bromochloroacetic-acid and Carcinoma--Embryonal

Necrotic testicular tumors are relatively frequent and can present a significant diagnostic challenge. Because of differing treatments for seminomas versus nonseminomas, accurate diagnosis is critical. Eleven totally (n=9) or almost totally (n=2) necrotic testicular tumors were retrieved from our consult files. The submitting pathologists favored benign processes in 4 cases, Leydig cell tumor in 1, and lymphoma in 1. The cases were evaluated for histologic features and, when material was available, by immunostaining with 7 antibodies: keratin (AE1/AE3), OCT4, placental alkaline phosphatase, alpha-fetoprotein (AFP), CD117, CD30, and S100. Only distinct reactivity in a cellular distribution in the necrotic zone was considered positive; nuclear reactivity alone was scored for OCT4 and membrane reactivity for CD117 and CD30. Mean patient age was 35 years (range 16-63). Mean tumor size was 19 mm (range 7-53). All patients presented with unilateral testicular masses (6 right, 5 left); 2 also had acute pain. The combination of histologic features, immunostains and, in 1 case, serum AFP permitted classification of 8 tumors (4 seminomas, 3 embryonal carcinomas, 1 yolk sac tumor). Three were not classifiable. The necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 (4/4) and CD117 (3/3) but negative for keratin (0/4) and CD30 (0/4). The necrotic embryonal carcinomas had associated coarse intratubular calcifications and were positive for keratin (2/3), OCT4 (2/2), and CD30 (3/3). OCT4 stained 1 unclassifiable tumor, which lacked other specific markers. We did not find placental alkaline phosphatase, AFP, and S100 stains useful, although S100 did highlight tumor "ghost" cells in 1 case. Other features in most cases included intratubular germ cell neoplasia (6/11), tubular atrophy/hyalinization (10/11), tumor "ghost" cells (10/11), scar (9/11), and inflammation (10/11). Of the 5 patients with available follow-up, 3 were free of disease at 1, 5, and 8 years after orchiectomy (2 necrotic seminomas and 1 germ cell tumor, unclassified). One patient with yolk sac tumor (age 63 y) developed widespread metastases after 15 months and died of disease. The final case was initially misinterpreted as "testicular infarction, no malignancy" and 16 months later the patient developed a large retroperitoneal seminoma. Most totally necrotic testicular tumors can be placed into clinically important groups by assessment for coarse intratubula

Topics: Adolescent; Adult; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Embryonal; Disease-Free Survival; Endodermal Sinus Tumor; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Male; Middle Aged; Necrosis; Octamer Transcription Factor-3; Orchiectomy; Proto-Oncogene Proteins c-kit; Seminoma; Testicular Neoplasms; Young Adult

Following the differentiation of cultured stem cells is often reliant on the expression of genes and proteins that provide information on the developmental status of the cell or culture system. There are few molecules, however, that show definitive expression exclusively in a specific cell type. Moreover, the reliance on a small number of molecules that are not entirely accurate biomarkers of particular tissues can lead to misinterpretation in the characterization of the direction of cell differentiation. Here we describe the use of technology that examines the mass spectrum of proteins expressed in cultured cells as a means to identify the developmental status of stem cells and their derivatives in vitro. This approach is rapid and reproducible and it examines the expression of several different biomarkers simultaneously, providing a profile of protein expression that more accurately corresponds to a particular type of cell differentiation.

Topics: Acetamides; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Biomarkers; Carcinoma, Embryonal; Cell Differentiation; Embryonal Carcinoma Stem Cells; Flow Cytometry; Gangliosides; Glycosphingolipids; Humans; Keratins; Neoplastic Stem Cells; Neurons; Peptides; Pluripotent Stem Cells; Proteoglycans; Proteome; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stage-Specific Embryonic Antigens; Tretinoin; Tubulin

Correctly diagnosing a metastatic germ cell tumor after chemotherapy may be challenging because of the diverse morphological manifestations of postchemotherapy tumors. Both OCT4 and CD30 are sensitive markers for the identification of primary embryonal carcinomas; however, loss of expression of CD30 (65%) has been reported in metastatic embryonal carcinomas after chemotherapy. The present study was conducted to evaluate the expression patterns of OCT4 and CD30 in postchemotherapy metastatic embryonal carcinomas and to compare their utility as diagnostic tools. Twenty-five cases of metastatic embryonal carcinoma after chemotherapy were immunohistochemically analyzed for CD30, OCT4, and cytokeratin AE1/AE3 expression. The staining intensities and the percentages of positively staining tumor cells were recorded. Nineteen (76%) of 25 cases revealed diffuse, moderate to strong nuclear OCT4 staining in postchemotherapy embryonal carcinomas. Among these 19 OCT4-positive cases, 8 also revealed diffuse and moderate to strong membranous CD30 staining. Seven of these OCT4-positive cases retained focal and weak CD30 expression. The remaining 4 OCT4-positive cases demonstrated a complete loss of CD30 expression. The 19 OCT4-positive cases showed a positive but variable cytokeratin AE1/AE3 expression pattern. Six (24%) of 25 cases were negative for both CD30 and OCT4 but demonstrated diffuse and strong cytokeratin AE1/AE3 staining. OCT4 is a useful diagnostic marker to identify metastatic embryonal carcinomas after chemotherapy, with a better sensitivity than CD30.

Topics: Adult; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Embryonal; Cisplatin; Evaluation Studies as Topic; Humans; Keratins; Ki-1 Antigen; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Octamer Transcription Factor-3; Retrospective Studies; Sensitivity and Specificity; Testicular Neoplasms

Although intratubular embryonal carcinoma has been described adjacent to invasive embryonal carcinoma, to our knowledge it has not been reported as an isolated finding. We present in this report the histologic and immunohistochemical findings of 2 cases of intratubular embryonal carcinoma. One case was exclusively intratubular embryonal carcinoma without an invasive component in the same testis. A malignant mixed germ cell tumor in the contralateral testis had been previously excised. The second case is predominantly composed of intratubular embryonal carcinoma adjacent to a malignant mixed germ cell tumor. In one case, the intratubular embryonal carcinoma was immunoreactive for CD30, AE1/AE3, cytokeratin 7 focally, and p53. It was negative for cytokeratin 20, p21, and alpha-fetoprotein. These findings are strongly supportive of the opinion that intratubular embryonal carcinoma is the precursor of invasive embryonal carcinoma.

Topics: Adult; Anion Exchange Protein 1, Erythrocyte; Antiporters; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Embryonal; Germinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-1 Antigen; Male; Neoplasms, Multiple Primary; Precancerous Conditions; Testicular Neoplasms; Tumor Suppressor Protein p53

We studied cytokeratin (CK) expression immunohistochemically in 64 seminomas using a panel of commercially available antikeratin antibodies and tested for association of CK expression with patient age, tumor size, stage, and outcome. Seventeen embryonal carcinomas were compared with seminoma. CK7, CAM 5.2, AEI/AEIII, and wide-spectrum screening keratin (WSK) were positive in 41%, 30%, 36%, and 36% of the seminomas, respectively. CK20 and high-molecular-weight keratin (HMWK) were negative in all cases. CD30, placental alkaline phosphatase (PLAP), and epithelial membrane antigen (EMA) were positive in 6%, 100%, and 2% of cases, respectively. There were no differences in patient age, stage, tumor size, or outcome between CK-positive and CK-negative seminomas. CK7, CAM 5.2, AEI/AEIII, and WSK were positive in 100%, 88%, 94%, and 88% of embryonal carcinomas, respectively. CK20 and HMWK were negative in all cases. CD30, EMA, and PLAP were positive in 100%, 12%, and 76%, respectively. CKs are present in seminoma, and their presence is not associated with a difference in patient age, stage, or outcome. In cases such as small needle biopsy specimens, CK and CD30 stains may be useful in separating seminoma from embryonal carcinoma.

Topics: Adult; Aged; Alkaline Phosphatase; Carcinoma, Embryonal; Germinoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Staging; Seminoma; Testicular Neoplasms

The present report of a 25 year old woman with a primary ovarian angiosarcoma is supplemented by histochemical and ultrastructural studies and reviews the literature of this extremely rare neoplasm. Since this ovarian tumor, especially in young women, may constitute a diagnostic pitfall, problems relating to differential diagnosis are emphasized. Although the origin of this neoplasm appears to occur most likely from the rich ovarian vasculature, other less conventional histogenetic theories such as a possible origin in mixed mullerian tumor, in teratoma or in other ovarian germ cell tumors have also been proposed and are considered in this paper.

Topics: Actins; Adult; Carcinoma, Embryonal; Cytoplasmic Granules; Diagnosis, Differential; Factor VIII; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Ovarian Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1; Sertoli-Leydig Cell Tumor; Vimentin

NCR-G3 cells were established from a testicular embryonal carcinoma and are highly multipotential, differentiating into trophectoderm cells upon exposure to retinoic acid. Differentiated NCR-G3 cells begin to produce human chorionic gonadotropin (hCG), a trophectoderm-specific hormone. We have previously isolated the up-regulated genes at the early stage of differentiation. One of them was found to be a heat shock protein gene. The heat shock protein gene (HSP90) is induced at the early stage of differentiation and decreases to the basal level or under the basal level at the later stage. We speculate that heat shock per se induces the differentiation of human EC cells. With exposure to heat, NCR-G3 cells began to express a series of differentiation markers such as cytokeratin and hCG. Heat, which is classically known to induce heat shock proteins, is able to differentiate an embryonal cell line into trophectoderm lineages, implying a new recognized function of a heat-like event in early differentiation.

Topics: Carcinoma, Embryonal; Cell Differentiation; Chorionic Gonadotropin; Ectoderm; Gene Expression Regulation, Developmental; Heat-Shock Response; HSP90 Heat-Shock Proteins; Humans; Immunohistochemistry; Keratins; Male; Testicular Neoplasms; Tretinoin; Trophoblasts; Tumor Cells, Cultured

In testicular germ cell tumors the CD30 antigen has been shown to be regularly expressed in embryonal carcinoma and was thus suggested as a marker for this particular neoplasm. Very recently, it has been proven that the monoclonal antibody Ber-H2 is suitable for the detection of this membrane antigen in paraffin sections. We conducted an immunohistochemical study to investigate the CD30 expression in a large series of different presentations of seminoma (ie, pure, mixed, and spermatocytic) because there is evidence from several sources that embryonal carcinoma is histogenetically closely related to, and probably derives from, seminoma. Sections from formalin-fixed, paraffin-embedded tissue from 38 cases of testicular seminomas were immunostained for the demonstration of the CD30 antigen using the monoclonal antibody Ber-H2, cytokeratins, and placental alkaline phosphatase following an indirect streptavidin-peroxidase regimen. In selected cases, immunostainings were performed on consecutive sections to investigate a possible colocalization of CD30 and cytokeratins in seminoma. Specific immunostaining for CD30 in seminoma cells could be detected in single minute foci in 4 of 21 cases of pure classic seminoma. Seminomatous components of mixed tumors showed CD30 positivity in single, but also multiple, foci in 7 of 14 cases. CD30 immunoreactivity in seminoma cells occurred with and without colocalized expression of cytokeratin. Spermatocytic seminoma (n = 3) as well as intratubular germ cell neoplasia in tumor adjacent parenchyma (n = 36) were negative in all cases investigated. We conclude that in testicular germ cell tumors, the expression of CD30 is not restricted to embryonal carcinoma but can also be found focally in seminoma, adding further evidence for a close relationship between these two tumors. The prevalence of CD30 expression in seminomatous components of mixed tumors, as well as the coexpression with cytokeratins, suggest that CD30 expression in seminomas might indicate their upcoming transformation to embryonal carcinoma. This conclusion coincides with a model featuring seminoma in a central role of germ cell tumor development.

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Biomarkers, Tumor; Carcinoma, Embryonal; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Male; Middle Aged; Seminoma; Testicular Neoplasms

The wide range of epithelial and mesenchymal lines of differentiation seen in hepatoblastoma suggests that this tumor derives from a pluripotent stem cell. In order to test this hypothesis, seven hepatoblastomas of various subtypes were investigated for the presence of cells with the features of the oval cells found during hepatocarcinogenesis in rodents that are thought to be closely related to hepatic stem cells. The specimens were investigated by electron microscopy, electron microscopic immunocytochemistry, and immunohistochemical staining for cytokeratins nos. 7, 8, 18, and 19. Small epithelial cells (SEC) corresponding to the oval cells of the rat and the "small cells" found in human liver disease with chronic ductular reaction, both of which are thought to be related to hepatic stem cells, were found. The SEC were oval and exhibited intercellular junctions, tonofilament bundles, and a biliary epithelium-type cytokeratin profile. They were found in small numbers in fetal hepatoblastoma and in moderate numbers in embryonal hepatoblastoma. In small cell hepatoblastoma, nearly all the tumor cells exhibited SEC-like ultrastructural features and a corresponding cytokeratin profile. Thus, cells with the features of hepatic stem cells are detectable in hepatoblastoma. Their numbers vary according to the subtype, reflecting the differing degrees of differentiation of the various subtypes, consistent with the theory propounded in the literature that embryonal and, with further differentiation, fetal tumor cells derive from precursor small cells. The findings support the hypothesis that hepatoblastoma derives from a pluripotent, probably entodermal or even less committed, stem cell.

Topics: Animals; Carcinoma, Embryonal; Child; Epithelium; Hepatoblastoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Microscopy, Electron; Microscopy, Immunoelectron; Rats; Stem Cells