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Endodermal sinus tumor: a clinical and pathological correlation.

Endodermal sinus tumors occur in the gonads and in a variety of extragonadal locations, particularly as the malignant component of sacral teratomas. Light and electron microscopic studies as well as the presence of alpha fetoprotein support the concept that these lesions arise from germ cells that migrate from the extraembryonic yolk sac. These tumors in all locations are highly malignant and metastasize to lymph nodes, lung, liver and bone. Peritoneal implants are seen from tumors in the ovary, testis, and following ventriculoperitoneal shunts for yolk sac tumors of the pineal gland. There is no satisfactory therapy for the endodermal sinus tumor, regardless of location, when there are distant metastases at the time of diagnosis; however, we have documented complete regression of metastases in one child following therapy with vinblastine, bleomycin, and cis-platinum. Nine of 13 boys with endodermal sinus tumors of the testis survived in this series of patients. All survivors were treated with orchiectomy and lymph node excision. Surgical excision combined with chemotherapy and radiation led to survivors in children with large extragonadal pelvic and retroperitoneal tumors. We recommend vigorous multimodal therapy with surgery and chemotherapy. Radiation is given to the primary lesion when it is too extensive for initial resection or to eradicate residual disease following chemotherapy. Alpha fetoprotein is a valuable tumor marker.

Adolescent↗

Conservative management of testicular endodermal sinus tumor in childhood.

Endodermal sinus tumor is the most common testicular neoplasm in childhood. The management of children with this neoplasm remains controversial. We have treated prospectively 5 children with stage I endodermal sinus tumor with limited surgery and no adjuvant therapy. The median patient age at diagnosis was 21 months (range 5 to 24 months). All children underwent an inguinal orchiectomy with high ligation of the spermatic cord. Retroperitoneal node dissection was not performed in any case and no child received adjuvant chemotherapy or radiation therapy. All patients were well without evidence of recurrent disease at a median followup of 46 months (range 19 to 72 months). Because these tumors usually are localized at the time of diagnosis, rarely spread to the retroperitoneal nodes and have a biological marker in most cases, and because good salvage chemotherapy is available for patients with relapse, we believe that nonmetastatic testicular endodermal sinus tumors in children can be managed with radical orchiectomy alone. Retroperitoneal node dissection is not necessary and adjuvant therapy is not indicated if markers return to normal. Further treatment should be reserved for the rare child with relapse.

Castration↗

Endodermal sinus tumour of the posteroinferior mediastinum resembling dumbbell neuroblastoma in a child.

A male infant presenting with paraplegia due to intraspinal extension of an endodermal sinus tumour in the posteroinferior mediastinum is reported. Dumbbell tumours are usually observed in mediastinal neuroblastomas, and rarely in rhabdomyosarcomas of the chest wall. The present case demonstrates the clinical similarity of endodermal sinus tumours to neuroblastomas with extradural extension. Therefore, endodermal sinus tumours should be considered in the differential diagnosis of posterior mediastinal masses, because of the distinctly different treatment from that for other tumours.

Combined Modality Therapy↗

Variant forms of alpha-fetoprotein transcripts expressed in human hematopoietic progenitors. Implications for their developmental potential towards endoderm.

Hematopoietic stem cells have been identified as multipotent cells that give rise to all adult hematopoietic lineages. Although the hematopoietic lineage is derived from the mesodermal germ layer in the embryo, recent data suggest that bone marrow cells with an antigenic profile consistent with that of hematopoietic stem cells can also differentiate to cell types of the endodermal lineages, such as hepatocytes. However, the molecular mechanisms associated with these events are entirely unknown. For decades, alpha-fetoprotein (AFP) has been used as a differentiation marker for endodermal cells, because it was thought that the transcription of AFP mRNA is tightly regulated in a developmental and tissue-specific process. In this report we describe two new variant forms of AFP transcripts in human hematopoietic progenitors that are not expressed in mature cells. The variant AFP (vAFP) cDNA sequences isolated from a multipotent hematopoietic cell line, K562, revealed that the vAFP differed from the authentic transcript, consisting of 15 exons, by replacing exon 1 of AFP with one or two exons located in the 5'-untranslated region of the AFP gene. In addition to the K562 cell line, vAFP transcripts were detected in normal bone marrow, thymus, and brain but were not detected in normal spleen, intestine, liver, or the hepatocellular carcinoma cell line, HepG2. This suggests expression in normal hematopoietic progenitors. This hypothesis was confirmed by the finding that CD34(+)Lin(-) hematopoietic progenitor cells purified from cord blood by flow cytometric sorting also expressed the variant transcripts. These results suggest that some hematopoietic progenitors are in a state that permits them to express certain types of transcripts that have been considered unique to endoderm.

Base Sequence↗

Alpha1-antitrypsin and alpha-fetoprotein. Protein markers in endodermal sinus (yolk sac) tumors.

A combined immunocytochemical and quantitative serum and tissue study was performed on a group of endodermal sinus (yolk sac) tumors, localizing and measuring both alpha1-antitrypsin (AAT) and alpha-fetoprotein (AFP) in tumor tissue and patient sera. Utilizing indirect immunofluorescent and triple-sandwich immunoperoxidase methods, both proteins were demonstrated within intra- and extracellular periodic acid-Schiff-positive hyaline globules characteristic of the tumor, as well as within the cytoplasm of tumor epithelial cells lining endodermal sinuses, where AAT deposition predominated. Tumor tissue extracts confirmed the presence of significant quantities of both proteins, and pretreatment serum elevations of both showed a parallel decline during therapy. In this study, AAT is characterized as a tumor protein marker for the first time, and a parallelism between AAT and AFP is demonstrated in both serum and tumor tissue. These findings represent additional supportive evidence for the yolk sac origin of endodermal sinus tumors in man.

Child↗

Composition of the aliphatic components of suberin of the endodermal fraction from the first internode of etiolated sorghum seedlings.

The stems from etiolated seedlings of Sorghum bicolor were separated into epidermal and endodermal fractions by manually removing the stele from the cortex. The epidermal fraction was shown to contain a lipid polymer whose monomeric composition was characteristic of cutin with dihydroxyhexadecanoic acid as a major component (25%). The endodermal fraction contained a lipid polymer whose monomeric composition was characteristic of suberin: hexadecanoic acid 12%, octadecenol 6%, octadecenoic acid 23%, omega-hydroxyhexadecanoic acid 17%, hexadecanedioc acid 8%, omega-hydroxyoctadecenoic acid 8%, and octadecenedioic acid 12%. This endodermal polymer is thought to be the suberin component of the Casparian band.

Journal Article↗

Fluorescein-conjugated Bandeiraea simplicifolia lectin as a marker of endodermal, yolk sac, and trophoblastic differentiation in the mouse embryo.

The Bandeiraea simplicifolia lectin I (BSA-I) conjugated to fluorescein isothiocyanate was used as a histochemical reagent to study the mouse embryos from fertilization to early somitogenesis. No lectin binding could be detected on the embryonic cells in the preimplantation embryo. Lectin labeled intensely the zona pellucida. In the implanting embryos lectin binding was detected along the subtrophectodermal and Reichert's membrane, in the cytoplasm of the parietal and visceral endoderm, and the trophoblastic giant cells, but not in the ectodermal cells. Studies on explanted blastocyts cultured in vitro disclosed that the cytoplasmic BSA-I binding sites in trophoblastic cells develop gradually. In the 9-day somitic embryo BSA-I reacted with epithelial cells of the yolk sac, but not with the mesenchymal cells. A continuity between the lectin-reactive endoderm and the foregut epithelium could be demonstrated. These data indicated that BSA-I lectin can be used as a histochemical probe for endodermal (yolk sac) and trophoblastic differentiation in the peri-implantational mouse embryo.

Animals↗

Prolonged survival with conventional cisplatinum/vinblastine/bleomycin therapy alone for mediastinal endodermal sinus tumour.

Combination chemotherapy with cisplatin, vinblastine, and bleomycin (PVB) is considered to be the best treatment for disseminated non-seminomatous germ cell tumours, with a 70% long term disease-free survival rate. For one subgroup of patients, those with primary mediastinal endodermal sinus tumours, results with PVB have been disappointing and more intensive regimens with major toxicity have recently been proposed. We report a patient who, following standard PVB chemotherapy, is one of the longest reported survivors of mediastinal endodermal sinus tumours. Optimal chemotherapy for endodermal sinus tumours is yet to be determined.

Adult↗

The histogenetic-embryologic basis for reappearance of alpha-fetoprotein in endodermal sinus tumors (yolk sac tumors) and teratomas.

The mechanism of neosynthesis of the human tumor-associated fetal antigen alpha-fetoprotein (AFP) in a variable percentage of patients with testicular, ovarian and extragonadal germ cell tumors has generally been considered unknown or beyond any simple explanation. Of decisive importance is the cellular basis for AFP production 1. in ontogenesis and 2. in malignancy as dependent on an exact tumor histogenesis. Based on (1) the histogenetic-embryologic classification of germ cell tumors and the concept of yolk sac tumor (or endodermal sinus tumor), (2) the available clinical and experimental observations, and (3) the immunofluorescent localization of AFP in the endodermal sinus tumor of the human testis, it is concluded that AFP synthesis in these neoplasms is explained by the fact that they contain yolk sac endoderm, which produce AFP analogous with the physiological AFP synthesis by the fetal yolk sac in early embryogenesis.

Adult↗

Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart.

We report the cDNA cloning and characterization of mouse GATA-4, a new member of the family of zinc finger transcription factors that bind a core GATA motif. GATA-4 cDNA was identified by screening a 6.5-day mouse embryo library with oligonucleotide probes corresponding to a highly conserved region of the finger domains. Like other proteins of the family, GATA-4 is approximately 50 kDa in size and contains two zinc finger domains of the form C-X-N-C-(X17)-C-N-X-C. Cotransfection assays in heterologous cells demonstrate that GATA-4 trans activates reporter constructs containing GATA promoter elements. Northern (RNA) analysis and in situ hybridization show that GATA-4 mRNA is expressed in the heart, intestinal epithelium, primitive endoderm, and gonads. Retinoic acid-induced differentiation of mouse F9 cells into visceral or parietal endoderm is accompanied by increased expression of GATA-4 mRNA and protein. In vitro differentiation of embryonic stem cells into embryoid bodies is also associated with increased GATA-4 expression. We conclude that GATA-4 is a tissue-specific, retinoic acid-inducible, and developmentally regulated transcription factor. On the basis of its tissue distribution, we speculate that GATA-4 plays a role in gene expression in the heart, intestinal epithelium, primitive endoderm, and gonads.

Amino Acid Sequence↗

Human endodermal sinus tumour in nude mice and its markers for diagnosis and management.

Two human endodermal sinus tumours (yolk sac tumours) were transplanted successfully into nude mice. The transplanted tumours maintained not only morphological characters, such as Schiller-Duval bodies, but also the ability to synthesise alpha-fetoprotein, lactic dehydrogenase 1, liver and bone type alkaline phosphatase, and some human serum proteins. Since these tumours produced lactic dehydrogenase 1 but not the other four isozymes of lactic dehydrogenase, this isozyme, like alpha-fetoprotein, seems to be a good marker for the diagnosis and management of cases of endodermal sinus tumour. One of the two tumours produced another fetal antigen or carcinoembryonic antigen in addition to alpha-fetoprotein. These two endodermal sinus tumours, with their various markers in nude mice, will be useful in studies on diagnostic markers.

Alkaline Phosphatase↗

Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. II. Immunostaining for type IV collagen and its precursors.

Antibodies to type IV collagen were linked with peroxidase and used for direct immunostaining of Reichert's membrane and the associated cells of the rat parietal yolk sac. Immunostaining was observed throughout the thickness of Reichert's membrane and within the endodermal cells arranged as a single layer on its inner side. The immunostaining of endodermal cells was mainly present in the cisternae of rough endoplasmic reticulum (rER) and in the Golgi apparatus, where it could occur in any saccule, but predominated in the GERL elements and associated prosecretory granule-like structures. Moreover, the secretory granule-like structures present in the ectoplasm next to Reichert's membrane were also immunostained. Finally, immunostaining was observed in multivesicular bodies and occasionally in secondary lysosomes. The antigenicity detected by immunostaining in Reichert's membrane is attributed to type IV collagen itself, whereas the antigenicity of endodermal cells is assigned to precursors of this collagen. It is proposed that initial precursors arise in rER cisternae, migrate to Golgi saccules, and pass to the GERL element, where they accumulate into prosecretory granules, which, perhaps by fusion with one another, become secretory granules. The secretory granules in turn migrate to the cell surface where they release their content, which becomes the type IV collagen of Reichert's membrane. Some diversion from this pathway may account for the immunostaining of multivesicular bodies and lysosomes.

Animals↗

Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. III. Immunostaining for laminin and its precursors.

Reichert's membrane and the endodermal cells of the parietal yolk sac were examined for the presence of laminin antigenicity using anti-laminin antibodies and the peroxidase-antiperoxidase sequence. Immunostaining was observed through the full width of Reichert's membrane and within endodermal cells. In these cells immunostaining was observed in rough endoplasmic reticulum (rER) cisternae and Golgi apparatus. The Golgi staining could occur in any saccule, but predominated in components interpreted as the last saccule of the stack, the GERL element, and associated prosecretory granules. The secretory granules found in the ectoplasm were also immunostained. Finally, multivesicular bodies showed some staining. The immunostaining of Reichert's membrane indicates the presence of laminin itself, while that of rER cisternae and the Golgi apparatus is attributed to laminin precursors. Presumably the biosynthesis of laminin occurs along the usual protein pathway, that is, from rER through Golgi saccules and the GERL element to secretory granules, which release their content into Reichert's membrane. The laminin immunostaining of Reichert's membrane and endodermal cells is similar to that of type IV collagen. It is, therefore, likely that the two substances are processed and secreted simultaneously.

Animals↗

Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells.

The transcription factor Oct-4 is a marker of pluripotency in mouse and human embryonic stem (ES) cells. Previous studies using a tetracycline-regulated Oct-4 transgene in the ZHBTc4 cell line demonstrated that downregulation of Oct-4 expression induced dedifferentiation into trophoblast, a lineage mouse ES cells do not normally generate. We found that transfection of Oct-4-specific short interfering RNA significantly reduced expression and functional activity of Oct-4 in mouse and human ES cells, enabling its role to be compared in both cell types. In mouse ES cells, Oct-4 knockdown produced a pattern of morphological differentiation and increase in expression of the trophoblast-associated transcription factor Cdx2, similar to that triggered by suppressing the Oct-4 transgene in the ZHBTc4 cell line. In addition, downregulation of Oct-4 was accompanied by increased expression of the endoderm-associated genes Gata6 and alpha-fetoprotein, and a gene trap associated with primitive liver/yolk sac differentiation. In human ES cells, Oct-4 knockdown also induced morphological differentiation coincident with the upregulation of Gata6. The induction of Cdx2 and other trophoblast-associated genes, however, was dependent on the culture conditions. These results establish the general requirement for Oct-4 in maintaining pluripotency in ES cells. Moreover, the upregulation of endoderm-associated markers in both mouse and human ES cells points to overlap between development of trophoblast and endoderm differentiation.

Animals↗

Endodermal sinus tumor of the nasopharynx and previous mature congenital teratoma.

Congenital teratoma of the nasopharynx is a rare tumor that has shown consistently benign behavior. In contrast, endodermal sinus tumor, even more unusual nasopharyngeal germ cell tumor, displays consistently aggressive behavior with most reports documenting early death of the patient. We report the clinicopathological features of a case of endodermal sinus tumor of the nasopharynx that developed in a 3-year-old girl who had a mature teratoma excised from the same site in the neonatal period. Local recurrence of the endodermal sinus tumor was followed by disseminated disease and death within 18 months.

Child, Preschool↗

Extragonadal endodermal sinus tumours. Report of a case.

A case is described of endodermal sinus tumour originating in the sacro-coccygeal region in a man 20 years of age. Of the hitherto presented cases of endodermal sinus tumour of a gonadal origin, 24 out of 42 patients have died. Of 21 patients in whom the disease was of an extragonadal origin, 18 have died. Thus, the prognosis seems to be less favourable in patients with extragonadal tumours. The best prognosis has been reported in boys with endodermal sinus tumours of a testicular origin operated before the age of 2 years.

Abdominal Neoplasms↗

Lateral supratentorial endodermal cyst: case report and review of literature.

OBJECTIVE AND IMPORTANCE: Epithelial cysts of the central nervous system are unusual entities, with the majority reported to occur in the spinal canal. More unusual is the intracranial presentation, which shows a predilection for midline localization in the posterior fossa, brainstem, and suprasellar regions. This report discusses the differential diagnosis, pathogenesis, radiographic presentation, and therapeutic considerations of a laterally positioned cerebral convexity endodermal cyst. CLINICAL PRESENTATION: A 49-year-old right-handed man presented with approximately a 30-month history of short- and long-term memory difficulties. A magnetic resonance imaging study revealed a large, nonenhancing, extra-axial cystic lesion overlying the right lateral frontal convexity. INTERVENTION: A right frontoparietal craniotomy exposed a large extra-axial cyst with an opaque, yellowish-white membrane containing a mucoid fluid. Histological analysis disclosed a layer of unremarkable, ciliated columnar epithelium with a basement membrane that stained positive for cytokeratin, periodic acid-Schiff, and Alcian blue. No evidence of either a muscular or cartilaginous layer around the mucosa was present to further delineate neurenteric versus bronchogenic origin of the cyst. CONCLUSION: This case involved the occurrence of a solitary endodermal cyst as an extra-axial mass localized over the lateral frontal lobe. The lateral supratentorial localization of this lesion illustrates the need for consideration of the pathogenesis of this entity as well as its diagnostic differentiation from other cystic abnormalities in this region. A review of the histochemistry of endodermal, neuroepithelial, and other cerebral cysts is presented.

Central Nervous System Cysts↗

Management of advanced endodermal sinus tumor of the ovary with preservation of reproductive function.

Endodermal sinus tumor of the ovary occurs primarily in children and young adults. This tumor is classified as a germ cell tumor which comprises approximately 5% of all ovarian tumors. In the past, patients with this highly malignant tumor had low survival. However, with the evolution of effective adjunctive chemotherapeutic regimens, specifically vincristine, actinomycin D, and cyclophosphamide, survival rates have improved. In an attempt to continuously improve survival rates, other combination chemotherapeutic regimens are currently under investigation. Unlike epithelial ovarian malignancies, endodermal sinus tumor can be monitored by a specific tumor marker, alpha-fetoprotein (AFP). Serum levels of AFP can be followed from the preoperative period through the course of chemotherapy. When elevated, AFP has excellent predictability that persistent disease is present. Because this disease presents primarily in young females, preservation of reproductive function is of utmost importance. We report a case of advanced endodermal sinus tumor which was managed with conservative surgery only, followed by radical combination chemotherapy, resulting in preservation of normal reproductive function and total resolution of disease documented by second-look laparotomy.

Adolescent↗