Yolk Sac Component Research Articles

α-Fetoprotein Production by a Malignant Mixed Müllerian Tumor of the Ovary

Elevated levels of α-fetoprotein (AFP), a fetal serum protein, usually signal the development of hepatoma or germ cell tumors, including endodermal sinus tumors. We report the case of a 52-year-old woman with an α-fetoprotein-producing malignant mixed Müllerian tumor (MMMT) of the ovary. Serum AFP was 5348 ng/ml at diagnosis. Immunohistochemistry confirmed that the carcinomatous component of this biphasic tumor was the seat of AFP production. After three cycles of combination chemotherapy, the patient achieved a complete remission. Serum AFP was strongly correlated with response to treatment. This is the first report of AFP production by a MMMT of the ovary without a yolk sac component.

Surgical Resection Alone Is Effective Treatment for Ovarian Immature Teratoma in Children and Adolescents: A Report of the Pediatric Oncology Group and the Children’s Cancer Group

This study was conducted to evaluate the routine use of chemotherapy, with its attendant long-term effects, in children and adolescents after the surgical removal of ovarian immature teratoma. Forty-four girls who underwent laparotomy for complete removal of an ovarian tumor containing pure immature teratoma between 1995 and 1996 served as subjects. Patients were classified as having stage I cancer when disease was found in the ovary only with negative peritoneal washings. Among the patients who had adequate staging, no stage II disease was observed. Follow-up for the first 2 years included frequent measurements of serum levels of α-fetoprotein (AFP) and diagnostic imaging studies of the chest and pelvis. Thereafter, patients returned annually for regular physical examinations. At diagnosis, the age range of the subjects was 1.5 to 20 years. Four girls were lost to follow-up, two shortly after surgery and two within 2 years. Nineteen patients were followed for more than 5 years, and four had undergone surgery less than 2 years earlier. Histologic examination found no embryonal carcinoma, choriocarcinoma, or germinoma. Fifteen patients were classified as having grade 1 tumors, 12 had grade 2 tumors, and 2 had grade 3 tumors. On central pathology review, 13 patients were found to have tumors containing microscopic foci of a yolk sac tumor that was previously undetected. Unilateral salpingo-oophorectomy was the treatment selected in 28 patients (64 percent). Only one hysterectomy was necessary. Lymph node samples, obtained from 16 patients, showed mature gliomatosis in three patients. Three subjects had positive peritoneal washings, all of which contained only mature teratomatous or immature glial cells. The 13 patients with ovarian immature teratoma plus yolk sac tumor were slightly older (median, 12 years) than those with pure teratoma (median, 10 years) and were more likely to have larger tumors. Fifty-five percent of the girls with immature teratoma had grade 1 disease, compared with only 8 percent of those whose teratoma contained a yolk sac tumor. Conversely, 46 percent of the children with immature teratoma plus yolk sac tumor were classified as having grade 3 disease, compared with 6 percent of those without yolk sac tumor. Ten of the 13 girls (80 percent) with yolk sac components had measurable levels of AFP, compared with only 10 of 31 of the girls (34 percent) with no yolk sac tumor elements. Furthermore, the median level of AFP was 252 among children with yolk sac tumor, compared with 25 among those without yolk sac tumor. Ovarian immature teratoma containing yolk sac tumor was less likely to rupture during removal than immature teratoma (8 vs. 32 percent). No patients died. There was one malignant recurrence in a 12-year-old girl who had a large ovarian immature teratoma with yolk sac tumor, an initial serum AFP level of 1045 ng/ml, and peritoneal washings and lymph nodes positive for gliomatosis. A sharp rise in her serum AFP level at 18 weeks signaled a recurrence. Two nodules containing grade 2 immature teratoma with yolk sac tumor were found in her liver. She was disease free 57 months after four courses of cisplatin, etoposide, and bleomycin therapy. Two other patients required additional surgical procedures. Both girls underwent exploratory laparotomy for a pelvic mass. One contained ovarian mature cystic teratoma and mature glial implants. The other was composed of multiple mature glial implants on the peritoneal surfaces and on the surface of the remaining ovary, which was removed. Both patients had normal serum AFP levels that did rise, and both continue to be well without additional symptoms. Normal adolescent follicular cysts were frequently observed among the entire study group. Am J Obstet Gynecol 1999;181:353–358

Combined yolk sac tumor and adenocarcinoma in a gastric stump

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. Immunohistochemical and molecular techniques were used to define the mutation pattern of p53 in both components of the tumor. Single-strand conformation polymorphism and sequencing analyses demonstrated the same pattern of p53 mutation in the adenocarcinomatous and yolk sac tumor components. 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.

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.

Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours.

We describe the cloning and initial characterization of a novel cDNA from human embryonal carcinoma (EC) cells. This cDNA, which we named human growth differentiation factor 3 (hGDF3), encodes the homologue of mouse GDF3, a TGFbeta superfamily member belonging to the Growth/Differentiation Factors. We have analysed the expression of hGDF3 in human embryonal carcinoma cell lines and in primary testicular germ cell tumours of adolescents and adults (TGCTs). Expression of hGDF3 in human EC cell lines is stem cell-specific, is down-regulated upon RA-mediated differentiation and is increased upon culture of the cells in the presence of activin A. In TGCTs, hGDF3 expression is low in seminomas, while expression in non-seminomas is readily detectable and appears to be associated with the EC and yolk sac components in the tumours. We have also mapped the hGDF3 locus to the short arm of human chromosome 12, a region consistently overrepresented in human testicular germ cell tumours. Thus, hGDF3 represents an embryonal carcinoma stem cell-associated marker both in vitro and in vivo.

Erythropoietin in mouse avascular yolk sacs is increased by retinoic acid.

Erythropoiesis begins first in the visceral yolk sac (VYS) of the embryo; however, the involvement of erythropoietin (EPO) in yolk-sac erythropoiesis has not been studied adequately. This study reports the expression of EPO in normal and hypoxic VYSs and alterations in yolk sac components induced by retinoic acid (RA) in mice. Gravid mice (plug day = day 0 of gestation) were given one oral dose of 60 mg/kg of RA in olive oil on days 6, 6.5, 7, 7.5, or 8 of gestation and were sacrificed 2.5, 3, or 3.5 days later. Control mice received olive oil without RA. None of the dams developed anemia, but more than 80% of the embryos of the dams that received RA on day 6, 6.5, or 7 of gestation had avascular yolk sacs (AVYs) and anemia. In these AVYs, the adenosine triphosphate (ATP) level was as low as 18-59% of that in the control VYSs. Reverse transcription-polymerase chain reaction and Southern analysis of products demonstrated that mRNA for EPO receptor (EPR) was expressed in both VYSs and AVYs on days 9-11 of gestation, and EPO mRNA was present in VYSs and AVYs on days 9 and 10 of gestation and in vehicle-exposed VYSs on day 11 of gestation. Furthermore, enzyme immunoassay of EPO indicated that AVYs contained more EPO protein than control VYSs. Light microscopy revealed that, in AVYs, in addition to the defective hemopoietic cells, the endodermal layer was exclusively altered: The presence of focal proliferated regions and the separation from the mesenchyme led to a single layer from which some immature cells seemed to be migrating. Immunolocalization of EPO showed its presence in all components of VYSs with a characteristic distribution pattern: In the endodermal layer, cells with positive EPO staining decreased as gestation advanced, and erythroid precursor cells showed positive staining. In AVYs, the proliferated endodermal cells had EPO in abundance; in the separated regions, the distinction between positive and negative EPO staining became clearer than that in the control VYSs, and the immature cells in the lumens also had EPO. EPR was seen on the cell surface of the corresponding cells that reacted to EPO. These findings suggest that VYSs not only produce EPO temporarily but also respond to the oxygen content in situ. EPO and EPR appear to be synthesized in the endodermal cells of the VYSs that are likely to respond to the circumstances induced by RA.

Robb-Smith Type Malignant Histiocytosis Associated with a Mediastinal Germ Cell Tumor

A 22-year-old Japanese man with a mediastinal germ cell tumor with mixed teratoma and hepatoid alpha-fetoprotein positive, and glandular yolk sac components, also demonstrated widely disseminated malignant histiocytosis involving the lungs, liver, pancreas, spleen, bone marrow and lymph nodes. Sensitivity to chemotherapy was acute and the patient died of disseminated intravascular coagulation syndrome within four months of his initial presentation.

Multiple antigens in the rat visceral yolk sac induce teratogenic antisera

Preparative isoelectric focusing was used to fractionate the supernatant from a homogenate of day 19 rat visceral yolk sac. Three fractions, of pI ranges 3.5-5.0, 5.0-7.0, and 7.0-9.0, were isolated and used to immunize rabbits, by four or six weekly injections, each containing 5 mg protein. The resulting antisera were all teratogenic when injected into rats on day 9 of gestation, but widely differing potencies were observed. The most potent antiserum was that against yolk sac components focusing in the pI 7.0-9.0 range: An optimum teratogenic dose of 50 mg protein per kg body weight was observed, and a dose of 100 mg/kg was shown to cause 100% embryonic resorption. Antiserum against the fraction focusing in the pI 3.5-5.0 range was the least teratogenic: A significant incidence of embryonic malformation and death was seen only at doses of 600 mg/kg and above. The two fractions that yielded the more teratogenic antisera were refocused over narrower pH ranges, yielding four subfractions in the pI 5.0-7.0 range and eight subfractions in the pI 7.0-9.0 range. Antisera against each of these 12 fractions were raised in rabbits; most of these antisera were shown to be teratogenic, although of differing potencies. It is concluded that the yolk sac contains many antigens that can elicit antibodies with teratogenic and yolk sac-localizing properties.

Ovarian Mucinous Cystadenocarcinoma Producing α-Fetoprotein

Common epithelial ovarian tumors associated with alpha-fetoprotein (AFP) production are rare. A case of ovarian mucinous cystadenocarcinoma producing both AFP and carcinoembryonic antigen (CEA) is presented. A 53-year-old postmenopausal woman with right adnexal tumor underwent total hysterectomy and right salpingo-oophorectomy. Preoperative serum CEA and AFP levels were elevated to 660 and 1,120 ng/ml, respectively, and both decreased to their normal ranges after surgery. Histologically, the right ovarian tumor was diagnosed as a mucinous cystadenocarcinoma, composed of both intestinal-type cells and endocervical-type cells. Intestinal-type cells were identified ultrastructurally, with cells resembling neuroendocrine cells as well as gobletlike cells with many mucinous granules. Yolk sac or teratomatous components were not identified. By the immunoperoxidase technique, CEA was positive in well to moderately differentiated mucinous cells lining lumina, whereas AFP-positive cells were intermingled with CEA-positive cells in moderately differentiated epithelia.

Immunocytochemical evidence of heterogenous origin of α-fetoprotein in immature teratoma of the ovary

α-Fetoprotein (AFP) has been found to be clinically important in the management of patients with gynecologic malignancies. Serum AFP levels are used as tumor markers for ovarian tumors, namely endodermal sinus tumors (EST) and embryonal tumors. In two cases of immature teratoma of the ovary without a yolk sac component, evidence for AFP production was found in a wide variety of cells of both endodermal and ectodermal origin suggesting a heterogeneous origin of AFP. To complement this finding, a summary of the ontology of AFP along with current and potential uses of an antigenically active tumor marker are presented.

Nonseminomatous malignant germ cell tumors in children. Multidrug therapy in Stages III and IV.

Thirty-five children with Stage III and IV nonseminomatous malignant germ cell tumors were treated, between June 1, 1977 and December 31, 1982, at Institut Gustave-Roussy, Villejuif, France, and Hospital General de Ninos, Buenos-Aires, Argentina: 11 sacrococcygeal, 12 ovarian, 6 testicular, 5 intrathoracic, and 1 intrabdominal site. All of them had yolk sac component with high level of AFP, seven had also elevated level of HCG. Thirteen patients had primary chemotherapy, 18 received chemotherapy after incomplete surgical excision, and 4 patients with testicular Stage III tumors had chemotherapy immediately following retroperitoneal lymphadenectomy after orchiectomy, because of persistently elevated AFP levels. The chemotherapy regimen for 1 year's duration, repeated every 21 days, and consisted of 6 courses of dactinomycin-Cytoxan (cyclophosphamide) D1 to D5 and vincristine, Adriamycin (doxorubicin) D21, bleomycin D23, and cisplatin D24. Only three patients received complementary radiotherapy. The toxicity of the chemotherapy regimen was severe, but only one death was due to the therapy (pulmonary fibrosis with bleomycin). The number of surviving patients without evidence of disease was 12 of 16 for Stage III and 12 of 19 for Stage IV. The 25-month survival rate was 63% with a follow-up of 11 months to 5.5 years (median, 22 months). This constitutes a dramatic improvement when compared with the survival rate of 21% of 48 similar patients treated at Institut Gustave-Roussy between 1968 and 1977 with surgery, radiotherapy, and chemotherapy (methotrexate, dactinomycin, and Cytoxan).

Diffuse embryoma of the testis. A distinctive form of mixed germ cell tumor.

Two testicular tumors characterized by a diffuse, orderly arrangement of embryonal, yolk sac, and trophoblastic elements are described as examples of a newly recognized form of mixed germ cell neoplasia. In one case, ribbons of embryonal carcinoma and yolk sac tumor wound around one another to create a distinctive necklace pattern. In the second case, differentiation of the yolk sac component was more advanced with the formation of numerous clusters of cells resembling hepatocytes. Tumors with these patterns are appropriately designated diffuse embryomas to distinguish them from polyembryomas and other forms of malignant mixed germ cell tumor.

Alpha-fetoprotein, alpha-1-antitrypsin, and transferrin in gonadal yolk-sac tumours.

Since gonadal yolk-sac tumour in pure form or as a component of mixed germ cell tumour is in the majority of patients highly malignant, its histological recognition is of great prognostic importance. Yolk-sac tumour may assume various different histological guises, which have hitherto caused considerable terminological confusion; the present paper is aimed at correlating these morphological diversities with biochemical features which are consistent with yolk-sac differentiation. Using an enzyme-bridge immunoperoxidase technique, a series of 16 gonadal germ cell tumours with a yolk-sac component were screened for the presence of alpha-fetoprotein, alpha-1-antitrypsin, and transferrin. These proteins, normally produced by human yolk sac, were demonstrable in all the morphological patterns of yolk-sac tumour we have previously described. Six malignant non-germ cell tumours were submitted to the same investigations, and no evidence of the three protein markers was found in five; one tumour, however, an oat cell carcinoma of the bronchus, stained positively for transferrin.

Features of prognostic significance in testicular germ cell tumours.

One hundred and one testicular tumours previously diagnosed as "teratoma" were examined and 93 of the patients were followed up. These neoplasm were assigned to one of three groups. Those compared exclusively of somatic tissues were the only tumours referred to as teratoma. The second group was exclusively extra embryonic and consisted of either yolk sac or choriocarcinoma. Neoplasms in the third group were called mixed germ cell tumours and incorporated somatic and extra embryonic tissue and occasionally seminoma. The patients with teratomas showed a very low mortality whereas pure yolk sac tumours proved highly malignant. In mixed germ cells tumours the malignant nature of the yolk sac components was maintained even when combined with somatic elements, but when seminoma was also present the survival rate was significantly improved. It would appear the yolk sac tumour tissue occurs more frequently in adult testicular neoplasms than was previously suspected and in mixed germ cell tumours it can be expected to dictate behaviour except when combined with seminoma.

The effect of trypsin and other enzymes on feline pneumonitis virus.

Journal Article The Effect of Trypsin and Other Enzymes on Feline Pneumonitis Virus Get access Arthur Brown, Arthur Brown From the Departments of Bacteriology and Parasitology and of Biochemistry, The University of Chicago, Chicago 37, Illinois Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret K. Itatani, Margaret K. Itatani From the Departments of Bacteriology and Parasitology and of Biochemistry, The University of Chicago, Chicago 37, Illinois Search for other works by this author on: Oxford Academic PubMed Google Scholar James W. Moulder James W. Moulder From the Departments of Bacteriology and Parasitology and of Biochemistry, The University of Chicago, Chicago 37, Illinois Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 91, Issue 2, July 1952, Pages 184–190, https://doi.org/10.1093/infdis/91.2.184 Published: 01 July 1952 Article history Received: 27 March 1952 Published: 01 July 1952