 0.4) as well as the PI (cutoff value 0.6) was thus 95.2%, which was significantly superior to that obtained by using the serum SCC (76%) (cutoff value, 1.5 ng/mL). CONCLUSIONS: Evaluating the presence or absence of intratumoral blood flow, together with blood flow resistance, in tumor vessels using TV-CDU thus may be more useful to differentiate malignant (SCC) from benign cystic teratomas of the ovary than by measuring serum SCC levels.     

Radiotherapy in malignant teratomas.

Twenty-seven patients with malignant teratoma, 19 of which received radiation, are presented and the radiation response analyzed. Radiotherapy seems most effective in the palliation of undifferentiated (embryonal) teratoma of the gonads and sacrococcygeal region in early childhood. It is less effective, yet useful, in undifferentiated gonadal and sacrococcygeal teratomas of older children and adults, but seems of little value in carcinomatous ovarian dermoids and in malignant mediastinal teratomas.     

Histogenetic analysis of ovarian germ cell tumors by DNA fingerprinting.

The histogenesis of ovarian germ cell tumors (11 mature teratomas, three malignant transformations of mature teratomas, two immature teratomas, and four dysgerminomas) was investigated genetically using minisatellite DNA probes 33.15 and 33.6 for person-specific restriction fragment length polymorphism (DNA fingerprint) analysis. The DNA fingerprints of six ovarian teratomas were identical with those of mononuclear cells from each host, while some polymorphic bands observed in the host mononuclear cells were lost in the DNA fingerprints of the other five cases. The cases of malignant transformation of mature teratoma and immature teratoma showed that some polymorphic bands of DNA fingerprints from the host mononuclear cells were absent in the tumor tissues. In four cases with dysgerminomas, the DNA fingerprints of tumors were completely identical with those of the respective host mononuclear cells. The present results suggest that mature cystic teratomas of the ovary arise from germ cells arrested at various stages of meiosis, while immature teratomas are derived from postmeiotic germ cells. Malignant transformation may occur exclusively in the mature teratomas arising from postmeiotic germ cells. Dysgerminomas develop from premeiotic oogonia (primordial germ cells). Thus, DNA fingerprints are a useful and sensitive tool for identifying the pathogenesis of germ cell tumours.     

26例原发性纵隔恶性生殖细胞瘤的诊治

目的:探讨原发性纵隔恶性生殖细胞瘤的诊治及外科手术的作用.方法:对26例收治的原发性纵隔恶性生殖细胞瘤的临床资料进行回顾性分析.结果:22例手术治疗患者中,11例根治性切除,10例姑息性切除,1例探查,手术并发症发生率及死亡率分别为18.2%和9.1%,其中12例术后给予以顺铂为主的联合化疗,4例予以放疗.手术治疗患者术后病理为无性生殖细胞瘤12例,精原细胞瘤5例,未成熟畸胎瘤5例.3例未成熟畸胎瘤及1例胚胎癌患者明确诊断后未手术而给予放疗或放、化疗.本组26例患者中仅2例精原细胞瘤生存满5年,17例已证实死亡,除2例手术死亡外均死于肿瘤复发转移.结论:原发性纵隔恶性生殖细胞瘤的治疗应强调以化疗为主的综合治疗,外科切除只宜做为阶段性的辅助手段,手术时机把握应以具体患者情况而定.     

Diagnosis and treatment of mediastinal teratomas]

Among 221 operated patients with primary tumors and cysts of the mediastinum teratomas were observed in 54 (24.4%). The diagnosis of mediastinal teratodermoids should be complex. Clinically in benign teratomas the localization and character of the process were determined precisely in 94%, histogenesis--in 35%, in malignant teratomas--the proper localization was determined in 90%, the tumor character--in 78%, histogenesis--in 26%. For malignant tumors the combination therapy with intensive telegamma therapy prior to and after surgery was employed. Resectability in malignant teratomas made 73%, the postoperative mortality--in 5.5%. A five-year survival following radical surgery in patients with malignant teratoma was 37%. In inoperable teratoblastomas it seems rational to use intensive split course telegamma therapy with a total focal dosage of 5,500-6,500 rad.     

Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study.

PURPOSE: To determine whether the 3-year event-free survival (EFS) of children with completely resected immature teratomas is greater than 85%. PATIENTS AND METHODS: Patients with immature teratomas treated at Pediatric Oncology Group or Children's Cancer Group institutions were eligible. Pathology was centrally reviewed to confirm diagnosis and tumor grading. Follow-up included physical examination, measurement of tumor markers (alpha fetoprotein and human chorionic gonadotropin), and imaging. All patients were monitored for events, defined as tumor recurrence, second malignancy, or death. RESULTS: Seventy-three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study. Primary tumor sites included ovarian (n = 44), testicular (n = 7), and extragonadal (n = 22). However, on review, 23 patients had foci of yolk sac tumor (n = 21) or primitive neuroectodermal tumor (n = 2), whereas 50 had pure immature teratomas. Twenty-five patients had increased alpha fetoprotein (n = 18), human chorionic gonadotropin (n = 5), or both (n = 2); nine had foci of yolk sac tumor on review. Pathology review identified 23 patients with grade 1, 29 with grade 2, and 21 with grade 3 immature teratomas. With a median follow-up of 35 months, the overall 3-year EFS was 93% (95% confidence interval, 86% to 98%), with 3-year EFS of 97.8%, 100%, and 80% for patients with ovarian, testicular, and extragonadal tumors, respectively. Only four of 23 patients with immature teratoma and malignant foci developed recurrence, suggesting that surgical resection followed by close observation are effective treatment. Overall, five patients had disease recurrence 4 to 7 months from diagnosis, and four (80%) are disease free after platinum-based therapy. The fifth patient has residual tumor after cisplatin, etoposide, and bleomycin treatment requiring further therapy. CONCLUSION: Surgical excision is safe and effective treatment for 80% to 100% of children with immature teratoma.     

卵巢成熟畸胎瘤恶变的预后规律

目的：探讨卵巢成熟畸胎瘤恶变的生物学特性及预后规律。方法：对１８例卵巢成熟畸胎瘤恶变的生存率、平均缓解时间、复发转移规律及预后影响因素进行分析,以同期治疗的３５例卵巢未成熟胎瘤作对照。结果：卵巢成熟畸胎瘤恶变的中位发病年龄较未成熟畸胎瘤晚１０年,３、５、１０年生存率较卵巢未成熟畸胎瘤低（Ｐ＜０．０５）,术后复发转移率较卵巢未成熟畸胎瘤高（Ｐ＜０．０５）,术后平均缓解时间较未成熟畸胎瘤短（Ｐ＜０．０     

Immature teratomas: identification of patients at risk for malignant recurrence

We investigated the significance of immature elements in an otherwise benign teratoma in 28 patients with immature teratomas diagnosed and treated at the Childrens Hospital of Los Angeles from 1941 to 1986. Different characteristics, including age, sex, primary tumor site, type of surgery (complete resection vs. partial resection or biopsy), and preoperative levels of alpha-fetoprotein (AFP) were analyzed to evaluate their association with risk of subsequent local malignant recurrence. After a median follow-up of 6 years, 21 patients are alive with no recurrence of the tumor (72% event-free survival). One patient died from infection after surgery and six patients had local malignant tumor recurrence within 1 year from diagnosis. Of the 28 patients, 12 had AFP levels measured at diagnosis. Eight patients had normal levels with no further evidence of tumor recurrence, and four had elevated levels with three tumor recurrences. Our experience demonstrates that only at the time of diagnosis do AFP levels correlate with a subsequent malignant behavior of these tumors (P = .004). Those patients with immature teratomas and elevated AFP levels at diagnosis should receive adjuvant chemotherapy after the initial surgical resection.     

Management of primary intracranial germ cell tumors

Primary intracranial germ cell tumors are rare and usually localized in the pineal and the suprasellar regions. They are divided into the following histologic types: germinoma, teratoma (mature, immature, malignant), choriocarcinoma, embryonal carcinoma, endodermal sinus tumor (yolk sac tumor), and mixed tumors. Clinically, they are manifested with ocular signs or signs of obstructive hydrocephalus. Localized germinomas are treated with radiation therapy and exhibit a relatively good prognosis. Chemotherapy is reserved for disseminated germinomas. Mature teratomas are treated with surgery. The rest of germ cell tumors are managed with various combinations of surgery, chemotherapy, and radiotherapy depending on the tumor type. If the tumors secrete beta-human chorionic gonadotrophin (hCG) or alpha-fetoprotein (FP), these tumor markers can be used to accurately monitor response to treatment. Prognosis is best for germinomas and mature teratomas and worst for choriocarcinomas and embryonal carcinomas.     

More Cases of Benign Testicular Teratomas are Detected in Adults than in Children. A Clinicopathological Study of 543 Testicular Germ Cell Tumor Cases

Benign testicular teratomas are always thought to be pediatric neoplasms and previously all the teratoid tumors in the adult testis regarded as malignant. Recently, three publications reported benign testicular teratomas in adulthood and the latest WHO classification refers them as “prepubertal type of teratomas” which rarely appear in adulthood. These neoplasms behave benign and seemingly analogous independently whether they appear in pre- or postpubertal patients. The aim of our study was to investigate the frequency of benign testicular teratomas both in children and adults. 593 cases of testicular neoplasms were found in a period of 17 years ranging from 1998 to 2014 in the archive of our department (Department of Pathology, Medical Center, Pécs University). 543 cases diagnosed as germ cell tumor which have all been further evaluated in conjunction with the clinical data available. Of all germ cell tumor cases 14 (2.5 %) were pure teratomas. Ten out of 14 were the WHO-defined “conventional” teratoma, 4 of the 14 were the “benign or the so called prepubertal type” from which three occurred in adult patients. Only one of the 14 occurred in childhood, indicating that benign prepubertal type teratomas –which are regarded generally as childhood tumors- are more frequently detected in adults than in children. Benign adult testicular teratomas comprised 21 % of all pure teratoma cases in our series. Practicioners in the field have to be aware of its existence also in adulthood to avoid overtreatment and not to expose their patients to unnecessary chemotherapy, retroperitoneal lymphadenectomy (RLA) and the potential complications of these interventions.     

Telomerase activity in germ cell cancers and mature teratomas.

BACKGROUND: An inverse relationship has been reported between the presence of telomerase enzymatic activity and the induction of differentiation in human tumor cell lines. Male germ cell tumors represent an attractive clinical model to assess this relationship further because high telomerase activity is present in normal germ cell progenitors and in embryonal carcinomas that can differentiate into mature teratomas. To investigate how telomerase activity and the differentiation state of germ cell tumors are related, telomerase activities and telomere lengths were measured in benign testicular tissues, germ cell cancers, and mature or immature teratomas. METHODS: By use of a modified telomeric repeat amplification protocol (TRAP) assay, telomerase activity was measured in four specimens of benign testicular tissue, in 27 germ cell cancers, in seven mature teratomas, and in one immature teratoma. Telomere lengths were measured in all specimens by restriction digestion of genomic DNA and Southern blot hybridization analysis. Associations between telomerase activity and tissue histopathology were assessed with two-sided Fisher's exact tests. RESULTS: Telomerase activity was detected in all examined germ cell cancers and in the benign testicular tissue specimens. In marked contrast, telomerase activity was not detected in any mature teratoma (P<.0001). Very long telomeres were detected in some mature teratomas, consistent with telomerase repression as a late event in teratoma formation. The immature teratoma, with malignant transformation, had high telomerase activity. CONCLUSION: Telomerase is active in germ cell cancers and repressed in mature teratomas. The absence of telomerase activity may contribute to the limited proliferative capacity of mature teratomas. These findings support the existence of an inverse relationship between telomerase activity and the differentiation state of clinical germ cell tumors.     

Embryonal carcinoma of the testis

Long-term survival rates were correlated with selected clinical features in 479 patients with embryonal carcinoma of the testis and 33 patients with endodermal sinus tumor (infantile embryonal carcinoma, yolk sac tumor). In the period 1977 to 1982 embryonal carcinoma accounted for 26.8% of newly diagnosed germ cell tumors and 43% of nonseminomatous germ cell tumors entered in the Centralized Cancer Patient Data System. Among patients with embryonal carcinoma, over 80% were diagnosed in the 15-to-34 year age group. Seventy-four percent of the patients had metastatic disease at the time of diagnosis, and 50% of these had distant metastases, attesting to the aggressiveness of embryonal carcinoma and its tendency to early hematogenous spread. Despite the highly malignant nature of the tumor, the overall 5-year survival rate with treatments used was an excellent, 88%. Survival was correlated with the extent of disease at the time of diagnosis; the 5-year actuarial survival rates for patients with localized, regional, and distant disease were 98%, 96%, and 74%, respectively. Endodermal sinus tumor was uncommon (1.8% of all testicular germ cell tumors), occurred predominantly in the younger age group (0-24 years), and in 50% of the cases was localized to the testis. The survival rate for the 33 patients with this form of tumor was slightly worse than for the "adult form" of embryonal carcinoma. The authors conclude that survival of patients with embryonal carcinoma has greatly improved over the last decade as a result of improved methods for early detection of metastatic deposits and the effectiveness of newer chemotherapies in the treatment of disseminated disease.     

原发颅内恶性畸胎瘤34例分析

目的:总结颅内恶性畸胎瘤的临床特点,探讨其诊断方法和外科治疗效果。方法：34例原发颅内恶性畸胎瘤均经手术切除和病理证实。根据患者的临床表现和神经影像学检查,确定肿瘤的生长方式;结合手术效果对临床资料进行回顾性分析。结果：34例中,有6例术前诊断为畸胎瘤;行肿瘤全切除14例,手术死亡率为32．4％。23例肿瘤呈侵袭性生长,其术后存活时间与非侵袭性生长者比较,差异有显著性（P＜0．05）。结论：颅内恶性畸胎瘤术前不易诊断,尤其是位于鞍区者;肿瘤的侵袭性生物学行为是手术治疗效果不良的主要原因;保护下丘脑、脑干功能和解除脑积水是外科治疗的关键;全面的组织病理学检查、血清及脑脊液肿瘤标志物检测是诊断和治疗的重要依据。     

Chemically induced differentiation of murine embryonal carcinoma in vivo: transplantation of differentiated tumors

Murine embryonal carcinoma tumors were induced to differentiate in vivo by administration of retinoic acid. Six long-term surviving animals had seven slowly growing tumors which were transplanted s.c. into strain 129 mice. Untreated embryonal carcinomas were transplanted as controls. All of the 16 control transplants grew rapidly and killed their hosts within 25 days. All of the 24 transplants of retinoic acid-differentiated tumor survived. Sixteen experimental transplants originating from five original tumors showed no or slow growth for up to 16 weeks and were found to be histologically benign cystic teratomas. Two original tumors gave rise to eight relatively rapidly growing transplants. One tumor resulted in four histologically similar solid tumors which resembled chondrosarcomas, and the second tumor gave rise to four histologically similar solid tumors which proved to be a mixture of glioma and chondrosarcoma. Examination of the tumor sources of these latter transplants showed benign cystic teratomas with focal solid, mitotically active cellular areas which were histologically similar to the transplants. These data confirm that retinoic acid-induced differentiation of murine embryonal carcinoma cells results in altered biological potential of these cells and usually the formation of a benign teratoma. Rarely (about 1 per 2 X 10(8], the resulting differentiated cells will give rise to rapidly growing, histologically malignant tumors. One can predict such biological propensity when solid, mitotically active areas in the original tumor are found.     

Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962-1987

A retrospective analysis has been made of all patients with pineal and CNS germ cell tumors who were treated at The Royal Marsden Hospital between 1962-1987. A total of 67 new cases were seen: 17 had initial histological verification of tumor type and the remainder were tested for radiosensitivity with a dose of 20 Gy following a shunting procedure. Patients with germ cell or radiosensitive tumors were treated with a uniform policy of whole neuraxis radiotherapy giving 50 Gy to the local tumor and 30 Gy to the remaining brain and spinal cord. Nonresponding lesions continued with local fields to a dose of 50 Gy. Patients were divided into three groups (a) germinoma and radiosensitive tumours, 34 cases; (b) malignant teratoma, 12 cases; (c) non-germ cell, 21 cases. Median follow-up is 83 months (range 2-246 months). Overall and cause specific actuarial 5/10 year survival were for group 1, 81.7%/69.4% and 86.5%;/86.5%; group 2, 18.2%/18.2% and 18.2%/18.2%, and group 3, 64.3%/46.8% and 64.3%/52.6%, respectively. No patient in group 1 treated during the last 12 years has recurred. Univariate analysis of factors at presentation, showed that neurological performance status (p less than .001) as well as tumor type (p less than .001) correlated with outcome. Recurrence was confined to the primary site in only 1 of 4 patients in group 1 compared to 6 of 9 patients in group 2 and 9 of 10 patients in group 3. No isolated spinal recurrence occurred in group 1 patients. A total of eight patients have received platinum containing chemotherapy for recurrence (6 cases) or adjuvant therapy (4 cases). Germinomas appear to respond better than teratomas, all of which have recurred rapidly following initial partial response. Shunting and radiosensitivity testing remains the treatment of choice for tumors compatible with germinoma. Craniospinal irradiation is associated with low morbidity providing spinal growth is complete and is recommended in older patients as salvage following spinal recurrence is unsatisfactory. Aggressive combined modality approaches with surgery, radiotherapy and chemotherapy need to be investigated to improve results in CNS teratoma.     

Chemotherapy of advanced malignant teratomas.

Between 1977 and November 1979 we have treated 53 patients with malignant teratomas (43 males, 10 females). Thirty (70%) out of the 43 male patients had advanced and bulky disease at the time of presentation. Using different drug combinations in a sequential manner as described below, results are as follows: of the initial 33 male patients, 22 (67%) have discontinued treatment (mean 9.5 months). Nineteen have responded completely and 3 have static computed tomography (CT) nodules. Life-table analysis projects a survival of 66% (analysis at 1 December 1979). Nine out of 10 ovarian teratoma patients are alive. Adverse prognostic factors at the start of treatment were recognized in 9/10 male patients and the 1 female patient who have died. Although the survival of patients with malignant teratomas has improved dramatically, there are still problems with drug resistance in patients with very advanced disease. Patients with these tumours should continue to be treated in centres specializing in managing what has now become a potentially curable disease in most cases.     

Apoptosis and proliferative activity in mature and immature teratomas of the mediastinum.

BACKGROUND: Mediastinal teratomas are the most frequent mediastinal germ cell tumor. Whereas mature teratomas are benign tumors, immature teratomas are malignant. The purpose of this study was to find characteristics that could be used to distinguish between the growth and prognosis of the two teratoma types. METHODS: Twenty-four mediastinal teratomas (18 mature and 6 immature) were examined for apoptosis by 3'-end labeling of DNA and stained immunohistochemically for proliferating cell nuclear antigen, Bcl-2, Bax, p53 protein, and alpha-fetoprotein (AFP) expression in formalin fixed, paraffin embedded specimens. RESULTS: AFP was expressed in both immature teratomas and mature teratomas. Whereas p53 protein was expressed by most teratomas, p53 gene mutation was observed in only one patient with an immature teratoma in which the same mutation occurred in all tumor tissue components tested. Bax protein expression was relatively diffuse in mature teratomas but was focally expressed in immature teratomas. Bcl-2 protein was expressed focally in both mature and immature teratomas. Although the proliferative index was significantly higher in immature teratomas compared with mature teratomas (P < 0.001), the apoptotic index (AI) was significantly higher in mature teratomas compared with immature teratomas (P < 0.05). All patients except one in this study remain alive and disease free after undergoing tumor resection. CONCLUSIONS: The relatively high AI in mature teratomas may be due to the overexpression of the p53 protein. In contrast, immature teratomas exhibited higher proliferative activity and lower rates of apoptosis, which may explain the more aggressive behavior of these tumors. However, patients with immature mediastinal teratomas have a good prognosis if the tumor is resected completely after chemotherapy.