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PubMed1985

Intracranial germ-cell tumors: natural history and pathogenesis.

The natural history of primary intracranial germ-cell tumors (GCT's) is defined from 389 previously published cases, of which 65% were germinomas, 18% teratomas, 5% embryonal carcinomas, 7% endodermal sinus tumors, and 5% choriocarcinomas. Intracranial GCT's display specificity in site of origin. Ninety-five percent arise along the midline from the suprasellar cistern (37%) to the pineal gland (48%), and an additional 6% involve both sites. The majority of germinomas (57%) arise in the suprasellar cistern, while most nongerminomatous GCT's (68%) preferentially involve the pineal gland (p less than 0.0001). The age distribution of afflicted patients is unimodal, centering with an abrupt surge in frequency in the early pubertal years; 68% of patients are diagnosed between 10 and 21 years of age. Nongerminomatous GCT's demonstrate an earlier age of onset than do germinomas (p less than 0.0001). Prolonged symptomatic intervals prior to diagnosis are common in germinomas (p = 0.0007), in suprasellar GCT's (p = 0.001), and among females (p = 0.02). Parasellar germinomas commonly present with diabetes insipidus, visual field defects, and hypothalamic-pituitary failure. Nongerminomatous GCT's present as posterior third ventricular masses with hydrocephalus and midbrain compression. Germ-cell tumors may infiltrate the hypothalamus (11%), or disseminate to involve the third ventricle (22%) and spinal cord (10%). Among a subpopulation of 263 conventionally treated patients, two factors were of prognostic significance: 1) histological diagnosis; germinomas were associated with significantly longer survival than nongerminomatous GCT's (p less than 0.0001); and 2) staging of the extent of disease; this emphasizes the ominous character of involvement of the hypothalamus (p = 0.0002), third ventricle (p = 0.02), or spinal cord (p = 0.01). Specific recommendations regarding the necessity of histological diagnosis and staging of the extent of disease are made in light of modern chemotherapeutic advances. The pathogenesis of GCT's may be revealed by their specificity of origin within the positive (suprasellar cistern-suprachiasmatic nucleus) and negative (pineal) regulatory centers for gonadotropin secretion within the diencephalon. The abrupt rise in age distribution at 10 to 12 years suggests that the neuroendocrine events of puberty are an "activating" influence in the malignant expression of these embryonal tumors.

Adolescent↗

PubMedDate not supplied

Evaluation of cis-dichlorodiammineplatinum(II) in children with advanced malignant diseases: Southwest Oncology Group Studies.

Two schedules of cis-dichlorodiammineplatinum(II) (cis-platinum) were evaluated for therapeutic efficacy and toxicity in children with malignant diseases resistant to standard therapy. Initially, cis-platinum was given as a rapid iv bolus injection at a dose of 15 mg/m2/day for 5 days every 3 weeks. The second schedule of cis-platinum was a dose of 1 mg/kg/week administered as an 8-hour infusion with mannitol. furosemide, and hydrating fluids. Using the daily schedule, no responses were seen among 23 children with acute lymphatic leukemia and only eight responses were noted among 47 children with solid tumors. Using the weekly schedule, three responses were noted among 25 children with solid tumors. Responses were observed in seven children with neuroblastoma, two with osteosarcoma, one with embryonal testicular carcinoma, and one with an endodermal sinus tumor. With one exception (a 4-year-old child with neuroblastoma), all responses were of short duration. The most common side effects with both schedules were nausea and vomiting which were usually controlled with antiemetics. The dose-limiting toxicity, especially on the 5-day schedule; was renal function impairment. Only one child who received cis-platinum weekly as an 8-hour infusion with diuresis had elevation of the serum creatinine level. Protocols are being initiated to determine the therapeutic effectiveness and toxicity of combination therapy with cis-platinum in children with neuroblastoma and osteosarcoma.

Bone Marrow↗

PubMed1985

Chemotherapy trials in recurrent primary intracranial germ cell tumors.

Gonadal germ cell tumors respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar tumors may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure germinoma, germ cell tumors of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 patients with recurrent CNS germ cell tumors using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the patients were germinoma (4), endodermal sinus tumor (2), embryonal carcinoma (1), and mixed tumor - germinoma plus choriocarcinoma (1). There were 7 males and 1 female with a median age of 13 years. The primary tumor arose in the pineal region in 6 and was multicentric in 2. Seven patients had local recurrences and one developed an initial recurrence in the spinal canal. Three patients had CNS metastases at relapse and 2 had systemic metastases. Objective responses were documented in 7 of 14 trials (50%). Responses were observed with cyclophosphamide (80 mg/kg) in 3 of 4 patients for 2+, 3, and 5 mos, cisplatin (120 mg/m2) in 1 of 2 patients for 2+ mos, and the VAB 6 protocol (vinblastine, bleomycin, cyclophosphamide, actinomycin-d, cisplatin) in 3 of 5 patients for 5, 8, and 18 mos. The median duration of response was 5 mos. (2+-18). High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well as VAB 6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma. Good palliation may be achieved with chemotherapy alone with acceptable morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

From the archives of the AFIP. Malignant germ cell tumors of the ovary: radiologic-pathologic correlation.

Malignant germ cell tumors are the most common malignant ovarian neoplasms in girls and young women. The most well known of these neoplasms are dysgerminoma, immature teratoma, endodermal sinus tumor, and a mixture of two or more of these elements. All malignant germ cell tumors, especially immature teratoma, can be associated with mature (benign) teratoma. These tumors are generally large and have a complex but predominantly solid appearance on cross-sectional images. Elevated serum alpha-fetoprotein and human chorionic gonadotropin levels can help establish the diagnosis. Cystic areas of calcifications suggestive of mature teratoma do not exclude a co-existing malignant neoplasm.

Female↗

PubMed1983

Evaluation of five tumor markers (AFP, CEA, hCG, hPL and SP1) in monitoring therapy and follow-up of patients with testicular germ cell tumors.

61 patients with seminoma and 113 with nonseminomatous germ cell tumors of the testis were treated according to the histology, stage of disease, and serum levels of tumor markers (CEA, AFP, hCG, hPL and SP1). 33 were stage I, 63 stage II, and 78 stage III patients. Most patients with seminoma, mature teratoma, immature teratoma, and 'pure type' embryonal carcinoma, as well as the latter three types with seminomatous admixture, had normal serum levels of the markers. Sometimes, slightly elevated levels of hCG suggested the presence of metastases. But, serial measurements of the markers were seldom useful in monitoring therapy. The 5-year tumor-free survival rates were favorable: 100% for stage I and II disease; and 57 or 44% for, respectively, stage III seminoma or the other tumors amounting to 10% of the nonseminomatous group. The role of the five markers was significant in patients with teratoma with malignant transformation, choriocarcinoma, endodermal sinus tumor (EST), and embryonal carcinoma or teratocarcinoma with an admixture of EST or choriocarcinoma or both. Elevation of a marker was a grave prognostic sign. The 5-year survival rates were 100, 16, and 4% for stages I, II and III disease, respectively. An elevated level of one or more of the markers assayed was always useful for monitoring therapy. Decreasing level indicated regression. However, return of an elevated level to normal did not indicate eradication of all tumor and called for diagnosis by imaging modalities. Constantly elevated or increasing marker levels during treatment indicated resistance to therapy. An increasing level from any nadir during remission indicated recurrence. Elevated levels of any of the five markers tested were as important as imaging modalities, and often more sensitive.

Carcinoembryonic Antigen↗

PubMed1998

DNA content of ovarian immature teratomas and malignant germ cell tumors.

OBJECTIVE: Ovarian germ cell tumors (GCT) show greater histologic and biologic heterogeneity than their testicular counterparts and remain poorly understood. Ploidy analysis was performed on ovarian GCT registered on Pediatric Oncology Group germ cell tumor protocols 9048 and 9049 to distinguish biologically distinct subsets of immature teratomas and malignant ovarian germ cell tumors. METHODS: Tumors from 22 patients (mean age 12 years) were analyzed and classified according to the submitting diagnosis; when pure samples of different histologic subtypes within a single tumor were possible, these were analyzed separately. Archival tissue was disaggregated and Feulgen stained; DNA index (DI) was determined by static image analysis utilizing internal normal cells as diploid controls. RESULTS: 26 histologic subtypes from 22 patients were analyzed. The tumors of 18 patients were composed of a single histologic subtype according to the submitting institution, including 6 dysgerminomas, 8 immature teratomas (IT), and 4 endodermal sinus tumors (EST). Two tumors contained both IT and EST components that were separately analyzed. Two tumors were classified as mixed germ cell tumors; 1 showed multiple intermingling subtypes unable to be separately analyzed and the second showed three histologic subtypes separately analyzed (IT, EST, embryonal carcinoma). From a total of 15 malignant histologic GCT subtypes in 14 patients, all but 2 demonstrated a DI of 1.4-2.4 (mean 1.85). Two diploid malignant GCT (1 EST, 1 dysgerminoma) were both associated with gonadoblastoma. Overall, 11 IT subtypes were analyzed and 9 were diploid (2 grade 1, 5 grade 2, and 2 grade 3). Two tumors originally submitted and classified as pure IT (grades 2 and 3) were aneuploid with a dominant diploid and a secondary aneuploid peak (both DI 1.7). On central review, both of these tumors demonstrated the presence of subtle patterns of EST that were unrecognized by the submitting institution and were much too small for separate analysis. Analysis of the 3 patients containing sufficient IT and EST to be separately analyzed all showed a diploid IT component and an aneuploid EST component. CONCLUSIONS: Analysis of ploidy data suggests that polyploidization is a consistent finding in malignant ovarian GCT arising in normal patients, similar to the data for adult testicular GCT. Immature teratomas in this pediatric population, however, are most commonly diploid, regardless of grade. The development of EST within an IT is associated with the development of an aneuploid clone. Therefore, the finding of such a clone in an IT may be of diagnostic utility, as EST may be difficult to recognize. Last, the development of a malignant GCT in patients with gonadal dysgenesis may be pathogenetically different from those arising in normal patients, in that polyploidization is not required.

Adolescent↗

PubMed1990

Cytogenetic and molecular analysis of human male germ cell tumors: chromosome 12 abnormalities and gene amplification.

We report karyotypic analysis of 24 male germ cell tumors (GCTs) with clonally abnormal karyotypes biopsied from testicular and extragonadal lesions from 20 patients belonging to the histologic categories seminoma, teratoma, embryonal carcinoma, choriocarcinoma, and endodermal sinus tumor. Chromosomes 1, 7, 9, 12, 17, 21, 22, and the X chromosome were nonrandomly gained in these tumors. Nonrandom structural changes affected most frequently chromosomes 1 and 12, the latter as i(12p) and/or del(12)(q13----q22). The i(12p) was seen in 90% of tumors which included all histologic subtypes and gonadal as well as extragonadal presentation. Our present results, along with those from published data on fresh GCT biopsies, establish that i(12p) is a highly nonrandom chromosome marker of all histologic as well as anatomic presentations of GCTs. in contrast, we found del(12)(q13----q22) exclusively in nonseminomatous GCTs (NSGCTs) and mixed GCTs (MGCTs) occurring in 44% of such lesions. Because successful cytogenetic analysis of fresh tumor specimens is not always possible, we developed a method based on DNA analysis to detect i(12p) as increased copy number of 12p. In addition to the changes affecting chromosome 12 identified above, we have detected, for the first time, cytological evidence of gene amplification in the form of homogeneously staining regions (HSRs) and double minute chromosomes (dmins) in treated as well as untreated primary extragonadal and metastatic GCTs and confirmed the presence of amplified DNA in one of these tumors at the molecular level by the in-gel renaturation method. Hybridization of DNA from cultured cells from an HSR-bearing tumor with a panel of probes for genes known to be amplified or otherwise perturbed in diverse tumor systems did not identify the amplified gene, suggesting amplification of a novel gene or genes. This study comprises the largest series of GCT cytogenetics attempted so far. Notably, it includes data on a series of primary mediastinal tumors, a group which previously has not been studied in any detail.

Blotting, Southern↗

PubMed2004

Evaluation of genomic changes in a large series of malignant ovarian germ cell tumors--relation to clinicopathologic variables.

Malignant ovarian germ cell tumors (mOGCT) affect women in their reproductive years, making fertility-saving treatment important. A reliable prediction of the clinical behavior is essential for an optimal therapeutic approach. The genetic changes and molecular mechanisms underlying these rare tumors remain poorly understood. To address these issues, we performed DNA ploidy analysis by high-resolution image cytometry in a series of 47 mOGCT and correlated the findings with the DNA copy number changes detected by comparative genomic hybridization (CGH) and clinical outcome. Of 47 tumors, 15 were diploid, 14 were tetraploid, 2 were polyploid, and 13 were aneuploid. All the immature teratomas were diploid, in contrast to the dysgerminomas and endodermal sinus tumors. The International Federation of Gynecology and Obstetrics (FIGO) staging, residual tumors after surgery, and DNA ploidy distribution were significant, independent prognostic factors in survival analysis. The study revealed that the number of DNA copy number aberrations was increased in tetraploid and aneuploid tumors as compared to diploid tumors. Furthermore, a high percentage of aneuploid nuclei in a sample were associated with a complex CGH profile of the tumor in question. The present study confirms that DNA aneuploidy assessment by image analysis may be linked to genetic instability, which is detected as genetic aberrations by CGH. DNA ploidy gives significant prognostic information in addition to the clinical stage in mOGCT with FIGO stage II-IV.

Adolescent↗

PubMed1981

Sacrococcygeal teratomas: a review of 68 cases.

Sixty-eight cases of sacrococcygeal teratoma were reviewed and graded according to the quantity of immature tissue present. Seventy-five percent were benign (grade 0), 11.8% immature (Grades 1-3), and 13.2% malignant. Although the immature component in most tumors was neuroepithelial, in two cases it was exclusively renal. There were no instances of local recurrence or metastasis of immature elements. The malignant lesions were all endodermal sinus tumor, stained positively for alpha-fetoprotein and were uniformly fatal, with an average duration of survival of 8.9 months. Early adequate treatment of sacrococcygeal teratomas results in a favorable prognosis. This experience is different from that reported for immature ovarian teratomas. Immature metanephric tissue in sacrococcygeal teratomas should be interpreted the same way as immature neuroepithelial elements. Immature sacrococcygeal teratomas should be separated from tumors containing malignant elements because of their vastly different prognoses.

Adolescent↗

PubMed1979

[Alpha-1-fetoprotein in tumour tissue (author's transl)].

Using the indirect immunoperoxidase method, alpha 1-fetoprotein (AFP) can be demonstrated in paraffin sections of tumours by light-microscopy. Among 160 tumour preparations it was demonstrated in five of six endodermal sinus tumors, 19 of 40 teratomas, the three hepatoblastomas and 9 of 16 primary liver-cell carcinomas. Among 15 rhabdomyosarcomas, 15 Wilms tumours, 15 neuroblastomas and 15 other malignant tumours only one rhabdomyosarcoma contained AFP. No AFP was demonstrated in 35 various benign tumours and various other human tissue samples. Distribution of AFP-producing cells in tumour tissue is generally focal samples. In malignant teratomas AFP was found only in areas which corresponded to an endodermal sinus tumour or an embryonic carcinoma. The practical significance of the results consists of (1) demonstration and localisation of AFP in tumour tissue; (2) aiding the differential diagnosis and classification of tumours and their metastases; and (3) recognition of pathogenetic connection between embryonic carcinoma and endodermal sinus tumour.

Carcinoma, Hepatocellular↗

PubMed1983

Yolk sac tumor of the bladder.

A 1-year-old white boy presented with hematuria and was found to have a large polypoid bladder mass. Light and electron microscopic, and immunohistochemical diagnosis was a yolk sac (endodermal sinus) tumor. This is the first case of a primary yolk sac tumor of the bladder to be described in the English literature.

Humans↗

PubMed1990

[Second malignant tumor in children. Report of 22 cases].

Between 1965 and 1988, at the Children's Hospital of Buenos Aires, 22 children developed two successive malignant tumors of different histology. The first tumor was diagnosed between 3 months and 12 years of age: 13 retinoblastoma, 2 rhabdomyosarcoma, 2 non-Hodgkin lymphoma, 2 Hodgkin disease, 1 brain stem glioma, 1 endodermal sinus tumor and 1 Ewing sarcoma. Familial cancer was registered in 6 patients. Children were treated with surgery, intensive chemo and radiotherapy. The second malignancy developed after 2 to 13 years: 10 osteosarcoma, 2 Ewing sarcoma, 2 rhabdomyosarcoma, 2 glioblastoma, 1 medulloblastoma, 1 synoviosarcoma, 1 fibrosarcoma, 1 thyroid carcinoma, 1 acute lymphoblastic leukemia and 1 acute myeloblastic leukemia. In 17 patients, the tumor developed in irradiated field. There was no evidence of the first tumor and only 1 patient was still under chemotherapy. Oncologic treatment was frustrating for these second tumors and 18 children died. Three are alive with no evidence of disease at 2 years, 2 years and 4 months and 3 years after diagnosis. One patient was lost to follow-up. It if postulated that second malignant tumors are consecutive to genetic predisposition and/or to the oncogenic effect of chemo and radiotherapy. The intensity of each treatment modality must be reduced as much as possible to obtain survival while limiting the secondary effects.

Argentina↗

PubMed1979

Germ cell neoplasms arising in gonadoblastomas.

Gonadoblastomas have a propensity to give rise to germ cell neoplasms. This study analyzes the clinicopathologic findings in six phenotypic females with features of 46,XY pure gonadal dysgenesis who developed germinomas and other germ cell tumors in gonadoblastomas. All stages in the evolution of germinoma from the germ cells of gonadoblastoma were observed, including in situ, incipient, microinvasive, and metastatic varieties. Admixtures with teratoma and endodermal sinus tumor occurred in two patients. Germ cell tumors which originate in gonadoblastomas appear to have the same clinical behavior and response to therapy as those that arise de novo in the ovary, testis or extragonadal sites. Although it is debatable whether gonadoblastomas are true neoplasms or blastomatoid dysgenetic malformations, their potential for giving rise to fully malignant germ cell neoplasms must be recognized.

Adolescent↗

PubMed1992

Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.

Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.

Adolescent↗

PubMedDate not supplied

[Germ cell tumors in children. Evaluation of regional cases over a 23 year period].

UNLABELLED: A retrospective study on germ cell tumors on children is reported. The purpose of this study was to evaluate some prognostic factors (age, sex, site, histology, treatment) as well as to compare the casistic of Puglia Region with the results of the National literature. 45 patients (30 females, 15 males) aging 2 days-12 years observed in three Pediatric Centres of Bari into 23 years. Primary site of the tumor was: ovary 9, testis 9, sacrococcygeal 16, and others site 11 (head 4, mediastinum 2, pelvis 2, abdomen 2, gluteus 1). HISTOLOGY: teratoma 31, choriocarcinoma 1, embryonal carcinoma 7, endodermal sinus tumor 5, germinoma 1. TREATMENT: surgery 35 patients, surgery+chemotherapy 6, surgery+chemotherapy+radiotherapy 4. Results of treatment: 37 of 41 valuable patients achieved a response (34 complete, 3 partial response); 4 patients had no response. Of the 37 patients that have had a complete or partial remission, 8 subsequently relapsed; of these 8 patients, 5 obtained a second remission after second line therapy, 3 are dead for progressive disease. Better prognosis was observed in children with gonadal tumors treated with surgery alone.

Child↗

PubMed1985

[A case of immature mediastinal teratoma].

A case of mediastinal immature teratoma was treated with a multimodality approach that included surgery, chemotherapy, and radiotherapy. Serum alpha-fetoprotein at admission was elevated and changed in parallel with the therapy and tumor growth. The patient died of sudden respiratory failure 18 months after admission. Mediastinal immature teratoma with elevated serum levels of alpha-fetoprotein carries a poor prognosis, as does endodermal sinus tumor. We concluded that this condition should most probably be treated with a combination of intensive chemotherapy, surgical resection, and radiotherapy.

Adolescent↗

PubMed1992

Peritoneal cytology of uncommon ovarian tumors.

Peritoneal cytology has been well established as a diagnostic and staging tool in the management of the common epithelial tumors of ovary. Germ cell, mesenchymal, and sex-cord stromal tumors are much less frequently encountered in peritoneal specimens, often with cytologic features that may pose problems in differential diagnosis. This report presents the cytomorphology of the ascitic fluid in cases of endodermal sinus tumor, dysgerminoma, and Sertoli-Leydig-cell tumor, and peritoneal washings in a case of ovarian malignant mixed mullerian tumor. The cytologic features of Sertoli-Leydig-cell tumors have not been well described. Careful correlation of peritoneal cytologic findings, cell-block preparations, and immunocytochemistry with the cytohistologic features of these tumors is crucial for correct tumor classification.

Adolescent↗

PubMed1994

Malignant germ cell tumors of the ovary: 20-year report of LAC-USC Women's Hospital.

Thirty-six patients with malignant germ cell tumors (GCT) of the ovary were treated during the period from 1971 to 1990. Twenty-five of these patients underwent initial surgery at this institution; 11 were referred after initial surgery. Endodermal sinus tumor (EST) was the most common subtype (N = 13), followed by immature teratoma (IMT) N = 11), dysgerminoma (N = 9), and mixed germ cell tumor (N = 3). Eight of nine patients with dysgerminoma and 14 of 27 patients with non-dysgerminomatous germ cell tumors had stage I disease. Surgical staging resulted in a change of stage in 10 of 31 patients; seven were upstaged, and three were downstaged. Thirty-five of 36 patients are alive with no evidence of disease at a median follow-up of 47 months (range 12-210 months). Two of nine patients with dysgerminoma received postoperative radiotherapy; two additional patients required radiotherapy for recurrence. Twenty-five of 27 patients with non-dysgerminomatous tumors were treated with combination chemotherapy. Second-look laparotomy was done in 18 patients, four of whom had positive results. Three of the four patients with positive second-look laparotomy results remain free of disease after salvage chemotherapy; the fourth patient died of progressive grade 3 IMT. Nineteen of 27 patients undergoing fertility-preserving surgery have resumed normal menses, and four of these have delivered normal infants. The other eight patients remain on oral contraceptives. We conclude that surgical staging provided important information in this study of 36 patients with ovarian germ cell malignancies. As noted by many previous reports, combination chemotherapy (developed during the past 20 years) has dramatically improved prognosis for this group of patients. Second-look laparotomy (SLL), especially for patients with advanced disease, was able to identify patients requiring additional therapy. Most patients with this disease can retain their normal, uninvolved ovary with preservation of normal menstrual and reproductive function.

Journal Article↗