CD10 expression in epithelial tissues and tumors of the gynecologic tract: a useful marker in the diagnosis of mesonephric, trophoblastic, and clear cell tumors.

We tested 417 cases of formalin-fixed, paraffin-embedded normal or hyperplastic gynecologic tissues as well as neoplasms involving the gynecologic tract with a monoclonal antibody against CD10 (clone 56C6), with special emphasis on epithelial and epithelial-like structures and tumors. CD10 was always expressed in mesonephric remnants (mesonephric remnants of the uterine cervix, epoophoron, rete ovarii) and tumors (mesonephric adenocarcinoma of the uterine cervix, tumors of wolffian origin of the broad ligament and ovary). CD10 was also positive in the syncytiotrophoblast, cytotrophoblast, and intermediate trophoblast of normal gestations, partial and complete moles, choriocarcinoma, and placental site trophoblastic tumors. Finally, CD10 was positive in several metastatic neoplasms to the gynecologic tract (100% in metastatic renal clear cell and intestinal carcinomas and melanomas). In contrast, CD10 was almost invariably negative in müllerian epithelia of the female genital tract and in their corresponding tumors, with the exception of focal expression found in squamous epithelia and tumors with squamous differentiation. Thus, the expression of CD10 may be useful in the establishing the diagnosis of mesonephric and trophoblastic tumors and in the differential diagnosis between gynecologic clear cell carcinoma (always negative) and metastatic clear cell carcinoma of renal origin.

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Female adnexal tumours of probable Wolffian origin: an immunohistochemical study comparing tumours, mesonephric remnants and paramesonephric derivatives.

AIMS: To establish an immunohistochemical profile of presumed female adnexal mesonephric tumours (FATWO) for diagnostic purposes and to compare the findings with those of mesonephric and paramesonephric derivatives in order to establish supportive evidence for a mesonephric origin. METHODS AND RESULTS: Standard immunohistochemistry was performed on formalin-fixed tissues. Tumours, mesonephric remnants and paramesonephric structures generally show positive staining for vimentin, CAM 5.2 and cytokeratins 7 and 19 but are negative for CK20 and 34 beta E12. EMA is positive in both mesonephric and paramesonephric derivatives but is negative in the tumours. Glutathione S-transferase mu (GST mu) is generally positive in both tumours and mesonephric derivatives but negative in paramesonephric structures. CONCLUSIONS: Immunohistochemistry plays little part in the diagnosis of FATWO. The tumours are generally cytokeratin and vimentin-positive and EMA-negative. GST mu, as a marker for the mesonephric duct, is a useful adjunct. Our findings of the study support but do not prove that FATWOs are of mesonephric origin.

Immunohistochemical type distinction of alpha-fetoprotein in various alpha-fetoprotein-secreting tumors.

In order to clarify the histogenesis of alpha-fetoprotein (AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various organs were examined by the peroxidase-antiperoxidase method for AFP, and paradoxical concanavalin A staining. Yolk sac-type AFP was found in yolk sac tumors, embryonal carcinomas, solid teratomas, (yolk sac) endodermal cell tumors, adenocarcinomas (stomach, ovary or lung) and metastatic liver cancers. Hepatic-type AFP was demonstrated in hepatocellular carcinomas, hepatoblastomas, solid teratomas and a stomach cancer. Yolk sac-type AFP was observed in the neighboring liver cells of metastatic liver cancers without relation to the type of AFP in primary cancers. The results from serum analyses of preoperative tumor-bearing patients (68 cases) were coincident with those from immunohistochemical stainings.

Expression of intermediate filaments and other special markers by testicular germ cell tumors. With reference to embryogenesis.

Distribution of intermediate filament proteins (IFs) and several special markers was studied in 39 testicular germ cell tumors and 8 embryos and foetuses. The similarity and difference between development of germ cell tumor and embryogenesis were immunohistochemically investigated. Seminoma and embryonal carcinoma, as tumoral counterparts of undifferentiated germ cells, were characterized by little IF expression. This study revealed that the maturing and differentiating process in germ cell tumor is different from normal embryonal development and the tumor cells showed leaping maturing steps in tumorigenesis. Immunostaining for IFs helped to discover the further differentiation occurring in embryonal carcinoma and to demonstrate heterogeneous elements in non-seminoma germ cell tumors, which sometimes might not be apparent by light microscopical observation of H&E staining section. According to the findings, two patterns in mixed germ cell tumors are suggested; i.e., combined and diffuse types. The mechanism of tumorigenesis of the two types is supposed to be different. Clinically, the prognosis of most patients with testicular germ cell tumor is fairly good because of the improved chemotherapies that are dependent on histological diagnosis.

Primary yolk sac tumor of the cerebellar vermis: case report.

A rare case of yolk sac tumor in the cerebellar vermis is reported. A 2-year-old boy developed headaches, vomiting, and an unsteady gait. Later a tumor was demonstrated in the medial part of the cerebellum by gadolinium-enhanced magnetic resonance imaging (MRI). The tumor was totally removed, and the surgery was followed by chemotherapy. Soon after surgery the elevated alphafetoprotein (AFP) levels in the serum and cerebrospinal fluid were observed to decrease to normal levels. Three months later enhanced MRI showed a lesion in the vermis without any elevation of AFP, and the lesion turned out to be a granuloma. Six months after the second surgery a tumor recurred that could not be totally removed. Cranial radiotherapy was given together with chemotherapy, which resulted in a decrease of AFP to the normal range. The patient is doing well without any elevation in AFP at 1 year 6 months after onset. Related problems in the diagnosis and treatment of yolk sac tumors are discussed.

Growth of a human yolk sac tumor cell line with yolk sac-derived functions in selenium-supplemented chemically defined synthetic medium.

A human yolk sac tumor cell line, TG1, which was established from a testicular yolk sac tumor, was found to replicate continuously in a chemically defined medium supplemented with Na2SeO3 (ISRPMI). TG1 produced several plasma proteins and growth factors: albumin, alpha-fetoprotein (AFP), ferritin, carcinoembryonic antigen, beta-2-microglobulin, polyamine, neuron specific enolase, tissue polypeptide antigen, transferrin (Tf), epidermal growth factor, and platelet derived growth factor. By analysis of lentil lectin (LcHA)-affinity electrophoresis, to examine the microheterogeneity of carbohydrate chains of synthetic glycoproteins, TG1 cells cultured with ISRPMI produced only LcHA reactive Tf and AFP based on core fucose attached to asparagine-linked N-acetylglucosamine residues instead of LcHA-nonreactive Tf and AFP produced by TG1 cells cultured with fetal bovine serum (FBS)-containing medium. alpha 1-6 Fucosyltransferase activity was significantly greater in the TG1 cells cultured with ISRPMI (39.9 +/- 1.5 pmol.h-1.mg-1 protein) than cultured with FBS-containing media (18.2 +/- 1.2 pmol.h-1.mg-1 protein). These results have indicated that the selective increase of alpha 1-6 fucosyltransferase occurred when the cells were cultured with the FBS-free synthetic media.

Fine-needle aspiration cytology of an endometrioid-like variant of yolk sac tumor.

A 36-year-old male with a history of immature teratoma and embryonal carcinoma of the testis was admitted to the hospital for abdominal pain and fever. A CT scan revealed a large right abdominal mass. The patient's serum alpha-fetoprotein (AFP) was 46.8 ng/ml (reference < 25 ng/ml). Fine-needle aspiration (FNA) of the mass revealed malignant glandular cells. Chemotherapy was instituted, followed by resection of the large abdominal mass. The tumor was grossly encapsulated, consisting of large areas of necrotic, hemorrhagic tissue surrounded by smaller, multiloculated cysts. Microscopically, the tumor had a villoglandular pattern and variably stratified tall columnar cells. A prominent feature of the columnar cells was supranuclear and subnuclear vacuolization. Intracytoplasmic PAS-positive, diastase-resistant hyaline globules were occasionally present. AFP by immunoperoxidase was prominent within the tumor. This recurrence of the previously diagnosed testicular teratoma with embryonal carcinoma represents a yolk sac tumor with components strongly resembling endometrioid carcinoma, a variant only recently described in eight cases of ovarian origin (Clement et al.: Am J Surg Pathol 1987; 11(10):767-778). We believe this is the first reported case of an endometrioid-like variant of testicular yolk sac tumor and also the first report of the FNA cytology findings in this variant.

An endodermal sinus tumor in the cerebellopontine angle.

Immunohistochemical and ultrastructural findings in a primary intracranial endodermal sinus tumor are reported in this paper. The tumor cells exhibited AFP, CEA and anti-alpha-1-trypsin positive immunoreactivity immunocytochemically. Aggregates of electron-dense material in the extra- and intracellular spaces and amorphous basement membrane-like substance were seen extracellularly by electron microscopy. The clinicopathological, immunocytochemical and ultrastructural features were consistent with the criteria for primary intracranial sinus tumor.

[Molecular heterogeneity of alpha-fetoprotein in ovarian or extragonadal yolk sac tumor].

The molecular heterogeneity of alpha-fetoprotein (AFP) in yolk sac tumor (YST) was investigated. The study included 14 sera from YST, 78 sera from primary hepatocellular carcinoma (PHC), 5 fetal yolk sac (YS) culture fluids and 4 fetal liver culture fluids. The microheterogeneity of AFP was assessed by differences in reaction with AFP carbohydrate chain and lectins, and concanavalin A (Con A), Lens culinaris hemagglutinin (LCH) and phytohemagglutinin E (PHA-E) affinity crossed-line immunoelectrophoresis was used to fractionate AFP. It was found that AFP in YST or YS had similar subfraction patterns and differed clearly from AFP in PHC or fetal liver. Characteristic features of AFP subfraction in YST or YS were the presence of a LCH weakly-reactive subfraction and a high proportion of both Con A non-reactive and PHA-E strongly-reactive subfractions. The LCH weakly-reactive subfraction was specifically found in YST or YS, but was not found at all in PHC or in fetal liver. This variant is known to exist in amniotic fluid at an early stage of gestation, and is assumed to have a carbohydrate chain with both fucose and bisecting N-acetyl-glucosamine. The present findings therefore suggest that glycosylation of AFP in YST takes place by retro-genetic differentiation toward fetal yolk sac, but not toward fetal liver, and these studies confirm the suggested yolk sac origin of ovarian, as well as extragonadal, yolk sac tumor.

Plasma protein and apolipoprotein synthesis by human yolk sac carcinoma cells in vitro.

Three human yolk sac carcinoma cell lines were characterized for the expression of several markers. Each of the cell lines expressed alpha-fetoprotein, without detectable levels of chorionic gonadotropin, and the level of alpha-fetoprotein expression increased dramatically when the cultures were held without passage for extended periods. The secretion of a number of plasma proteins was documented by metabolic labeling, immunoprecipitation, and gel analysis. The major plasma proteins detected were alpha-1-antitrypsin, alpha-fetoprotein, transthyretin, beta-2 microglobulin, and plasminogen, with lower levels of transferrin and complement C4 released. Apolipoproteins B, E, and A1 were secreted in high levels as well and were found in the form of lipoprotein particles. Time course experiments on the synthesis of apolipoproteins E and A1 indicated that, as with alpha-fetoprotein, the level of synthesis increased substantially when the cultures were held without passage. The results indicate that these yolk sac carcinoma cells display a protein expression profile similar to that observed for the human yolk sac, and the possibility that the cells may have the potential to differentiate is discussed.

Production of 13 plasma proteins by human testicular yolk sac tumor transplanted into nude mice.

Thirteen human proteins were found in plasma and cystic fluid of mice bearing human testicular yolk sac tumor. Six of them, alpha-fetoprotein, prealbumin, albumin, alpha 1-antitrypsin, hemopexin and transferrin, had been previously demonstrated to be produced by yolk sac tumors. The syntheses of the remaining seven, namely apolipoprotein A1, retinol-binding protein, alpha 2HS-glycoprotein, haptoglobin, apolipoprotein B, C5 component and anti-hemophilic factor, have been demonstrated for the first time.

Rete testis hyperplasia with hyaline globule formation. A lesion simulating yolk sac tumor.

The presence of eosinophilic, hyaline globules in association with epithelial hyperplasia was noted in the rete testis of three patients with germ cell tumors. In the more florid examples, this proliferation formed a solid and microcystic pattern that, in association with the hyaline globules, mimicked a yolk sac tumor component. However, the bland cytologic features of the cells and the conformation to the configuration of the rete testis were keys to its reactive nature. A subsequent review of 48 testicular specimens containing well-defined areas of the rete testis showed hyaline globule formation in the rete testis or tubuli recti in 16 of 27 germ cell tumors, one of five other testicular tumors (four stromal tumors and one plasmacytoma), and none of 16 nonneoplastic cases. Many of the cases that had hyaline globules also showed epithelial hyperplasia. Further analysis demonstrated an incidence of rete testis invasion by neoplasm in cases that had hyaline globules, with or without epithelial hyperplasia, that was significantly higher (p less than 0.01) than that seen in neoplastic cases lacking hyaline globules. We concluded that this pseudoneoplastic reaction developed secondary to invasion of the rete testis by tumor. Immunostains supported the nonneoplastic nature of the proliferative lesions and indicated that the globules represented various proteins that had been absorbed from the lumen of the rete testis by the epithelial-lining cells but not successfully secreted.

Laminin in testicular germ cell tumours. An immunohistochemical study.

Thirty-five testicular germ cell tumours comprising 16 yolk sac tumours, 15 embryonal carcinomas and 13 seminomas were examined for the presence and distribution of laminin using an indirect immunoperoxidase technique. In addition, nine normal yolk sacs and 23 carcinomas of the lung were studied. All the yolk sac tumours were positively stained for laminin. Both extra- and intracellular staining were found. Hyaline, eosinophilic material present within the tumours was positively stained, although with varying intensity. In 12 out of 15 embryonal carcinomas, laminin was found as a membrane staining but cytoplasmic staining also occurred. In 10 out of 13 classical seminomas, a membrane staining of many tumour cells was found, while cytoplasmic staining occurred in only a few seminomas. In all but one of the yolk sacs, laminin was present in the membrane beneath both the mesoblastic outer cell layer and the visceral endoderm. Intracellular staining was seen in some of the cells in both cell layers. In nine out of 23 carcinomas of the lung, laminin occurred extra- as well as intracellularly. Thus, this study showed that in normal yolk sacs the presence of laminin was not found to be particularly associated with any of the cell layers. Likewise, demonstration of laminin within yolk sac tumours did not define different patterns or subtypes of the yolk sac tumour. In addition, demonstration of laminin was not found to be useful in differentiating either between yolk sac tumours and embryonal carcinomas or between seminomas and non-seminomatous germ cell tumours. The findings add, however, interesting knowledge to histogenesis and embryogenesis.

Primary pulmonary alpha-fetoprotein-producing malignant germ cell tumor.

We are reporting the clinical and pathologic features of a primary, pulmonary, malignant germ cell tumor associated with a marked elevation of serum alpha-fetoprotein (38,427 ng/mL) and lactate dehydrogenase activity (756 U/L), in a 26-year-old female. This controversial, rare neoplasm has not been extensively discussed in the pathology literature. We emphasize the clinical importance of establishing this diagnosis in view of the favorable response to chemotherapy shown by malignant germ cell tumors.

Cell differentiation in sacrococcygeal teratomas. An immunohistochemical and follow-up study.

The cell differentiation properties of thirty-four sacrococcygeal teratomas (SCT) and their five recurrences were immunohistochemically studied for the expression of different classes of intermediate filament proteins, muscle actin (MA) and S-100 protein. Out of thirty-nine tumors twenty-three were SCTs with only mature tissue elements, seven immature teratomas, five pure endodermal sinus tumors (EST) and four ESTs or embryonal carcinomas (EC) combined with mature components. Cytokeratin positivity was found in all epithelial structures and sometimes also in smooth muscle and primitive mesenchymal cells. An intense cytokeratin immunoreactivity was observed in EC and EST components. Muscle markers, desmin and MA were present in smooth and striated muscle cells. Focal desmin positivity was also found in some epithelial structures in two cases. Glial tissue positive for glial fibrillary acidic protein (GFAP) was found in twenty-eight out of thirty-nine tumors. Some cases with no apparent glial tissue in hematoxylin and eosin staining showed glial differentiation as proved by GFAP positivity. In six out of eleven choroid plexus-like tissues GFAP positive cells were observed. S-100 protein showed an intense distribution of immunoreactivity outside neural tissue, and focal positivity was observed in malignant epithelial structures. Immunohistochemical markers did not reveal any prognostic significance in teratomas. Our findings, however, showed some aberrant features of cell differentiation from normal mature tissue components but closely parallel to those found in normal fetal development.

Germ cell neoplasms of head and neck soft tissues: a pathologic spectrum of teratomatous and endodermal sinus tumors.

Germ-cell neoplasms, in particular teratomas with immature and mature somatic type tissues, are some of the most commonly found tumors in children. Approximately 5% of these neoplasms appear in one of several extracranial sites in the head and neck region. This study reports the clinical, pathologic and immunohistochemical findings in six germ-cell neoplasms occurring in the neck and facial areas. A mass was recognized at birth in five children, and the sixth patient was 2 1/2 years old at diagnosis. Four of the six neoplasms contained one or another element of endodermal sinus tumor; two of these had a mixed pattern of endodermal sinus tumor and teratoma. The other two cases were purely teratomas. The serum alpha-fetoprotein was known to be elevated in three children whose tumors had endodermal sinus elements; it returned to normal level in two of the children, but remained high in the one fatal case. Placental alkaline phosphatase and alpha-fetoprotein were demonstrated immunohistochemically in two of the three cases, with available tissue containing endodermal sinus tumor. Teratomatous metastases in ipsilateral cervical lymph nodes were found in one patient with a pure teratoma; that patient is disease-free one year after surgery. Only nine previous examples of endodermal sinus tumor have been reported in the head and neck region, exclusive of the central nervous system. There is one other case in the literature of a congenital cervicothyroidal teratoma with metastatic disease. These six neoplasms illustrate the clinical and pathologic spectrum in this nosologically homogeneous, but morphologically diverse, category of tumors.