Malignant Germ Research Articles

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.

An old patient with growing teratoma syndrome of the ovary

Abstract Growing teratoma syndrome (GTS) is a rare complication of malignant ovarian germ cell tumors. A 52-year old woman was admitted to our Gynecological Oncology Department with metastatic multiple abdominal masses. Her initial gynecological history presented an immature teratoma of the ovary 3 years previously, and she underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic-paraaortic lymphadenectomy and omentectomy. She received three cycles of bleomycin, etoposide and cisplatin (BEP) regimen after surgery. Although the tumor markers were within normal limits, multiple metastatic lesions were detected in the 3rd month of follow-up. The patient was referred to our gynecological oncology department, optimal debulking including resection of the tumoral lesions localized on the liver, diaphragm, peritoneum, sigmoid colon, omentum and retroperitoneum was performed. Histopathology of all samples revealed mature teratoma. This syndrome should be remembered when a tumor is refractory to chemotherapy and growth of the tumor still continues after resection of the initial tumor.

Pregnancy following surgery and chemotherapy for ovarian germ cell tumors.

e16550 Background: Malignant ovarian germ cell tumours(OGCT) are a rare disease, accounting for 2% of all malignant ovarian tumours diagnosed in Ireland between 1994 - 2010. They affect a younger population than epithelial ovarian cancer, with the highest number of cases in the second and third decade. In this report, we present a review of patients treated in a tertiary referral centre. Methods: We performed a retrospective review over a 26 year period in our institution. We examined clinical records, pathology, pharmacy and surgical databases to identify patients with ovarian germ cell tumours who were treated in our institution. Results: During the period 1986 – 2012, twenty patients were treated and followed at this institution for malignant ovarian germ cell tumor (OGCT). Eighteen patients are alive and well at a median follow up of 14.5 years (range 0.5 – 26). Nineteen patients received platinum based chemotherapy with a median number of four cycles (range 2 – 6) required to achieve complete remission. Twenty percent of patients had yolk sac histology; the next commonest were immature teratomas and mixed germ cell tumour (10 & 15% respectively). The commonest chemotherapy regimen used was BEP (bleomyocin, etoposide and cistplatin). Six patients (30%) underwent resection of residual disease post chemo revealing mature teratoma/necrotic tissue. During follow up, four patients had progressive or recurrent disease. Two patients at resection had mature teratomas found on histological examination. The remaining two patients (10%) had progressive disease and died within a short time period. In our patient population, nine of nine attempting pregnancy have been successful. There have been 12 pregnancies carried to term; mother and child in each case are well. At a median follow up of 14.5 years (range 0.5 – 26), there have been no second malignancies and no toxicities attributable to chemotherapy. Conclusions: We have shown that platinum based chemo in OGCT is associated with preservation of fertility in these young women. In our series there have been no adverse affects in women or their infants. Platinum based chemo highly successful in curing OGCT and this confirms that it is associated with preserved fertility in these young women.

Multicenter randomized controlled clinical study for the operative treatment of malignant ovarian germ cell tumors

To investigate the operative treatment for first-treated patients with malignant ovarian germ cell tumors who need preservation of fertility. The clinical data of 105 patients who were treated with fertility-sparing surgery in 11 hospitals from 1992 to 2010 were collected to evaluate the outcomes of different primary surgical operative procedures. All 105 cases were performed the surgeries that preserved fertility and divided into three groups according to the surgical approaches, comprehensive staging surgery group: 47 cases (44.8%) received comprehensive staging surgeries that including the ipsilateral oophorectomy + omentectomy + retropertoneal lymph node dissection ± appendectomy + multiple biopsies;oophorectomy group:45 cases (42.9%)received ipsilateral oophorectomy ± biopsy of contralateral ovary ± omentectomy;tumor resection group:13 cases (12.4%) received enucleation of the mass with preservation of the ovary. Differences were compared among the three groups of patients in the surgery-related indicators, complications, fertility and prognosis. (1) Surgery-related indicators:the average blood loss of the comprehensive staging surgery group, the oophorectomy group and the tumor resection group were 496, 104 and 253 ml, the mean operation time were 176, 114 and 122 minutes, respectively, and there were significant differences among three groups (P = 0.011, P = 0.000). (2) Complication:the surgical complication rates of the three groups were 17% (8/47), 0 and 1/13, with significant differences (P = 0.015). (3) Reproductive function status: the pregnancy rate and birth rate of the three groups were no significant differences (9/19 vs. 7/19 vs. 2/3, P = 0.515; 8/19 vs. 5/19 vs. 2/3, P = 0.636). (4) PROGNOSIS: the recurrence rate of the three groups were significant differences [13% (6/47) vs. 0 vs. 2/13, P = 0.013], but the death rate with no significant differences [6% (3/47) vs. 0 vs. 0, P = 0.129]; The five-year survival rate of three different groups were 89%, 100% and 100% (P > 0.05), while disease free survival rate were 85%, 100% and 83% (P < 0.05), respectively. Compared with comprehensive staging surgery, oophorectomy group have higher surgical security and satisfactory prognosis, considerable pregnancy rates and birth rate. The tumor resection security may be reliable, but the prognosis is poor.

Clinical and Radiologic Signs of Relapsed Ovarian Germ Cell Tumor: Tissue Is the Issue

Malignant ovarian germ cell tumor is a rare disease, but with current treatment strategies including surgery and platinum based chemotherapy survival is excellent. After treatment, intensive followup is indicated to encounter tumor relapse at an early stage. This case describes a 22-year-old female with a history of common variable immune deficiency (CVID) who underwent a resection of a large ovarian germ cell tumor followed by 4 cycles of cisplatin and etoposide resulting in clinical complete remission. During followup, she developed a mass at the umbilicus and ascites. Initially, the cytology of the ascites was interpreted as tumor positive, suspicious of relapse of the disease, but tumor markers remained negative. However, during laparoscopy it turned out to be a mature teratoma, which can develop after chemotherapy, the so called growing teratoma syndrome. In retrospect, the ascites was false positive. This case shows that current diagnostic tools are not sufficient to distinguish between vital tumor and mature teratoma and can be misleading. Tumor biopsy and/or laparoscopic inspection are therefore indicated.

920 The Effects of N-Acetyl-L-Cysteine on Bleomycin Induced Apoptosis Were Determinated in Malignant Testicular Germ Cell Tumours by Flow Cytometry

920 The Effects of N-Acetyl-L-Cysteine on Bleomycin Induced Apoptosis Were Determinated in Malignant Testicular Germ Cell Tumours by Flow Cytometry

Abstract 4910: Apoptotic effects of curcumin and bleomycin alone or in combination on malignant testicular germ cells

Abstract Aims: Testicular cancer is the most common cancer among young men of reproductive age. Bleomycin is a frequently used drug for the treatment of several malignancies and is part of the chemotherapy protocols in testicular cancer, but side effects are common. Bleomycin increases oxidative stress which has been shown to induce apoptosis in cancer cells. Curcumin (diferuloylmethane), an active component of the spice turmeric, has been demonstrated to induce apoptosis in several types of malignancies. However, no study has been carried out so far to elucidate its possible anticancer activity and interaction with Bleomycin in testicular cancer cells. Methods: In this study, we investigated the effects of Curcumin and Bleomycin alone or in combination on apoptosis-signalling-pathways. We determined the cytotoxic effect of Bleomycin and Curcumin on NTera-2 (NT2) cells using 3-(4,5) dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and measured apoptosis signalling pathway markers such as Caspase-3, Caspase-8, Caspase-9 activities and Bcl-2, Bax and Cyt-c levels in NT2 cells incubated with Bleomycin in the presence or absence of Curcumin. Results: Median lethal dose (LD50) of Bleomycin on NT2 cell viability as 400 μg/ml after an incubation of 24 h and LD50 of Curcumin as 20 μM. Treatment with Bleomycin (400 μg/ml) and Curcumin (20 μM) alone for 24 h caused 3.2-fold and 3-fold increase in caspase-3 activity, 3.4-fold and 2-fold increase in caspase-8 activity, 2.9-fold and 2.8 fold increase in caspase-9 activities respectively. These treatments alone also caused 2-fold increase in Bax and 2-fold increase in cytoplasmic Cyt-c levels while leading 2-fold decrease in Bcl-2 levels. Combination of Curcumin with Bleomycin induced Caspase-3,-8,-9 activities more than their separate effects in NT2 cells. Specifically combination of Curcumin (20 μM) with Bleomycin (400 μg/ml) induced 4.2-fold increase in Caspase-3, 4.3-fold increase in caspase-8 activity, 4-fold increase in caspase-9 activity, 3-fold increase in cytoplasmic Cyt-c levels and 3-fold decrease in Bcl-2 levels.Conclusion: Bleomycin has proven to be an essential component of the cisplatin-based chemotherapy regimens, used in the treatment of testicular cancer. However, the use of Bleomycin is limited because of Bleomycin-induced pneumonitis, a complication occurring in approximately 10% of patients treated with Bleomycin and fatal in approximately 10% of the cases. Our observations suggest that the effects of Bleomycin on apoptosis-signalling-pathways were improved by Curcumin. Co-administration of Bleomycin with Curcumin could be a new strategy to use less dosage of Bleomycin and prevent patients from Bleomycin-induced side effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4910. doi:1538-7445.AM2012-4910

"Mixed germ cell testicular tumor" in an adult female

The androgen insensitivity (testicular feminization) syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5–10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

Clinical analysis of 15 cases of malignant ovarian germ cell tumors with lung metastasis

To investigate the clinical characteristics, diagnosis, treatment and prognosis of malignant ovarian germ cell tumors (MOGCT) with lung metastasis. Fifteen patients of MOGCT with lung metastasis treated in Peking Union Medical College Hospital from Jan. 1982 to Dec. 2010 was retrospectively analyzed. (1) Clinical characteristics: the average onset age of these 15 patients is (23 ± 11) years old (6 - 48 years). The majority of these patients presented with abdominal pain (8/15) or irregular vaginal bleeding (4/15) as their initial symptoms. The primary tumor located in the left ovary in 8 cases, right ovary in 6 cases, and both sides in only 1 case. Metastatic lesions were confined to the lung in 12 patients, while the other 3 patients were found to have multi-site distant metastasis. (2) DIAGNOSIS:all 15 cases included 9 pure non-gestational ovarian choriocarcinoma (NGOC), 3 MOGCT containing choriocarcinoma component (one mature teratoma with choriocarcinoma component, one endodermal sinus tumor with embryonal carcinoma and choriocarcinoma components, one choriocarcinoma with dysgerminoma component), 2 embryonal carcinoma, one immature teratoma. Only one patient in these 15 cases was correctly diagnosed before surgery. (3) Time of lung metastasis:of 12 MOGCT with choriocarcinoma component, 11 patients were found to have lung metastasis in the course of their primary treatment, only 1 had lung metastasis 2 months after the synthetic treatment finished. Three MOGCT patients without choriocarcinoma component were all found to have lung metastasis when tumor relapsed in the advanced stages of the disease. (4) TREATMENT:all 15 patients received multi-agent chemotherapy combined with surgery. The mean courses of chemotherapy for these patients were 16 courses (5 - 43 courses). (5) PROGNOSIS: of these 15 cases, complete remission was obtained in 10 patients of NGOC or mixed ovarian germ cell tumors with choriocarcinoma component, 3 patients (one NGOC, one endodermal carcinoma and one immature teratoma, respectively) died in the course of treatment as result of tumor progression, 2 progressed cases (one NGOC and one endodermal carcinoma respectively) abandoning therapy were lost to follow up. MOGCT with lung metastasis are more often to found in NGOC patients. These patients could obtain high complete remission rate after standard multi-agent chemotherapy combined with surgery. The prognosis of MOGCT with lung metastasis containing choriocarcinoma component are better than that of those without containing choriocarcinoma component.

Bilateral Testicular Epidermoid Cysts

Testicular epidermoid cysts are the most common benign tumors of the testes, but account for only 1-2% of all testicular tumors. In a young man presenting with a testicular mass, a high index of suspicion must be maintained for the malignant testicular germ cell tumor, which is 50-times more common than testicular epidermoid cyst. Bilateral testicular epidermoid cysts are a very rare condition, with only a few reports in the literature. It is extremely important in this condition to make a correct pre-operative diagnosis on imaging to enable a testis-sparing surgery.

Prostate Tissue Within Teratoma Component of Malignant Mixed Germ Cell Tumor

Prostate Tissue Within Teratoma Component of Malignant Mixed Germ Cell Tumor

Pregnancy Outcomes After Conservative Surgical Management of Ovarian Neoplasms Treated at a Single Institution

Conservative surgical management of ovarian neoplasms can result in favorable oncologic and obstetric outcomes. All reproductive-age women (18-45 years old) with stage IA to stage IIC ovarian neoplasms (N = 161) were retrospectively identified from a single institution's tumor registry between 1990 and 2007. Operative, pathological, outpatient, and delivery records were reviewed to confirm histological findings, stage, extent of surgical resection, adjuvant treatment, oncologic outcomes, and pregnancy outcomes. Women who underwent conservative surgical management for ovarian neoplasms (n = 61 [37.9%]) were identified, including those with low malignant potential (LMP, n = 36), epithelial (n = 12), germ cell (n = 6), and sex cord (n = 7) tumors. Thirteen women conceived 23 pregnancies, producing a pregnancy rate of 25.0% overall and of 68.4% for those attempting conception. Women with LMP tumors conceived most pregnancies and had the highest number of antenatal complications. Of those receiving adjuvant chemotherapy (n = 8), 12.5% were able to conceive after their treatment and with no reported congenital anomalies. Pregnancy after a diagnosis of ovarian neoplasm did not impact disease recurrence (0% vs 7.7%, P = 0.56) or survival (100% vs 100%, P = 1.0). Conservative surgery may be an acceptable option for reproductive-age women with early-stage ovarian neoplasms. We report pregnancy and oncologic outcomes for a cohort of women managed conservatively for LMP, epithelial, germ cell, and sex cord ovarian neoplasms.

Malignant mediastinal germ cell tumors: Clinical findings and diagnostic and therapeutic problems

縦隔悪性胚細胞性腫瘍（MGCT）の診断および治療アプローチを再確認するために，切除例の検討を行い，臨床上の問題点を明らかにした．対象は，1993～2006年に昭和大学関連3病院で切除したMGCT8例で，21～69歳，すべて男性．部位は前縦隔6例，中縦隔2例．AFP高値2例，HCG高値1例，両マーカーとも高値1例，上昇なし4例であった．組織検査は，CT下針生検4例，傍胸骨生検1例，縦隔鏡1例，未施行2例で，生検を行った6例中5例で，最終病理と一致した．初回治療は，化療4例（CR2例，PR2例），放治1例（NC），手術3例で，最終病理診断は，Seminoma3例，Yolk sac tumor1例，Adenocarcinoma with teratoma1例，Embryonal carcinoma1例，その他2例であった．MGCTの治療に際しては，化療の効果は良好であることからマーカー陽性例は速やかな抗癌剤治療が必要である．MGCTのなかに比較的高齢者，あるいは中縦隔発生例があることは留意すべき点である．

Outcomes after bleomycin, etoposide and cisplatin combination chemotherapy in patients with ovarian yolk sac tumor

Objective: The aim of this study was to evaluate the oncologic and reproductive outcomes of patients with ovarian yolk sac tumor after bleomycin, etoposide, cisplatin (BEP) chemotherapy following surgery. Methods: Of 145 patients with histologically confirmed malignant ovarian germ cell tumor, 43 had yolk sac tumor and received BEP chemotherapy after surgery. A retrospective analysis of these patients was performed. Results: The mean age of 43 patients was 24.8 years (range, 7 to 59 years). Thirty eight patients were iparous. Of 179 BEP chemotherapy cycles, grade 1~2 hematologic and non-hematologic adverse events occurred in 46 cycles in 21 patients. Thirty nine patients showed complete remission, 1 patient showed partial remission, and 3 patient had progressive disease during BEP chemotherapy. After median follow-up time of 57 months (range, 3 to 153 months), 5 patients had recurrent disease and three of them died of disease. The 5-year recurrence free survival rate and overall survival rate were 86% and 94%, respectively. After chemotherapy, all but one premenarchal patients had normal menstruation. Of them 5 patients tried to conceive and 3 of them succeeded in pregnancy. Conclusion: BEP chemotherapy was very safe and effective in patients with ovarian yolk sac tumor. Survival outcomes are excellent and reproductive outcomes are promising after BEP chemotherapy.

Malignant ovarian germ cell tumors: A retrospective analysis of the Russian Cancer Research Center

16105 The aim of this study was to analyse treatment results of patients with malignant ovarian germ cell tumors (MOGCT) between 1990 and 2006. A total of 117 patients with MOGCT were retrospective...

Primitive Neuroectodermal Tumor Arising in a Testicular Teratoma with Retroperitoneal Metastasis: Report of an Interesting Case with Review of Literature

Teratomas with malignant transformation occur in approximately 3 to 6% of patients with metastatic germ cell tumors treated with platinum-based chemotherapy. The histology of the nongerm cell (somatic) malignant elements most commonly includes carcinoma and various types of sarcomas; however, so far as the primitive neuroectodermal tumors (PNETs) are concerned the experience is quite limited. There are only seven documented case reports and occasional series of PNET in association with testicular teratoma either in the primary site or in the metastatic location. We report a relatively unusual case of PNET arising in a malignant mixed germ cell tumor in a 35-year-old man.

Mixed Nonseminomatous Germ Cell Tumor Presenting as a Subcutaneous Tissue Mass

Extragonadal germ cell tumors most commonly arise in the midline of the retroperitoneum or the mediastinum. Primary tumors involving the skin are very rare. Only one case of malignant primary germ cell tumor located in the skin has been reported. We present the case of a 44-year-old white man with a primary subcutaneous mixed nonseminomatous germ cell tumor. This man had a long-lasting subcutaneous lump of the breast, which became painful. Surgery revealed 3 juxtaposed nodules. Microscopic examination showed a mixed germ cell tumor with a 90% immature teratoma component and a 10% embryonal carcinoma component. Testicular ultrasound and computed tomography of the chest, abdomen, pelvis, and brain were normal. Serum human chorionic gonadotrophin, beta-human chorionic gonadotrophin, alpha-fetoprotein, and lactate dehydrogenase were within normal ranges. A further surgical excision was performed. The patient is presently alive with no evidence of disease after a follow-up of 7 years. Review of the literature indicates that primary cutaneous extragonadal germ cell tumors usually occur as cutaneous or subcutaneous solitary nodules or as ulcerated lesions. They mainly consist of mature teratomas in children. Only 2 cases have been reported in adults.

A successful IVF–pregnancy in a patient who underwent conservative surgery followed by a regimen of cisplatin, vinblastine and peplomycin to treat an advanced ovarian mixed germ cell tumour: A Case Report

Mixed germ cell tumours of the ovary, one type of malignant ovarian germ cell tumours (MOGCTs), are rare gynaecologic cancers usually affecting young women. We report the case of a patient with an advanced ovarian mixed germ cell tumour who underwent fertility-saving surgery followed by a chemotherapy regimen of cisplatin, vinblastine and peplomycin. The patient was disease-free 8 years after initial presentation. She conceived and gestated dichorionic twins after IVF-embryo transfer. To the best of our knowledge, the patient is the first to be treated successfully with the combination chemotherapy regimen and then conceive safely using assisted reproductive technology (ART).

Malignant ovarian germ cell tumours: Long-term treatment outcome

5132 Background: Malignant ovarian germ cell tumors (MOGCT) constitute less than 5% of all ovarian malignancies. Conservative surgery followed by platinum based combination chemotherapy is the stan...

Role of reactive oxygen species in cisplatin-induced apoptosis of human malignant testicular germ cell lines

Role of reactive oxygen species in cisplatin-induced apoptosis of human malignant testicular germ cell lines