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Nuclear deoxyribonucleic acid content (ploidy) of endodermal sinus (yolk sac) tumor.

Paraffin sections from 30 endodermal sinus (yolk sac) tumors were Feulgen-stained, and nuclear DNA content (ploidy) was assessed through DNA cytophotometry using the microTICAS image analysis system. The series consisted of 20 ovarian, 8 testicular, 1 sacrococcygeal, and 1 mediastinal tumors. Of the 30 endodermal sinus (yolk sac) tumors 29 were shown to be aneuploid, whereas the remaining tumor which exhibited the recently described primitive intestinal or enteric pattern was diploid and may thus be considered a neoplasm showing a somewhat higher degree of differentiation as compared to tumors showing the other histologic patterns of endodermal sinus (yolk sac) tumors.

Aneuploidy↗

Immunohistochemical study of hepatic and enteric structures in testicular endodermal sinus tumors.

Features of hepatic and enteric tissue have been detected in serial sections of 2 out of 6 endodermal sinus tumors (EST) and embryonal carcinomas of the testis showing endodermal sinus areas. Hepatic nests, which appeared as tubules, cords and giant multinucleated cells, were PAS-positive as well as immunoreactive for alphafetoprotein (AFP) and cytokeratin (CK). Enteric tubules were found within EST areas and were characterized by their lack of cell atypism. The presence of diffuse PAS-, AFP- and CK-reactivity in cytoplasm, together with a brush border or an apical staining for CEA, were quite distinctive. EST showed a potential for both intra- and extraembryonal endodermic development and may be interpreted as a monophyletic teratoma.

Humans↗

Second-look laparotomy in endodermal sinus tumor: a report of two patients with normal levels of alpha-fetoprotein and residual tumor at reexploration.

The role of second-look laparotomy in the management of patients with endodermal sinus tumor of the ovary is controversial. We report two women who converted to a normal alpha-fetoprotein (AFP) level during treatment with combination chemotherapy, yet were found to have residual endodermal sinus tumor at second-look laparotomy. In view of the limited experience with this rare disease, we continue to recommend second-look laparotomy for patients who have completed chemotherapy for endodermal sinus tumor of the ovary, regardless of the serum AFP level.

Adolescent↗

[Endodermal sinus tumor of ovary--analysis of 35 cases].

Thirty-five patients with pure endodermal sinus tumor of the ovary treated in our hospital from 1962 to 1984 are reported. There were 8 Stage I, 13 Stage III lesions and 14 with recurrent tumor from other hospitals. All the patients were treated by surgery followed by chemotherapy including single drug or combined chemotherapy. Five of 7 patients on high-dose DDP (120 mg/M2) responded. Two of the Stage I patients survived for 33 and 39 months. One of 2 patients by AcFuCy regime was free of tumor for 82 months. Four of 6 patients with advanced tumor treated by VAC regime responded, but only one was alive without evidence of tumor for 30 months. In 21 patients treated with other combination or single drug chemotherapy before 1980, only one (Stage Ia) is alive. It is indicated that surgery combined with multi-drug chemotherapy is the best management and high-dose DDP, VAC and AcFuCy are effective in treating pure endodermal sinus tumor of the ovary. Monitoring of serum AFP levels of the patients with endodermal sinus tumor can predict the course of the disease.

Adolescent↗

The endodermal origin of digestive and respiratory tract APUD cells. Histopathologic evidence and a review of the literature.

Twenty-seven small cell carcinomas of the lung and three tumors of the large intestine with combined adenocarcinomatous and small cell and/or anaplastic carcinoid-type histologic features were studied by light and electron microscopy. It was shown that the small cells have morphologic characteristics of APUD cells. Also presented are the histologic features of a carcinoma of the lung with large cell undifferentiated carcinoma, adenocarcinoma, squamous cell carcinoma, and giant cell carcinoma areas in the primary site and in several metastatic foci. Two of the renal metastases showed small cell carcinoma. The combined tumors and the numerous other similar neoplasms described in the literature and reviewed here suggest an endodermal origin for digestive and respiratory tract APUD cells based on the hypothesis that cancer is a clonal proliferation, and mucous and squamous cell differentiation is an endodermal rather than neural crest characteristic. The ultrastructural features of tumors of cells of known neural crest origin, including a medullary carcinoma of the thyroid, three carotid body tumors, a pheochromocytoma, and two cutaneous melanomas were compared with those of other APUD cell tumors including small cell carcinomas of the lung, two bronchial carcinoids, a carcinoid of the appendix, and a carcinoid of the kidney. Cells of the latter group sometimes possessed cytoplasmic tonofibrils, round compact masses of cytoplasmic microfilaments, and ductal lumina. These features were lacking in the former group and may signify a different embryologic origin. The histologic, histopathologic, and embryologic evidence regarding the origin of digestive and respiratory tract APUD cells is reviewed, showing that the former are, and the latter probably are, of endodermal and not neuroectodermal origin.

APUD Cells↗

[Ultrastructure of endodermal sinus tumor of the ovary (author's transl)].

The ovarian endodermal sinus tumor is a relatively rare type of malignant neoplasm. Ultrastructurally, the tumor cells proved to have numbers of ribosomes, glycogen granules and well-developed rough endoplasmic reticulum surrounding the mitochondria. The photomicroscopically visible hyaline globules were observed as round homogeneous non-structural substances both in and outside the cytoplasm. It was surmised that it is synthesized in the rough endoplasmic reticulum. The tumor cells could be classified into three types on the basis of the forms of cytoplasmic organella and intracellular homogeneous spheres. The first type of cell proved to be well-developed cytoplasmic organella, with a few small spheres and a large aggregate of glycogen granules and ribosomes. The second type of cell proved to have extensive non-structural cytoplasm and a number of largesized spheres. The third type was deemed to be of the intermediate type. In other words, it was assumed that morphological changes were responsible for the tumor cells changing from the first type to the second type. A similarity was noted between these ultrastructures and the yolk sac endodermal cells of the very initial stage, therefore the name endodermal sinus tumor was assumed to be adequate.

Adult↗

Diagnostic value of hyaline globules in endodermal sinus tumor: report of two cases.

Two cases of ovarian endodermal sinus tumor are reported. The cytologic preparations were obtained from ascitic and/or autopsy specimens. The findings on Papanicolaou-stained smears included clustering of malignant cells, pleomorphism of nuclei and cytoplasmic vacuolization and thus resembled those seen in cases of mucinous cystoadenocarcinoma of the ovary. Hyaline globules, characteristic of the alpha-fetoprotein-synthesizing (AFP-synthesizing) cells found in endodermal sinus tumor, were observed inside the cells with periodic-acid-Schiff (PAS) stain. The presence of PAS-positive hyaline globules can be regraded, therefore, as a diagnostic clue to endodermal sinus tumor in an appropriate clinical setting and in the presence of AFP production.

Adult↗

Identification of mRNA species that code for extra-embryonic endodermal cytoskeletal proteins in differentiated derivatives of murine embryonal carcinoma cells.

The messenger RNA species that code for two extra-embryonic endodermal cytoskeletal proteins (Endo A and Endo B) have been identified. Endo A and Endo B messenger RNA species are differentially expressed. They are absent, or at basal levels, in undifferentiated embryonal carcinoma cells (F9.22 cell line) and relatively abundant in parietal endoderm (PFHR9 cell line) or in embryonal carcinoma cells that have been induced, by retinoid acid, to differentiate to parietal endoderm. Endo A and Endo B messenger RNA can be detected in F9.22 cells 48 to 72 h after exposure to retinoic acid, which is coincident with the expression of Endo A and Endo B proteins. The size of Endo A and Endo B messenger RNA has been determined by denaturing methyl mercury hydroxide agarose gels to be 2.0 +/- 0.1 and 1.5 +/- 0.2 kilobases, respectively.

Animals↗

Endodermal sinus tumor of the vagina: radiation therapy and progeny.

BACKGROUND: Extraovarian endodermal sinus tumor generally originates in the vagina or cervix of young girls. Some 50 cases are known, all younger than 3 years of age. Many were treated with outdated regimens, and there are 5-year survival data on only nine of them. We describe a curative outcome of primary radiation only. CASE: A 40-year-old woman had a history of localized endodermal sinus tumor of the vagina, stage I, treated by brachytherapy at the age of 6 months. Radiation had a severe impact upon the later functioning of her pelvic organs, with marked deformity of the pelvic floor, vagina, urethra, and bones of the pelvic outlet. She conceived by homologous insemination at the age of 34. Delivery was by cesarean at 31.5 weeks' gestation. CONCLUSION: Current forms of management give preference to limited excisional surgery and multi-agent chemotherapy, analogous to that used for the treatment of endodermal sinus tumor of the ovary. This is the first report of a patient treated by radium needles and the only known patient who had a subsequent pregnancy.

Adult↗

[A case of endodermal cyst in front of the pontomedullary junction].

We reported a rare case of an endodermal cyst on the posterior fossa. The patient was a 51-year-old woman with tinnitus, ear blockage and a mild swallowing disturbance. MR images revealed a cystic mass 5 cm in diameter in front of the pontomedullary junction. Gadolinium-enhanced images showed some spotty lesions in the cystic mass. The brain stem was compressed strongly by the mass. The left vertebral artery was involved in the mass. Total removal of the tumor was performed via the transcondylar approach. During the operation the lower cranial nerves, the bilateral vertebral artery and the vertebral union were recognized. The cystic mass consisted of a yellow colored thin wall and a watery fluid which contained some small hard lesions. Histopathological examination of the cyst wall revealed a single layer of ciliated columnar epithelium, and that of the small lesions showed histiocytes and granulation. Immunohistochemically, the cyst wall was stained by an epithelial membrane antigen and a carcinoembryonic antigen. From these histopathological findings, the final diagnosis of the cystic lesion was an endodermal cyst. Twenty such cases have been reported to date since Afshar reported a case of an endodermal cyst on the posterior fossa in 1981. There are many types of cystic lesions in the intracranial region, and immunohistochemical studies are necessary for diagnosis of these intracranial cysts.

Brain Diseases↗

Endodermal sinus tumors in the head and neck region.

Extragonadal germ cell tumors of the head and neck region account for only 5% of all benign and malignant germ cell tumors. Endodermal sinus tumors (EST) of the head and neck region are rare. We report three patients with EST of head and neck region over a period of 10 years; the primary sites of tumor were orbit, maxillofacial region and retroauricular region. Histopathological examination revealed malignant teratoma with predominant endodermal sinus pattern in two, and pure EST in one patient. Serum alpha fetoprotein (AFP) was elevated in all three patients. Two patients had initial surgery but did not receive adjuvant chemotherapy, as the parents refused it. Partial remission was achieved in the other patient who received chemotherapy (cisplatin, bleomycin and vinblastin) and the patient died of infection after four courses of chemotherapy.

Endodermal Sinus Tumor↗

Participation of endodermal epithelial cells on the synthesis of plasma LDL and HDL in the chick yolk sac.

We ultrastructually examined the chick yolk sac endodermal epithelium and evaluated our findings in combination with the biochemical analysis of serum and yolk lipoproteins. Twenty-five to 30 nm-sized particles were demonstrated to be a principal element of the extracellular yolk mass and these were determined to be yolk very low density lipoprotein (VLDL). The particles were shown to be taken up by the epithelial cells via coated pits and engulfed by plasma membrane invaginations together with yolk subdroplets, another element of the yolk mass. Through apical vacuoles, the two yolk elements were incorporated into yolk drops, which were identified to be one of the lysosomal structures by a cytochemical procedure using acid phosphatase (AcP)ase activity. During the last week of incubation, which is the final third of the incubation period, the digestion seemed to progress rapidly in the yolk drops, which came to resemble lipolysosomes; lipoprotein production became active as expressed by an enlarged Golgi apparatus. The newly produced lipoprotein particles were electron-lucent and irregular in size (50-120 nm). They were sequestered in secretory vacuoles and secreted from the vascular surface of the epithelial cells. Finally, the particles were thought to be taken into the vitelline circulation as plasma lipoproteins. The major component of lipoprotein in serum was determined to be low density lipoprotein (LDL) and high density lipoprotein (HDL), while cholesterol content was found to increase during incubation. We concluded that endodermal epithelial cells participate the synthesis of plasma LDL and HDL. For this synthesis the cells probably apply lipids and apo-protein generated from yolk VLDL degradation.

Acid Phosphatase↗

Hex expression suggests a role in the development and function of organs derived from foregut endoderm.

Hex is a divergent homeobox gene expressed as early as E4.5 in the mouse and in a pattern that suggests a role in anterior-posterior patterning. Later in embryogenesis, Hex is expressed in the developing thyroid, lung, and liver. We now show Hex expression during thymus, gallbladder, and pancreas development and in the adult thyroid, lung, and liver. At E10.0, Hex is expressed in the 3rd pharyngeal pouch, from which the thymus originates, the endodermal cells of liver that are invading the septum transversum, the thyroid, the dorsal pancreatic bud, and gallbladder primoridum. At E13.5, expression is maintained at high levels in the thyroid, liver, epithelial cells lining the pancreatic and extrahepatic biliary ducts and is present in both the epithelial and mesenchymal cells of the lung. Expression in the thymus at this age is less than in the other organs. In the E16.5 embryo, expression persists in the thyroid, pancreatic, and bile duct epithelium, lung, and liver, with thymic expression dropping to barely detectable levels. By E18.5, expression in the thyroid and bile ducts remains high, whereas lung expression is markedly decreased. At this age, expression in the pancreas and thymus is no longer present. Finally, we show the cell types in the adult thyroid, lung, and liver that express Hex in the mature animal. Our results provide more detail on the potential role of Hex in the development of several organs derived from foregut endoderm and in the maintenance of function of several of these organs in the mature animal.

Animals↗

SEM characterization of a cellular layer separating blood vessels from endoderm in the quail embryo.

The associations between the developing blood vessels and both endoderm and splanchnic mesoderm in quail embryos at stages 9-11 were examined by using scanning electron microscopy. Embryos were pinned ventral-side up on agar plates and the endoderm was surgically removed prior to fixation and dehydration. This procedure exposes a netlike layer of cells closely apposed to the ventral surface of paraxial mesoderm and all visible blood vessels; we are calling this the subvascular layer. Development of this layer proceeds rostral-to-caudal, and lateral-to-medial, with the earliest stages of formation being visible over the unsegmented paraxial mesoderm of the segmental plate. The subvascular layer increases markedly in density slightly medial to the innermost boundary of the intraembryonic vascular plexus. Cells of this layer eventually establish a continuous sheet beneath the lateral plate and paraxial mesoderm and the notochord. With maturation, the cells of the subvascular layer approach confluence. The spatial and temporal patterns of development of the embryonic vascular tissues and the subvascular layer are closely correlated, suggesting a possible role for the subvascular layer in normal embryonic vascular development.

Animals↗

Vertebrate head induction by anterior primitive endoderm.

In vertebrates the antero-posterior organization of the embryonic body axis is thought to result from the activity of two separate centers, the head organizer and the trunk organizer, as operationally defined by Spemann in the 1920s. Current molecular studies have supported the existence of a trunk organizer activity while the presence of a distinct head inducing center has remained elusive. Mainly based on analyses of headless mutants in mice, it has been proposed that the anterior axial mesoderm plays a determining role in head induction. Recent gain- and loss-of-function studies in various organisms, however, provide compelling evidence that a largely ignored region, the anterior primitive endoderm, specifies rostral identity. In this review we discuss the emerging concept that the anterior primitive endoderm, rather than the prechordal plate mesoderm, induces head development in the vertebrate embryo.

Animals↗

Distribution of the titf2/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair.

Titf2/foxe1 is a forkhead domain-containing gene expressed in the foregut, in the thyroid, and in the cranial ectoderm of the developing mouse. Titf2 null mice exhibit cleft palate and either a sublingual or completely absent thyroid gland. In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF-2) result in the Bamforth syndrome, characterized by thyroid agenesis, cleft palate, spiky hair, and choanal atresia. Here, we report a detailed expression pattern of TTF-2 protein during mouse embryogenesis and show its presence in structures where it has not been described yet. At embryonic day (E) 10.5, TTF-2 is expressed in Rathke's pouch, in thyroid, and in the epithelium of the pharyngeal wall and arches, whereas it is absent in the epithelium of the pharyngeal pouches. According to this expression, at E13.5, TTF-2 is present in endoderm derivatives, such as tongue, palate, epiglottis, pharynx, and oesophagus. Later in embryogenesis, we detect TTF-2 in the choanae and whiskers. This pattern of expression helps to define the complex phenotype displayed by human patients. Finally, we show that TTF-2 is a phosphorylated protein. These results help to characterize the domains of TTF-2 expression, from early embryogenesis throughout organogenesis, providing more detail on the potential role of TTF-2 in the development of endoderm and ectoderm derived structures.

Animals↗

Experimental analysis of the transdifferentiation of visceral to parietal endoderm in the mouse.

The visceral endoderm (VE) of isolated extraembryonic regions (ExEmbs) of 7 days postcoitum (dpc) prestreak mouse conceptuses have been shown to convert readily to parietal endoderm (PE). The present study addresses the following three unanswered questions. On what does conversion depend, how rapidly does it occur, and is it an enduring general property of a residual small population of relatively immature cells? In situ hybridization reveals that change in cell state occurs within 2 days of culture. Deprivation of the mesoderm also promotes it in later ExEmbs. Conversely, the conversion to PE in isolated 7 dpc ExEmbs is suppressed by grafting 8 dpc or 9 dpc mesoderm. Hence, the conversion provides an example of transdifferentiation that is promoted by the absence of extraembryonic mesoderm. The presence of mesoderm seems to be necessary to enable the VE to grow rather than convert to PE, as occurs if it retains contact with the extraembryonic ectoderm.

Animals↗

Paracrine action of FGF4 during periimplantation development maintains trophectoderm and primitive endoderm.

FGF4, a member of the fibroblast growth factor (FGF) family, is absolutely required for periimplantation mouse development, although its precise role at this stage remains unknown. The nature of the defect leading to postimplantation lethality of embryos lacking zygotic FGF4 is unclear and little is known about downstream targets of FGF4-initiated signaling within the various cellular compartments of the blastocyst. Here we report that postimplantation lethality of Fgf4(-/-) embryos is unlikely to reflect strictly mitogenic requirements for FGF4. Rather, our results suggest that FGF4 is required to maintain trophectoderm and primitive endoderm identity at embryonic day 4.5. This result is consistent with the reported in vitro activity of FGF4 in maintaining trophoblast stem cells and with the requirement for receptor tyrosine kinase signaling in primitive endoderm formation. Thus, postimplantation lethality of Fgf4(-/-) embryos likely results from the failure of proper differentiation and function of extraembryonic cell types.

Animals↗