Erratum to: Successful long-term remission following repeated salvage surgery in a patient with chemotherapy-resistant metastatic non-seminomatous germ cell tumor: an additional report to Int J Clin Oncol 2007; 12:485–487
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Surgical oncology
Salvage therapy
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Gonadoblastomas have a propensity to give rise to germ cell neoplasms. This study analyzes the clinicopathologic findings in six phenotypic females with features of 46,XY pure gonadal dysgenesis who developed germinomas and other germ cell tumors in gonadoblastomas. All stages in the evolution of germinoma from the germ cells of gonadoblastoma were observed, including in situ, incipient, microinvasive, and metastatic varieties. Admixtures with teratoma and endodermal sinus tumor occurred in two patients. Germ cell tumors which originate in gonadoblastomas appear to have the same clinical behavior and response to therapy as those that arise de novo in the ovary, testis or extragonadal sites. Although it is debatable whether gonadoblastomas are true neoplasms or blastomatoid dysgenetic malformations, their potential for giving rise to fully malignant germ cell neoplasms must be recognized.
Gonadoblastoma
Dysgerminoma
Germinoma
Immature teratoma
Endodermal sinus tumor
Gonadal dysgenesis
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Eleven male patients had germ cell tumors of the testis (7), mediastinum (3), or retroperitoneum (1) in which non-germ cell malignancies developed. Such malignant non-germ cell elements were present in the primary excisions of five patients and were subsequently found in additional resected tissue in 10 of 11 patients. In the patients who had multiple pathology specimens examined, a progression from atypia to predominant non-germ cell malignancy was often found. The authors believe these malignant elements arose within teratomatous foci, since eight of nine cases had teratoma in the primary tumor, and teratoma was found in subsequently resected tissue in one additional case. Cisplatin therapy frequently "unmasked" the non-germ cell malignant elements by destroying the more chemosensitive germ cell cancers. The prognosis was worst for five patients who developed progressive embryonal rhabdomyosarcoma: two of these patients died of local spread of tumor, whereas a third died of metastatic sarcoma. Only one patient, who had total surgical excision of rhabdomyosarcoma, survived. Other forms of sarcoma that developed within germ cell tumors did not appear to adversely affect the prognosis beyond that of teratoma. It is currently recommended, when feasible, that patients with teratoma and sarcoma undergo total surgical excision. Further treatment with cisplatin regimens, after eradication of the germ cell component, has not been helpful. The role of other forms of chemotherapy remains speculative.
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The histogenesis of extragonadal germ cell tumors remains an enigma. The majority of patients with retroperitoneal tumors are male, and careful histologic evaluation reveals preinvasive intratubular germ cell neoplasia (ITGCN) or scars in the testis suggesting a so-called "burnt out" germ cell tumor. However, in the testes of patients with primary mediastinal germ cell tumors, no ITGCN has been described in the literature to date. The authors report the first case of simultaneous germ cell neoplasia in the mediastinum and the testis, providing further insights into the biology and origin of these lesions.The authors report the pathologic features and cytogenetic findings in an adult male with a mediastinal germ cell tumor and asymmetric testis. This patient died shortly after diagnosis.A locally invasive mediastinal nonseminomatous germ cell tumor was associated with ITGCN in one testis. Metastases were not present clinically or on autopsy during a detailed and systematic examination of retroperitoneal lymph nodes and other viscera. Neither an invasive germ cell tumor nor a scar was found in either testis (both testes were serially sectioned and entirely examined histologically).The findings of this study suggest that the mediastinal tumor is a primary neoplasm with concomitant in situ lesion in one testis, suggesting a more generalized defect of germ cell and thus providing new information about the unresolved issue of the histogenesis of extragonadal germ cell tumors. This article presents a review of the literature concerning the issues highlighted by this case and discusses the hypotheses regarding the development of extragonadal germ cell tumors.
Histogenesis
Mediastinal tumor
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BACKGROUND The histogenesis of extragonadal germ cell tumors remains an enigma. The majority of patients with retroperitoneal tumors are male, and careful histologic evaluation reveals preinvasive intratubular germ cell neoplasia (ITGCN) or scars in the testis suggesting a so-called "burnt out" germ cell tumor. However, in the testes of patients with primary mediastinal germ cell tumors, no ITGCN has been described in the literature to date. The authors report the first case of simultaneous germ cell neoplasia in the mediastinum and the testis, providing further insights into the biology and origin of these lesions. METHODS The authors report the pathologic features and cytogenetic findings in an adult male with a mediastinal germ cell tumor and asymmetric testis. This patient died shortly after diagnosis. RESULTS A locally invasive mediastinal nonseminomatous germ cell tumor was associated with ITGCN in one testis. Metastases were not present clinically or on autopsy during a detailed and systematic examination of retroperitoneal lymph nodes and other viscera. Neither an invasive germ cell tumor nor a scar was found in either testis (both testes were serially sectioned and entirely examined histologically). CONCLUSIONS The findings of this study suggest that the mediastinal tumor is a primary neoplasm with concomitant in situ lesion in one testis, suggesting a more generalized defect of germ cell and thus providing new information about the unresolved issue of the histogenesis of extragonadal germ cell tumors. This article presents a review of the literature concerning the issues highlighted by this case and discusses the hypotheses regarding the development of extragonadal germ cell tumors. Cancer 1997; 79:1031-6. © 1997 American Cancer Society.
Histogenesis
Mediastinal tumor
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Extragonadal germ cell tumors are extremely rare and account for only 3%-5% of all germ cell tumors. These tumors are rarely associated with metachronous primary testicular germ cell tumors. We report the fourth case of a primary germ cell tumor occurring after the treatment of a primary CNS germ cell tumor in a 27 year-old male with embryonal cell carcinoma of the testicle 9 years after the treatment of a germ cell tumor of the pineal gland. This represents the first case of a non-seminomatous germ cell tumor of the testicle after a CNS germ cell tumor. This case illustrates the importance of long term follow-up and self-examination in patients with extragonadal germ cell tumors.
Testicle
Embryonal carcinoma
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During the past 10 years, high-dose chemotherapy (HDCT) has emerged as a feasible and curative treatment option for patients with multiply relapsed and/or refractory germ-cell tumors. Increasing experience and the results from clincial trials have helped to optimize the application of HDCT and to define its role in the salvage concepts for germ-cell tumors. Int. J. Cancer 83:839–840, 1999. © 1999 Wiley-Liss, Inc.
Salvage therapy
Refractory (planetary science)
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Gonadal ridge
Histogenesis
Germ line development
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Endodermal sinus tumor
Immature teratoma
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Hailemariam et al.1 described the simultaneous occurrence of a mediastinal germ cell tumor and intratubular germ cell neoplasia in the testis in a patient age 32 years. They postulated that both lesions originated in a common germ cell source. A germ cell line can certainly give rise to two different germ cell neoplasms. This explanation was actually offered to account for the association between hematopoietic malignancy and mediastinal germ cell tumor in the same host.2 Other examples of somatic neoplasms arising in patients with germ cell tumors abound.3, 4 In fact, to carry this hypothesis even further back on the histogenesis pathway, it is possible that all multiple tumors occurring in a given patient, be they simultaneous or metachronous, represent different neoplastic manifestations of a pluripotent stem cell element, be the element germ cell3 or otherwise.5 Had the young patient survived the mediastinal germ cell tumor, he may indeed have been at increased risk of developing malignancies other than the tumor of the left testis. The specific type of subsequent cancer may depend partly on alterations in the microenvironment that is "bathing" the stem cell in question.6 In fact, changes in the cellular milieu caused by irradiation6 and/or chemotherapeutic agents3 may explain the occurrence of treatment-related cancers in general. It is important, however, to point out that despite advances in molecular genetics, we are not quite able to delineate, clearly, the clonality of cells within a single tumor,7, 8 let alone track genetic changes that can occur during the progression, including metastasis9, 10 and recurrence,11 of a given tumor; and we are even less prepared to track such changes in different tumors arising in the same patient. K. C. Lee M.D.*
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