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PubMed2004

The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from endometrioid and clear cell carcinomas.

Yolk sac tumors (YSTs) have a variety of morphologic patterns, some of which can resemble either endometrioid adenocarcinoma (EAC) or clear cell carcinoma (CCC). Immunohistochemical staining for alpha-fetoprotein (AFP) is usually only focal and thus is not always helpful in the diagnosis of YST, and pancytokeratin (CK) is expressed by all three tumors. We studied a battery of immunohistochemical markers with specific attention to the utility of cytokeratin 7 (CK7) in differentiating YST from EAC and CCC. A total of 46 ovarian tumors were retrieved for this study: 16 YST, 19 EAC, and 11 CCC. The three groups were analyzed for the expression of CK7, AFP, Leu-M1 (CD15), EMA, and WT1 by immunohistochemistry. In addition, CK and c-kit (CD117) were studied in the YSTs. All of the YSTs tested (100%) were positive for CK. CK7 was considered negative in all 16 YST cases (100%), although a few tumor cells (1%-2%) stained in 4 cases. In contrast, 17 of 19 EACs and all 11 CCCs had diffuse 3+ to 4+ positivity for CK7; the two other EACs showed 2+ positivity for CK7 (40% and 30% of the tumors). AFP was positive in 12 of 15 YSTs (80%), but was generally focal with 1+ staining in 10 cases (67%); only 2 cases were 3+. All of the EACs and CCCs were negative for AFP. Leu-M1 was 1+ in 9 of 15 YSTs (60%), while the remaining 6 were considered negative. Leu-M1 was positive in 10 of 15 EACs tested (67%), but the staining was variable with 1 case 3+, 3 cases 2+, and 6 cases 1+. In the CCCs, 10 cases (91%) were 3+ to 4+, and 1 case was 1+. EMA was essentially negative in 15 of 15 YSTs (100%), with 3 completely negative and 12 showing very focal (<5%) staining. Eight of 12 EACs showed 4+ staining, 3 showed 3+ staining, and 1 showed 2+ staining. All of the 11 CCCs (100%) showed 4+ staining. WT1 was negative in all cases of YST and CCC; 16 of 18 EAC tested (89%) were negative for WT1, but 2 (11%) were 4+ positive. C-kit was negative in all YSTs. In conclusion, it is important for pathologists to be aware that YSTs may mimic EACs and CCCs and that this distinction is important for the clinical management of patients with these tumors. AFP staining is focal in most YST, so an absence of staining does not exclude this diagnosis. CK7 and EMA are essentially negative in YST but are diffusely positive in CCC and EAC, making them useful markers for differentiating YSTs from both CCCs and EACs. Leu-M1 may also be helpful for distinguishing YSTs from CCCs.

Adenocarcinoma, Clear Cell↗
PubMed2006

Increasing expression of extracellular matrix metalloprotease inducer in ovary tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters.

Ovary cancer invasion is responsible for both local tissue destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell-derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesized that EMMPRIN isoverexpressed in ovary tumors. Immunohistochemical analysis of EMMPRIN was performed in tissue microarrays of ovary neoplasms including 84 cases of serous adenocarcinoma, 23 cases of mucinous adenocarcinoma, 10 cases of endometrioid adenocarcinoma, 12 cases of yolk sac tumor, 12 cases of clear cell carcinoma, 8 cases of dysgerminoma, 8 cases of granulosa cell tumor, 6 cases of transitional cell carcinoma, and 6 cases of Brenner tumor. All malignant ovary tumors showed significant immunohistochemical expression of EMMPRIN. The EMMPRIN scores in malignant ovary tumors were significantly higher than their nontumor counterparts (313+/-28 for serous adenocarcinoma; 308+/-25 for mucinous adenocarcinoma; 187+/-19 for endometrioid adenocarcinoma; 265+/-23 for yolk sac tumors; 87+/-13 for clear cellcarcinoma; 126+/-15 for dysgerminoma; 243+/-26 for granulosa cell tumor; 87+/-16 for transitional cell carcinoma). The EMMPRIN score was significantly higher in serous adenocarcinomas than in serous adenomas and serous borderline tumors and was correlated with nodal stage. Our findings show for the first time that EMMPRIN is overexpressed in all malignant ovary tumors.

Adenocarcinoma↗
PubMed2006

Recent advances in the pathology and classification of ovarian germ cell tumors.

In recent years, our knowledge of ovarian germ cell tumors has increased, and their classification has evolved. The introduction of cisplatin-based chemotherapy and the discovery of tumor markers, including alpha-fetoprotein and human chorionic gonadotropin, have dramatically changed the clinical outlook for most of these patients. In this review, recent advances in the classification and pathology of ovarian germ cell tumors are discussed. Where appropriate, comparisons are made with testicular germ cell tumors. The last section of the article discusses the pathogenesis of germ cell tumors. This review will emphasize the articles written in the last 10 years and those that have significantly advanced our knowledge of germ cell tumors in past decades.

Carcinoid Tumor↗
PubMed1985

[The role of the structural characteristics of ovarian dysgerminoma in its prognosis].

The paper discusses the results of a retrospective analysis of the clinical course of ovarian dysgerminoma. The clinical and morphological peculiarities of 22 cases were evaluated. The cases were identified as "classical", unmixed dysgerminoma. Patients were divided into two study groups: (I) those with good prognosis and (2) patients with fast advancing disease. The patients of the first study group were found to have "classical" dysgerminoma, while those of the second study group revealed typical dysgerminomas with areas characteristic of tumor of the endodermal sinus, or atypical areas (a detailed morphological description of the latter is given). Some atypical areas showed structures indistinguishable between dysgerminoma and tumor of the endodermal sinus. The latter tumor was more frequent in recurrent and metastatic lesions. This makes the case for monitoring tumor process by histological examination of tumor at different stages of its progression and offers means for individually-tailored chemotherapy.

Adolescent↗
PubMedDate not supplied

Primary intracardiac yolk sac tumor.

A 2-year-old male child presented with fever, complete heart block, and congestive cardiac failure. Echocardiography showed a dumbbell-shaped mass in the right ventricle and right atrium. He was operated on with a provisional diagnosis of rhabdomyoma. Histopathology and immunohistochemistry of the resected tumor revealed a malignant germ cell tumor with predominant yolk sac differentiation.

Biomarkers, Tumor↗
PubMed1997

The role of subfractionation of alpha-fetoprotein in the treatment of pediatric surgical patients.

Subfractionation of serum alpha-fetoprotein (AFP) is a useful method to discriminate between yolk sac tumors, hepatic malignancies, and benign liver diseases in adults but has not been validated in infants and children. AFP subfractionation was performed on AFP-positive sera from 73 infants and children. AFP subfraction profiles were classified into three common types: (1) yolk sac type, (2) hepatoblastoma type, and (3) benign hepatic type, according to the reactivity of individual AFP samples to lectins. In 68 of 73 samples (93.2%), AFP subfraction profiles were accurately classified into these three types, and an atypical AFP subfraction profile resembling the hepatoblastoma type was found in sera from five infants (6.8%). Differentiation between hepatoblastoma and hepatitis when patients are very young can be difficult. Subfractionation is more accurate when patients are older. This technique was found to be useful in the diagnosis of neonatal ovarian tumors, in recurrent hepatoblastoma/ yolk sac tumor with low serum AFP, and in the differential diagnosis of hepatic mass (malignancy versus hyperplastic nodule) in the liver with long-standing cholestasis. Estimation of serum AFP subfraction profiles facilitates the differential diagnosis of various AFP-positive pediatric diseases, such as hepatoblastoma, hepatoma, hepatitis or germ cell tumors. This test is inexpensive, can be carried out within 48 hours, and should be performed for the differential diagnosis of pediatric liver disease.

Adolescent↗
PubMedDate not supplied

Cytologic features of functioning stromal cells in a yolk sac tumor of the ovary. A case report.

BACKGROUND: Functioning stromal cells are sometimes seen in primary and metastatic ovarian neoplasms. However, the cytologic features of functioning stromal cells have been described only rarely. CASE: A 19-year-old woman had an alpha-fetoprotein-producing ovarian yolk sac tumor with functioning stroma. Her preoperative serum testosterone level was elevated. Imprint cytology showed that the functioning stromal cells had centrally located nuclei with low nuclear/cytoplasmic ratios. Occasionally these cells had vacuolated cytoplasm, suggesting the presence of lipids. In sharp contrast, the yolk sac tumor cells had more pleomorphic and hyperchromatic nuclei. We were able to distinguish between neoplastic and functioning stromal cells on the basis of these findings. In addition, immunostaining for inhibin on imprint cytologic slides was of great help in identifying functioning stromal cells. CONCLUSION: Because functioning stromal cells may unexpectedly induce hormonal effects in a variety of ovarian tumors, it is important to identify such cells in cytologic specimens.

Adult↗
PubMed2002

Fine-needle aspiration biopsy of nonteratomatous germ cell tumors of the mediastinum.

We assessed the usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis of mediastinal germ cell tumors (GCTs). In the archives of 3 pathology departments, we found records of 7 patients with mediastinal GCTs who underwent mediastinal FNAB as part of the diagnostic workup. The FNAB smears, results of the immunocytochemical analysis, the corresponding histologic findings, and the clinical charts were reviewed. All patients were men (age range, 24-44 years; mean, 32 years). One patient had a history of testicular mixed GCT 10 years earlier. The 6 primary mediastinal GCTs consisted of 3 seminomas and 3 yolk sac tumors. Based on the cytologic features and immunocytochemicalfindings, a cytologic diagnosis of GCT was made in 5 cases, including the case of metastatic GCT In 2 cases, the differential diagnosis was between poorly differentiated carcinoma and GCT Results of ancillary studies were noncontributory in 1 case, and the aspirate of the second case demonstrated extensive necrosis. Our findings demonstrate that a diagnosis of mediastinal GCT, primary or secondary, can be established with a high degree of accuracy on the basis of FNAB. Immunocytochemical analysis helps confirm the diagnosis.

Adult↗
PubMed2001

Gonadal malignant germ cell tumors express immunoreactive inhibin/activin subunits.

OBJECTIVE: Inhibin and activin are proteins produced by ovarian granulosa cells and testicular Sertoli cells and are members of the transforming growth factor-beta superfamily. Since increased circulating levels of immunoreactive inhibin were detected in women with malignant ovarian tumors, they were proposed as tumor markers for ovarian carcinoma. Immunohistochemical studies later confirmed the presence of inhibin and activin subunits in granulosa cell tumors and epithelial ovarian cancer, as well as in Sertoli and Leydig cell testicular cancer. However, there is discrepant information on the detection of inhibin and activin in malignant germ cell tumors (MGCT). The aim of the present study was to evaluate the immunohistochemical expression of the inhibin/activin alpha, betaA and betaB subunits in ovarian and testicular MGCT specimens using polyclonal antisera. METHODS: The ovarian tissue samples were composed of 19 MGCT, including dysgerminoma (n=18) and yolk sac tumor (n=1). The testis specimens included classic seminomas (n=20), embryonal carcinomas (n=7), choriocarcinomas (n=2), and yolk sac tumor (n=1). RESULTS: Ovarian and testicular malignant germ cell tumors expressed positive staining for inhibin/activin alpha, betaA and betaB subunits, with some variations between and within individual tumors: while ovarian dysgerminomas were diffusely positive for alpha, betaA and betaB, testicular tumors expressed alpha and betaB subunits, whereas betaA staining was weak. CONCLUSIONS: The present results show positive staining for inhibin/activin subunits in ovarian and testicular MGCT, suggesting a possible role in tumorigenesis with the resultant clinical implication.

Activins↗
PubMed1996

Comparative analysis of cell surface antigens expressed by cell lines derived from human germ cell tumours.

The pattern of cell surface antigen expression of a set of cell lines derived from human germ cell tumours and corresponding to various cell phenotypes found within these tumours was studied using immunofluorescence. Twenty-two different antibodies were used. Many of these antibodies have been noted to recognise epitopes that are either preferentially expressed by embryonal carcinoma (EC) cells, or by more differentiated cell types. Using scatter plots and rank correlations, 6 groups of antibodies were distinguished with respect to their staining patterns on the cell lines tested. Several antibodies showed a specific staining pattern in relation to the differentiation state of the cells. Two groups of antibodies included those recognising high m.w. glycoproteins (antibodies TRA-1-60, TRA-1-81, GCTM2, 3-177, K4 and K21) and the ganglioseries glycolipid antigens SSEA-3 and -4 (antibodies MC631 and MC813-70). These antibodies mostly stained EC cells but not other cell types, confirming previously published data. However, one of these groups, comprising antibodies K4 and MC631, was more exclusively associated with the EC cell phenotype than was the other group. Antibodies recognising the liver isozyme of alkaline phosphatase (TRA-2-49 and TRA-2-54) also reacted strongly with most EC cell lines, although they reacted significantly with a number of other cell lines as well, whereas antibodies to the placental isozyme tended to react only weakly with EC cells. The antibodies recognising the ganglioseries glycolipids GD2 and GD3 (VIN2PB22 and VINIS56) preferentially stained cells with neuroectodermal characteristics. Other antibodies showed a heterogeneous staining pattern for the cell lines with different phenotypes. The data obtained from the cell lines were, in general, similar to data obtained from immunohistochemical studies on tissue sections of primary germ cell tumours of the adult testis, including carcinoma in situ.

Adult↗
PubMed1994

Combined choriocarcinoma and yolk sac tumor arising in Barrett's esophagus.

A patient with primary adenocarcinoma with yolk sac and trophoblastic differentiation occurring in Barrett's esophagus is reported. Yolk sac differentiation at this site has not been described previously. The diagnosis of germ cell differentiation initially was suggested by the finding of elevated serum tumor marker levels. The patient experienced disease remission after cytotoxic chemotherapy. Germ cell differentiation may be difficult to identify in small biopsy samples, which may not be representative of the tumor as a whole. The finding of germ cell differentiation defines therapy and predicates for a relatively good prognosis, which is contrast to adenocarcinoma. Because of the significance of germ cell differentiation in the selection of appropriate therapy, immunostaining for germ cell tumor markers is suggested in all patients with adenocarcinoma who are younger than 50 years.

Adenocarcinoma↗
PubMed1993

Ovarian masses in children: a review of 91 cases of malignant and benign masses.

Ovarian masses in children are uncommon. We reviewed all cases of ovarian masses presenting to this hospital from 1979 to 1990. Ninety-one patients fulfilled the criteria and had medical records available. All patients were less than 18 years old. Four were diagnosed antenatally. Thirty-four tumors presented prior to 8 years of age and 1 (2.9%) was malignant. Fifty-eight tumors presented after 8 years of age and 18 (33%) were malignant. Seventy-two patients had benign disease and 19 had malignant tumors. Of those with benign disease 22 had simple or epithelial cysts, 25 had teratomas, 13 had torsion with cyst formation, 3 had granulosa cell tumors, and 9 had other less common lesions. Analysis of symptoms could not distinguish between benign and malignant lesions; however, age was less (P < .03) and tumor size smaller (P < .001) in patients with benign lesions. Benign lesions presented at a mean age of 8.8 years. Fifty-four patients had an ultrasound, all were diagnostic: simple mass (14), complex mass (8), or cyst (32). Mean size of the masses was 9.5 x 7.7 cm. Fourteen patients had a contralateral ovarian cyst. The malignant lesions included 14 germ cell tumors (4 endodermal sinus, 4 teratoma, 2 choriocarcinoma, 2 dysgerminoma, 1 embryonal, and 1 mixed), 4 epithelial tumors (1 mucinous cystadenocarcinoma, papillary cystadenocarcinoma, papillary serous cystadenocarcinoma, and endometrioid adenocarcinoma), and one patient with leukemic infiltration (ALL). Germ cell tumors presented at a mean age of 11.8 years. Eight of these patients had an ultrasound and all showed a mass (7) or cyst (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood.

This article provides a comprehensive review of the current literature and summarizes the experience of the German cooperative protocols for nontesticular germ cell tumors (MAKEI) on the use of alpha 1-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG) for diagnostic evaluation in pediatric oncology. Based on this evaluation, this review proposes guidelines for the initial diagnostic work-up for children with clinically suspected secreting tumors. AFP and beta-hCG represent the characteristic tumor markers of malignant epithelial liver tumors and malignant germ cell tumors (GCT). They play an important role in the initial diagnostic evaluation as well as in the follow-up examination during therapy. Current therapeutic strategies for both tumor types include preoperative chemotherapy followed by delayed tumor resection. Therefore, it is essential for the pediatrician in charge to be aware of the broad differential diagnosis of elevated AFP and beta-hCG. In a well-defined clinical setting, these tumor markers allow clinical diagnosis without histological confirmation, but the physiologically elevated AFP serum levels in infancy or unrecognized benign conditions, such as hepatic diseases or hereditary disorders, must also be considered as differential diagnoses. Therefore, the laboratory investigations should include liver parameters in all patients to exclude hepatic disease. In addition, pregnancy must be excluded in adolescents. Careful history taking and clinical examination will further help to rule out metabolic disorders or ataxia teleangiectasia that are associated with elevated AFP levels. Having excluded these conditions, elevated AFP levels above the age-related normal range (with or without high beta-hCG), indicate malignant epithelial liver tumors in primary liver lesions. At virtually all other sites, the diagnosis of a malignant GCT with a substantial yolk sac tumor and/or choriocarcinoma component can be established. Pancreaticoblastoma should be considered in the differential diagnosis of tumors of the upper abdomen, and biopsy must be performed. Other childhood tumors are rarely associated with AFP or beta-hCG production, usually at only moderately elevated serum levels, and in most patients these tumors can be excluded by clinical and radiological examination.

Biomarkers, Tumor↗
PubMed2006

A primary pure yolk sac tumor of the lung exhibiting CDX-2 immunoreactivity and increased serum levels of alkaline phosphatase intestinal isoenzyme.

Malignant extragonadal germ cell tumors primary to the lung are quite uncommon lesions, but pure yolk sac tumor is even more exceptional. This is believed to be the first reported case of yolk sac tumor of the lung in which an intense and diffuse immunoreactivity for CDX2, a marker of intestinal differentiation reportedly expressed also in gonadal yolk sac tumor, was associated with increased serum levels of the alkaline phosphatase intestinal isoform. Nine months after radical surgery and adjuvant chemotherapy, the patient is alive and well without evidence of recurrent or metastatic disease and with serum levels of the alkaline phosphatase intestinal isoform within normal limits. The pathologist should be aware of yolk sac tumor arising in the lung and that alkaline phosphatase intestinal isoform could become an additional serum marker for such a tumor.

Alkaline Phosphatase↗