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Developmental alterations of alpha-fetoprotein sugar chain in amniotic fluids analyzed by lectin affinity electrophoresis.

Affinity electrophoresis of human alpha-fetoprotein (AFP) in amniotic fluid from pregnant women between 6 to 42 weeks of gestation and in the serum of a yolk sac tumor was performed with concanavalin A (Con A), lentil lectin (LCA), erythroagglutinating phytohemagglutinin (E-PHA) and Allomyrina dichotoma lectin (allo A). Separated AFP bands were detected by sensitive antibody-affinity blotting. In the first trimester, amniotic fluid AFP showed elevated percentages of Con A-nonreacting AFP (AFP-C1) and LCA weakly-reacting AFP (AFP-L2) as previously reported. Additionally, high percentages of E-PHA strongly-reacting AFP (AFP-P5) and E-PHA-reacting AFP (AFP-P4) were observed. E-PHA-nonreacting AFP (AFP-P1), E-PHA weakly-reacting AFP (AFP-P3f), allo A-nonreacting AFP (AFP-A1) and asialo-AFP, AFP-A1 s, were present only in amniotic fluids from 6 to 17 weeks of gestation. With advancing gestation, percentages of AFP-C1, AFP-P4 and AFP-P5 decreased and AFP-L2, AFP-P3f, AFP-A1, and AFP-A1 s disappeared by the end of 18 weeks. The glycoforms of serum AFP of the yolk sac tumor resembled those of amniotic fluid AFP in the early gestational stages.

Amniotic Fluid↗

Primary yolk sac tumor of the rectum.

Extragonadal germ cell tumors are well recognized in men but have rarely been reported in women. Reports have primarily focused on the pediatric population and have suggested a poor prognosis for extragonadal yolk sac tumors. A 23-year-old woman with a yolk sac tumor arising in the rectum is described. A review of the English-language literature (MEDLINE 1966-1998) regarding extragonadal germ cell tumors in females is provided. Treatment with four courses of cisplatin, etoposide, and bleomycin was followed by surgical resection of the involved area. No residual tumor was identified. She remains disease free 3.5 years later. Previous reports are limited by the small number of patients, focus on the pediatric population, and treatment before the availability of cisplatin. Extragonadal germ cell tumors in women are extremely rare but can be successfully treated with aggressive chemotherapy and surgery similar to testis cancer.

Adult↗

Transformation of ovarian dysgerminoma to yolk sac tumor: evidence for a histogenetic continuum.

Dysgerminoma has traditionally been considered an end-stage neoplasm without potential for further differentiation. Although there have been several reports of transformation of testicular seminoma to yolk sac tumor, a similar event has not been previously reported in dysgerminoma of the ovary. Three cases of ovarian germ cell tumor (two pure dysgerminomas and one mixed germ cell tumor with dysgerminoma and yolk sac components) that revealed histologic changes compatible with early transformation to yolk sac tumor are described. In general, the areas of transformation were located at the periphery of the tumor lobules which otherwise had features of typical dysgerminoma. They were characterized by the presence of microcysts and small glandular structures, which though not readily identified on H&E became more evident with stains for keratins, alpha-fetoprotein, and blood group-related antigen. The small size and focal nature of change, and the apparent transition favor the interpretation that this change represents transformation rather than admixture of two germ cell components. The relationship of dysgerminoma to the solid variant of yolk sac tumor is discussed and an alternate histogenetic scheme in which dysgerminoma represents the stage of earliest differentiation from which other non dysgerminomatous tumors may arise is presented. Although previously proposed for testicular germ cell neoplasia, this scheme has not yet been applied to their ovarian counterparts.

Adolescent↗

Is it feasible to diagnose germ-cell tumors by fine-needle aspiration biopsy?

Fine needle aspiration biopsy is an extremely useful procedure for the diagnosis of germ cell tumors. Most of the subtypes can be easily recognized and differentiated from other subtypes. For difficult cases clinical pathologic correlation may be extremely helpful in establishing a precise diagnosis. Mixed germ cell tumors may cause some difficulty if one of the components is predominant. Immunohistochemistry may also play an important role in arriving at a definitive diagnosis.

Biopsy, Needle↗

Gonadoblastoma with dysgerminoma in one ovary and gonadoblastoma with dysgerminoma and yolk sac tumor in the contralateral ovary in a girl with 46XX karyotype.

A case of gonadoblastoma with dysgerminoma in the left ovary and gonadoblastoma with dysgerminoma and yolk sac tumor in the right of a 10-year-old girl is reported. Her karyotype was 46XX, normal female type. A case of a gonadoblastoma without a Y chromosome is very rare. Furthermore, the prognosis for gonadoblastoma accompanied by germ cell tumors other than dysgerminoma was very poor in the past, but the patient remains well 25 months after the first operation.

Child↗

A study on the microheterogeneity of alpha-fetoproteins produced by yolk sac and germ cell tumors.

BACKGROUND: It is generally believed that the lower the grade of differentiation of glycoprotein-producing cells, the more often modification by bisecting N-acetylglucosamine (GlcNAc) or fucose (Fuc) at the sugar chain of the glycoprotein or increase in branching of side chains occurs. We examined the characteristics of the alpha-fetoprotein (AFP) sugar chain stored in amniotic and exocoelomic fluid during 5-9 weeks of gestation and analyzed serum-derived AFP of patients with germ cell tumors. METHODS: Total AFP concentrations in embryonic fluid at 5-9 weeks of gestation (n = 11) and serum of patients with germ cell tumors (n = 7) were measured using a radioimmunoassay (RIA) method. The percentages of AFPs reactive with Lens culinaris agglutinin (LCA), concanavalin A (Con A), erythroagglutinating phytohemagglutinin-E4 (E-PHA) and Ricinus communis agglutinin-120 (RCA 120) were obtained by lectin-affinity electrophoresis coupled with antibody-affinity blotting. RESULTS: It was revealed that at 5-9 weeks of gestation, AFP variants that had been modified by the Fuc residue, which bound to the GlcNAc residue at the reducing end of the sugar chain, and bisecting GlcNAc residues gradually decreased as pregnancy advanced; however, the presence of N-acetylneuraminic acid (Neu5Ac) at the nonreducing ends changed little. CONCLUSIONS: It appears very likely that the changes in the relative amounts of AFP variants in the embryonic fluid during early pregnancy were due to differentiation of the yolk sac. The grade of differentiation of yolk sac tumors was very similar to that of the normal yolk sac at around 6 weeks of gestation.

Adult↗

Microcystic Leydig cell tumors mimicking yolk sac tumor: a report of four cases.

We report four cases of Leydig cell tumor of the testis with a microcystic pattern that mimicked yolk sac tumor. The patients ranged in age from 27 to 35 years and, except for one tumor that was discovered incidentally, presented with testicular masses. All tumors were intratesticular, and three were well circumscribed by a rim of fibrous tissue, whereas one showed minor, focal extension into the adjacent testis. The tumors typically had a vaguely lobular architecture subdivided by fibrous bands. Three of the cases had a complex microcystic appearance caused by individually vacuolated cells and coalescent cystic spaces; this pattern accounted for the majority of two tumors. Another case had focal collections of Leydig cells with prominent cytoplasmic vacuoles but lacked the coalescent spaces. The microcyst contents ranged from optically clear to eosinophilic or lightly basophilic, with the latter having the staining qualities of acid mucopolysaccharide. Three tumors had uniform, bland nuclei and low mitotic rates (<1 mitotic figure per 10 high power fields), but one had marked, random nuclear pleomorphism and an average mitotic rate of five mitotic figures per 10 high power fields. By immunohistochemistry, all were diffusely positive for vimentin; two of three were positive for inhibin, and one showed focal positivity for cytokeratin (CAM 5.2). All were negative for alpha-fetoprotein and placentalike alkaline phosphatase and, apart from having microcystic and solid areas, lacked other features typical of yolk sac tumor. Clinical follow-up ranged from 2 months to 2 years with no patient having recurrence or metastasis. The distinction of Leydig cell tumor from yolk sac tumor has important clinical implications because patients with the former usually receive only clinical follow-up, but the latter often requires chemotherapy.

Adult↗

Embryonal carcinoma of the pineal gland with yolk sac tumor differentiation. A case report.

Twenty three old male patient was diagnosed as a pineal gland tumor and was operated in neurosurgical ward. He died four weeks later due to pneumonia and respiratory failure. Clinical diagnosis was based on computer tomography (CT) and magnetic resonance image (MRI) examination. Histological study of a biopsy and autopsy specimens showed embryonal carcinoma with yolk sac tumor differentiation. The diagnosis was supported by positive cytokeratin, placental alkaline phosphate and alpha-fetoprotein immunostainings.

Adult↗

Pineal yolk sac tumor in a 65-year-old man.

A 65-year-old man presented with a case of pure yolk sac tumor in the pineal region. The patient was admitted with a gait disturbance and elevated alpha-fetoprotein levels in serum and cerebrospinal fluid. He underwent total resection of the tumor. Cisplatin-vinblastine-bleomycin therapy was interrupted because of severe syndrome of inappropriate secretion of antidiuretic hormone, and there was recurrence of the tumor. Five months after the operation, he died in spite of carboplatin-etoposide therapy. A review of the literature revealed no previous report of pineal yolk sac tumor in an elderly patient. Problems in the diagnosis and treatment of such cases are discussed.

Aged↗

Spinal cord compression of primary extragonadal giant yolk sac tumor.

STUDY DESIGN: Case report. OBJECTIVE: To report an adult male patient with a primary extragonadal giant yolk sac tumor presenting with acute spinal cord compression. SETTING: Faculty of Medicine, University of Dicle, Diyarbakir, Turkey. METHOD: A 31-year-old man was referred to our department with a diagnosis of Pott's disease, a complaint of back pain and gait difficulty for 2 weeks. Neurological examination showed spastic paraparesis and hypoesthesia below the L2 dermatome level. He also had urinary incontinence. Abdominal computed tomography and lumbar magnetic resonance imaging study revealed a giant cystic mass lesion located in the psoas muscle. Posteriorly, the third lumbar vertebral body was destructed and the tumor was compressing the dural sac. A combined anterior and posterior approach was performed. Pathological diagnosis was a yolk sac tumor. RESULT: His neurological status improved during the postoperative course. A chemotherapy protocol was given including bleomycin, etoposide and cisplatin. Five months after the last chemotherapy, he was brought to the emergency unit in sepsis and died despite antibiotherapy. CONCLUSION: Yolk sac tumor should be considered in young adult male patients presenting with acute paraparesis even without any signs or medical history of a testis tumor. These tumors may be unresectable; however, decompression of neural structures and stabilization of the spine with instrumentation may cause substantial improvement in neurological deficit and pain relief.

Adult↗

A 18 years study of testicular tumours in Jodhpur, western Rajasthan.

The present study based on WHO histologic typing of testicular tumours deals with 100 cases recorded in the files of the Department of Pathology from 1969 to 1987. These tumours accounted for 2.57% malignancies of male genital system. Maximum number of tumours were recorded in the third and fourth decades. Right testis was affected in 60% cases. Scrotal swelling was the predominant presenting feature, followed by pain. Five cases of testicular tumours were observed in undescended testis. Germ cell tumour of one histologic type constituted 76% of testicular tumors. Germ cell tumors of more than one histologic type were 23%. One case (1%) belonged to lymphoid and haemopoietic system and was of large cell lymphocytic lymphoma. Amongst the germ cell tumors with one histologic type, seminoma (34%) and embryonal carcinoma (28%) were predominant while teratocarcinoma was a predominant tumour in combination group.

Adolescent↗

Metastasis of an intracranial germinoma through a ventriculoperitoneal shunt: recurrence as a yolk-sac tumor.

Extraneural metastases of intracranial germinomas, although infrequent, are associated with a generally poor prognosis despite the high radiosensitivity of localized primary tumors. Ventriculoperitoneal shunts have been implicated in facilitating metastatic spread of primary intracranial germinomas. We present a case of a successfully irradiated suprasellar germinoma recurring after 13 months as an intra-abdominal yolk-sac tumor in a young man. The tumor was eradicated with a combination of systemic chemotherapy and local irradiation, with no residual viable tumor cells confirmed at final surgical extirpation. The role of cerebrospinal fluid (CSF) shunts in metastases, mixed germ-cell tumor histology, and tumor markers in recurrences as well as radiation doses and volumes for treating primary tumors are discussed. Systemic chemotherapy may be utilized as prophylaxis against shunt metastases when CSF drainage is necessary.

Abdominal Neoplasms↗

Comparative genomic and in situ hybridization of germ cell tumors of the infantile testis.

Chromosomal information on germ cell tumors of the infantile testis, ie, teratomas and yolk sac tumors, is limited and controversial. We studied two teratomas and four yolk sac tumors using comparative genomic hybridization (CGH) and in situ hybridization. No chromosomal anomalies were found in the teratomas by any of the methods, not even after CGH on microdissected tumor cells. All yolk sac tumors showed aneuploidy, loss of parts of 4q and 6q, and gain of parts of 20q. Underrepresentation of parts of 8q and overrepresentation of parts of 3p, 9q, 12p, 17, 19q, and 22 were detected in most cases. In addition, one recurrent yolk sac tumor after a sacral teratoma was studied, showing a highly similar pattern of imbalances. While CGH demonstrated loss of 1p36 in one testicular yolk sac tumor, in situ hybridization revealed loss of this region in all yolk sac tumors. High-level amplification of the 12q13-q14 region was found in one yolk sac tumor. MDM2, of which the encoding gene maps to this chromosomal region, was found in all cases using immunohistochemistry, whereas no p53 could be detected. Accordingly, no mutations within exons 5 to 8 of the p53 gene were observed. These data prove the absence of gross chromosomal aberrations in teratomas of the infantile testis and show a characteristic pattern of gains and losses in the yolk sac tumors. Besides confirmation of previously found anomalies, recurrent losses of 1p21-31 and 4q23-33 and gains of 9q34 and 12p12-13 have not been reported before. While genetic inactivation of p53 seems unimportant in the pathogenesis of these tumors, biochemical inactivation by MDM2 might be involved. These data support the existence of three entities of germ cell tumors of the human testis: teratomas and yolk sac tumors of infants, seminomas and nonseminomas of adolescents and young adults, and spermatocytic seminomas of the elderly, each with its own specific pathogenesis.

Aneuploidy↗

Aneuploidy of human testicular germ cell tumors is associated with amplification of centrosomes.

Testicular germ cell tumors occur in three age groups. Seminomas and nonseminomas of adults, including mature teratomas, and the precursor carcinoma in situ (CIS) are aneuploid. This also holds true for yolk sac tumors of newborn and infants, while the mature teratomas of this age are diploid. In contrast, spermatocytic seminomas occurring in the elderly contain both diploid and polyploid cells. Aneuploidy has been associated with centrosome aberrations, sometimes related to overexpression of STK15. Aneuploidy of non-neoplastic germ cells has been demonstrated in the context of male infertility, a risk factor for the development of seminoma/nonseminoma. We investigated aneuploidy, centrosome aberrations and the role of STK15 in different types of testicular germ cell tumors as well as in normal and disturbed spermatogenesis. The aneuploid seminomas and nonseminomas tumors (including CIS) showed increased numbers of centrosomes, without STK15 amplification or overexpression. Four out of six infantile teratomas had normal centrosomes, the remaining two and an infantile yolk sac tumor showed a heterogeneous pattern of cells with normal or amplified centrosomes. Spermatocytic seminomas had two, four or eight centrosomes. Germ cells in seminiferous tubules with disturbed spermatogenesis shared both aneuploidy and centrosome abnormalities with seminomas/nonseminomas and showed a more intense STK15 staining than those with normal spermatogenesis and CIS. Therefore, aneuploidy of testicular germ cell tumors is associated with amplified centrosomes probably unrelated to STK15.

Adolescent↗

Pure gastric yolk sac tumor that was diagnosed after curative resection: case report and review of literature.

We recently experienced an 87-yr-old man with gastric yolk sac tumor. Preoperative diagnosis was poorly differentiated adenocarcinoma in the cardia of stomach without apparent metastasis. A total gastrectomy was performed. The precise histological examination after surgery revealed the tumor was composed of pure gastric yolk sac tumor without adenocarcinomatous components. The surgical margin and the resected lymph nodes were histologically negative for the tumor and a curative resection was performed. Five months after the operation, enlargement of the intraabdominal lymph nodes occurred with elevation of serum alpha fetoprotein (AFP), and the patient died 2 mo later. Gastric yolk sac tumors are very rare, and only six cases of gastric yolk sac tumors have been previously reported in the literature. Five out of six cases are accompanied by components of adenocarcinoma, and our present case is the second report of pure gastric yolk sac tumor to the best of our knowledge.

Adenocarcinoma↗

Classification and pathology of testicular germ cell and sex cord-stromal tumors.

Germ cell tumors of the testis are the most frequent testicular neoplasms, with seminoma predominating. The pathologist must be able to discriminate between seminoma and nonseminomatous germ cell tumors as well as sex cord-stromal tumors and metastatic lesions. Appropriate therapy and accurate prognostic information are dependent on the proper classification of testicular neoplasia. Characteristic histologic features, serum markers, and immunohistochemistry are helpful in this regard. Sex cord-stromal tumors comprise a small minority of testicular neoplasms. It remains critically important not to confuse these neoplasms with testicular germ cell or metastatic tumors, and, again, recognition of the characteristic histologic features, immunohistochemical findings, and clinical information is diagnostic. The urologist can provide the pathologist with key clinical information in the attempt to make a correct diagnosis.

Carcinoma, Embryonal↗

Renal cell carcinoma antigen is expressed by yolk sac tumors and yolk sac elements of embryonal carcinomas.

Renal cell carcinoma antigen is a rather specific marker for normal and neoplastic renal tissue. We investigated the expression of this antigen in 34 gonadal and extragonadal germ cell tumors, including 8 pure yolk sac carcinomas and 26 embryonal carcinomas, 15 of which were combined with teratomas, seminomas, and dysgerminomas. Renal cell carcinoma antigen was demonstrated in all 8 yolk sac tumors and 21 of 26 embryonal carcinomas (81%). In yolk sac tumors, renal cell carcinoma antigen reactivity was diffusely present throughout the tumors. In embryonal carcinomas, this marker was identified only in yolk sac components. Both intracytoplasmic and membranous staining patterns were present. No reactivity was noticed in embryonal carcinoma cells, seminoma, dysgerminoma, and other components of teratomas. The study suggests an antigenic similarity between renal tubules and yolk sac tumors. Furthermore, the renal cell carcinoma antigen may be used as an addition to the panel of immunocytochemical markers for yolk sac carcinomas.

Adolescent↗

Intrapericardial yolk sac tumor associated with acute myocarditis.

An occult intrapericardial yolk sac tumor occurred in a 3-year-old girl with a fatal outcome. At autopsy, a 5.5-cm mass surrounded the base of the heart and compressed the left atrium posteriorly. Histologically, the tumor was a pure yolk sac tumor. Postmortem chemical analyses of the blood revealed an alpha-fetoprotein level greater than 7000 microg/L. Acute myocarditis of both ventricles was also found.

Acute Disease↗