The immunohistochemical diagnostic panel for epithelial mesothelioma: a reevaluation after heat-induced epitope retrieval.

The immunohistochemical diagnosis between epithelial mesothelioma and adenocarcinoma is currently based on the use of a panel of antibodies to adenocarcinoma-associated antigens and a few antibodies to mesothelial-associated antigens. Since the introduction of epitope retrieval methods, the sensitivity of many antibodies has been enhanced. Thus, a reevaluation of the mesothelioma/adenocarcinoma diagnostic panel becomes necessary. We studied 268 paraffin-embedded formalin-fixed tumor samples that included 57 epithelial mesotheliomas and 211 adenocarcinomas of various origins, comparing an extensive antibody panel with and without heat-induced epitope retrieval (HIER). Marked increase in the sensitivity of several antibodies, with no loss of specificity, was found when HIER was used. After statistical analysis, the antibodies to the epithelial glycoproteins carcinoembryonic antigen, BerEp4, and Bg8 emerged as the best discriminators between adenocarcinoma and epithelial mesothelioma within the entire panel. The mesothelium-associated antibodies, HBME-1, calretinin, and thrombomodulin were less sensitive and less specific than the former, although they were found to be useful on certain cases. Antibodies to cytokeratins and vimentin, although of minor diagnostic value in this context, may be helpful to evaluate the quality of antigen preservation. This study confirms the value of immunohistochemistry to accurately distinguish mesothelioma from adenocarcinoma when an antibody panel approach is used. The addition of heat-induced epitope retrieval methods increases the effectiveness of the procedure and is recommended for most of the antibody panel members.

HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma.

The monoclonal antibody, HBME-1, generated against the microvillous surface of mesothelial cells, has been shown to have significant reactivity in histologic sections of follicular-derived thyroid malignancies. We examined the diagnostic utility of HBME-1 in thyroid fine-needle aspiration (FNA) specimens. Twenty-four aspirates from 23 patients were evaluated. Only cases with adequate cell blocks and tissue follow-up were studied. Immunocytochemical analysis was performed on air-dried, direct smears and on sections from Bouin's-fixed, paraffin-embedded cell blocks with a standard avidin-biotin peroxidase complex method with epitope retrieval. The same immunostaining technique was applied to the corresponding formalin-fixed tissue sections. Eight (57%) of the 14 malignant aspirates showed strong cytoplasmic and/or membrane immunoreactivity for HBME-1. The cell-block and direct-smear preparations were positive in five of seven papillary carcinomas (one follicular variant), one of one minimally invasive follicular carcinoma, and one of four hybrid tumors with mixed papillary and follicular features. An additional hybrid tumor case was focally positive only in the smear slide. The eighth positive case was an adenosquamous carcinoma of the larynx that invaded into the thyroid (smear preparation was negative for this case). The 10 benign lesions were negative. All of the malignant-tumor tissue sections were positive for HBME-1, and focal positivity was seen in 5 of 10 benign resection specimens. We conclude that a positive immunostain for HBME-1 on a thyroid FNA is supportive evidence that the lesion is a carcinoma, that a negative result for HBME-1 does not preclude the diagnosis of thyroid carcinoma, and that HBME-1 can be effectively applied to thyroid FNA specimens and can be a valuable adjunct in the cytologic diagnosis of thyroid malignancies.

Enhanced functional capacity of the peritoneal macrophages as antigen presenting cells after aclacinomycin treatment in mice.

Aclacinomycin (ACM) is an oncostatic of the anthracycline family, largely used in patients and experimentally in mice. ACM has been reported to enhance phagocytosis, secretion of free oxygen radicals and of interleukin 1. Its injection is also followed by an increase of the cytotoxic and cytostatic activity of murine peritoneal macrophages. In the present work we investigated whether ACM modifies the antigen-presenting cell capacity of murine peritoneal macrophages. Purified T lymphocytes were cultured with peritoneal macrophages from either normal or ACM treated mice (4 mg/kg day -4) which were previously incubated with phytohemagglutinin. The T cell proliferative response was greater in cultures with normal macrophages, indicating that macrophages from ACM-treated mice had a better antigen presenting activity than normal untreated macrophages.

[Tumor of the ovarian juvenile granulose cells. Presentation of a case with an immunohistochemical and ultrastructural study]. / Tumor de células de la granulosa juvenil del ovario. Presentación de un caso con estudio inmunohistoquímico y ultraestructural.

Female, 5 years old; first pregnancy of term, eutocic, weight 3,100 g; breast fed, complete vaccination program. A bronchial pathology that was present seven months later, yielded with medical treatment. Her illness started on September, 1984 after sever trauma by horse kick, presenting with a tumor in left illiac fossa; there was pain, improved by analgesics; the tumor continued to grow up to 5 x 6 cm in diameter, painful on palpation, causing hospital admission. Thirty days later an ultrasonographic study reported an ovoid echogenic and echolucid mass of 6.5 cm in left ovary; an infra-umbilical laparotomy was performed, finding a left ovarian tumarration, ovoid, pink white, with vascular areas, 24 x 18 x 15 cm at maximal diameters, solid, smooth and bright; at section there was gray-white, nodular tissue, with cystic cavities, 0.5 cm. Electronic microscopy an immunochemistry study were carried out in order to confirm the diagnosis of juvenile granulosa cell tumor. The patient died seven months later.

[Juvenile granulosa-cell tumor of the ovary. Immunohistochemical and ultrastructural study]. / Tumor de células granulosas juvenil del ovario. Estudio inmunohistoquímico y ultraestructural.

In 1977 Scully first described the juvenile granulosa cell tumor of the ovary (JGCT) as a special variation of the granulosa cells tumor, which occurs in the two first decades of life, and 97% of the cases show characteristic microscopic and histological features. Five previous cases have been reported concerning the ultramicroscopic characteristics of this ovarian neoplasia. The purpose of this paper is to report the immunohistochemical and ultrastructural characteristics in a case of OJCGT which occurred in a four year old girl with isosexual precocious pseudopuberty. The presence of vimentin and absence of keratin was proven immunohistochemically in this ovarian neoplasia. Intermediate filaments were found ultrastructurally. The combined use of immunohistochemical and ultrastructural techniques has proven to be of extraordinary usefulness for the differential diagnosis between epithelial and non epithelial ovarian tumors and adds a new and highly specific method to characterize and differentiate the cells of embryonic carcinoma, choriocarcinomas and endodermal sinus tumors which are keratin positive.

Cellular differentiation in ovarian sex-cord-stromal and germ-cell tumors studied with antibodies to intermediate-filament proteins.

Seventy ovarian sex-cord-stromal and germ-cell tumors were immunohistochemically studied for the presence of intermediate-filament proteins of different types used as markers for cellular differentiation. Cells of ovarian granulosa-cell tumors constantly expressed vimentin and appeared to lack cytokeratin. Two tumors previously classified as granulosa-cell tumors were reclassified as poorly differentiated "common" epithelial tumors based on their cytokeratin positivity, vimentin negativity, and morphologic features. Dysgerminomas and Leydig-cell tumors showed only vimentin positivity. Tubular structures in androblastomas, which are considered to represent Sertoli-cell differentiation, were cytokeratin positive, and thus differed from the majority of normal Sertoli cells that are known to express vimentin and not cytokeratin. Embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors showed cytokeratin positivity in the neoplastic cells whereas vimentin was observed in the stromal cells. In immature teratomas, epithelial differentiation was demonstrated with cytokeratin antibodies, and neural and glial differentiation was also frequently demonstrated by immunostaining with antibodies to neurofilaments and glial fibrillary acidic protein. The results show that antibodies to intermediate filaments can be used in the differential diagnosis between ovarian epithelial and nonepithelial tumors, and they provide a very accurate additional method to characterize the cellular differentiation of ovarian neoplasms.

Ovarian sex-cord tumor with annular tubules. Case report with ultrastructural findings.

An ovarian sex-cord tumor with annular tubules (SCTAT) and with Charcot-Böttcher bodies in a 29-year-old woman with primary infertility, secondary amenorrhea, and without evidence of the Peutz-Jeghers syndrome was studied by light and electron microscopy. At laparotomy, a right ovarian tumor was removed, and there was no evidence of metastases. The patient has been well and disease free for a period of 3 months after surgery. The tumor was histologically composed of nests of cells arranged in complex tubules with hyaline bodies. Ultrastructurally, cells were joined by specialized junctions along their lateral adjacent borders. Microvilli and cilia were absent. Concentrically arranged membranes were seen in the cytoplasm. Charcot-Böttcher filaments were seen in paranuclear region. The findings of Charcot-Böttcher filament in an ovarian SCTAT support the hypothesis of the Sertoli nature of this neoplasm.