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PubMed1990

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.

Actins↗

PubMed2003

Application of mesothelin immunostaining in tumor diagnosis.

Mesothelin is a differentiation antigen that was first described as the antigenic target of the monoclonal antibody K1. Using this antibody, it was demonstrated that mesothelin is strongly expressed in normal mesothelial cells, mesotheliomas, nonmucinous ovarian carcinomas, and some other malignancies. Immunostaining with the K1 antibody was suggested to be useful in the diagnosis of mesothelioma in the early 1990s. This, however, could not be further explored until recently because of the lack of commercially available anti-mesothelin antibodies. In a recent investigation by this author, all epithelioid mesotheliomas and about 40% of the lung adenocarcinomas reacted with the 5B2 anti-mesothelin antibody, which has only recently become commercially available. It was concluded that immunostaining with this antibody has limited value in discriminating between these conditions. The aim of the current study was to further investigate the potential application of the 5B2 antibody in tumor diagnosis. Mesothelin expression was evaluated in formalin-fixed, paraffin-embedded samples of normal tissues and in 471 tumors of various origins. The carcinomas that most frequently exhibited strong mesothelin reactivity were nonmucinous carcinomas of the ovary (14 of 14 serous, 3 of 3 endometrioid, 6 of 8 clear cell, and 4 of 4 transitional cell carcinoma), and adenocarcinomas of the pancreas (12 of 14), the ampulla of Vater (3 of 3), endometrium (7 of 11), lung (14 of 34), and liver (7 of 19 cholangiocarcinomas). The carcinomas that did not express mesothelin included renal cell carcinomas, hepatomas, carcinomas of the thyroid, adrenal cortical carcinomas, prostatic adenocarcinomas, and carcinoid tumors. All germ cell tumors, with the exception of teratomas, were consistently negative for mesothelin. Because of the strong mesothelin expression in nonmucinous carcinomas of the ovary, but not in a variety of tumors with which these lesions may be confused (eg, clear cell carcinoma of the ovary versus endodermal sinus tumor or renal cell carcinoma, clear cell type; transitional cell carcinoma of the ovary versus TCC of the urinary tract), immunostaining for this marker could be useful in establishing the differential diagnosis. The strong mesothelin expression in the large majority of pancreatic ductal adenocarcinomas (12 of 14), but not in normal pancreas, confirms that this marker may have some diagnostic utility in discriminating between neoplastic and nonneoplastic pancreatic ductal epithelium. The mesothelin expression in about one-third of the cholangiocarcinomas, but not in hepatomas, suggests that this marker may have some utility in distinguishing between these two malignancies when they are poorly differentiated. In the group of small round blue cell tumors, only desmoplastic small round cell tumors exhibited mesothelin positivity (7 of 12). Of the soft tissue tumors, only the epithelial component of biphasic synovial sarcomas (9 of 9) expressed mesothelin. These findings indicate that, in some instances, mesothelin immunostaining can assist in the diagnosis of these tumors. Finally, the strong mesothelin reactivity seen in the adenomatoid tumors (3 of 3) provides further support for a mesothelial derivation for this lesion.

Antigens, Neoplasm↗

PubMed1985

Chemotherapy of extragonadal germ cell tumors.

Forty-nine patients with histologically proven germ cell tumors arising in extragonadal sites were retrospectively reviewed. Included in the review were an additional seven patients with undifferentiated tumors with a pathologic appearance compatible with that of a germ cell tumor and elevated levels of serum biomarkers (beta subunit of human chorionic gonadotropin [beta-HCG] +/- alpha-fetoprotein [AFP]. Nineteen patients had a pure seminoma arising in an extragonadal site, whereas 30 patients had nonseminomatous germ cell tumors. Seven patients had primary undifferentiated tumors with elevated levels of serum biomarkers. Sixteen (84%) of the 19 patients with pure extragonadal seminomas with normal levels of serum AFP are alive and free of disease. Eighteen of these 19 patients received platinum-containing regimens and four had received prior chemotherapy that failed. Of the patients with nonseminomatous germ cell tumors, 12 (40%) of the 30 are alive and free of disease with vinblastine/bleomycin +/- cisplatin (13 patients) or CISCAII (cisplatin, cyclophosphamide, and doxorubicin) (nine patients) alternating CISCAII/VBIV (eight patients) chemotherapy. None of the seven patients with undifferentiated germ cell tumors are alive and free of disease. Three of the five patients with pure anterior mediastinal endodermal sinus tumors treated with chemotherapy remain alive and free of disease. Of the seven patients with choriocarcinomas arising in extragonadal sites, three are alive and free of disease. A classification for patients with extragonadal germ cell tumors incorporating site of origin, histology, and likelihood of being truly extragonadal is proposed. The implications of this classification are discussed.

Abdominal Neoplasms↗

PubMed1993

Treatment of ovarian malignant germ cell tumors with preservation of fertility.

Conservative operation and postoperative chemotherapy were given to 15 patients with malignant germ cell tumors of the ovary with the preservation of fertility and ovarian functions. Four patients, one with endodermal sinus tumor and three immature teratoma, had full term deliveries after the operation. The possibility was discussed to preserve young women's fertility and ovarian function in treating their malignant germ cell tumors.

Adolescent↗

PubMed1984

Benign and malignant ovarian tumors in children and adolescents. A review of 63 cases.

Sixty-three patients (15 months to 17 years of age) with ovarian tumors were seen. Fifty-six patients had germ cell tumors and 7 epithelial tumors, 6 patients had bilateral tumors, 47 patients had teratomas (41 benign, 3 with embryonic tissue, and 3 malignant), 6 germinomas, 1 endodermal sinus tumor, and 2 mixed germ cell tumors. Of the patients with epithelial tumors, six had cystadenomas and one cystadenocarcinoma. Abdominal pain was the most common symptom, and an abdominal mass the most common sign. A calcification on abdominal films was seen in 29 patients with benign teratoma. At surgery, the opposite ovary was bivalved or biopsied in 31 patients with benign tumors. Two patients had teratomas burried in the ovarian tissue. Among 47 patients with benign tumors, 37 have remained well after the operation and 10 were lost to follow-up. Two girls with embryonic teratoma are well 71 and 19 months after diagnosis but the third died with embryonal carcinoma. Of the 13 patients with malignant tumors, 8 are alive disease free 4 1/2 to 17 years after diagnosis, 4 are dead, and 1 is lost to follow-up (disease free 15 months after diagnosis).

Adolescent↗

PubMed1992

[Clinical picture of tumors from the mesoblastoma group in women].

Yolk Sac Tumor (YST) originating from the primitive reproductive cells reminds with its microscopic construction a gallbladder or an endodermal sinus thus the name endodermal sinus tumor, Yolk sac tumor, mesoblastoma vitellinum Teilum. There have been presented here two cases of YST of different locality with unusual development of one of them and rapid course in the both cases. In both discussed cases the survival period exceeds 3 months. Both patients are still alive and the period from the day of diagnosis and operation is in one case 26 months and in the second one 11 months.

Adult↗

PubMed1985

Basement membrane structures in tumors of the ovary.

The location and amount of the basement membrane (BM) components collagen IV and laminin were studied in ovarian epithelial, sex cord-stromal and germ cell tumors. BM structures were found in the epithelial stromal interface of benign surface epithelial tumors and, though discontinuous, around well-differentiated tumor islets, being less well developed in invasive undifferentiated neoplasms. The stromal components in Müllerian mixed tumors had less distinct BM structures, a finding useful for the classification of these neoplasms. Thecomas and fibromas had scanty collagen IV and laminin; granulosa cell tumors contained large amounts of BM material. A fine diffuse BM-positive pattern occurred in dysgerminomas and endodermal sinus tumors; BM structures in cystic teratomas were distinct. Collagen IV and laminin were well-developed in benign and slow-growing tumors with epithelial components and in their metastases, but less distinct in stromal tumors and highly malignant undifferentiated tumors, showing the usefulness of this method for the clinical and biological classification of such tumors.

Adenocarcinoma↗

PubMed1992

Genetics and biology of human ovarian teratomas. III. Cytogenetics and origins of malignant ovarian germ cell tumors.

This report presents cytogenetic data on three cases of malignant ovarian germ cell tumors. All were diagnosed as malignant teratoma; case 1 with yolk sac elements; case 2 with elements of endodermal sinus tumor, embryonal carcinoma, and choriocarcinoma; and case 3 with yolk sac elements and embryonal carcinoma. Metaphase cells from each tumor, and normal tissue from the host, were karyotyped and scored for centromeric heteromorphisms in an attempt to determine the mechanism of origin. The karyotypes were 79,XXX,+1,+3,-6,+8,+12,+14,-15,+17, +20,+21,+22;49,XX,+8,+12,+22; and 48,XX,+3,+14, respectively. The analysis of centromeric heteromorphisms and DNA fingerprints of host and teratoma using the M13 probe revealed that one case originated from a germ cell before the first meiotic division. Normal host tissue was not available in case 2, but several centromeric markers were heterozygous in the tumor, indicating either meiosis I error or complete failure of germ cell meiosis. In the third case the centromeric heteromorphisms that were heterozygous in the host appeared to be homozygous for certain chromosomes and heterozygous for others in the tumor. These results suggest that germ cell teratomas could arise by the fusion of two ova.

Adolescent↗

PubMed2005

Outcome and prognostic factors in ovarian germ cell malignancies.

OBJECTIVES: This study was undertaken to investigate the outcome and prognostic factors in patients with ovarian germ cell malignancies (OGCMs). METHODS: A total of 93 patients with OGCMs were retrospectively reviewed, among whom 84 patients had primary treatment at Chang Gung Memorial Hospital (CGMH) between 1984 and 2003. The other nine patients were primarily treated outside and referred for follow-up (n = 1), adjuvant chemotherapy (n = 4), or salvage therapy after recurrence (n = 4). The clinicopathological and treatment-related characteristics were analyzed for association with the occurrence of tumor persistence/recurrence or death. RESULTS: Of the study patients, 32 had dysgerminoma (DSG), 29 immature teratoma (IMT), 23 endodermal sinus tumor, 7 mixed germ cell tumors, and 1 each had choriocarcinoma and embryonal carcinoma. The median follow-up of survivors was 66 months (range, 12-236 months). The median time to recurrence or progression was 8 months. There were 11 treatment failures with 6 died of cancer. The 5-year survival rate was 97.4% for those primarily treated at CGMH. Histology (DSG/IMT versus non-DSG/IMT) (P < 0.0001) and International Federation of Gynecology and Obstetrics stage (P = 0.001) were significantly associated with treatment failure, while histology (P = 0.0004), salvage high-dose chemotherapy (HD-CT) after primary chemotherapy failed (P = 0.0405), and residual tumor after salvage surgery (P = 0.0014) were significant prognostic factors for overall survival. CONCLUSIONS: Prognosis of OGCMs is excellent if managed with standard treatment initially. Aggressive HD-CT with salvage surgery needs to be applied for recurrent/persistent disease after primary chemotherapy.

Adolescent↗

PubMedDate not supplied

[Juvenile granulosa-cell tumor of the ovary. Immunohistochemical and ultrastructural study].

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.

Biomarkers, Tumor↗

PubMed1982

Treatment of recurrent and persistent germ cell tumors with cisplatin, vinblastine, and bleomycin.

Four patients were treated with vinblastine, cisplatin, and bleomycin for recurrent or persistent germ cell tumors. In all patients a clinical response was achieved. In 2 patients complete response was attained and they are free of disease following second-look laparotomy. One had a mixed germ cell tumor that persisted as dysgerminoma following primary chemotherapy. The other was a true hermaphrodite with pure dysgerminoma. In patients with endodermal sinus tumor transient response was achieved, but the tumors recurred and the patients died within 6 months.

Adolescent↗

PubMed1983

[A new serological diagnostic method for malignant ovarian tumors of germ cell origin. Detection of antibodies to large glycopeptides isolated from F9 cells].

Whether the presence of antibodies in patients sera to large glycopeptides (LGP) isolated from a murine teratocarcinoma cell line (F9) can be useful in diagnosing malignant ovarian tumors of germ cell origin was examined by Farr's assay. We measured the binding ability to LGP by Farr's assay of human sera from 188 patients with various ovarian tumors and 110 normal volunteers. All of the 9 patients with dysgerminoma showed negative results (less than 200 cpm). Except the cases with dysgerminoma, 9 (64%) of the 14 patients with malignant ovarian tumors of germ cell origin were found positive (more than 200 cpm). Of these 9 positive cases, 4 cases with endodermal sinus tumor (EST), 2 cases with immature teratoma, one each with immature teratoma plus EST, choriocarcinoma, and mature solid teratoma were included. In contrast, all of the sera from benign ovarian tumors (111 cases), other malignant ovarian tumors (54 cases) and normal nonpregnant women (110 cases) were found negative. These result indicated that Farr's assay of anti-LGP antibodies in sera is useful in diagnosing ovarian germ cell tumors.

Adolescent↗

PubMed1997

[Germ-cell tumors of the brain--their course and management].

Germ-cell tumors (GCT) of the CNS constitute a small group with an incidence varying in the range 0.1 to 3.4 per cent of all primary brain neoplasms. In the WHO classification of brain tumors they are differentiated in a separate group, and further subdivided into: germinoma, teratoma (mature, immature, malignant), embryonal carcinoma, choriocarcinoma, endodermal sinus tumor and mixed germinal tumors. Of them germinoma is the most frequently encountered (41-65 per cent of all GCT), whereas the incidence rate of mixed GCT may reach 32 per cent Mainly median structures are being involved--III ventricle (pineal region and hypothalamo-hypophyseal structures), basal ganglia, with isolated cases being described in corpus callosum, cerebellum, medulla oblongata and spinal cord. Eleven patients with a total of 13 verified GCT are presented (in one instance germinomas involving the pineal body and suprasellar region are simultaneously established). The clinical course data, results of the diagnostic examinations done (CT, brain angiography, tumor markers), treatment carried out--surgical, radio- and chemotherapy, as well as the outcome of the long-term follow-up study of patients are analyzed. Three patients have mixed GCT. It is of interest to note a case where ten years after the removal of a benign teratoma in the pineal region, germinoma in the same location is diagnosed and removed.

Adolescent↗

PubMed1995

Malignant germ cell tumors of the ovary: a study of 20 cases.

In a study of 20 patients diagnosed with malignant ovarian germ cell tumors between 1961 and 1993, clinical and pathologic findings were evaluated. Of the 20 patients, seven (35%) had dysgerminoma, two (10%) endodermal sinus tumor, three (15%) malignant teratoma, one (5%) malignant struma ovarii, one (5%) primary ovarian carcinoid, two (10%) benign teratoma with malignant transformation, and four (20%) combination germ cell tumor. Twelve patients (60%) had stage IA, five (25%) stage IC, and three (15%) stage IIIC. Twelve patients (60%) underwent conservative surgery and eight (40%) had at least bilateral salpingo-oophorectomy. At follow-up, 18 patients (90%) were alive free of disease, one (5%) had died of disease, and one (5%) had died of intercurrent disease. The actuarial 5-year survival rate was 93.3%. It is concluded that for young women who wish to preserve child-bearing capacity, regardless of the stage of the tumor, fertility-preserving surgery with complete surgical staging followed, if necessary by cisplatin-based combination chemotherapy is an appropriate and definitive treatment in the absence of involvement of the contralateral ovary and uterus. For patients in whom child-bearing capacity is not an issue, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy with complete staging, followed if necessary by chemotherapy.

Adolescent↗

PubMed1992

Pediatric malignant ovarian tumors: a 43-year review.

Thirty-eight girls with malignant ovarian tumors were reviewed and studied during a 43-year period, 1945 to 1988 inclusive. The age range was 3 to 16 years. Eighteen girls were prepubertal and 16 were pubertal at diagnosis. Precocious puberty was noted in 4 children. The most common presenting symptoms and signs were pain, abdominal swelling, and pelvic mass. Emergency surgery for acute pain (? appendicitis) was needed in only 7 patients. Tumor size and cysts did not relate to histology or outcome. Tumors were classified histologically (germ cell, sex cord/stromal, epithelial tumors). Twenty-one (54%) of the patients survived 1 to 27 years (median, 8 years). Sixteen were left with ovarian tissue, 11 functioning. Diagnosis and treatment have been aided by better noninvasive radiological methods, tumor markers, newer and better chemotherapy, and pathological review and reclassification of these tumors as pediatric experience slowly increases. We can make at least four statements that differ from our past experience: (1) pure endodermal sinus tumor was previously confused histologically with embryonal carcinoma; (2) gonadoblastoma is associated with 45,X/46,Y, 45,X, or 46,Y karyotype and is known to be premalignant; (3) sex cord/stromal tumors are not necessarily malignant and metastatic behavior cannot be predicted from the histology; and (4) currently, epithelial tumors are classified as cystadenomas and are considered to be borderline malignancy. Current management should aim at both cure and preservation of fertility with conservative surgery whenever possible. The future must lie in chemotherapy.

Adolescent↗

PubMedDate not supplied

Germ cell tumors of the ovary: is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors?

Thirty-three patients with germ cell tumor of the ovary were seen at Kidwai Memorial Institute of Oncology (KMIO), Bangalore, between 1996 and 1999. Twelve patients had endodermal sinus tumor (EST), 11 dysgerminoma, seven mixed germ cell tumor, and three immature teratoma. Thirteen patients had bulky residual disease of >10 cm after the primary surgery. All but one patient received a combination of bleomycin, etoposide, and cisplatin (BEP) either as neoadjuvant (NACT, 3 cases) or as adjuvant therapy (28 cases). In the present study, all 11 patients with dysgerminoma achieved sustained complete remission (CR), irrespective of the size of residual disease at the time of chemotherapy. Four out of six cases (66.6%) with bulky nondysgerminomatous tumor achieved CR, which was sustained in three cases and one recurred. Fifteen of the remaining 16 (93.7%) nonbulky, nondysgerminomatous tumors achieved CR, which was sustained in 14 cases and recurred in one. This study indicates that there may be a role for aggressive cytoreductive surgery, either primary/interval or at the time of second-look laparotomy, in selected patients with nondysgerminomatous germ cell tumor of the ovary.

Adolescent↗

PubMed1979

Radioimmunoassay of alpha-fetoprotein in children with primary intracranial tumors.

Serum alpha-fetoprotein (AFP) was measured in 10 cases of primary brain tumors in children (4 cases of medulloblastoma, 4 cases of germ cell tumor and 2 cases of astrocytoma). As a result, elevation in AFP was observed only in a case of embryonal carcinoma that showed partial mixture of germinoma. The absence of AFP elevation in 3 other cases of pure germinoma (atypical teratoma; pinealoma) agrees with reports which describe that, in the germ cell tumor of the gonads, a rise in AFP is not observed in pure seminoma but is found in embryonal carcinoma and endodermal sinus tumor (yolk sac tumor). The fluctuations in AFP in serum and cerebrospinal fluid are considered to be of significance in the diagnosis and treatment of primary intracranial malignant germ cell tumors.

Adolescent↗

PubMed1990

MR imaging of pineal tumors.

MR images of pineal region tumors were analyzed in 26 patients with histologically proved tumors: seven germ-cell tumors, six astrocytomas, five teratomas, three pineoblastomas, two meningiomas, one dermoid, one epidermoid, and one metastasis. In an attempt to identify specific MR characteristics of these lesions, Gd-DTPA was administered to six patients. CSF and blood serum were assayed for alpha-fetoprotein (AFP) and human chorionic gonadotropin-beta subunit (HCG-beta) in 18 patients. MR findings were correlated with age, sex, the presence of biochemical tumor markers, and surgical outcome. We found that the most important factors in the determination of tumor type were the patient's age and the tumor markers. Increased levels of both HCG-beta and AFP were specific for patients with malignant teratomas and undifferentiated germ-cell tumors. HCG-beta alone was elevated in the patient with choriocarcinoma; only AFP was elevated in the patient with an endodermal sinus tumor. Tumor markers were not present in other patients in this series. The tumor size and the presence of fat were also helpful in determining tumor type. Hemorrhage was rare, seen only in the patient with a choriocarcinoma. Gd-DTPA did not enhance diagnostic specificity but aided in the detection of tumor seeding through CSF. We conclude that, although MR is sensitive in the detection of pineal region tumors and provides superb anatomic detail, MR signal characteristics are usually nonspecific. Correlation with the patient's age and the tumor markers significantly improves diagnostic accuracy.

Adolescent↗