Germ cell tumors.

The development of modern surgical staging and effective chemotherapy regimens has markedly improved outcome of treatment of ovarian germ cell tumors. Almost all patients with completely resected tumors will survive their disease. Those with tumors other than dysgerminoma should all receive adjuvant chemotherapy. Patients with stage IA dysgerminoma can safely be observed, whereas those of higher stage should probably receive chemotherapy, although radiotherapy may be an option in selected patients, particularly older ones or those with other serious illness. Patients with advanced disease should all be treated with chemotherapy. Most dysgerminoma patients will be cured, as will many with other cell types; however, there is room for improvement in the latter group, and continued investigation is appropriate.     

Germ cell-like telomeric length homeostasis in nonseminomatous testicular germ cell tumors

Telomere maintenance plays an important role in cell proliferation and tumor survival. Human male germ cells, which carry long telomeres and express telomerase, give rise to a highly heterogeneous group of malignant tumors. We compared telomeric length and telomerase activity between two major histological types of primary testicular germ cell tumors. Fifteen out of 16 seminoma samples revealed telomeric restriction fragment (TRF) length below 13 kb; the remaining seminoma showed a major TRF fraction of 18 kb and a distinct minor fraction of above 23 kb length. In contrast, all 13 samples from nonseminomas showed TRF length >/=23 kb, which is similar to that reported in human sperm. Nine out of 11 seminoma specimens and six out of seven nonseminomas studied showed moderate to high telomerase activity, the only telomerase-negative nonseminoma being pure mature teratoma. These results indicate to a major difference in telomeric length between seminomas and nonseminomas, which is apparently unrelated to the presence of telomerase activity, and suggest a germline-like homeostasis of telomeric length is preserved in human nonseminomas. Oncogene (2000) 19, 4075 - 4078.     

Germ cell tumors

PURPOSE OF REVIEW: This review provides an overview of some of the recent pre-clinical and clinical developments in germ cell tumors. RECENT FINDINGS: Recent epidemiological studies highlight the variations in the geographic and ethnic distribution of germ cell tumors and the changing incidence of seminoma versus nonseminoma in the population. Additional studies are continuing to identify risk factors for germ cell tumors. Expression profiling, both at the gene and protein levels, is beginning to identify, at the molecular level, some of the factors associated not only with germ cell pluripotency but also with the different histologic subtypes of germ cell tumors. Work in the area of identifying potentially new serum tumor markers in germ cell tumor, as well as the role of the traditional tumor markers in predicting outcome to therapy is ongoing. Data is emerging on the role of positron emission tomography in evaluating residual lesions in seminoma. Evolving data on chemotherapy, radiation, and surgery further complements and clarifies information on these treatment modalities, and their potential toxicities, in the management of germ cell tumors. SUMMARY: Ongoing preclinical and epidemiological studies highlight the complexities underlying germ cell tumor pathogenesis. With enhanced understanding of some of these processes, treatments, particularly for advanced stages, will continue to evolve.     

Germ cell tumors (II): VAB II in metastatic testicular cancer.

Between June 1974 and January 1976, 50 patients with metastatic non-seminometous testicular carcinoma were treated with the VAB II protocol. The induction phase consisted of vinblastine (0.4 mg/kg) and actinomycin D (0.02 mg/kg) on day 1. Bleomycin (0.5 mg/kg) was given by continuous infusion for 7 days, and cis-diammine-dichloroplatinum (II) (DDP) (1 mg/kg) was given on day 8. A weekly maintenance of vinblastine and bleomycin, with actinomycin D and DDP on a rotating schedule was given followed by vinblastine, actinomycin D and chlorambucil every 3--4 weeks. Therapy was discontinued after 30--36 months of treatment in the face of continued remission. The response rate was 50% CR, 34% PR with 60% CR and 36% PR in previously untreated patients. Second-look surgery and excision of residual lesions was performed in selected cases. Alopecia, mucositis, nausea, and vomiting were universal. One patient died in the postsurgical period of toxicity from the combination of bleomycin and high concentrations of oxygen. There were seven instances of allergic reactions to DDP. Eleven of 25 complete responders and 4 partial or minor responders who underwent excision of stable disease remain alive from 19 to 35 months following start of therapy, 12 of them without evidence of disease.     

Pathology of testicular germ cell tumors.

The pathology report on a testicular germ cell tumor should include the following information: Tumor type: The histologic type of tumor present. If the tumor is of mixed type, the components should be listed, in order of relative abundance. The pathologist may endeavor to give a numeric estimate of the percentages of each element. Staging information: The size of the tumor should be listed. Local spread--into rete testis, tunica albuginea, epididymis, and spermatic cord--should be listed. If the cord is involved, possible involvement of its surgical resection margin should be assessed. Vascular/lymphatic invasion should be assessed for its presence or absence. Status of the remainder of the testis: Evidence of cryptorchidism or other dysgenetic features should be mentioned. Such features may imply a greater risk for the development of a contralateral tumor. Also, the presence of normal spermatogenesis elsewhere in the uninvolved testis should be reported. This finding may suggest a relatively decreased risk for contralateral tumor development and is a likely indicator of fertility should the patient consider sperm banking prior to retroperitoneal surgery and chemotherapy. The finding of mature sperm in the epididymis is an easy way to confirm spermatogenesis in the testis. Incidental findings: Lipomas or hydroceles of the cord, adrenal rests, and adnexal cysts may be found. The pathologist plays a crucial role in the diagnosis of germ cell tumors. In addition to elucidating tumor type, the pathologist is relied upon for precise local staging and for the classification of metastases, all of which have important implications in determining optimal therapy. As the clinical management of germ cell tumors evolves, the pathologist will continue to play a role in defining those features that have a bearing on patient outcome.     

Germ cell tumors of the ovary

PURPOSE: Malignant ovarian germ cell tumors (MOGCTS) are rare but curable at all stages of disease. This review gives an outline of the management of this disease. METHODS: We performed a literature search in the PubMed of almost all relevant articles concerning MOGCTs on pathology, prognostic factors, surgery, post-operative therapy and late effects of therapy. The available literature is mainly composed of retrospective reviews and articles. RESULTS: Prognostic factors include stage, amount of residual tumor, histologic type and raised tumor markers. For patients with early stage disease, cure rates approach 100%, while for those with advanced-stage disease are at least 75%. Appropriate surgical treatment for patients where fertility needs to be preserved consists in laparotomy with unilateral salpingo-oophorectomy (USO) and resection of all visible disease. For patients with advanced-stage disease, the role and the extent of debulking surgery remain controversial despite its routine use. However, it is suggested a benefit from minimal residual disease at completion of primary surgical cytoreduction with both non-platinum and platinum-based chemotherapy regimens. Second-look surgery clearly is not indicated in patients with early stage non-dysgerminoma or in all patients with dysgerminoma. However, teratoma patients may benefit from secondary cytoreduction. Three courses of bleomycin, etoposide and cisplatin (BEP) is the current standard adjuvant chemotherapy and four courses of BEP are recommended in case of bulky residual tumor after surgery. More evidence is required to show that surveillance is a safe option. There is a hint that high-dose chemotherapy may play a role in relapsed patients. The majority of MOGCTs patients who undergo fertility-sparing surgery and chemotherapy retain their gonadal and reproductive function. There is an increasing concern about life-threatening long-term effects of treatment. CONCLUSION: MOGCTs are rare neoplasms that affect girls and young women and have excellent prognosis at all stages of disease with optimal therapy. The majority of MOGCTs patients retain their reproductive function.     

Germ cell tumors in Indian children

The present paper is a retrospective study of one hundred and thirty five germ cell tumors seen in children at the University Hospital, Varanasi during a period of 21 years. These tumors constituted 7.5% of all solid tumors in the pediatric age group. Histologically 89 tumors (65.9%) were benign and 46 (34.1%) were malignant. Eighty percent of ovarian and all the testicular germ cell tumors were malignant. Thirty per cent of the tumors were located in the sacrococcyx. The ovaries were the next common site. There were 80 girls, 53 boys, and 2 cases in which the sex was not recorded. The predominance amongst girls was mainly due to the more frequent involvement of ovaries as compared to the testes. Twenty nine of the children were in the first year of life. The factors probably responsible for the higher incidence of malignancy, the differences in anatomic location, and the sex distribution in comparison to other reports have been examined and discussed.     

Bronchial carcinoid tumors.

Twenty-eight pulmonary carcinoid tumors were reviewed histologically and clinically. Hematoxylin-and-eosin-stained sections were utilized, as well as special stains, including the argyrophil and argentaffin reactions. The 22 tumors located centrally, at the level of primary or segmental bronchi, had a microscopic appearance distinct from those located more peripherally. One peripheral tumor that was large in size appeared much more aggressive histologically, and was designated an atypical carcinoid. The origin of carcinoid tumors from Kulchitsky cells in the lung, the distinction of peripheral tumors from chemodectomas, and the relationship of bronchial carcinoids to bronchial epithelial hyperplasias and oat cell carcinomas are discussed.     

Maternal smoking and testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a non-parent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, non-seminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons.     

Biology of testicular germ cell tumors

Germ cell tumors are derived from cells of the germ cell lineage and are the most common solid malignancies to affect young Caucasian men between the ages of 15 and 40 years. All testicular germ cell tumors develop from the same precursor lesion, intratubular germ cell neoplasia unclassified, which in turn is thought to arise from malignant transformation of a primordial germ cell or gonocyte. These tumors are characterized by extreme chemosensitivity and are considered a model for curative disease. In spite of this, a small subset of patients with metastatic disease fail to achieve a complete response with cisplatin-based chemotherapy or relapse from complete remission. Understanding the molecular biology may help the design of new therapies for those patients with a poor prognosis and could also improve the treatment of cancer in general. Current understanding of the role of genetic and epigenetic factors in the etiology of germ cell tumors and the biochemical mechanisms underlying chemotherapy sensitivity and resistance is discussed in detail in this review.     

Germ cell tumors of the testis following orchiopexy

Out of 335 patients with testicular neoplasms, cryptorchidism was concomitant in 84 cases (25%). 28 patients underwent orchiopexy at the age of 5-52 years. Tumor was detected, on the average, 14,4 years after the operation. Orchiopexy contributes to carcinogenesis in the undescended testicle. The rate of incidence of non-seminomatous tumor is relatively higher in patients after orchiopexy than in untreated cases of cryptorchidism. Patients with undescended testicle should be referred to a group at high risk and be followed up.     

Biology of testicular germ cell tumors

Germ cell tumors are derived from cells of the germ cell lineage and are the most common solid malignancies to affect young Caucasian men between the ages of 15 and 40 years. All testicular germ cell tumors develop from the same precursor lesion, intratubular germ cell neoplasia unclassified, which in turn is thought to arise from malignant transformation of a primordial germ cell or gonocyte. These tumors are characterized by extreme chemosensitivity and are considered a model for curative disease. In spite of this, a small subset of patients with metastatic disease fail to achieve a complete response with cisplatin-based chemotherapy or relapse from complete remission. Understanding the molecular biology may help the design of new therapies for those patients with a poor prognosis and could also improve the treatment of cancer in general. Current understanding of the role of genetic and epigenetic factors in the etiology of germ cell tumors and the biochemical mechanisms underlying chemotherapy sensitivity and resistance is discussed in detail in this review.     

Peripheral pulmonary carcinoid tumors.

The light microscopic and ultrastructural features of five asymptomatic peripheral carcinoids presented as distinct pulmonary solitary nodules are described. By conventional microscopy the tumors displayed a variety of histologic patterns, the most unusual one showing tumor cells embedded in a richly vascular hyalinized stroma and forming papillary structures or cystic spaces lined by low cuboidal cells which ultrastructurally bore a strong resemblance to intermediate or transitional forms between types I and II pneumocytes. A striking feature of these tumors was their rich vasculature associated with a marked perivascular sclerosis composed of basement membrane-like material and collagen fibrils most likely produced by the increased numbers of pericytes surrounding these sclerotic vessels. The clinical implications, biologic behavior, and association of these tumors with other pulmonary neoplasms are also discussed.     

Synchronous bilateral testicular germ cell tumors of different histologic type. Pathogenetic and practical implications of bilaterality in testicular germ cell tumors.

Patients with a germ cell tumor (GCT) in one testicle are prone to develop cancer in the contralateral testicle. Metachronous development of a GCT in the remaining testicle occurs in 3% of patients. The synchronous development of bilateral GCT occurs in 0.5% of patients. Bilateral testicular neoplasms are almost always identical histologically. Only five cases of synchronous bilateral GCT of different histologic types have been reported in the literature. The authors report the sixth case of this uncommon phenomenon and discuss its clinical and pathogenetic implications.     

Molecular biology of testicular germ cell tumors

Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.