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Biology of testicular tumors.

Testicular tumors arise from the germ cell line and therefore exhibit characteristics of both neoplastic and normal growth and differentiation. Experimental model systems of animal and human tumors have been reviewed with emphasis on the biologic characteristics of these tumors. The embryonal carcinoma cell is the totipotential stem cell that resembles normal germ cells in many ways and is capable of differentiating along the somatic pathways to form endoderm, mesoderm and ectoderm cell types (teratoma) or along extraembryonic pathways to form trophoblast (choriocarcinoma) or yolk sac (endodermal sinus tumor). Markers of the extraembryonic cell types have been defined, and the cell surface characteristics of embryonal carcinoma cells are being intensively studied. Clarification of the biology of testicular tumors will provide the basis for future rational therapy.

Animals↗

Ovarian malignant luteinized thecoma--an unusual tumor in an adolescent.

Malignant luteinized thecoma is an extremely rare ovarian tumor. The fifth reported case of this tumor presenting in a 13-year-old epileptic child on anticonvulsant therapy with a rapidly enlarging pelvic-abdominal mass is discussed. At laparotomy, bilateral ovarian involvement, massive ascites, and omental and bowel serosal metastases were present. The pathological diagnosis was difficult with initial diagnoses of ovarian edema, endodermal sinus tumor, and ovarian fibrosarcoma. The final diagnosis of malignant luteinized thecoma was made by recognizing the presence of lutein cells with foamy vacuolated cytoplasm and intracytoplasmic staining for oil red O. Electron microscopy also demonstrated vacuolated cells with multiple fat globules. After surgical debulking the patient was treated with combination chemotherapy with complete response. The similarities of this case to three previously reported bilateral thecomas presenting in children on anticonvulsant therapy is discussed.

Adolescent↗

N-myc amplification and neuron-specific enolase production of a neuroblastoma cell line and germ cell tumor cell lines.

N-myc gene amplification of the gynecological malignant tumor cell lines and a neuroblastoma cell line was studied by the Southern hybridization method along with the production of neuron-specific enolase (NSE) by these cell lines. N-myc amplification and NSE production were observed side by side in three cell lines: neuroblastoma cell line HSNB, endodermal sinus tumor cell line HAEST, and malignant teratoma cell line HUOT. However, N-myc amplification and NSE production disappeared gradually following successive passages of the HAEST and HUOT lines. With respect to the HUOT line, these parameters disappeared along with the cells of nervous origin. N-myc amplification and NSE production were not observed in nine other cell lines.

Female↗

Primary chemotherapy and the role of second-look laparotomy in non-dysgerminomatous germ cell malignancies of the ovary.

In view of the rarity of germ cell tumors of the ovary, it is not surprising that little information exists about the indications for and significance of findings at second-look laparotomy in patients with these tumors. For this reason, we have reviewed 16 patients who received primary chemotherapy for malignant germ cell tumors of the ovary at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1976 and 1983. Eleven of them underwent a second-look laparotomy after completion of their therapy. Primary therapy consisted of surgery, usually unilateral oophorectomy, and cis-platinum-based VAB chemotherapy. The histologic diagnoses were six immature teratomas, five endodermal sinus tumors, four mixed germ cell tumors, and one nongestational choriocarcinoma. Stage distribution was as follows: Stage IA, eight patients; Stage IC, one patient; Stage IIA, one patient; Stage III, four patients, and unstaged, two patients. The ages ranged from 15 to 56 years, with the mean of 29 years. All of the 11 patients undergoing second-look laparotomy were found to be free of disease. They are alive and have been continuously free of disease from 9 to 77 months (mean 39 months). This paper discusses primary chemotherapy and the role of the second-look laparotomy and suggests its value in modifying treatment, predicting cure, and safely stopping therapy in patients with germ cell malignancies of the ovary.

Adolescent↗

Myxoid leiomyosarcoma of the ovary: analysis of three cases.

The first three cases of myxoid leiomyosarcoma occurring in the ovary are reported. Two cases in stage III were found in postmenopausal patients and a further case was found in stage I in a 32-year-old. All masses were large and gelatinous with cystic change, necrosis, and hemorrhage, but both uteri and ligaments and contralateral adnexa appeared normal. Microscopically, the tumors showed a predominantly reticular meshwork of elongated cells surrounded by abundant basophilic material. While electron microscopy proved inconclusive due to nondifferentiation, the use of monoclonal antibodies against smooth muscle actin demonstrated a smooth muscle type of differentiation. The differential diagnosis of this rare ovarian condition includes other myxoid ovarian lesions, such as ovarian edema, myxoma, endodermal sinus tumors, and the sarcomatous component of malignant mixed müllerian tumor and carcinosarcoma, as well as lymphovascular tumors. Since mitotic count due to decreased cellular density is unusually low in myxoid leiomyosarcoma, capsular rupture and clinical stage seem to be more reliable prognostic markers. The highly aggressive behavior of myxoid leiomyosarcoma parallels that of typical ovarian leiomyosarcoma. Two of the three patients in this series died of tumor at 13 and 24 months after diagnosis; the other patient is free of disease at 3 years after diagnosis.

Actins↗

Malignant ovarian germ cell tumors: the experience at the Hospital de la Santa Creu i Sant Pau.

From 1979 to 1990, 33 patients with pathologically confirmed malignant ovarian germ cell tumors (MOGCT) were referred after initial surgical procedure at the Department of Oncology, Hospital de la Santa Creu i Sant Pau. The median age was 22 years (range, 10 to 39). Stage distribution was as follows: stage I, 12 patients; stage II, 6 patients; stage III, 11 patients; stage IV, 3 patients; and unstaged, 1 patient. The histologic diagnoses were 10 dysgerminomas, 4 endodermal sinus tumors, 11 immature teratomas, and 8 mixed germ cell tumors. Twenty-eight out of the thirty-three patients received postoperative chemotherapy with POMB-ACE-PAV or other platinum-containing regimens. One patient with stage IV disease failed to respond to chemotherapy and she died. Sixteen out of the twenty-eight treated patients had second-look laparotomy, which showed mature teratoma in six and persistent malignant teratoma in one patient. This last patient had complete remission with second regimen. No patient has developed recurrence. With a median follow-up of 66 months (range, 10 to 133), 32 patients (97%) are alive without evidence of disease. These data confirm that platinum-containing regimens have dramatically improved the prognosis for patients with MOGCT. This paper discusses primary chemotherapy and the role of the second-look in these patients.

Adolescent↗

Experience with the management of ovarian germ cell tumors in Chinese patients.

Treatment results of 37 consecutive patients with primary ovarian germ cell tumors (OGCTs) were analyzed. Thirty-three were referred after initial laparotomy and four were first seen at relapse. Four patients with stage I dysgerminoma and grade 1 immature teratoma were observed after operation without recurrence. There was also no relapse in eight patients with dysgerminoma given postoperative irradiation (whole abdomen, median 30 Gy). Twenty-five patients (3 dysgerminomas, 11 immature teratomas, 9 endodermal sinus tumors, and 2 mixed germ cell tumors) received short-term cis-platinum-based chemotherapy. Six out of eight measurable tumors treated by chemotherapy had complete remission. Complete follow-up information was obtained in 35 out of 37 patients. The 4-year actuarial survival rates of the whole group and those referred immediately after initial surgery were 94.1 and 100%, respectively. cis-Platinum was substituted by carboplatin in eight cases but this did not affect treatment result. Nonetheless, deaths occurred in two of four patients referred at relapse with extensive disease and initially treated with suboptimal regimens. Chemotherapy-induced side effects were common but mostly tolerable and were related to cis-platinum and bleomycin. The results of this series show that cis-platinum-based chemotherapy is so effective that nearly 100% cure can be achieved in OGCTs and suggest that it is important to institute optimal chemotherapy from the start. On the other hand, common side effects of treatment and possible late toxicities make it desirable for future studies to see whether chemotherapy intensity could be reduced in patients with good prognosis.

Adolescent↗

Sequential combination chemotherapy for malignant germ cell tumors of the ovary.

Fourteen patients with malignant ovarian germ cell tumors were treated postoperatively with a short-term, sequential regimen combining cisplatin, vincristine, methotrexate, bleomycin, dactinomycin, cyclophosphamide, etoposide, Adriamycin (Adria Laboratories, Columbus, OH), and vinblastine (POMB/ACE/PAV). Two patients had Stage I disease, Five had Stage II, five had Stage III, and two had Stage IV. The histologic diagnosis was immature teratoma in five cases (two cases were Grade 2 and three cases were Grade 3) endodermal sinus tumor in two cases, dysgerminoma in three cases, and mixed germ cell tumors in four cases. The chemotherapy regimen appeared to be highly effective against all histologic types, including advanced stages, with 12 of 14 (86%) overall sustained remissions. The median duration of treatment was 5 months. The toxicity of the regimen, which contained low total doses of cisplatin and bleomycin, was only moderate. After a median follow-up of 53+ months, 13 patients were alive without evidence of disease. The results and toxicity obtained were compared with those from other currently used regimens. Also, some comments on initial surgery and second-look surgery are given.

Adolescent↗

Shunt-related abdominal metastasis of cerebral teratocarcinoma: report of an unusual case and review of the literature.

OBJECTIVE AND IMPORTANCE: Internal drainage of cerebrospinal fluid to the abdominal cavity via a ventriculoperitoneal shunt (VPS) is a common procedure for therapy of obstructive hydrocephalus; because this condition is often caused by brain tumors blocking the natural cerebrospinal fluid pathways, the VPS as an artificial anastomosis can provide the means for the spreading of tumor cells by the cerebrospinal fluid. We report the case of a VPS-related abdominal metastasis of a teratocarcinoma and review the pertaining literature. CLINICAL PRESENTATION AND INTERVENTION: A 24-year-old man with a history of three brain tumors that were operated on when the patient was 14, 21, and 23 years of age developed an acute ileus 7 months after VPS insertion for cerebral teratocarcinoma. Intraoperatively, a massive abdominal tumor was observed, which turned out to be a peritoneal metastasis of the aforesaid brain tumor. The patient died as a result of his illness 1 month later. RESULTS: To date, 58 VPS-related metastases of brain tumors have been described. The male-to-female ratio is 1.6:1, the mean age at shunt insertion is 12.2 years, and the interval between shunt operation and diagnosis of metastases is 16.8 months. During the observation time, 69.2% of the patients died as a result of their illness or abdominal metastases. The most common sources of the metastases were germinomas (27.7%), medulloblastomas (19.1%), and endodermal sinus tumors (10.3%). CONCLUSION: The presented case is only the second VPS-related abdominal spreading of a cerebral teratocarcinoma. Metastases via VPS are rare but should be considered as a possible complication and mode of systemic spread in patients with primary intracranial malignancy.

Adolescent↗

[Cellular localization of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and carcinoembryonic antigen (CEA) in malignant germ cell tumors of the ovary using immunoperoxidase technique (author's transl)].

An immunohistologic study of germ cell tumors of the ovary was undertaken to investigate a correlation of the histology with the presence of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and carcinoembryonic antigen (CEA) in the tissue specimens. A positive reaction for AFP was consisted of dark brownblack granular intracytoplasmic deposits and some of hyaline globules were also positive in some instances. There was tissue localization of AFP in 9 of 10 embryonal carcinomas (endodermal sinus tumor, Teilum) and in 4 of 5 solid teratomas. Two patients with embryonal carcinoma positive for AFP had normal serum level in AFP. A positive staining for HCG was found in 4 embryonal carcinomas and in 2 solid teratomas; it was consisted of dark brown cytoplasmic deposits localized exclusively to syncytiotrophoblast giant cells. The tumor cells positive for AFP but negative for HCG, and vice vasa indicated that these two carcinoembryonic proteins were produced by different cells. The localization of CEA was also studied in 3 embryonal carcinomas. None of embryonal carcinomas and 3 solid teratomas were reacted to CEA; it was consisted of a dark brown deposit localized in cell surface of stratified squamous cells and tall columnar cells forming glandular structure. All of the histologically immature neural components were negative for these carcinoembryonic proteins.

Adolescent↗

Pineal tumors.

From 1972-1985, 30 patients with pineal area tumor have been treated with combinations of surgery and irradiation, no patient receiving chemotherapy as a primary recommendation. Patients ranged between 3 and 69 years of age, 18 were male and 12 female. In 18 patients a tissue diagnosis was made initially, 14 patients required shunts before definitive management and in 8 of the 14 tissue diagnosis was made at the same time. Eight patients had no surgical intervention at any time. Patients who have received irradiation have had whole brain irradiation, local field irradiation, or craniospinal irradiation. Two elderly patients died rapidly of their malignant processes before definitive treatment could be given. Only one patient with a non neoplastic lesion was seen. This was a bleed from an AVM with no underlying tumor. One patient with a pineocytoma was not irradiated. Overall, two-thirds of our patients are alive 5 to 15 years after treatment. There has been no surgical mortality and minimal morbidity from biopsy. Late effects of treatment include one patient with mild hearing loss and three patients with endocrinopathies amenable to medical treatment. We believe that tissue diagnosis allows optimal field design and dose recommendations to be made by the radiotherapist in addition to defining prognosis. In our experience, endodermal sinus tumor and pineoblastoma are highly malignant, and in view of their poor prognosis with conventional management consideration of more radical treatment with a possible role for chemotherapy is suggested.

Adolescent↗

Treatment of germ cell tumors in the pineal region.

The authors retrospectively analyzed 107 patients with primary intracranial germ cell tumor (GCT), who were treated at the Department of Neurosurgery, Yonsei Medical Center between January 1986 and January 1996. The incidence of GCT was 2.8% in pediatric patients with intracranial tumor. Of the 107 tumors, 60 were located in the pineal region, 30 in the suprasellar region, 16 in basal ganglia or the thalamic region, and 1 in the posterior fossa. The 60 pineal GCT consisted of 39 germinomas (29 pure germinomas, 6 germinomas with STGC, 4 germinomas mixed with teratoma), 5 mature teratomas, and 16 nongerminomatous GCT. Thirty patients underwent surgery: their operations took the form of total resection in 14 cases, subtotal resection in 10, and biopsy in 6. Thirty patients (27 with germinomas, 3 with endodermal sinus tumors) were managed without surgery on the basis of radiological findings and tumor markers. The 5-year survival was 91% for 39 patients with germinomas, 80% for 5 with mature teratomas, and 49% for 16 with nongerminomatous GCT. Univariate analysis of prognostic factors with the Kaplan-Meier survival curve showed that histological tumor type, radiological findings, results of tumor marker studies, and response to trial radiation or chemotherapy were highly correlated with outcome. Chemotherapy was beneficial as the method of trial treatment in pineal GCT and treatment in recurrent tumors. The administration of trial chemotherapy or radiotherapy without tissue biopsy is well justified as a treatment modality in pineal GCT suspected on the basis of radiological findings and tumor marker studies. Aggressive multimodality approaches with surgery, radiotherapy, and chemotherapy are necessary to improve the outcome in these tumors. We propose new protocol for treatment of germ cell tumors in the pineal region, which is based on a minimally invasive approach.

Adolescent↗

Metachronous gonadal and extragonadal primary germ cell tumors: two case reports.

Bilateral synchronous or metachronous germ cell tumors (GCT) of the testis are recognized in 2-3% of patients. Extragonadal GCT in the mediastinum or the retroperitoneum have been rarely reported in patients with primary GCT of the testes. Two patients were observed with two separate primary GCT; in 1 a retroperitoneal embryonal carcinoma was successfully treated with chemotherapy and surgery and a new primary developed 14 years later in the testicle as a seminoma. A second patient had a primary teratocarcinoma of the testes treated with surgery only; 4 years later he developed a mediastinal endodermal sinus tumor, which was fatal. These cases suggest that not only is the remaining testicle at risk for a second primary GCT, but also that extragonadal sites impose a similar risk and monitoring of patients should consider all potential sites for the development of GCT.

Adult↗

Identification of two different surface epitopes of human ovarian epithelial carcinomas by monoclonal antibodies.

Monoclonal antibodies (Mabs) against human ovarian mucinous and serous carcinoma were obtained by the Mab technique. Their reactivities against human tumors were tested by indirect immunofluorescence. One of the Mabs, named 4C7, derived from the spleen cells of mice immunized with mucinous carcinoma line OVA-1, reacted to ovarian mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma but did not react to ovarian serous carcinoma. Another Mab, 3C2, obtained from the spleen cells of mice immunized with serous carcinoma line HOC-21, reacted to serous carcinoma and endometrioid carcinoma of ovary, but never reacted to mucinous carcinoma or mesonephroid carcinoma. Neither of the Mabs reacted to other types of ovarian carcinomas such as undifferentiated carcinoma, dysgerminoma, endodermal sinus tumor, and malignant teratoma of ovary, and also did not react to any benign ovarian tumors or other normal human tissues. Both Mabs 3C2 and 4C7 had no reactivity to carcinoma of other organs such as stomach, colon, lung, lymphoid system, and kidney and also did not react to human lymphocytic or carcinoembryonic antigen as confirmed by using many human cell lines and surgically resected samples. Since the cross-reactivities of these Mabs were limited within the ovarian epithelial carcinomas, it is suggested that two distinct epitopes are expressed on the ovarian epithelial carcinomas. One epitope, identified by Mab 4C7, is expressed only on mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma, while the epitope, identified by Mab 3C2, appears only on serous and endometrioid carcinoma.

Adenocarcinoma, Mucinous↗

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.

Adolescent↗

Biochemical markers for testicular germ-cell tumors in relation to histology and stage: some experiences from the Danish testicular cancer (DATECA) Study from 1976 through 1981.

The DATECA Project was started in January 1976 and includes all patients with testicular cancer in Denmark. During the first 6 years, 1246 patients entered the joint protocol for histology, staging, management, and clinical use of tumor markers. Only 746 DATECA patients fulfilled the claims for being ideally monitored with preoperative as well as postoperative serologic marker determinations. The overall prevalence of marker positivity, that is, elevated preoperative values of alpha-fetoprotein (AFP) and/or human chorionic gonadotrophin (HCG) was 8% for patients with seminoma and 63% for patients with nonseminomatous disease. The prevalence of increased marker concentration in serum was correlated to stage (higher prevalence in higher stages) and to prognosis (marker-negative patients had a better prognosis than did marker-positive patients). An increased concentration of AFP or HCG was correlated with the presence of a primary endodermal sinus tumor and choriocarcinoma component, respectively.

Alkaline Phosphatase↗

Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases.

BACKGROUND: Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients. METHODS: The current study is a retrospective review of 74 patients with MOGCT treated by conservative surgery, retaining the uterus and contralateral ovary to preserve ovarian function, with or without chemotherapy. RESULTS: The mean age of the patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31 dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%). There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4 Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients (63.5%). The overall mean follow-up period was 52.1 months. There were 7 recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I disease was 98.2% and that for patients with advanced disease stages was 94.4%. During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these women resumed normal menstrual function on completion of chemotherapy. Fourteen healthy live births were recorded in the chemotherapy group and there were no documented birth defects. There was 1 case of infertility (1.4%). CONCLUSIONS: The surgical approach in young patients with MOGCT confined to a single ovary should aim to preserve fertility. Advanced disease is not usually accompanied by contralateral ovarian disease and should not necessarily contraindicate conservative surgery. The majority of these patients who have received combination chemotherapy resume normal ovarian function and can expect a normal fertility rate and healthy offspring.

Adolescent↗

[Ovarian tumors in childhood: apropos of a review of cases].

OBJECTIVE: Our objective was to evaluate the incidence and behavior of ovarian tumors in our population. PATIENTS AND METHODS: Between 1984 and 1994, all clinical charts with the diagnosis of ovarian tumors were reviewed retrospectively. Of 158 tumors in females below 14 years of age, 7 were located in the ovary (4.4%). Clinical presentation, diagnostic methods, histology, treatment and survival were evaluated. RESULTS: The mean age of the patients was 11.3 years (range: 7 months-13.5 years). One child was asymptomatic, 4 complained of abdominal pain, 3 with vomiting and 3 with urinary symptoms. Palpable abdominal masses were found in all, with abdominal distension in 2, ascytes, general malaise and precocious puberty each in one case. Alpha-fetoprotein was elevated in 3 cases and CA 125 in 1. Image studies revealed pleural effusion in one X-ray abdominal mass in 6 abdominal X-rays, which was confirmed by echography in all girls. Histology revealed benign teratoma (3), endodermal sinus tumor (1), malignant teratoma (1), granulosa cell tumor (1) and mixed teratoma and dysgerminoma (1). Treatment consisted in surgical resection (7), total in 5 cases (stage I) and subtotal in 2 (one malignant teratoma and one TSE, stages III). Chemotherapy was added initially in 2 stage III tumors and after relapse in 3. Radiotherapy was not given. Six girls survived. CONCLUSIONS: We comment on the low incidence of these tumors, which can be well diagnosed by using echography. Mixed histology may be misdiagnosed. Chemotherapy may rescue the worse prognostic cases.

Adolescent↗