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PubMed1985

Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report).

Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.

Adolescent↗
PubMed1985

Retroperitoneal germ cell tumors in childhood. A clinical and pathologic study of 11 cases.

During the last 54 years at the Children's Hospital 11 children (10 female, 1 male) had been treated for an extragonadal germ cell tumor arising in the retroperitoneum. There were eight teratomas (five mature, three immature), two endodermal sinus tumors and one tumor with a mixture of both components. Abdominal pain or discomfort was the usual presenting complaint, with the average age at diagnosis being 18 months. On physical examination, each child had a palpable abdominal mass usually localized in the upper quadrants. The finding of calcification, bone or teeth, on radiologic study was most helpful in establishing a preoperative diagnosis of teratoma. The preferred treatment for children with mature and immature teratomas is complete surgical resection; decisions regarding adjuvant therapy for patients with immature tumors must be evaluated on an individual basis. The prognosis remains guarded for children with unresectable primaries or those with endodermal sinus tumor. Of three tumor-related deaths, two were due to metastatic endodermal sinus tumor and one resulted from extensive local growth by immature teratoma. Successful management of children with endodermal sinus tumor requires surgery aimed at debulking or complete resection in combination with aggressive adjuvant chemotherapy.

Child, Preschool↗
PubMed1985

Endodermal sinus tumor of the vagina. The role of primary chemotherapy.

Endodermal sinus tumor of the vagina, a rare pediatric malignancy, was managed with primary chemotherapy (vincristine, dactinomycin, cyclophosphamide [VAC]) followed by local excision without radical surgery or pelvic irradiation. Treatment-related complications were acceptable, and there is no evidence of disease 30 months after discontinuing all therapy (50 months after diagnosis). As a treatment option, primary chemotherapy is viewed as a highly attractive alternative modality, preserving potential reproductive and sexual function in long-term survivors, and appears to be the treatment of choice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Iridium afterloading curietherapy in the treatment of pediatric malignancies. The Institut Gustave Roussy experience.

Between 1972 and 1980, 58 children with malignant tumors underwent iridium 192 (192Ir) curietherapy at the Institut Gustave Roussy. Data from only 45 of them were reviewed (bilateral retinoblastoma and salvage procedures were excluded). The pathologic diagnosis was rhabdomyosarcoma in 75% of cases, yolk sac tumor in 13% of cases, malignant mesenchymoma in two cases, clear cell carcinoma in two cases, and undifferentiated sarcoma in one case. The two major sites were pelvis-perineum (64.5%) and head and neck (31%). The treatment was essentially based on a combination of chemotherapy, which was adapted to the histologic type of the tumor, and curietherapy. Partial surgery was carried out in certain cases, either before chemotherapy for diagnostic purposes, or after chemotherapy to remove infiltrative residual tumor. External beam radiotherapy was used in a few cases in lymph node irradiation. The radioactive material was 192Ir, using afterloading techniques, either intracavitary or interstitially or both. The tumor dose, calculated by computerized dosimetry, was 60 to 65 Gy delivered over 5 to 7 days in the majority of cases. Two patients were lost to follow-up. Thirty-five patients (78%) are alive with no evidence of disease after a mean follow-up period of 5 years. Eight patients died, one of complications related to chemotherapy and seven of the evolution of their disease. The late-complication rate, studied in 33 patients with a minimum follow-up period of 3 years, is 18% (6/33). Curietherapy seems to be a preferable conservative treatment in children with localized and accessible malignant tumors.

Adolescent↗
PubMed1985

Anterior mediastinal endodermal sinus (yolk sac) tumor in a female infant.

The first known case of primary anterior mediastinal endodermal sinus (yolk sac) tumor in a female patient, occurring in a 20-month-old infant, is reported. The child presented with cough, fever, and listlessness. Chest x-ray revealed a right anterior mediastinal mass. At thoracotomy a large anterior mediastinal tumor extending from the neck to the diaphragm was found, and was almost totally resected. Microscopically, the tumor displayed many of the histologic patterns observed in EST. Other neoplastic germ cell elements were not identified. The ultrastructural and immunohistochemical findings further confirmed the diagnosis. Serum alpha-fetoprotein (AFP) level, determined during surgery, was elevated to 65,200 ng/ml, whereas serum beta-human chorionic gonadotropin level was normal. Postoperatively, combination chemotherapy consisting of vinblastine, bleomycin, cisplatin, dactinomycin, cyclophosphamide, and doxorubicin was administered with a maintenance program. After 18 weeks on this regimen all the findings were normal, including serum AFP level. The child is well and disease-free 25 months after diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Cisplatin and etoposide salvage therapy and resection of the residual tumor in pretreated germ cell testicular cancer.

Thirty-two consecutive patients with pretreated germinal testis cancer received three to four inductions of cisplatin and etoposide therapy (PE). Patients not pretreated, or only partially pretreated with bleomycin (B), also received this drug for a maximum of 12 doses. Sixteen patients underwent secondary surgery for the removal of residual masses. Twelve (37.5%) entered complete remission (CR) with chemotherapy alone, and an additional 9 cases (28%) were rendered tumor-free by surgery. The 21 disease-free patients (65.5%) received two further inductions and no maintenance. Toxicity was moderate, and 1 of the 16 patients who underwent surgery died postoperatively of pulmonary embolism. After a median follow-up period of 26 months (range, 9-60), 2 patients have died in CR and 15 (47%) are currently alive and have been continuously disease-free. The major determinant of tumor response was prior therapy. Eleven of 14 (78%) patients who were not pretreated with cisplatin achieved a continuous disease-free status versus only 4 of the 18 pretreated patients (22%, P less than 0.01). In this set of cases, complete responders to prior PVB therapy did better than incomplete responders treated for tumor progression. It can be concluded that normal-dose PE +/- B therapy, followed by surgical resection of the residual tumor, is a satisfactory salvage therapy in patients not pretreated with cisplatin and is also active in complete responders to prior PVB therapy.

Adolescent↗
PubMed1986

Ovarian endodermal sinus tumor with intestinal differentiation.

A 12-year-old girl was admitted to the hospital for evaluation of an abdominal mass. A preoperative computed tomography scan showed a large tumor in the pelvis. The serum alpha-fetoprotein level was 2,170,000 ng/ml. A 3000-g left ovarian neoplasm was resected. It was encapsulated and showed focal microcystic degeneration, necrosis, and hemorrhage. Microscopically, it was composed of gland-like spaces containing mucin-positive material and surrounded by scant fibrovascular tissue. The epithelial cells were low columnar with immature oval, basophilic nuclei. Immunoperoxidase staining for alpha-fetoprotein and alpha1-antitrypsin were positive. Enzyme histochemistry was negative for alkaline phosphatase and positive for alpha-naphthyl acetate esterase. Electron microscopy, including freeze-fracture analysis, showed desmosomes and tight junctions. No gap junctions were identified. Actin filaments, glycogen, and microvilli were abundant. This is the first case of an ovarian endodermal sinus tumor with exclusive enteric differentiation.

Adolescent↗
PubMed1986

A human testicular germ cell tumor with borderline histology between seminoma and embryonal carcinoma secreted beta-human chorionic gonadotropin and alpha-fetoprotein only as a xenograft.

Two macroscopically distinguishable components (designated soft and firm) of a human testicular germ cell tumor with borderline histology between seminoma, embryonal carcinoma and yolk sac tumor, were maintained as xenografts in nude mice for over 20 passages. Levels of beta-human chorionic gonadotropin (beta-HCG) and of alpha-fetoprotein (AFP) were normal in the patient's serum and were undetectable by immunohistochemical studies of the surgical specimen. The xenografted soft part, however, with morphologic characteristics of an embryonal carcinoma, secreted beta-HCG and AFP during early passages. The firm variant, histologically resembling a seminoma, did not produce these markers. Chromosomal and flow cytophotometric analyses showed genetic differences between the clonally stable variants. A common origin, however, is indicated by two similar marker chromosomes present in both variants.

Animals↗
PubMed1986

Endodermal sinus tumor of the mediastinum. A report of seven cases and review of the literature.

Primary mediastinal endodermal sinus tumor is rare, and to date only 49 cases have been described in the English-language literature. Seven new cases are reported. Light microscopic examination showed characteristic features including papillary, reticular, tubular and solid growth patterns, complete or incomplete Schiller-Duval bodies and intracellular or extracellular periodic acid-Schiff-positive material. Immunohistochemical studies showed alpha-1-antitrypsin in seven, alpha-fetoprotein in seven, keratin in six, and carcinoembryonic antigen in four cases. The beta subunit of human chorionic gonadotropin, albumin, fibronectin, and transferrin were not found in any case. Electron microscopic studies performed in four cases showed intracellular and extracellular basement membrane-like material, multiple large multivesicular bodies, desmosomes and microvilli. Mediastinal endodermal sinus tumor can and must be differentiated from poorly differentiated adenocarcinoma metastatic or extending to the mediastinum because of the distinctly different prognoses and therapies. In spite of modern chemotherapy, the prognosis of mediastinal endodermal sinus tumor remains poor. The single most important prognostic indicator is whether the tumor mass can be completely excised before or after chemotherapy.

Adolescent↗
PubMed1986

Nongerminomatous malignant germ cell tumors in children. A review of 89 cases from the Pediatric Oncology Group, 1971-1984.

Clinical and morphologic features of 89 cases of childhood yolk sac tumor (YS) and embryonal carcinoma (EC) (29 associated with teratomas) submitted to the Rare Tumor Registry of the Southwest Oncology Group (1971-1979) or the Pediatric Oncology Group (1980-1984) between 1971 and 1984 were reviewed and submitted to statistical analysis. This review showed an improved survival for each 5-year period regardless of tumor site, no statistically significant difference between "pure" tumors and those mixed with other teratomatous components, no statistically significant difference between YS and EC in children, a better than reported prognosis for sacrococcygeal tumors occurring after the neonatal period, a particularly poor prognosis for neonatal "benign" sacrococcygeal teratomas resected without coccygectomy when they recur as YS, excellent survival for all testicular tumors regardless of age or the presence of EC, and the occurrence of mediastinal tumors in females.

Adolescent↗
PubMed1987

Malignant ovarian tumors in children and adolescents.

Eighteen patients aged 4 to 18 years (median, 10 years) were treated at the Children's Cancer Research Center of The Children's Hospital of Philadelphia (CHP) from September 1973 to September 1983 for malignant ovarian tumors. The pathologic categories were endodermal sinus tumor (eight patients), embryonal carcinoma (three patients), pure dysgerminoma (three patients), adenocarcinoma (three patients), and malignant granulosa-cell tumor (one patient). In 1973 and 1975, respectively, two patients with endodermal sinus tumors were treated with surgical removal with or without radiation therapy (RT) and chemotherapy with vincristine (Vc) and actinomycin D+ cyclophosphamide + Adriamycin (Adria Laboratories, Columbus, OH) (ACAdr); both developed local recurrence within 12 months and died of tumor. Since 1977, four of six patients with endodermal sinus tumors have been managed successfully with surgery followed by chemotherapy with cisplatin (P), bleomycin (B), vinblastine (Vb), and ACAdr; none received RT. One died of recurrent tumor and the other died of congestive heart failure attributed to Adriamycin (Adr). All three patients with embryonal carcinoma were well after surgical excision alone (one patient) or surgery and chemotherapy with cisplatin + bleomycin + vinblastine (PBVb) + ACAdr (two patients). Treatment of the remaining seven patients included excision alone (two patients) or excision and chemotherapy (five patients) with various combinations of Vc, ACAdr, and P. One patient with granulosa-theca cell tumor also received whole abdominal RT (3000 rad by external beam), and died of congestive heart failure attributed to Adr. The other six children were free of detectable tumor 16 months to 8 years from diagnosis. Chemotherapy with PBVb and actinomycin D + cyclophosphamide (AC) should be used in the postoperative management of young persons with malignant ovarian tumors. Adr is of doubtful value and may be considerably toxic. RT is of limited use and usually is not indicated.

Adenocarcinoma↗
PubMed1987

The treatment of advanced or recurrent malignant genitourinary tumors in children.

Wilms' tumor, embryonal rhabdomyosarcoma, and yolk sac tumor are the most frequently diagnosed malignant genitourinary tumors in children. The randomized therapeutic trials developed by the National Wilms' Tumor Study (NWTS) committee have produced significant improvements in the survival of Wilms' tumor patients. Those with Stage IV, favorable histology Wilms' tumor now have a 2-year survival rate of 87% to 93%. Patients with recurrent Wilms' tumor are being prospectively treated with new drugs and drug combinations with the goal of identifying active agents for inclusion in future therapeutic trials. Girls with localized embryonal rhabdomyosarcoma of the vagina have a 100% survival rate after treatment on the Intergroup Rhabdomyosarcoma Study (IRS) (IRS-1 or IRS-2). Primary treatment of patients with tumors of the prostate, bladder neck, or trigone with chemotherapy has demonstrated the need to establish local tumor control using surgery or radiation soon after diagnosis. The IRS-III currently is evaluating new drug combinations in this group of patients with locally advanced tumors. Patients with advanced yolk sac tumor have been treated using platinum-containing combination chemotherapy regimens with very encouraging results. Future research will evaluate the timing of second-look surgical procedures and the efficacy of etoposide-containing combination chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Identification of testicular atypical germ cells by an immunohistochemical technique for placental alkaline phosphatase.

The identification of atypical testicular germ cells is often difficult by by routine histologic examination. By immunohistochemical detection of placental alkaline phosphatase (PLAP) and by periodic acid Schiff staining of glycogen, atypical germ cells were easily identified in testicular samples. Forty-one fetal and adult testes were used for a preliminary study, and 121 testes from infants and adults with either cryptorchidism or germ cell tumors were studied for the presence of atypical germ cells. Two types of clear germ cells were differentiated histochemically, and one with PLAP-positive cell surfaces and glycogen-rich cytoplasm was considered to be atypical. The alkaline phosphatase of atypical germ cells appeared to be similar to that found in a few germ cells of early fetal testes. The atypical germ cells seemed to be multi-potential malignant cells capable of developing not only into seminoma but also into other germ cell tumors. Only in yolk sac tumor of infants were the atypical germ cells absent from tumor-adjacent seminiferous tubules.

Adult↗
PubMed1987

Intrapericardial yolk sac tumor in an infant girl.

This article is a report on the first known case of an intrapericardial yolk sac (endodermal sinus) tumor discovered in a 14-month-old girl. The patient presented with a systolic murmur, cardiomegaly, and manifestations of cardiac failure. At surgery a large, friable, intrapericardial mass with no evidence of extrapericardial spread was found. Histologic and immunohistochemical findings were diagnostic of yolk sac tumor. Following initial resection, chemotherapy, and a second resection 13 months after the first, the patient died 24 months after diagnosis. Tumor enlargement was associated with elevated serum alpha-fetoprotein levels.

Antineoplastic Agents↗
PubMed1987

Hepatoid carcinoma of the ovary. A newly described tumor.

Five cases of ovarian carcinoma with hepatoid features, three of them primary and two probably primary, are described. The tumor cells were arranged predominantly in sheets and contained moderate to abundant amounts of eosinophilic cytoplasm; varying numbers of tumor cells stained immunohistochemically for alpha fetoprotein. In contrast to the much younger age range of patients with ovarian hepatoid yolk sac tumors, the ages of the five patients with hepatoid carcinomas ranged from 42 to 78 (average, 63 years), and none of them had gonadal dysgenesis or recognizable germ cell components within their tumors. All the tumors presented as adnexal masses; in four cases they were Stage III and in one case, Stage IIB; this last tumor spread to the upper abdomen within 4 years. In three cases the clinical course and pathology findings indicated that the tumor had originated in the ovary; in the remaining two cases the tumors were interpreted as only probably primary in the ovary. Hepatoid carcinomas must be distinguished from other ovarian neoplasms, especially from hepatoid yolk sac tumors.

Adult↗
PubMed1988

Differences between subcutaneous and intraperitoneal forms of three human testicular teratocarcinomas in nude mice.

Three human testicular teratocarcinomas were serially passaged following subcutaneous transplantation into nude mice. Tumor cell suspensions from selected passages were injected intraperitoneally. The subcutaneous transplants of each tumor conserved the morphological characteristics of one component of the primary tumor, namely an embryonal carcinoma in one case and a yolk sac tumor in two. The latter maintained the capacity to synthesize alpha-fetoprotein (AFP). After intraperitoneal injection of cell suspensions, tumors, either attached to or even invading abdominal organs or in the form of free-floating tumor spheroids, were observed. AFP could be localized within the attached growths but not in the spheroids. A critical tumor volume and/or vascularization seemed to be necessary for AFP production in tumor cells. In spheroids from one tumor, cytogenetic analysis revealed both human and murine cells. Thus, these spheroids, apparently composed of tumor cells in the center and murine cells at the periphery, can not be considered to be embryoid bodies.

Animals↗
PubMed1988

Two human tumors with high basement-membrane-producing potential.

Two human tumors, an adenoid cystic carcinoma and a yolk sac tumor, were found by immunocytochemical, ultrastructural, and biochemical studies to contain abundant basement membrane matrix in contrast to the vast majority of human tumors which contained either an absent or scant basement membrane matrix. These tumors were established as xenografts in athymic (nude) mice. Both xenografts maintained characteristic histologic features, immunocytochemical localization of basement membrane components, and reasonable yields of native laminin and Type IV collagen throughout three successive transplant generations. Although only a small fraction of the yield of that of the murine Engelbreth-Holm, Swarm (EHS) sarcoma, the yield of the human basement membrane-producing tumors could be increased by rendering the mice lathyritic. The human basement membrane proteins so extracted were identical on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to their murine counterparts. These human tumors then represent a potential source of human basement membrane proteins.

Animals↗
PubMed1988

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.

Age Factors↗