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PubMed1987

Management of primary intracranial germ cell tumors of childhood.

Primary CNS germ cell tumors present several biologic and therapeutic concerns. Their predilection to midline locations (pineal and suprasellar) has discouraged until recently attempts at biopsy, much less radical surgical resection. Their heterogeneity (germinomas, embryonal carcinoma, endodermal sinus tumor, choriocarcinoma and malignant teratoma) has made uniform treatment planning unrealistic. Their rarity (less than 50 cases per year in USA) precludes a large institutional experience. More recently, with the use of microsurgical techniques, major resections are possible and accurate pretreatment histologic diagnosis can be established. Following surgery, patients should be staged with cerebrospinal fluid (CSF) cytology, serum and CSF tumor markers (alpha-fetoprotein and human beta-chorionic gonadotrophin) and myelography. The majority of patients will present with disseminated disease and require craniospinal radiotherapy. Chemotherapy should eventually prove to be an effective adjuvant treatment modality, not only for the highly radiosensitive germinoma with a good prognosis (5-year survival greater than 60%) following radiotherapy alone, but also for the radioinsensitive nongerminoma germ cell variants where longterm survival is unusual. Chemotherapy agents such as cyclophosphamide, cisplatin, vinblastine, VP-16 and bleomycin appear to be useful for patients with newly diagnosed and recurrent disease.

Adolescent↗
PubMed2000

Conservative surgical management of malignant ovarian germ cell tumors: the experience of the Gynecologic Oncology Unit at Ain Shams University.

PURPOSE: To evaluate the role of extended surgical staging in patients with malignant ovarian germ cell tumors in the presence of cisplatinum-based combination chemotherapy. MATERIALS & METHODS: 16 patients aged between 13 and 40 years (mean 20.5) diagnosed and treated for malignant ovarian germ cell tumors at the Gynecologic Oncology Unit. Ain Shams University, during the period from May 1994 to October 1999. RESULTS: Six patients were diagnosed with dysgerminoma, six with immature teratoma and four with endodermal sinus tumor. Only seven cases were primarily managed at the unit and were subjected to proper surgical staging as required by FIGO (two in each of the stages IC, IIC and IIIA and one in stage IV). However, the remaining nine cases were referred to the unit, six after having unilateral salpingo-oophorectomy and no surgical staging, one patient after total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH+BSO), and one with recurrent dysgerminoma in the retroperitoneum and mediastinum following suboptimal treatment. None of these cases were surgically re-explored and all including the first six cases were given the standard BEP chemotherapy for 4-6 courses (mean 5.8). Follow-up ranged from 7-72 months (mean 30.5). All patients are alive without any evidence of disease recurrence except for one patient with a stage IIIA immature teratoma who had a local and distant recurrence and is undergoing second-line chemotherapy. All patients have their menstrual function preserved except for three patients; one having 46,XX pure gonadal dysgenesis with a preoperative FSH level of 120 U/l and the eldest two patients having a TAH+BSO as they had completed their families. Three patients are currently pregnant. CONCLUSION: In view of the high chemosensitivity and curability of ovarian germ cell tumors and their occurrence in young patients, every effort should be made to preserve one ovary and the uterus for future reproduction even in advanced cases. The role of revisional surgical staging, in particular retroperitoneal lymphadenectomy in light of these data and those of others should be redefined in the future.

Adolescent↗
PubMed1986

Elevated serum alpha-fetoprotein associated with Sertoli-Leydig cell tumors of the ovary.

Two young girls are described who presented with amenorrhea, large ovarian masses, elevated serum alpha-fetoprotein (AFP), and signs of androgen excess. Whereas the findings of an ovarian mass and elevated serum AFP typically suggest an ominous diagnosis, ie, endodermal sinus tumor of the ovary, both of these patients were found at laparotomy to have Sertoli-Leydig cell tumors of the ovary. Unilateral oophorectomy rapidly led to undetectable AFP levels in both patients, and resumption of menses.

Adolescent↗
PubMed1981

Continued presence of nucleoli in human germ cell tumors during mitosis.

A series of human germ cell-derived tumors were examined for the presence of nucleoli which persist through mitosis. Embryonal carcinomas, seminomas, and the cytotrophoblasts of choriocarcinomas had persistent nucleoli in more than 70% of mitoses. The differentiated cells derived from embryonal carcinomas, endodermal sinus tumors, and the more differentiated elements of choriocarcinomas only rarely had persistent nucleoli. These nucleoli appeared to remain transcriptionally active.

Cell Nucleus↗
PubMed1999

Germ-cell tumors of the mediastinum.

Mediastinal germ-cell tumors (GCTs) usually occur within the anterior mediastinum, accounting for about 15% of all mediastinal cysts and tumors. They are associated with the thymus, presumably arising from extragonadal germ cells or thymic cells with germ-cell potential. Mediastinal seminoma develops primarily in young males with rare cases reported in females; likewise, embryonal carcinoma, endodermal sinus tumor or yolk-sac tumor, choriocarcinoma, and malignant mixed or combined GCTs also overwhelmingly affect males. Mature cystic teratoma affects males and females equally. The prognosis for mediastinal mature cystic teratoma and seminoma is very good. Nonseminomatous malignant GCTs of the mediastinum often present with advanced disease and do not respond as well to chemotherapy as their gonadal counterparts. Nonetheless, it is important to separate mediastinal GCTs from other undifferentiated malignant tumors, especially thymic carcinoma, which has a poor prognosis. Clearly, some patients with mediastinal GCTs respond very well to modern therapies.

Adolescent↗
PubMedDate not supplied

Pediatric germ cell tumors: protocol update for pathologists.

The therapy for pediatric germ cell tumors has historically been widely variable and institution dependent. The efforts to provide consistent, biology-driven therapy through Intergroup protocols has been a relatively recent phenomenon that has provided the framework for future protocol designs. The first Intergroup protocols confirmed that stage I malignant testicular germ cell tumors and immature teratomas at all sites in children could be treated with surgery alone followed by close observation. Future protocols currently in the planning stages may extend this low-risk category to stage I ovarian germ cell tumors of all histologic types. Low-stage extragonadal germ cell tumors may be placed in a new intermediate risk category. Particular pathologic issues that were raised and reported during the first protocols and that may impact on future protocol design include the presence and size of foci of endodermal sinus tumors within low-stage immature teratomas at all sites. Accurate staging will grow more critical in future protocols. The ability to recruit international cooperative groups will determine the success of chemotherapy tailored to specific subgroups that now must be lumped for statistical purposes. Lastly, companion biologic studies will be critical to defining the different subtypes of germ cell tumors and to determining predictors of biologic behavior.

Adolescent↗
PubMed1989

Malignant germ cell tumors of the head and neck in childhood.

From 1962 through 1987, four children were diagnosed at our institution with primary germ cell malignancies of the extracranial head and neck regions. Ages of the children ranged from 2 to 44 months. Histologic findings included 2 yolk sac carcinoma (endodermal sinus tumor), 1 malignant teratoma with nephroblastoma (Wilm's tumor), and 1 malignant teratoma with neuroblastoma (primitive neuroectodermal) components. Complete clinical and surgical staging was performed to rule out additional sites of disease. All patients initially underwent either biopsy or, when technically feasible, resection. Three patients received combination chemotherapy and two received irradiation. Three patients died of progressive disease. One patient who had yolk sac carcinoma of the temporomandibular region is alive and free of disease 40 months after therapy. Complete surgical resection is indicated for teratomatous tumors, if technically feasible. The malignant components of these tumors are sensitive to both chemotherapy and irradiation and combined therapy may be beneficial.

Cervical Vertebrae↗
PubMed1978

Immunochemical determination of human chorionic gonadotropin and alpha-fetoprotein in sera and tumors of patients with testicular cancer.

In several prospective studies during the past 5 years, we evaluated 400 patients with nonseminomatous and 60 with seminomatous testicular tumors with the use of serum and cellular AFP and HCG at the NCI. Ninety percent of the patients with nonseminomatous testicular tumors had elevated levels of either HCG and/or AFP that have been useful in detection, staging, prognosis, and monitoring the efficacy of the therapeutic modalities. Although 5% of the patients with pure seminoma had an elevated level of serum HCG, one must search for elements of nonseminomatous testicular tumor in these patients by serial section of the seminoma specimen. Elevated serum AFP in patients with designations of seminoma indicates the presence of an element of embryonal carcinoma and/or teratoma. We have localized these markers in various tumor cells by using the technique of indirect immunoperoxidase. The HCG is localized in syncytiotrophoblastic component of choriocarcinoma and syncytiotrophoblastic giant cells occasionally found in association with embryonal carcinoma, teratoma, and seminoma. The AFP is localized in embryonal and endodermal sinus tumor.

Adult↗
PubMed1990

Germ cell tumors of the thalamus and the basal ganglia.

Two cases of germ cell tumors (GCTs) of the basal ganglia are presented and 40 previously reported cases are reviewed. The incidence of GCTs of the basal ganglia and thalamus was estimated as less than 14% of all intracranial GCTs. All patients except for two (95%) were male, aged 7-19 years. The clinical course was usually slow. The major symptoms were hemiparesis, mental deterioration such as dementia or character change, precocious puberty, diabetes insipidus, oculomotor palsy, speech disturbance, and hemianopsia. Signs of intracranial hypertension did not occur until the late stages of the disease. The plain CT finding was characterized by an irregularly defined, slightly high-density area frequently accompanied by central low-density areas without significant mass effect. The tumors showed mild to moderate and nonhomogeneous contrast enhancement. An ipsilateral cerebral hemiatrophy was often found. MR images demonstrated the corresponding findings. GCTs of the basal ganglia had a high possibility of containing components other than germinoma such as choriocarcinoma, endodermal sinus tumor, and embryonal carcinoma. Thus, tumor markers in the serum, CSF, or cyst fluid were frequently positive. With recent refinement of microsurgical techniques as well as immunohistochemical study and measurements of tumor markers of serum, CSF, and cyst fluid, major resections of tumor, accurate pretreatment histologic diagnosis, and early determination of the specific types of this tumor appear to be readily possible. This is essential for effective treatment of patients not only with radiosensitive germinoma, but also those with radioinsensitive nongerminoma variants and a combination of them located in this region.

Adolescent↗
PubMed1984

Extracranial metastases in childhood primary intracranial tumors. A report of 21 cases and review of the literature.

A clinical and pathologic review of primary intracranial tumors (917 cases in a 62-year period) at The Hospital for Sick Children, Toronto, identified 21 cases with systemic metastases (2.3%). This included 15 cases of medulloblastoma and 1 case each of astrocytoma, meningeal sarcoma, malignant melanoma, ependymoblastoma, teratoma, and endodermal sinus tumor, adding to the pediatric literature of 94 previously reported cases (72 medulloblastoma and 22 cases of other brain tumors). Like adults, children with medulloblastoma tend to develop bone and bone marrow metastases, while those with other brain tumors frequently invade adjacent tissues, and then spread to regional lymph nodes and the lungs. The prognosis is almost uniformly fatal, although prolonged palliation could be achieved with radiation and/or chemotherapy. The pathogenesis of systemic metastases is related to breakage of the blood-brain barrier, whether at surgery, or with tumor invasion into vascular channels, and especially with preoperative systemic-cerebrospinal fluid shunting. Thirteen of 16 patients who developed systemic metastases, including 5 with peritoneal involvement, had ineffective or no millipore filters within their shunts, suggesting their possible prophylactic role against tumor dissemination. A greater understanding of the pathogenesis of systemic metastases may aid the design of future effective preventive measures.

Adolescent↗
PubMedDate not supplied

Orbital germ cell tumors revisited: a clinicopathological approach to classification.

Orbital teratomas are unilateral, congenital germ cell tumors, which present at birth with moderate to massive proptosis, leading to exposure keratopathy. They enlarge the orbit diffusely. Primary orbital teratomas cause axial or vertical proptosis, are usually unassociated with bony defects, and do not extend outside the orbit. Recurrence is unusual after an early excision without enucleation or exenteration. Combined orbital teratomas additionally involve periorbital and intracranial spaces, cause lesser degrees of proptosis, and typically are associated with defects of orbital bones. Their intracranial part is small as compared to the orbital one. A significant risk of recurrence exists even after a combined craniotomy, orbitotomy and plastic reconstructive surgery. Intracranial teratomas with secondary orbital spread present prenatally with polyhydramnois and hydrocephalus, due to a massive primary tumor replacing parts of the brain, and typically lead to stillbirth. One orbital teratoma with malignant change has been well documented. Included twins, monsters rather than neoplasms, represent parts of a second fetus in the orbit. Orbital yolk sac carcinomas or endodermal sinus tumors are malignant neoplasms affecting children, which frequently invade periorbital and intracranial spaces, and which may respond to chemotherapy and irradiation. Finally, a teratoma or a yolk sac carcinoma may rarely present as an intraocular tumor.

Female↗
PubMed1993

Age contrast in ovarian pathology.

BACKGROUND. Ovarian cancer accounts for approximately 23% of all gynecologic tumors and is the most common fatal gynecologic malignancy. These tumors can occur in women of all ages, but there are differences in the histologic types during various decades of life. CONCLUSIONS. During infancy and childhood, the predominant type of neoplasms are those of germ cell origin, such as teratomas, dysgerminomas, and endodermal sinus tumors. In adults, epithelial neoplasms, or tumors that originate from the epithelium that covers the ovarian surface, are the most common, accounting for almost 85% of all neoplasms after the age of 50 years. The peak incidence of benign epithelial tumors occurs between the ages of 20 and 40 years. Young women (30 to 40 years of age) are frequently affected by the so-called "tumors of low malignant potential," which have excellent prognosis. Older women, on the other hand, usually have the most aggressive forms of ovarian cancer, present with advanced disease, and have a dismal prognosis.

Adult↗
PubMed1998

Nonteratomatous germ cell tumors in children.

BACKGROUND/PURPOSE: Totipotential germ cells may give rise to a broad range of tumors. The teratomatous variety of germ cell tumors has been the subject of several large studies. The goal of the current study was to describe the clinical features of nonteratomatous germ cell tumors (NTGCT) by reviewing a large series of patients. METHODS: Between 1945 and 1997, there were 78 cases of nonteratomatous germ cell tumors (NTGCT's) in children at The Children's Hospital, Columbus. Their records were reviewed retrospectively. There were 35 boys and 43 girls (M:F ratio 0.8). Mean follow-up was 87 months. RESULTS: Histological subtypes included germinoma (33 cases, 42%), endodermal sinus tumor (24 cases, 31%), embryonal carcinoma (12 cases, 15%), gonadoblastoma (4 cases, 5%), mixed histology (4 cases, 5%), and choriocarcinoma (1 case, 2%). Forty-two tumors were in gonadal sites, but a significant percentage were extragonadal (36 cases, 46%). Forty-six patients (59%) had localized disease, 18 (23%) had regional disease, and 14 (18%) had metastases. Treatment consisted of surgery and selective chemotherapy and radiation. Complete tumor resection was more likely for gonadal (29 of 42, 69%) than extragonadal primaries (15 of 36, 41%; P < or = .05). Forty-nine (63%) of all patients survived, whereas 29 (37%) died of their disease. Survival in patients with gonadal primaries (32 of 42, 76%) exceeded that in patients with extragonadal primaries (17 of 36, 47%; P < or = .01). Survival in patients with localized disease (34 of 46, 74%) exceeded that in patients with regional extension or metastases (15 of 32, 47%; P < .05). CONCLUSIONS: This study highlights the fact that tumor location, gonadal versus extragonadal, was important in determining prognosis, whereas tumor histology was not. This may be the result of a higher rate of complete tumor resection for gonadal primaries and underscores the important role of surgery in the optimal treatment of these unusual tumors.

Adolescent↗
PubMed1999

Chromosome abnormalities of eighty-one pediatric germ cell tumors: sex-, age-, site-, and histopathology-related differences--a Children's Cancer Group study.

The chromosomes of 81 pediatric germ cell tumors (GCTs) were analyzed as part of two clinical treatment trials, INT-0098 and INT-0097, conducted by the Children's Cancer Group. The analysis of chromosome results showed differences with respect to sex, age, tumor location, and histology. Sixteen of 17 benign teratomas of infants and children less than 4 years old and from gonadal and extragonadal locations were chromosomally normal. Twenty-three malignant GCTs from gonadal and extragonadal locations of the same age group were endodermal sinus tumors and varied in their karyotypic findings. The most common abnormalities were gains of 1q and chromosome 3. Of eight benign ovarian teratomas from older girls, five with normal G-banded karyotypes were determined to be homozygous for Q-band heteromorphisms, suggesting a meiosis II error. Among the 12 malignant ovarian GCTs from older girls, the common abnormalities were loss of 1p/gain of 1q, +3, +8, +14, and +21. Four of eight extragonadal tumors from older boys demonstrated +21; one had +X. Five of the eight had associated constitutional chromosome abnormalities, including one trisomy 21 and three with Klinefelter syndrome. The testicular GCTs of adolescents had abnormalities resembling those found in adult testicular GCT, including near-triploidy, loss of chromosomes 11, 13, and 18, and gain of chromosomes 7, 8, the X chromosome, and an isochromosome 12p. The gain of an isochromosome 12p was only frequent in the tumors from adolescent boys. Deletion of 1p/gain of 1q and +3 were the most common abnormalities among the malignant tumors from both sexes.

Abdominal Neoplasms↗
PubMed1994

Ovarian and extragonadal malignant germ-cell tumors in females: a single-institution experience with 43 patients.

From 1978 to 1992, 276 patients (pts) with MGCT were treated in our institution. Forty-three of the pts were female (15.5%). Median age at diagnosis was 20 years (newborn-70). Histology was dysgerminoma (D) in 14 pts (including 2 anaplastic D), endodermal sinus tumor (EST) in 9 pts, immature teratoma in 10 pts and mixed tumors in 10 pts. Primary locations were as follows: ovary (O) 33 pts and extragonadal (EG) 10 pts (pineal in 4 cases, mediastinum in 3, sacrum in 2 and pharynx in 1). Stage: I in 20 (16 O, 4 EG), II in 7 (5 O, 2 EG), III in 12 (10 O, 2 EG) and IV in 4 (2 O, 2 EG). Serum AFP was elevated in 20/22 non-dysgerminoma pts, HCG in only 5 pts and LDH in 15/36 pts. TREATMENT RESULTS: Ovarian tumors: all but one pt (biopsy only) underwent surgery: unilateral oophorectomy was performed in 15 pts and bilateral oophorectomy (+/- hysterectomy, +/- others) in 17 pts. Fourteen pts were rendered disease-free, 8 pts had residual tumor (RT) < 2 cm and 11 RT > 2 cm. Chemotherapy (PVB or BEP) was given to 28 pts, radiotherapy to 2 pts and no additional treatment to 3. Finally, 30 pts achieved complete response (CR) and none have relapsed at a median follow-up of 43 months. EG tumors: None of the pts underwent radical surgery. Radiotherapy was applied to 4 pineal tumors and BEP or PVB were given to all 10 pts. To date 6 pts are disease-free, 1 is alive with mature teratoma, 2 are alive with disease and 1 died of toxic effects. The projected overall survival of the series as a whole is 89% at 10 years, and it is significantly higher for pts without EST (p < 0.02) and for pts with AFP < 1000 (P < 0.01) and age < 22 years at diagnosis (p < 0.01). The projected event-free survival at 10 years is 80.4% (87.7% for ovarian tumors vs. 54% for extragonadal, p = 0.05). No events were recorded after 28 months. CONCLUSIONS: The present results reflect the dramatic effectiveness of cisplatin-based chemotherapy for ovarian MGCT and confirm that unilateral oophorectomy can preserve fertility without compromising cure. Age > 22 years, histology (EST) and serum AFP > 1000 ng/ml are possible prognostic factors (univariate analysis) to be tested in an independent body of data on cisplatin-treated patients.

Adolescent↗
PubMed1985

Cellular differentiation in ovarian sex-cord-stromal and germ-cell tumors studied with antibodies to intermediate-filament proteins.

Seventy ovarian sex-cord-stromal and germ-cell tumors were immunohistochemically studied for the presence of intermediate-filament proteins of different types used as markers for cellular differentiation. Cells of ovarian granulosa-cell tumors constantly expressed vimentin and appeared to lack cytokeratin. Two tumors previously classified as granulosa-cell tumors were reclassified as poorly differentiated "common" epithelial tumors based on their cytokeratin positivity, vimentin negativity, and morphologic features. Dysgerminomas and Leydig-cell tumors showed only vimentin positivity. Tubular structures in androblastomas, which are considered to represent Sertoli-cell differentiation, were cytokeratin positive, and thus differed from the majority of normal Sertoli cells that are known to express vimentin and not cytokeratin. Embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors showed cytokeratin positivity in the neoplastic cells whereas vimentin was observed in the stromal cells. In immature teratomas, epithelial differentiation was demonstrated with cytokeratin antibodies, and neural and glial differentiation was also frequently demonstrated by immunostaining with antibodies to neurofilaments and glial fibrillary acidic protein. The results show that antibodies to intermediate filaments can be used in the differential diagnosis between ovarian epithelial and nonepithelial tumors, and they provide a very accurate additional method to characterize the cellular differentiation of ovarian neoplasms.

Animals↗
PubMed1992

Primary treatment failure in patients with malignant ovarian germ cell neoplasms.

Between 1970 and 1990, 160 patients with malignant non-dysgerminomatous ovarian germ cell tumors have been treated at our own institution. Primary therapy failed in 42 of these patients, who constitute the basis for this study. Seventeen patients had stage I disease, 5 stage II, 17 stage III, and 3 stage IV. Histologic type included 13 immature teratomas, 8 endodermal sinus tumors, and 21 mixed germ cell tumors. Primary therapy for 14 patients was surgery alone, for 23, surgery plus chemotherapy, for 2, surgery plus radiotherapy and for 3, all three modalities. Median progression-free survival from initial diagnosis lasted 6.8 months (range, 0.9-24 months). Thirty-four patients received chemotherapy as part of salvage; 5/11 (45%) who received VAC are disease-free, and 6/11 (55%) who received cisplatin combinations are disease-free. When primary VAC failed, 3/7 (43%) were salvaged with cisplatin combinations. When primary cisplatin combinations failed, 2/5 (40%) were salvaged. Twelve of the 42 patients (29%) are currently alive disease-free. Primary treatment failure was attributed to surgery alone for 14 patients (7 because of misdiagnosis), radiotherapy for 5, and toxicity for 1. Of the 22 patients who failed chemotherapy, 12 did so because of a suboptimal regimen, 3 because of possible dose-intensity problems, one because of non-compliance, and 6 for unexplained reasons. Patients with ovarian germ cell tumors have an excellent probability of cure with aggressive primary therapy, but successful salvage may be difficult when primary treatment fails.

Journal Article↗