Germ Cell Tumor Components Research Articles

CDX2 Expression in Yolk Sac Component of Testicular Germ Cell Tumors

CDX2 has been detected in the majority of colorectal adenocarcinoma cases and may be useful in determining the sites of origin of tumors. In this study, the authors evaluated CDX2 expression in germ cell tumors (GCTs) by immunohistochemistry. Forty cases of testicular GCTs and 8 cases of metastatic GCTs were retrieved for study. In the 40 cases of testicular GCTs, 13 were pure seminomas and 27 mixed GCTs. Yolk sac tumor (YST) was identified by morphology and glypican 3 staining in 20 testicular mixed GCTs. Of these 20 cases, 8 cases showed 1+ positivity for CDX2. Other primitive components of GCTs were negative. For the 6 cases of metastatic mixed GCT with YST, 4 cases were positive, 2+ in 2 cases and 1+ in 2 cases. The positivity of CDX2 in GCTs warrants including YST in the differential diagnosis of adenocarcinoma of unknown origin.

Pathogenesis of Choriocarcinoma: Clinical, Genetic and Stem Cell Perspectives

Choriocarcinoma is a unique malignant neoplasm composed of mononuclear cytotrophoblasts and multinucleated syncytiotrophoblasts that produce human chorionic gonadotrophin. Choriocarcinoma can occur after a pregnancy, as a component of germ cell tumors, or in association with a poorly differentiated somatic carcinoma, each with distinct clinical features. Cytogenetic and molecular studies, predominantly on gestational choriocarcinoma, revealed the impact of oncogenes, tumor suppressor genes and imprinting genes on its pathogenesis. The role of stem cells in various types of choriocarcinoma has been studied recently. This review will discuss how such knowledge can enhance our understanding of the pathogenesis of choriocarcinoma, enable exploration of novel anti-choriocarcinoma targeted therapy and possibly improve our insight on embryological and placental development.

Seminoma With Conspicuous Signet Ring Cells: A Rare, Previously Uncharacterized Morphologic Variant

We report 2 seminomas with conspicuous numbers of signet ring cells. The tumors occurred in men, 24 and 69 years of age, who presented with testicular masses; 1 seminoma was a component of a mixed germ cell tumor and the other was pure. The signet ring cells occurred in a multifocal fashion in areas of otherwise typical seminoma and comprised approximately 70% and 10%, respectively, of the tumors. They had large, translucent to clear cytoplasmic vacuoles that compressed the nuclei to a peripheral crescent. In 1 case, the vacuoles contained numerous refractile, nonpolarizable globular deposits that were shown to be glycogen on the basis of periodic acid-Schiff stain positivity that was abolished by pretreatment with diastase; in the second case, they mostly appeared "empty" and lacked periodic acid-Schiff positivity. The signet ring cells were mucicarmine, cytokeratin (AE1/3) and alpha-fetoprotein negative, but positive for OCT3/4 and CD117, the latter 2 being expected for seminoma cells. A review of 30 randomly selected seminomas identified very rare, inconspicuous signet ring cells in 43%. The presence of prominent signet ring cells in seminoma may cause confusion as it has not been described previously in detail, and a variety of neoplasms, particularly metastasis, may be considered. The description of this phenomenon expands the known morphologic spectrum of the most common testicular neoplasm.

Metachronous mature teratoma in the corpus callosum occurring 12 years after a pineal germinoma

The authors report a metachronous germ cell tumor with different histological type occurring 12 years after resection of a pineal germinoma. Histological examination of the original tumor revealed germinoma without any other component of germ cell tumor, and the patient underwent chemotherapy followed by 24 Gy of localized irradiation. Twelve years later, follow-up MR imaging showed a round mass in the genu of the corpus callosum. Two courses of chemotherapy were administered, but the tumor size remained stable. A second operation was performed and this second tumor was completely removed. The histological diagnosis was mature teratoma. The second tumor was considered as a metachronous mature teratoma rather than a recurrence of the original germinoma. To the authors' knowledge, this combination of metachronous germ cell tumor has not previously been reported in the literature.

Results with salvage chemotherapy with high dose carboplatin + etoposide and peripheral blood stem cell transplant in male choriocarcinoma

5091 Background: Choriocarcinoma in males is seen usually as a small component of a mixed germ cell tumor. Pure choriocarcinoma accounts for a poor prognosis, usually presenting with high level of human chorionic gonadotropin (hCG > 50,000 mIU/ml) and with pulmonary and non-pulmonary visceral metastases. Results with salvage chemotherapy in the past have been very poor with very few long-term survivors. Methods: Retrospective review of 184 germ cell patients treated with salvage high dose chemotherapy (HDCT) at Indiana University between 2–96 and 12–04 was presented (Proc Amer Soc Clin Oncol 24:228, abstract 4549, 2006). Thirteen of these patients had pure choriocarcinoma of the testis or choriocarcinoma syndrome (normal testes by palpation and ultrasound, normal serum alpha-fetoprotein, advanced hematogenous metastases, high level of hCG). Before HDCT, all the patients were treated with one or two regimens of standard cisplatin combination chemotherapy. HDCT regimen consisted of carboplatin 700 mg/m2 and etoposide 750 mg/m2 i.v. given for 3 consecutive days. A second course was given after hematologic recovery. Results: Toxicity was previously described (JCO 18:3346, 2000).The median survival was 19 months (range 5–90 months). Six patients (46%) are alive and continuously disease-free (cNED) with a median follow-up of 37 months (range 19–75). One additional patient is currently NED following subsequent chemotherapy and surgery. 3 of 7 patients with pure choriocarcinoma are cNED and 3 of 6 with choriocarcinoma syndrome are cNED. Six of 10 patients receiving HDCT as initial salvage therapy are cNED compared to 1 of 3 as third-line treatment. Conclusions: Salvage HDCT offers long-term disease-free survival and potential cure in patients with pure choriocarcinoma or choriocarcinoma syndrome that progressed after standard cisplatin combination chemotherapy. No significant financial relationships to disclose.

D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30

AbstractThe distinction between seminoma and embryonal carcinoma based on morphology alone can sometimes be problematic, requiring the use of immunohistochemistry to facilitate diagnosis. D2-40 is a monoclonal antibody that reacts with an oncofetal antigen expressed by fetal germ cells and testicular germ cell tumors. The diagnostic value of D2-40 immunohistochemistry in distinguishing seminoma from embryonal carcinoma has not been determined. D2-40 immunoreactivity was evaluated in a series of testicular germ cell tumors and compared with that of KIT (CD117) and CD30, to assess the relative utility of this marker in discriminating between seminoma and embryonal carcinoma. Forty testicular germ cell neoplasms were examined, which included 19 seminomas, three embryonal carcinomas, three teratomas, one yolk sac tumor, and 14 mixed germ cell tumors. The 14 cases of mixed germ cell tumors contained components of seminoma (n=7), embryonal carcinoma (n=11), teratoma (n=10), yolk sac tumor (n=2), and choriocarcinoma (n=1). All cases of pure seminoma and the seminomatous components of mixed germ cell tumors exhibited positive immunoreactivity for D2-40. Focal positivity for D2-40 was also observed in 29% of the embryonal carcinoma samples. D2-40 immunoreactivity in seminomas was characterized by diffuse membrane staining, whereas for embryonal carcinomas, staining was focal and distributed along the apical surfaces of the neoplastic cells. Immunohistochemical staining for KIT was observed in 92% of the seminoma samples and in none of the embryonal carcinomas. Conversely, CD30 expression was identified in 93% of the embryonal carcinoma samples and in none of the seminomas. Other germ cell components showed no immunoreactivity for D2-40, KIT, or CD30. KIT and CD30 are effective immunohistochemical markers in separating seminoma from embryonal carcinoma. Although a highly sensitive marker for seminomas, D2-40 positivity was also observed in a subset of embryonal carcinomas, thus limiting the utility of this antibody for discriminating between these two malignancies.

Immunohistochemical Analysis of Neuroendocrine (NE) Differentiation in Testicular Germ Cell Tumors (GCTs): Use of Confocal Laser Scanning Microscopy (CLSM) to Demonstrate Direct NE Differentiation from GCTs

Neuroendocrine (NE) differentiation is infrequent in testicular tumors and its histogenesis is not well understood. The present study is aimed at elucidating the pathway of neuroendocrine differentiation in germ cell tumors (GCTs) of the testis. In the analysis of 46 germ cell tumor components from 23 testicular tumors, we focused on GCTs with neuroendocrine differentiation, 7 teratoma, 1 embryonal carcinoma and 1 neuroendocrine carcinoma by immunohistochemical study and confocal laser scanning microscopy (CLSM) analysis. NE marker positive cells were noted in the tumor with collision of teratoma and embryonal carcinoma (E&T tumor), in the immature columnar cells of transitional form of embryonal carcinoma to teratoma (E-T cells) and neuroendocrine carcinoma cells, in addition to the well known mature intestinal mucosa in teratoma. Double staining for a NE marker (CGA) and a germ cell marker (PLAP) demonstrated the localization of both proteins in the same E-T cells confirmed by CLSM. Another finding, indicating the intimate relation between embryonal carcinoma and neuroendcrine differentiation, is that neuroendocrine carcinoma expressed a marker of embryonal carcinoma, CD30. The present results indicated that the NE cells might be differentiated from embryonal carcinoma, a view that has not been proposed before, but that is made in the present study using CLSM.

Glypican 3: A Novel Marker in Testicular Germ Cell Tumors

Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). We conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Our findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma.

Teratoma with Malignant Transformation: Experiences of the Cooperative GPOH Protocols MAKEI 83/86/89/96

The designation of a teratoma with malignant transformation (TMT) refers to the occurrence of somatic non-germ cell malignancies within a teratoma. While TMT is a rare but well recognised phenomenon in adult germ cell tumors (GCT), data on TMT in pediatric GCTs are lacking. Between 1982 and 2003, 641 patients with extracranial nontesticular pure teratoma (256 coccygeal, 246 ovarian, 139 other sites) were reported to the MAKEI protocols 83/86/89/96 by various, mainly German centres. Patients with teratoma and somatic malignancy were identified by database queries. Patients with malignant germ cell tumor components were excluded from this analysis. The clinical files were reviewed and re-evaluated centrally. Information was actualized by requisition to the participating hospitals. We identified nine patients (all female, age 0-39 years) meeting the histological criteria of TMT. Two patients had coccygeal teratomas and seven ovarian tumors. Carcinoma was the dominating malignancy (five of nine cases). Tumors with glial differentiation and embryonal tumors occurred in two cases each. Resection was performed in seven patients (including both coccygeal tumors) and adjuvant chemotherapy was administered in one of them. Two patients relapsed after resection, but both were cured with chemotherapy. Two patients suffered from advanced tumors and both were treated with primary chemotherapy. One patient was cured from the malignant component (astrocytoma), but the teratomatous components persisted. The other patient died as a result of progression of her malignant medulloepithelioma. Malignant transformation of pure teratomas constitutes a very rare entity in children and adolescents that is most commonly observed in postpubertal girls with ovarian teratoma. Compared to adult patients, similar malignant entities can be observed in association with teratoma. However, in our series, no sarcoma was diagnosed. In localised tumors, complete resection appears to be adequate, whereas chemotherapy should be considered in patients with R1- or R2-resection. Cisplatinum-based chemotherapy was effective as two of four relapsed patients survived tumor free. However, the ideal regimen has not yet been established and the known sensitivity of the histologic components to cytostatic drugs has to be considered in the choice of treatment. Further molecular biologic studies are necessary to understand the origin of these tumors.

Clonal Origin of Metastatic Testicular Teratomas

Testicular teratomas in adult patients are histologically diverse tumors that frequently coexist with other germ cell tumor (GCT) components. These mixed GCTs often metastasize to retroperitoneal lymph nodes where multiple GCT elements are frequently present in the same metastatic lesion. Neither the genetic relationships among the different components in metastatic lesions nor the relationships between primary and metastatic GCT components have been elucidated. We examined metastases from 31 patients who underwent primary retroperitoneal lymph node dissection for metastatic testicular GCT. All patients had metastatic mature teratoma with one or more other GCT components. This study included a total of 72 metastatic GCT components and 16 primary GCT components from 31 patients. Genomic DNA samples from each component were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. Loss of heterozygosity (LOH) assays for seven microsatellite polymorphic markers on chromosomes 1p36 (D1S1646), 9p21 (D9S171 and IFNA), 9q21 (D9S303), 13q22-q31 (D13S317), 18q22 (D18S543), and 18q21 (D18S60) were done to assess clonality. Twenty-nine of 31 (94%) cases showed allelic loss in one or more components of the metastatic GCTs. Twenty-nine of 31 mature teratomas showed allelic loss in at least one of seven microsatellite polymorphic markers analyzed. The frequency of allelic loss in informative cases of metastatic mature teratoma was 27% (8 of 30) with D1S1646, 34% (10 of 29) with D9S171, 37% (10 of 27) with IFNA, 27% (8 of 30) with D9S303, 46% (13 of 28) with D13S317, 26% (7 of 27) with D18S543, and 36% (10 of 28) with D18S60. Completely concordant allelic loss patterns between the mature teratoma and all of the other metastatic GCT components were seen in 26 of 29 cases in which the mature teratoma component showed LOH. Nearly identical allelic loss patterns were seen in the three remaining cases. In six cases analyzed, LOH patterns of each metastatic component were compared with each GCT component of the primary testicular tumor. In all six cases, each primary and metastatic component showed an identical pattern of allelic loss. Our data support the common clonal origin of metastatic mature teratomas with other components of metastatic testicular GCTs and with each component of the primary tumor.

Primary endodermal sinus tumor of the cerebellar hemisphere: a case report with review of the literature

Primary intracranial endodermal sinus tumors, which have been regarded as a rare histologic subtype, usually arise in the pineal and suprasellar regions and are often associated with components of other germ cell tumors. We report an extremely rare case of pure primary endodermal sinus tumor found in the cerebellar hemisphere. A 3-year-old boy was admitted to our institution because of gait disturbance, vomiting and deteriorated mental state. MR imaging revealed the presence of a round mass with heterogeneous enhancement in the left cerebellar hemisphere. Radical surgical removal of the tumor was performed, followed by adjuvant chemotherapy, consisting of etoposide, carboplatin and bleomycin. The patient has since attended regular follow-ups, without any neurological deficit or signs of recurrence in the 4 years since diagnosis.

Neck mass as the first presentation of testicular choriocarcinoma

Choriocarcinoma is a highly malignant tumor of the testis and usually occurs as a component of mixed germ cell tumor. The testicular enlargement may be subtle, and the patient may present with metastasis, the neck being one of its least reported locations. A case of testicular choriocarcinoma in a 24-year-old man who presented for the first time with metastatic neck mass is reported here. This presentation, although very rare, can be a great diagnostic and therapeutic challenge and should be considered in the differential diagnosis of cervical masses occurring in young males.

OCT4 Staining in Testicular Tumors. A Sensitive and Specific Marker for Seminoma and Embryonal Carcinoma

OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma. We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool. We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining. Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and “usual,” but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma: Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.

OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma. We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool. We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining. Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and “usual,” but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma.

OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma. We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool. We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining. Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and "usual," but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

A Case of Primary Ovarian Choriocarcinoma in a Postmenopausal Woman

Nongestational pure ovarian choriocarcinoma is an uncommon condition and accounts for less than 0.6% of all ovarian tumors. It occurs most frequently as a component of a mixed germ cell tumor, and the presence of other germ cell elements establishes the nongestational origin of the tumor. Providing that a pure choriocarcinoma in the ovary is gestational in origin is difficult but important, as a primary germ cell tumor of the ovary is said to have worse prognosis and require more aggresive treatment. Here we report a case of primary nongestational choriocarcinoma in postmenopause woman with the review of literature.

Gonadal teratomas: a review and speculation.

Teratomas of the ovary and testis are confusing because, despite histologic similarities, they exhibit different biologic behaviors, depending mostly on the site of occurrence and the age of the patient. Thus, most ovarian teratomas are benign, and most testicular teratomas are malignant, with the exception of those occurring in children. These general statements, however, do not hold true for ovarian teratomas that are "immature" or exhibit "malignant transformation" and for dermoid and epidermoid cysts of the testis, categories of ovarian and testicular teratomas that are malignant and benign, respectively. This review concentrates on some of the "newer" observations concerning these interesting and confusing neoplasms, including diagnostically deceptive patterns. It is the author's opinion that much of the confusion regarding gonadal teratomas can be clarified by the concept that the usual ovarian teratoma derives from a benign germ cell in a parthenogenetic-like fashion, whereas the typical postpubertal testicular example derives from a malignant germ cell, mostly after evolution of that originally malignant cell to an invasive germ cell tumor (ie, embryonal carcinoma, yolk sac tumor, etc). The postpubertal testicular teratomas can therefore be thought of as an end-stage pattern of differentiation of a malignant germ cell tumor. The pediatric testicular teratomas, as well as dermoid and epidermoid cysts of the testis, however, must derive from benign germ cells, in a fashion similar to most ovarian teratomas. The teratomatous components of mixed germ cell tumors of the ovary, on the other hand, likely have a pathogenesis similar to that of postpubertal testicular teratomas.

Identical Allelic Losses in Mature Teratoma and Other Histologic Components of Malignant Mixed Germ Cell Tumors of the Testis

Teratomas of the testis in post-pubertal patients are histologically diverse tumors that often coexist with other types of germ cell tumors. Using laser capture microdissection and loss of heterozygosity analysis, we investigated the clonality of mature teratoma and its relationship to other components of malignant mixed germ cell tumors to gain potential insight into the histogenetic relationship of teratoma with other germ cell tumor components. All 16 patients had mature teratoma as one component of their mixed germ cell tumors. The other histological subtypes included immature teratoma, seminoma, embryonal carcinoma, yolk sac tumor, and choriocarcinoma. Laser-assisted microdissection was performed on the formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 1p36.2 (D1S508), 2q22-32 (D2S156), 9p21-22 (D9S162), 11p13 (D11S903), 12q22-23 (D12S1051), and 18q21 (D18S46). Fourteen of 16 (88%) cases showed allelic loss in one or more components of the mixed germ cell tumors. Fourteen of 16 mature teratomas showed allelic loss in at least one of six microsatellite polymorphic markers analyzed. The frequency of allelic loss in mature teratoma was 50% (7 of 14) with D1S508, 33% (5 of 15) with D2S156, 58% (7 of 12) with D9S162, 43% (6 of 14) with D11S903, 20% (3 of 15) with D12S1051, and 33% (5 of 15) with D18S46. Completely concordant allelic loss patterns between mature teratoma and all of the other germ cell tumor components were seen in 10 of 14 tumors in which mature teratoma showed loss of heterozygosity. Our data support the common clonal origin of mature teratoma with other components of malignant mixed germ cell tumors of the testis.