Yolk Sac Tumor Component Research Articles

Rhabdomyosarcoma arising in mediastinal teratoma in anadult man: a case report

We report a case of rhabdomyosarcoma which occurred in a mediastinal teratoma in a 44-year-old man. Presentation symptoms were chest pain, hoarseness and a cough. Diagnosis was fortuitous, performed by the histological and immunohistochemical study of a mediastinal tumour biopsy specimen that showed embryonal carcinoma and yolk sac tumour components associated with the rhabdomyosarcoma. After cisplatin-based chemotherapy (bleomycin–etoposide–cisplatin), surgical resection of the residual mediastinal tumour was performed. Histological and immunohistochemical study of this tumour confirmed the presence of mature teratoma and embryonal rhabdomyosarcoma. Evolution was marked by a local extension of the mediastinal tumour, occurrence of multiple metastases and bone marrow involvement. The patient died 8 months after diagnosis despite chemotherapy and radiotherapy. A review of the literature reveals that the development of rhabdomyosarcoma in primary mediastinal teratomas is unusual in adults. The diagnostic, therapeutic and prognostic implications of such an association are reviewed.

Combined yolk sac tumor and adenocarcinoma in a gastric stump

BACKGROUND Extragonadal yolk sac tumors of the gastrointestinal tract are extremely rare neoplasms. Their greater rarity compared with other extragonadal yolk sac tumors suggests that different pathogenetic mechanisms could be involved according to the site of origin. This report describes a case of a combined yolk sac tumor and adenocarcinoma that arose in a gastric stump in a man age 61 years 43 years after he underwent distal gastric resection and gastrojejunostomy (Billroth II operation) for a benign duodenal ulcer. The coexistence of an adenocarcinomatous component with the yolk sac component suggests that the two histologic patterns may represent distinct phenotypes arising from a common mucosal epithelial cell. METHODS Immunohistochemical and molecular techniques were used to define the mutation pattern of p53 in both components of the tumor. RESULTS Single-strand conformation polymorphism and sequencing analyses demonstrated the same pattern of p53 mutation in the adenocarcinomatous and yolk sac tumor components. CONCLUSIONS This finding suggests that the two tumors could have been derived from the same cellular clone and supports the hypothesis that the two components represented a heterogeneous differentiation of the same tumor. Cancer 1999;85:1910–6. © 1999 American Cancer Society.

Combined yolk sac tumor and adenocarcinoma in a gastric stump

BACKGROUND Extragonadal yolk sac tumors of the gastrointestinal tract are extremely rare neoplasms. Their greater rarity compared with other extragonadal yolk sac tumors suggests that different pathogenetic mechanisms could be involved according to the site of origin. This report describes a case of a combined yolk sac tumor and adenocarcinoma that arose in a gastric stump in a man age 61 years 43 years after he underwent distal gastric resection and gastrojejunostomy (Billroth II operation) for a benign duodenal ulcer. The coexistence of an adenocarcinomatous component with the yolk sac component suggests that the two histologic patterns may represent distinct phenotypes arising from a common mucosal epithelial cell. METHODS Immunohistochemical and molecular techniques were used to define the mutation pattern of p53 in both components of the tumor. RESULTS Single-strand conformation polymorphism and sequencing analyses demonstrated the same pattern of p53 mutation in the adenocarcinomatous and yolk sac tumor components. CONCLUSIONS This finding suggests that the two tumors could have been derived from the same cellular clone and supports the hypothesis that the two components represented a heterogeneous differentiation of the same tumor. Cancer 1999;85:1910–6. © 1999 American Cancer Society.

Cytogenetic Analysis of a Mature Teratoma and a Yolk Sac Tumor Component of a Late Relapse of a Disseminated Testicular Nonseminoma

We report on the cytogenetics of a primary testicular nonseminoma, a residual mature teratoma after remission-induction chemotherapy, and a late relapse after 9 years of follow-up, in one patient. The late relapse was composed of a mature teratoma and a yolk sac tumor component. Cytogenetic comparison of the different tumors shows that progression of primary testicular nonseminoma to residual mature teratoma and to a late-relapse lesion is accompanied by net loss of chromosomes. In addition, our findings may suggest that transformation to viable cancer in a late-relapse lesion is accompanied by further chromosomal losses.

Preliminary observations for a new treatment in children with primary intracranial yolk sac tumor or embryonal carcinoma. Report of five cases.

The authors evaluated the effect of adjuvant therapy (preoperative chemotherapy combined with radiotherapy) followed by radical tumor removal in the treatment of children with primary intracranial yolk sac tumor, embryonal carcinoma, or mixed germ cell tumors containing yolk sac tumor components. Between 1988 and 1995, five consecutive patients were treated with adjuvant therapy followed by total tumor removal. The diagnosis was based on markedly elevated concentrations of serum alpha-fetoprotein (AFP) and/or beta-human chorionic gonadotropin (beta-HCG) in four children and the results of biopsy sampling in one child. The chemotherapy regimen consisted of cisplatin (20 mg/m2) and etoposide (60 mg/m2) daily for 5 days (one course) given three times at 4-weeks intervals. Radiotherapy consisted of 30 to 40 Gy to the whole brain or an area including all ventricles and a 15- to 20-Gy boost to the tumor site. Spinal radiation of 25 Gy was added in one patient. In all patients the serum level of AFP and beta-HCG gradually decreased during the adjuvant therapy and disappeared completely on its completion. In two of the five patients the tumor disappeared as well. In the other three patients the tumor size was moderately or markedly reduced and the remaining tumor was totally removed; there were no neurological deficits. Chemotherapy was maintained after the initial treatment and was repeated every 2 to 4 months for less than 2 years. All children are alive and well without recurrence at 33 to 118 months (average 88 months) after the start of adjuvant therapy. Our preliminary results indicate that adjuvant therapy consisting of combination chemotherapy with cisplatin and etoposide and concomitant radiotherapy, followed by removal of the tumor, is highly effective in the treatment of pediatric patients with primary intracranial yolk sac tumor, embryonal carcinoma, or mixed germ cell tumors containing yolk sac tumor components.

Histologically pure seminoma with elevated alpha-fetoprotein: a clinicopathologic study of ten cases.

Seminomas account for 50% of testicular germ-cell tumors, and more than 90% of these are classic seminomas. When patients with a histologically pure testicular seminoma show an elevated level of serum á-fetoprotein (AFP), it is generally assumed that an undetected focus of yolk sac tumor (YST) is present and the patient is managed with a treatment regimen for non-seminomatous tumor. We studied 10 cases of histologically pure seminoma with elevated levels of serum AFP in an attempt to identify any distinctive clinical, histopathologic, or immunohistochemical features. The patients ranged in age from 27 to 48 years (mean, 31 years). Eight patients had primary tumors of the testis, and two presented with supraclavicular and ileal tumors. The clinical stage at presentation varied: four tumors were stage I, four were stage II, and two were stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to 16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary tumors and metastases when present exhibited classic seminoma histology without other germ-cell components. The tumor cells expressed keratin in seven cases. The pattern of keratin immunoreactivity ranged from focal staining in five cases to moderate staining in two cases. All cases were negative for AFP, and the nine cases in which staining for CD30 (Ki-1) was performed were also negative. All four patients with stage I tumors underwent the conventional therapy for pure seminoma, i.e., orchiectomy and subsequent radiation therapy. Five patients received treatment for non-seminomatous tumors, i.e., chemotherapy after orchiectomy. Extensive work-up failed to detect the primary tumor in one patient, and he was treated for a non-seminomatous tumor, undergoing chemotherapy and irradiation. All patients are alive and well, and none has developed evidence of YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one patient who presented with an ileal metastasis recently developed a second primary extragonadal mediastinal mixed germ-cell tumor with YST and embryonal carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10-year disease-free follow-up. This study strongly suggests that minor elevations (</= 16 ng/ml) of AFP in patients with an otherwise pure seminoma may not indicate that there is a hidden focus of YST and that such patients should be treated with standard therapy for seminoma. Because this study includes very few patients, further studies are required to better understand the significance of borderline elevations of AFP in cases of histologically pure seminoma.

Ovarian endometrioid tumors with yolk sac tumor component, an unusual form of ovarian neoplasm. Analysis of six cases.

The clinical, morphological, and immunohistochemical findings in six cases of ovarian endometrioid tumors (five endometrioid carcinomas and one carcinosarcoma) with a yolk sac tumor (YST) component are described. The age of the patients ranged from 31 to 73 years (average, 53), and only two patients were premenopausal. Two cases were stage Ia tumors, three stage III, and one stage IV. A substantial postoperative elevation of alpha-fetoprotein (AFP) was seen in two patients and a mild increase in another two. All six patients had surgery and postoperative cisplatin-based chemotherapy regimens, four of whom died of tumor 3 to 14 months after surgery without response to treatment. Only a stage Ia patient is alive and well 1 year after surgery. The tumors were large (average, 17 cm). Benign endometrioid lesions were found in the homolateral ovary in two cases and in the contralateral ovary in another two. All cases had endometrioid ovarian carcinomas (EOC) of various types admixed with typical YST components. Immunohistochemically, EOC areas differed from YST in their positivity for OC 125, CA 19.9, and nuclear estrogen and progesterone receptors and in their negativity for AFP, which was conspicuously positive in the YST areas. The clinicopathological profile of ovarian endometrioid tumors with YST also differs from that of YST in that it occurs in the same age range as EOC, it shows coexistence of benign endometrioid lesions, and it has a poor response to chemotherapy. The histological pattern in transitional areas may be difficult to differentiate from "endometrioid-like" (enteroblastic) YST and clear cell tumors. Ovarian endometrioid tumors with YST component should be considered a variant of endometrial carcinoma. Its recognition is necessary in view of its unusually aggressive behavior and poor prognosis.

Interphase cytogenetics on paraffin sections of paediatric extragonadal yolk sac tumours

Germ cell tumours in children are more often extragonadal than in adults and the most frequent type is the yolk sac tumour. Limited cytogenetic data exist on extragonadal yolk sac tumours in children. We applied in situ hybridization (ISH) to interphase cell nuclei of four paediatric extragonadal pure yolk sac tumours and one yolk sac tumour component of a mixed germ cell tumour using paraffin-embedded tissue sections. The panel of chromosome-specific DNA probes was selected on the basis of their relevance in adult germ cell tumours and consisted of five DNA probes specific for the (peri)centromeric regions of chromosomes 1, 8, 12, and/or 17, X and/or one DNA probe specific for the subtelomeric region of chromosome 1 (p36.3). Only one tumour failed to show numerical and structural chromosome aberrations with the DNA probes used. The other four had an increased incidence of numerical chromosome aberrations with an over-representation of at least one chromosome. The DNA indices determined in the paraffin-embedded tumour material correlated well with the in situ hybridization findings. In only a few cases were chromosomes over-represented, when compared with the corresponding DNA indices. Recently, we have shown that the short arm of chromosome 1 is a non-random site of deletion in paediatric gonadal pure yolk sac tumours. The occurrence of similar deletions in one extragonadal pure yolk sac tumour and in one yolk sac tumour component, in conjunction with two further ISH reports, suggests that the loss of gene(s) in this region is an important event in the pathogenesis of paediatric malignant germ cell tumours of nearly all sites.

Diffuse Embryoma of the Testis:An Immunohistochemical Study of Two Cases

The authors report the histologic and immunohistochemical findings of two cases of diffuse embryoma of the testis, a distinct form of mixed-germ-cell tumor characterized by diffuse, orderly arrangement of embryonal carcinoma (EC) and yolk sac tumor (YST) with scattered trophoblastic components. The patients were 37 and 38 years old when they presented with a right testicular tumor, which was confined to the testis (stage I) in both cases. Histologically, the tumor was composed predominantly of intimately intermingled EC and YST components in almost equal proportion. The tumor cells were arranged in necklacelike fashion; the EC cells formed glandular structures rimmed by a single cell layer of YST cells. The YST component was highlighted by positive staining for alpha-fetoprotein and strong staining for cytokeratin, whereas the EC component was positive for Ki-1 (BerH2, CD30) antigen, was negative for alpha-fetoprotein, and stained more weakly for cytokeratin. The randomly distributed few trophoblastic elements stained for human chorionic gonadotropin. The patients are alive with no evidence of disease, 11 years and 9 months after surgery, respectively. This newly described but distinct variant of mixed-germ-cell tumor should be differentiated from polyembryoma, which is composed of multiple discrete embryoid bodies.

Ber-H2 expression in testicular germ cell tumors

Expression of CD30 antigen using the monoclonal antibody Ber-H2 was investigated in 52 testicular tumors: pure seminoma (19 cases), pure embryonal carcinoma (eight cases), and mixed germ cell tumors (25 cases). None of the seminomas expressed Ber-H2, whereas seven of eight pure embryonal carcinomas contained this antigen. In mixed germ cell tumors Ber-H2 was present in none of 10 seminomatous components, none of seven yolk sac tumor components, and 20 of 24 embryonal carcinoma components. Teratomatous elements (16 cases) failed to stain with Ber-H2. Also, foci of intratubular germ cell neoplasia (ITGCN) (31 cases) failed to express Ber-H2. Ber-H2 is useful in distinguishing embryonal carcinoma from seminoma and yolk sac tumor. The failure of expression of Ber-H2 in ITGCN, as in seminoma, supports the close relationship of seminoma with ITGCN.

Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors

Patients with mediastinal germ cell tumors (MGCT) have a high incidence of hematologic malignancies unrelated to cytotoxic chemotherapy. It has been suggested that these leukemic conditions originate from a MGCT progenitor cell capable of undergoing non-germ cell (hematopoietic) differentiation.To assess this hypothesis, histologic material from six patients with MGCTs associated with leukemia was examined using monoclonal and polyclonal antibodies capable of labeling cells of the different marrow cell lineages.Morphologically identifiable hematologic cells were found within the yolk sac tumor component of the MGCT in four of these patients. In three of the four cases, the cells consisted of poorly differentiated blast cells, whereas in the fourth, clusters of erythroblasts were identified. The leukemic cells within the MGCT and in the bone marrow had similar morphology, constant expression of the early progenitor cell marker CD34, and variable expression of more mature myeloid, monocytic, erythroid, and megakaryocytic markers. Three cases expressed p53, a nuclear protein associated with neoplastic transformation in a wide range of malignancies, including testicular cancers, but which rarely is reported in leukemias. Karyotype of the leukemia was assessed in five cases: two showed an i(12p), a cytogenetic marker of GCT not identified in the usual cases of leukemia.The results support the hypothesis that these leukemic conditions originate in the MGCT through a mechanism of differentiation from a yolk sac tumor-derived progenitor cell, with subsequent homing to the marrow.

Rete Testis Hyperplasia with Hyaline Globule Formation

The presence of eosinophilic, hyaline globules in association with epithelial hyperplasia was noted in the rete testis of three patients with germ cell tumors. In the more florid examples, this proliferation formed a solid and microcystic pattern that, in association with the hyaline globules, mimicked a yolk sac tumor component. However, the bland cytologic features of the cells and the conformation to the configuration of the rete testis were keys to its reactive nature. A subsequent review of 48 testicular specimens containing well-defined areas of the rete testis showed hyaline globule formation in the rete testis or tubuli recti in 16 of 27 germ cell tumors, one of five other testicular tumors (four stromal tumors and one plasmacytoma), and none of 16 nonneoplastic cases. Many of the cases that had hyaline globules also showed epithelial hyperplasia. Further analysis demonstrated an incidence of rete testis invasion by neoplasm in cases that had hyaline globules, with or without epithelial hyperplasia, that was significantly higher (p less than 0.01) than that seen in neoplastic cases lacking hyaline globules. We concluded that this pseudoneoplastic reaction developed secondary to invasion of the rete testis by tumor. Immunostains supported the nonneoplastic nature of the proliferative lesions and indicated that the globules represented various proteins that had been absorbed from the lumen of the rete testis by the epithelial-lining cells but not successfully secreted.

Human yolk‐sac tumor antigen 2G10: Biochemical characterization and significance as a serum antigen

The biochemical characterization of human yolk-sac tumor (YST) antigen 2G10, detected by monoclonal antibody (MAb) M912-2G10, was studied. Previous results indicated that glycolipids having a non-reducing terminal N-acetyllactosamine structure were the epitope of 2G10 on human erythrocytes. In this study, the glycoprotein nature of 2G10 on the infantile embryonal carcinoma line, MTE, was investigated. 2G10 activity, measured by a new enzyme-linked immunosorbent assay (2G10-ELISA), was recovered in residual fractions of MTE from which glycolipids were removed. Chromatographically, 3H-galactose-labelled 2G10 on MTE had a molecular weight (mw) of about 580 kDa, which decreased after pronase or alkaline-borohydride treatment. Our results indicate the glycoprotein nature of 2G10 on MTE. Furthermore, 2G10, both on erythrocytes and on MTE, was sensitive to galactosidase but not to neuraminidase and fucosidase, suggesting that terminal galactose is involved in the antigenic structure. It was also found by 2G10-ELISA that 2G10 sheds from tumor cells. Shedding occurs in nude mice transplanted with MTE as well as in patients with germ-cell tumors (GCTs). The serum level of 2G10 in non-tumor patients was low, but high levels were detected in patients with YSTs and with GCTs having YST components. Immunohistochemically, the presence of 2G10-positive YST components was shown in patients who had high serum levels of 2G10. Sera from other urogenital and childhood solid tumors did not have elevated 2G10. The mw of shed 2G10 was lower than that of 2G10 on the cell surfaces. Our results clearly indicate the usefulness of serum 2G10 as a tumor marker for GCTs having YST components.

Primary intracranial germ-cell tumors. A clinicopathological study of 14 cases.

Fourteen cases of primary intracranial germ-cell tumors are presented. Histologically, there were eight germinomas, three teratomas, and three germ-cell tumors of more than one histological type. Immunohistochemical studies revealed alpha-fetoprotein in yolk-sac tumor components in two cases and beta human choriogonadotropin in syncytiotrophoblastic giant cells in one case. One teratoma contained an unusual pleomorphic sarcomatous portion with features of early myoblastic differentiation. Comparison of intracranial with gonadal germ-cell tumors shows that the same subtypes are found in both locations with comparable incidence and similar biological behavior. The detailed World Health Organization classification of testicular germ-cell tumors should be applied to the histopathological classification of intracranial germ-cell tumors. Despite the critical location of intracranial germ-cell tumors, a good outcome can be achieved by optimal surgical excision. A primary microsurgical approach provides a histopathological diagnosis, which is indispensable for the proper choice of postoperative management.

Alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in testicular germ cell tumours. A prospective immunohistochemical study.

189 orchidectomy specimens with germ cell tumours (95 pure seminomas and 94 non-seminomas) were studied for the presence of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) with the indirect immunoperoxidase technique. All seminomas were AFP negative, while 66% of the non-seminomas were positively stained for AFP. 21% of pure embryonal carcinomas (EC), 25% of EC components in mixed tumours, all yolk sac tumour (YST) components, 20% of pure teratomas (T) and 47% of T components were AFP positive. In EC and YST the immunohistochemical staining depicted characteristic previously unrecognized histological structures, presumably representing patterns of further differentiation. HCG was demonstrated in all choriocarcinoma (CC) components in the syncytiotrophoblasts and in syncytiotrophoblast-like cells (STLC) in 8% of seminomas and 30% of non-seminomas. 70% of all non-seminomatous tumours were positively stained for AFP and/or HCG. Neither AFP nor HCG positivity of the tumour tissue was especially associated with metastatic disease. Carcinoma-in-situ (CIS) present in seminiferous tubules adjacent to the tumours was never positively stained for AFP, but for HCG in a few cases.

Possible liver cell differentiation in testicular germ cell tumours.

Germ cell tumours may imitate various structures of the developing embryo and foetus. Certain structures have, however, very rarely or never been observed in these tumours. Thus the presence of hepatic tissue in testicular germ cell tumours has not been reported. In a series of 37 non-seminomatous testicular tumours seven tumours contained epithelial structures showing morphological and functional resemblance to liver cell trabeculae. These structures were present in tumours with yolk sac tumour (YST) components and most of the tumours also contained teratoid elements. With the immunoperoxidase technique the epithelial structures were heavily stained for alpha-foetoprotein (AFP) and ferritin in all cases, while positive staining for albumin, prealbumin and transferrin was occasionally found. Alpha-I-antitrypsin and haemoglobin F were demonstrated in few scattered cells. Whether or not these epithelial structures should be included among the various patterns of YST or considered to be teratoid components is uncertain. It is suggested that examinations of the heterogeneity of the concomitant serologic AFP may support one or other assumption.

Distribution of tumor-associated antigens in the various histologic components of germ cell tumors of the testis.

The various histologic components of 39 germ cell tumors of the testis were studied with indirect labeled immunoperoxidase technique for the presence of the following tumor-associated antigens: alpha-fetoprotein (AFP), alpha 1-antitrypsin (A1AT), chorionic gonadotropin (HCG), specific pregnancy beta 1-glycoprotein (SP1), human placental lactogen (HPL), carcinoembryonic antigen (CEA), and ferritin (Fe). Embryonal carcinoma components were positive for AFP in 9/16, for A1AT in 6/16, for CEA in 2/16, and for Fe in 14/16. All yolk-sac tumor components were positive for AFP and Fe, and 8/13 contained A1AT and 2/13 CEA. Epithelium in teratoid components was positive for AFP in 5/14 cases, for A1AT in 8/14, for CEA in 7/14, and for Fe in 8/14. Syncytial trophoblast in choriocarcinoma components and syncytial giant cells were all positive for HCG, SP1 and HPL. In addition, tumor giant cells in two nonseminomatous tumors and in one seminoma contained HCG. Otherwise, all pure seminomas were negative for all antigens, except for Fe, which was positive in 12/16 cases. Demonstration of this functional aspect of germ cell tumors of the testis may clarify problems of classification and elucidate histogenesis. Furthermore, immunohistochemical demonstration of tumor-associated antigens is of value in the management of the patient as an indicator of which tumor markers should be used for monitoring the treatment. In addition, the presence of tumor-associated antigens may be used in prognostic evaluation.