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PubMed2004

Placental yolk sac tumor with divergent endodermal differentiation.

We report an intraplacental germ cell tumor that was an incidental finding in the placenta of a 34-year-old woman. On pathologic examination, the 4.0-cm tumor was well circumscribed with a thin fibrous capsule. It exhibited three major histologic patterns within a mesenchyme-like myxoid background: a primitive endodermal component, a well-differentiated enteric glandular endodermal component, and a component of fetal hepatic tissue. The primitive endodermal component, the hepatic component, and many parts of the enteric endodermal glandular component were immunoreactive for alpha-fetoprotein. We considered the lesion to be a unique example of a placental yolk sac tumor and only the second reported case of a placental yolk sac tumor.

Adult↗
PubMed2005

Involvement of adenomatous polyposis coli (APC) gene in testicular yolk sac tumor of infants.

The pathogenesis of testicular yolk sac tumor (YST) of infants is still unclear. Infantile YSTs rarely show isochromosome 12p or aneuploidy, which are common in adult germ cell tumors. On the other hand, recent epigenetic studies suggest the involvement of some tumor suppressor genes, including the adenomatous polyposis coli (APC) gene. In the present study, we examined 10 infantile pure YSTs for mutation, allelic loss, promoter methylation, and protein expression status of the APC gene to evaluate whether the APC gene plays a significant role in the pathogenesis of infantile YSTs. Loss of heterozygosity at 5q21, where the APC gene is localized, was detected in at least 3 (30%) of the 9 YSTs examined. None of the 10 YSTs showed mutations. Promoter methylation was detected in 7 (70%) of the 10 YSTs; among 7 YSTs showing methylation, 3 YSTs also harbored loss of heterozygosity at 5q21. Immunohistochemically, 8 infantile YSTs did not express the APC protein, whereas 2 YSTs without showing APC methylation, as well as germ cells of normal infantile testes, expressed this protein in the cytoplasm. These data indicate that inactivation of the APC gene, by allelic loss and/or promoter methylation, is related to the occurrence of infantile YSTs.

Adenomatous Polyposis Coli Protein↗
PubMed2006

Increasing expression of serine protease matriptase in ovarian tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters.

Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase in ovarian tumors and to assign clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 164 ovarian neoplasms including 84 serous adenocarcinomas, 23 mucinous adenocarcinomas, 10 endometrioid adenocarcinomas, six yolk sac tumors, 12 clear cell carcinomas, six dysgerminomas, eight granulosa cell tumors, four transitional cell carcinomas, five fibromas, and six Brenner tumors. All ovarian tumors except the fibromas and Brenner tumors showed significant expression of matriptase. The matriptase scores were significantly higher in the tumors than in their nontumor counterparts (304+/-26 for serous adenocarcinoma; 361+/-28 for mucinous adenocarcinoma; 254+/-17 for endometrioid adenocarcinoma; 205+/-19 for yolk sac tumor; 162+/-16 for clear cell carcinoma; 109+/-11 for dysgerminoma; 105+/-9 for granulosa cell tumor; and 226+/-18 for transitional cell carcinoma). Matriptase scores in serous adenocarcinoma were correlated with TNM stage and FIGO stage. Our findings demonstrate for the first time that matriptase is overexpressed in many malignant ovarian tumors. It may be a novel biomarker for diagnosis and treatment of malignant ovarian tumors.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Immunohistochemical heterogeneity of type 1 blood group antigen expressions in testicular germ cell tumors.

The immunohistochemical expression of type 1 blood group antigens (type 1 BGAs) was analyzed for 30 cases of testicular germ cell tumors (TGCTs), using monoclonal antibodies against DU-PAN-2, CA19-9, Lewis(a) (Le(a)), and Lewis(b) (Le(b)). DU-PAN-2 was expressed very frequently in all of the embryonal carcinomas (ECs). CA19-9 expression was demonstrated in 53% of ECs, but the number of positive cells was generally smaller than that for DU-PAN-2. CA19-9-negative ECs tended to show a higher number of DU-PAN-2-positive cells compared to CA19-9-positive ECs, and ECs in which DU-PAN-2 was more strongly expressed showed a relatively frequent expression of CA19-9. In 36% of seminomas and 56% of yolk sac tumors (YSTs), DU-PAN-2 was weakly expressed, and the positive cells were few in number. Little or no expression of CA19-9 was demonstrated in seminomas and YSTs. Regarding Le(a) and Le(b), the expressions were found to be limited to teratomas at a frequency of 57% and 86%, respectively, with the exception of one EC positive for Lea and one YST positive for Leb. Eighty-six percent of teratomas showed expressions of DU-PAN-2 and CA19-9. DU-PAN-2 was also seen in some intratubular malignant germ cells. The antibodies used were all negative for choriocarcinomas, syncytiotrophoblastic giant cells, and normal testicular tissues. The antigen expressions were predominantly observed on the surface of tumor cells developing luminal structures. In conclusion, although CA19-9 was relatively specific for ECs, it should be emphasized that ECs were rather characteristic of extensive DU-PAN-2 expression. Particularly in CA19-9-negative ECs, a combined analysis of DU-PAN-2 and CA19-9 would be helpful in confirming the histopathologic diagnosis of TGCTs. The clinical significance of DU-PAN-2 in ECs as a tumor marker remains to be clarified. Le(a) and Le(b) expressions were thought to be related to the differentiation or maturation rather than to the malignant transformation in TGCTs.

Adolescent↗
PubMed1978

Immunocytochemical localization of oncodevelopmental proteins in human germ cell and hepatic tumors.

In a combined tissue and serum study alpha-1-antitrypsin (AAT) and alpha-fetoprotein are demonstrated in parallel within tumor tissue inclusions in both endodermal sinus (yolk sac) tumors and malignant hepatomas, and AAT is demonstrated as a marker in both neoplastic and preneoplastic liver lesions occurring in oral contraceptive users, all in association with normal serum AAT phenotype. The tumor inclusions in the first two instances differ immunocytochemically from AAT liver cell globules found in inherited AAT deficiency, which are unreactive for alpha-fetoprotein. It is concluded that unlike the molecular basis of storage associated with AAT phenotypic variation, the tumor inclusions reflect a separate, nongenetic mechanism of AAT storage, which may be epigenetic in nature. AAT and alpha-fetoprotein both are synthesized normally in yolk sac and fetal liver, a parallelism which disappears soon after birth. The reexpression of both proteins in two distinct tumor types arising from endodermal origins (yolk sac and liver), suggests that these markers may represent reemerging fetal gene products, a phenomenon previously proposed only for alpha-fetoprotein, a prototypic "oncofetal antigen."

Contraceptives, Oral↗
PubMed1993

Long-term survival in malignant intracranial germ-cell tumors: a report of two cases and a review of the literature.

The authors report the successful treatment of two cases of malignant germ-cell tumor. A 12-year-old patient with a pineal immature teratoma and increase of alpha-fetoprotein serum levels was treated with total excision and cisplatin, vinblastine, and bleomycin (PVB) in combination given twice. One year later, he had a recurrence of tumor in the right occipital lobe, which was totally removed, and yolk sac tumor was verified. As subsequent adjuvant chemotherapy, PVB was given in four courses over 1.5 years, together with one course of cisplatin-etoposide (PE) therapy. The patient is well 5 years and 9 months after the first operation. In the second case, a 19-year-old patient with a pineal mixed germ-cell tumor, composed of germinoma, yolk sac tumor, and embryonal carcinoma, was treated with total excision, followed by four courses of PVB therapy and one of PE. She has done well in the 4.5 years since the initial treatment. Thus, aggressive extirpation of the lesion and subsequent combination chemotherapy using cisplatin and other multiple drugs, given in at least four courses over 1.5 years, even if tumor markers return to within normal limits, might provide successful treatment for malignant germ-cell tumors.

Adult↗
PubMed2004

Hepatoid malignancy of unknown origin--a diagnostic conundrum: review of literature and case report of collision with adenocarcinoma.

UNLABELLED: Hepatoid carcinomas are a group of neoplasms with features resembling hepatocellular carcinomas. Although rare, more cases have been noted to arise from various organs within the last decade. Differentiating these tumors is not only a challenge but also critical, since treatment modalities and operative strategies are dependent upon the exact nature of the hepatoid cancer. Based on a review of literature, we discuss the guidelines for differentiating these tumors and utilize these criteria to differentiate these tumors irrespective of their primary tissue of origin. We also describe an unusual case of hepatoid variant of primary peritoneal yolk sac tumor presenting with extensive carcinomatosis and as a collision with two synchronous primary colonic adenocarcinomas, neither of which has been reported to our knowledge to date, thereby falsely mimicking metastatic dedifferentiated colonic adenocarcinoma. CASE DESCRIPTION: A septuagenarian female presented with weight loss, chronic anemia and ascites associated with bloating. Her past history was significant for COPD, hysterectomy and a bilateral oophorectomy 40 years previously. A work up which included computed tomography (CT) and contrast enema revealed significant ascites with multiple peritoneal nodules causing ascending colonic obstruction. Celiotomy revealed the entire peritoneal surface to be studded with nodules, with the largest measuring 6.0 cm. Intraoperative ultrasound, prompted by the frozen section of nodules resembling liver tissue, revealed no intrahepatic nodules. Right colectomy, omentectomy and tumor debulking were performed. The postoperative course was uneventful except for ascitic leak that spontaneously resolved. DISCUSSION: The peritoneal nodules consisted of malignant cells arranged in cords that resembled liver tissue. In the absence of a primary identifiable liver disease, this is consistent with either hepatoid variant of primary yolk sac tumor or hepatoid carcinoma arising from the peritoneum. The right colectomy specimen revealed two mucosal ulcers consistent with colonic adenocarcinoma abutting two large tumor nodules on the serosal surface. Although grossly appearing to be contiguous, low power examination showed that the serosal nodule and the mucosal lesion were entirely different, and separated by a definite fibrous band. Immunohistochemical stains and patterns were used to differentiate the type of tumor. This article also discusses the criteria used to differentiate hepatoid yolk sac tumors (hepatoid-YSTs), hepatoid carcinomas and metastatic hepatocellular carcinomas and the phenomenon of opisthoplasia observed in certain malignancies. The difficulties encountered in identifying hepatoid carcinomas and current modalities used to differentiate these tumors are highlighted. The phenomenon of opisthoplasia and the challenges posed by this phenomenon in certain metastatic lesions are reviewed and explanations for the possible origins of hepatoid tumors are considered. CONCLUSION: The most likely explanation in our case is that the hepatoid tumor either originated from microscopic remnant ovarian tissue left behind or primarily from the peritoneum. With no evidence of yolk sac component within the colonic tumor or in the draining lymphatics, this essentially excludes the commonly observed metastatic dedifferentiation (opisthoplasia) of adenocarcinoma to primitive forms (also known as combination tumors). Based on analysis of various factors, including tumor behavior and response to chemotherapy, we conclude that our case was a hepatoid variant of yolk sac tumor presenting in an elderly woman with carcinomatosis. This unusual presentation of two entirely different primary malignancies in close proximity is defined as "collision tumor". This is the first reported case of collision tumors involving dual colonic and primary peritoneal hepatoid-YST. Identifying the exact type still remains to be the most challenging aspect in the diagnosis of hepatoid tumors.

Adenocarcinoma↗
PubMed2004

Pediatric urologic oncology: bladder, prostate, testis.

Although treatment for bladder, prostate, and testis cancer comprises a large part of adult urologic practice, the tumors that affect these organs in children are rare. Rhabdomyosarcoma,which affects the bladder, prostate, vaginal, and paratesticular areas,is treated with a combination of surgery, chemotherapy, and radiation. Most transitional cell carcinomas of the bladder and prepubertal testis tumors are managed surgically owing to the low stage at presentation. Application of the technical advances learned in adults with tumors of the bladder, prostate, and testis, combined with an understanding of the difference in tumor biology, helps urologists improve the treatment of these tumors in children.

Child↗
PubMed2000

Gastric adenocarcinoma with a yolk sac component: a case report and review of the literature.

Gastric yolk sac tumors (YST) are very rare and are mainly reported in elderly people. We present a case of a 36-year-old man with a poorly differentiated gastric cancer showing a mixture of adenocarcinoma and yolk sac tumor that metastasized to Virchow's node. Both biopsies, Virchow's node and gastric tumor, contained areas of adenocarcinoma and yolk sac tumor that stained strongly positive for alpha fetoprotein (AFP) by the immunohistochemistry method. A high level of serum AFP (38,200 ng/mL) was also noted in this case. The response to chemotherapy in this case of mixed gastric yolk sac tumor and adenocarcinoma was not as favorable as would be expected in a pure primary germ cell tumor.

Adenocarcinoma↗
PubMedDate not supplied

Pathology of germ cell tumors of the testis.

BACKGROUND: An increasing incidence of testis tumors has been noted over the second half of the 20th century. Congenital malformation of the male genitalia, prenatal risk factors, nonspecific and specific exposures in adulthood, and male infertility have all been associated with the etiology of germ cell tumors. METHODS: The histologic classification, pathology, and current concepts of testicular germ cell tumors are reviewed. RESULTS: Germ cell tumors occur at all ages. The tumors are identified as pure form (those of one histologic type) and mixed form (more than one histologic type). Over half of germ cell tumors consist of more than one cell type, requiring appropriate sampling for the correct diagnosis and correlation with the serum tumor markers. Burned-out germ cell tumors may occur in patients with metastatic disease with no gross evidence of a testicular tumor. CONCLUSIONS: Appropriate management of testis tumors relies on accurate pathology and classification of these tumors.

Adolescent↗
PubMedDate not supplied

Endometrioid-like variant of ovarian yolk sac tumor with foci of carcinoid: an ultrastructural study.

The endometrioid-like variant of ovarian yolk sac tumor is a rare neoplasm composed partially or completely of glandular tissue resembling endometrioid carcinoma, but identifiable histologically and immunohistochemically as an extraembryonic endodermally differentiated germ cell tumor. Only nine examples of this neoplasm have been published previously, and none was studied by electron microscopy. One of these rare neoplasms, the first documented to have foci of carcinoid, has recently been observed and studied ultrastructurally. Electron microscopic observations showed that the main component of the neoplasm had glandular epithelial cells with nuclear and cytoplasmic features difficult to distinguish from the cells of Müllerian endometrioid and endometrial adenocarcinoma, but a minor component of mucinous adenocarcinoma was confirmed as intestinal by the epithelial cells having characteristic microvilli with filamentous cores and rootlets. In addition, neuroendocrine cells present in the glands and in nests were readily identified ultrastructurally by their dense-core granules. Electron microscopy may be useful in supplementing light microscopic and immunohistochemical examination of this variant of yolk sac tumor.

Adult↗
PubMed1997

Primary germ cell tumors of the mediastinum: III. Yolk sac tumor, embryonal carcinoma, choriocarcinoma, and combined nonteratomatous germ cell tumors of the mediastinum--a clinicopathologic and immunohistochemical study of 64 cases.

BACKGROUND: Yolk sac tumor (YST), embryonal carcinoma (EC), choriocarcinoma (CC), and combined germ cell tumors (CGCTs) of the mediastinum are uncommon neoplasms. Only sporadic cases have been documented in the literature; therefore, the clinical behavior of these tumors when located in the mediastinum remains relatively unknown. METHODS: The clinical and pathologic features of 64 cases of primary YST, EC, CC, and CGCTs without teratomatous components were reviewed. The immunohistochemical findings in 29 cases were also analyzed using a panel of monoclonal and polyclonal antibodies in formalin fixed, paraffin embedded tissues. RESULTS: The patients were all men between the ages of 14 and 63 years (mean, 38.5 years). Their clinical symptoms included chest pain, shortness of breath, chills, fever, and superior vena cava syndrome. None of the patients had a previous history of testicular neoplasm or tumor elsewhere. Macroscopically, the lesions in 27 patients were described as large, soft, hemorrhagic, and in some cases necrotic, and varied in greatest dimension from 6 to 20 cm. Histologically, the tumors displayed morphologic features similar to those of their gonadal counterparts. Pure YSTs accounted for the majority of cases in this series (38 of 64, 60%), followed by pure CCs (8 of 64, 12%) and pure ECs (6 of 64, 9%). CGCTs accounted for only 18% of the total cases (12 of 64). YSTs showed a variety of growth patterns; however, the reticular pattern was the most commonly observed. ECs showed a more solid growth pattern with marked pleomorphism of the tumor cells and abundant areas of necrosis. CCs were characterized by the presence of cytotrophoblastic and syncytiotrophoblastic elements with frequent areas of necrosis and hemorrhage. The cases of nonteratomatous CGCT consisted of 5 cases of EC + YST, 2 cases of EC + seminoma, 4 cases of YST + seminoma, and 1 case of EC + CC. In clinical staging, 14 patients were Stage I, 6 were Stage II, and 19 were Stage III. Information on follow-up ranging from 1 month to 13 years was available for 40 patients. Seventeen patients with YST died of their tumors. Of these, 10 who presented with Stage III disease died within the first 2 years. Unfortunately, no clinical staging was obtained for the other 7 patients in this group, and they died within 6-36 months. It is noteworthy that 4 patients with YST have survived for more than 2 years; these patients presented in Stages I and II, and 2 of them received aggressive therapy with chemotherapeutic agents and radiation. Two patients with Stage III EC died within 2 years. The remaining 4 patients with EC were lost to follow-up. Eight patients with CC died within 6 months after initial diagnosis; 7 of them presented Stage III disease and only 1 presented with Stage I. In the nonteratomatous CGCT category, 2 patients with EC + YST died within 2 years after initial diagnosis, whereas 3 patients with YST + seminoma were alive after 4-9 years. CONCLUSIONS: The results of this study confirm the aggressive nature of primary nonseminomatous germ cell tumor of the mediastinum; 72% of the patients with adequate follow-up died of their tumors within 6-36 months after diagnosis, despite aggressive therapy. Clinical and pathologic staging of mediastinal YST, EC, and CGCT are important parameters that may be helpful in predicting the clinical outcomes of patients with these tumors. The authors' findings suggest that the majority of tumors that are not limited to the mediastinum at the time of diagnosis have more aggressive behavior. On the other hand, mediastinal choriocarcinomas appeared to follow a very aggressive clinical course, regardless of treatment modality or clinical tumor stage.

Adolescent↗