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PubMed1996

Inactivation of p16/CDKN2 and p15/MTS2 genes in different histological types and clinical stages of primary ovarian tumors.

To define the involvement of p16/CDKN2 and p15/MTS2 inactivation in ovarian tumorigenesis and the association of these inactivation events with histological types and clinical stages of ovarian tumors, we analyzed homozygous deletion and somatic mutation of p16/CDKN2 and p15/MTS2 genes, as well as hypermethylation of the 5'-CpG island of the p16/CDKN2 gene, in 49 primary ovarian tumors and 6 ovarian carcinoma cell lines. We found homozygous deletions of p16/CDKN2 and p15/MTS2 in 6 (12%) and 5 (10%) primary tumors, respectively. Somatic mutation of p16/CDKN2 was found in only 1 primary tumor, but mutation of p15/MTS2 was not detected in any sample. None of the 28 primary tumors or 6 cell lines was hypermethylated at the 5'-CpG island of p16/CDKN2. The incidence of inactivation of p16/CDKN2 in primary tumors was significantly higher in the advanced stages (7 of 29) than in the early stages (0 of 14). Seven of 9 alterations in p16/CDKN2 and p15/MTS2 were observed in serous (3 of 12), endometrioid (3 of 9) and clear-cell (1 of 4) carcinomas. However, only normal sequences of these genes were detected in mucinous carcinomas. Loss of heterozygosity (LOH) at the IFNA locus was detected in 1 of 19 (5%) tumors, but no change at the D9S171 locus was observed in 17 tumors. These results suggest that: (i) homozygous deletion is the main mechanism of inactivation of p16/CDKN2 and p15/MTS2 in ovarian tumorigenesis; (ii) inactivation of p16/CDKN2 and p15/MTS2 may be the histological type-specific events involved in ovarian tumorigenesis; and (iii) inactivation of p16/CDKN2 is potentially involved in the progression of ovarian tumors in advanced stages.

Carcinoma↗
PubMed1978

Mixed mesodermal tumor and clear cell carcinoma arising in ovarian endometriosis.

A case is reported of clear cell carcinoma, arising as several papillary masses from the lining of an endometrial cyst within the ovary, associated with a mixed mesodermal tumor arising in the stalk of the largest papillary nodule. The origin of this tumor from within a focus of endometriosis lends support to the theory that both the epithelial and mesodermal components are of Müllerian (Paramesonephric) origin.

Adenocarcinoma↗
PubMed1979

Electron microscopic findings in primitive neuroectodermal tumors of the cerebrum.

The fine structure of 3 primitive neuroectodermal neoplasms of the cerebral hemispheres was studied. The predominant tumor cells were undifferentiated cells with prominent nuclei and scanty cytoplasm containing few organelles. Ultrastructural evidence suggesting differentiation into ependymal, neuronal and possibly astrocytic elements was also present. This study suggests that the cell of origin of this tumor is a primitive multipotential cell of the cerebrum.

Adolescent↗
PubMed1980

Postirradiation mixed müllerian tumors of the uterus: a comparative clinicopathologic study.

Nine patients with mixed müllerian tumors (MMT) of the uterus associated with a history of prior pelvic irradiation were compared clinically and pathologically with 8 nonirradiation-associated MMT control patients. Patients with postirradiation tumors presented at a younger age and with symptoms indicative of extensive intraabdominal disease while the nonirradiation-associated control patients were initially evaluated for abnormal uterine bleeding only. Two-thirds of the postirradiation patient's neoplasms were classified as heterologous MMT (mixed mesodermal tumor) whereas 62% of the control patient's neoplasms were homologous MMT (carcinosarcoma). Regardless of clinical presentation or histologic composition both groups fared equally poorly with average survival times of six and seven months, respectively. We were unable to substantiate that some histologic components of uterine MMT denote a poorer prognosis than others or that the postirradiation MMT behaves any differently, in the course of time, from the sporadic type. When uterine MTT is encountered in a patient under 55 years of age, the possibility that pelvic irradiation was administered some years before should be raised.

Adult↗
PubMed1981

Ovarian neoplasms in children and adolescents in Ibadan, Nigeria.

Ovarian tumors diagnosed at the University College Hospital (UCH), Ibadan, Nigeria, in 169 patients less than 20 years of age have been analyzed. The most common tumor involving the ovaries of Nigerian children was Burkitt's lymphoma, which was bilateral in all cases. Germ cell tumors accounted for 67.1% of 76 non-Burkitt's tumors, while tumors of the sex cord stroma were encountered more frequently than epithelial tumors. Epithelial tumors were less frequently diagnosed than in previously reported series, and none was found in 122 patients under 14 years of age. It is suggested that Burkitt's lymphoma may primarily affect the ovaries and that the low frequency of epithelial tumors in Africans may be related to genetic differences in the metabolism of the female sex hormones.

Adolescent↗
PubMed1984

Acute lymphoblastic leukemia. Possible origin from a mediastinal germ cell tumor.

The case of acute lymphoblastic leukemia developing shortly after the diagnosis and treatment of a mediastinal germ cell tumor, is reported. The close temporal relationship of these two rare diseases and the presence of a population of mononuclear cells with features of lymphoblasts in the resected germ cell tumor, suggest that the leukemic process originated from the mediastinal tumor.

Adolescent↗
PubMed1985

Retroperitoneal germ cell tumors in childhood. A clinical and pathologic study of 11 cases.

During the last 54 years at the Children's Hospital 11 children (10 female, 1 male) had been treated for an extragonadal germ cell tumor arising in the retroperitoneum. There were eight teratomas (five mature, three immature), two endodermal sinus tumors and one tumor with a mixture of both components. Abdominal pain or discomfort was the usual presenting complaint, with the average age at diagnosis being 18 months. On physical examination, each child had a palpable abdominal mass usually localized in the upper quadrants. The finding of calcification, bone or teeth, on radiologic study was most helpful in establishing a preoperative diagnosis of teratoma. The preferred treatment for children with mature and immature teratomas is complete surgical resection; decisions regarding adjuvant therapy for patients with immature tumors must be evaluated on an individual basis. The prognosis remains guarded for children with unresectable primaries or those with endodermal sinus tumor. Of three tumor-related deaths, two were due to metastatic endodermal sinus tumor and one resulted from extensive local growth by immature teratoma. Successful management of children with endodermal sinus tumor requires surgery aimed at debulking or complete resection in combination with aggressive adjuvant chemotherapy.

Child, Preschool↗
PubMed1985

An appraisal of the World Health Organization classification of tumors of the central nervous system.

An important development in the classification of tumors of the central nervous system was the nomenclature recommended by the World Health Organization in 1979. Since then, wide usage has suggested that the classification be modified to account for problems that neuropathologists have encountered. Although no classification is ideal, modification of certain tumor categories, particularly from the perspective of childhood brain tumors, is desirable. These are discussed in detail. Greater emphasis on standardization of the localization of brain tumors is also recommended. This appraisal suggests changes that will allow a consensus on nomenclature of central nervous system tumors so that a workable classification is the end product.

Brain Neoplasms↗
PubMed1985

Revision of the World Health Organization classification of brain tumors for childhood brain tumors.

A classification for childhood brain tumors based upon revision of nomenclature of all brain tumors published by the World Health Organization (WHO) in 1979 is proposed. Applicability of the WHO classification scheme was tested in a combined study of the clinical and pathologic features of approximately 3300 brain tumors in children. It was found to be adequate for many of the neoplasms but unsuitable for a significant proportion, including a number of complex cerebral tumors for which there was no appropriate name. Nomenclature of poorly differentiated or densely cellular neuroepithelial tumors was simplified to reflect the current state of knowledge of neuroembryology and neuro-oncology, although the Committee members recognized that such a proposal would likely perpetuate the long-standing and continuing controversy relative to the nature and origin of these neoplasms.

Brain Neoplasms↗
PubMed1986

Bilateral testicular germ cell tumors. Report of nine cases and review of the literature.

In a series of 181 patients with testicular germ cell tumors, the phenomenon of bilateral involvement of the testicles was observed nine times (5%). Two patients evidenced a simultaneous bilateral tumor, and, in seven others, a second tumor occurred after an interval ranging between 8 months and 6 years and 11 months. The incidence, histologic findings, therapy, and prognosis of bilateral testicular tumors are discussed on the basis of a survey of the literature. Emphasis is placed on the significance of a long-term follow-up period as well as on the important role of sonography in the early detection of a contralateral tumor.

Adolescent↗
PubMed1988

Analysis of tumor heterogeneity in a patient with synchronously occurring female genital tract malignancies by DNA flow cytometry, DNA fingerprinting, and immunohistochemistry.

A case of a patient with bilateral ovarian cancer and a uterine malignant mesodermal mixed tumor with ascites and metastatic disease is presented. Flow cytometry, DNA fingerprinting, and immunohistochemistry were performed to assess the origin of these malignancies. Ploidy analysis showed that both ovarian tumors had different aneuploid stemlines (DNA index [DI] = 1.64, 1.85, right ovary and DI = 1.73, left ovary) indicating independent origins. One of the stemlines in the right ovary (DI = 1.64) was also present in the ascites cells, whereas omentum metastases showed the same stemline (DI = 1.73) as the left ovarian tumor. The uterine malignancy contained three aneuploid stemlines. The highest stemline was associated with epithelial differentiation, but a metastatic origin from the left ovarian tumor seems unlikely. DNA fingerprinting analysis revealed a common change in restriction fragment length pattern in the DNA from all tumor localizations as compared with the patient's constitutional DNA. These results indicate that DNA flow cytometry can be helpful in discriminating intragenital metastatic disease from multiple primary tumors.

Aged↗
PubMed1989

Disseminated primitive neuroectodermal tumor: diagnosis using immunocytochemistry, electron microscopy, and molecular probes.

A patient with a disseminated small cell tumor presented with hyperuricemia, gingival hypertrophy, lymphadenopathy, and bone marrow replacement with tumor cells. Initial histologic examination and clinical presentation were consistent with presumed marker silent lymphoma/leukemia. Despite initial treatment with and response to lymphoma/leukemia therapy the patient relapsed in the testis, bone marrow, pancreas, and skin whereupon subsequent and retrospective immunocytochemical, ultrastructural, cytogenetic, and molecular analysis led to the diagnosis of primitive neuroectodermal tumor (PNET). Despite extensive investigation and autopsy no primary site of tumor could be found demonstrating that PNET should be considered in the differential diagnosis of disseminated small cell tumors without an apparent primary.

Adolescent↗
PubMed1990

Two homologous mixed müllerian tumor lines of the ovary and their characteristics.

Two cell lines, NF and JoN, derived from human ovarian carcinosarcomas, were established in tissue culture and in nude mice. Both lines, growing in monolayers, showed morphologic features of adenocarcinoma cells (NF being aneuploid with a modal number of 53, and JoN being pseudodiploid with a modal number of 44). Intermediate filaments were demonstrated immunohistochemically; the JoN line expressed keratin, but not vimentin or desmin, whereas the NF line expressed vimentin and desmin, but not keratin. Plasminogen activator activity was found in both lines. It is concluded that both of these lines are potentially useful models for studying the diverse characteristics of malignant mixed Müllerian tumors.

Adenocarcinoma↗
PubMed1991

Synchronous bilateral testicular germ cell tumors of different histologic type. Pathogenetic and practical implications of bilaterality in testicular germ cell tumors.

Patients with a germ cell tumor (GCT) in one testicle are prone to develop cancer in the contralateral testicle. Metachronous development of a GCT in the remaining testicle occurs in 3% of patients. The synchronous development of bilateral GCT occurs in 0.5% of patients. Bilateral testicular neoplasms are almost always identical histologically. Only five cases of synchronous bilateral GCT of different histologic types have been reported in the literature. The authors report the sixth case of this uncommon phenomenon and discuss its clinical and pathogenetic implications.

Adult↗
PubMed1992

Sinonasal primitive neuroectodermal tumor arising in a long-term survivor of heritable unilateral retinoblastoma.

BACKGROUND: Patients who survive retinoblastoma (RB) are at risk for having second nonocular tumors, usually osteosarcomas, which often are fatal. Such patients almost always have bilateral RB. METHODS: This article reports a woman who, at the age of 1 year had been cured of a unilateral RB by radiation therapy and enucleation. Eighteen years later, she had a sinonasal small cell tumor that rapidly recurred and proved fatal 2 months after surgical debulking. The tumor was studied by immunohistochemistry and electron microscopic (EM) examination. RESULTS: It showed diffuse neuron-specific enolase staining, focal weak staining for chromogranin, synaptophysin, and Leu-7 monoclonal antibodies in paraffin-embedded, B5-fixed tissue (Great Lakes Diagnostics, Troy, MI). EM study showed an undifferentiated primitive neuroectodermal tumor with many polyribosomes, simple cell junctions, few microtubules, and rare dense core granules. CONCLUSIONS: The combined immunohistochemical, ultrastructural, and clinical features of the tumor were interpreted as a sinonasal primitive neuroectodermal tumor with early neuronal differentiation. The tumor was pathologically indistinguishable from poorly differentiated olfactory neuroblastoma (ONB) and Ewing sarcoma.

Chromogranins↗
PubMed1993

Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors.

BACKGROUND: Patients with mediastinal germ cell tumors (MGCT) have a high incidence of hematologic malignancies unrelated to cytotoxic chemotherapy. It has been suggested that these leukemic conditions originate from a MGCT progenitor cell capable of undergoing non-germ cell (hematopoietic) differentiation. METHODS: To assess this hypothesis, histologic material from six patients with MGCTs associated with leukemia was examined using monoclonal and polyclonal antibodies capable of labeling cells of the different marrow cell lineages. RESULTS: Morphologically identifiable hematologic cells were found within the yolk sac tumor component of the MGCT in four of these patients. In three of the four cases, the cells consisted of poorly differentiated blast cells, whereas in the fourth, clusters of erythroblasts were identified. The leukemic cells within the MGCT and in the bone marrow had similar morphology, constant expression of the early progenitor cell marker CD34, and variable expression of more mature myeloid, monocytic, erythroid, and megakaryocytic markers. Three cases expressed p53, a nuclear protein associated with neoplastic transformation in a wide range of malignancies, including testicular cancers, but which rarely is reported in leukemias. Karyotype of the leukemia was assessed in five cases: two showed an i(12p), a cytogenetic marker of GCT not identified in the usual cases of leukemia. CONCLUSIONS: The results support the hypothesis that these leukemic conditions originate in the MGCT through a mechanism of differentiation from a yolk sac tumor-derived progenitor cell, with subsequent homing to the marrow.

Adolescent↗
PubMed1992

Peritoneal cytology of uncommon ovarian tumors.

Peritoneal cytology has been well established as a diagnostic and staging tool in the management of the common epithelial tumors of ovary. Germ cell, mesenchymal, and sex-cord stromal tumors are much less frequently encountered in peritoneal specimens, often with cytologic features that may pose problems in differential diagnosis. This report presents the cytomorphology of the ascitic fluid in cases of endodermal sinus tumor, dysgerminoma, and Sertoli-Leydig-cell tumor, and peritoneal washings in a case of ovarian malignant mixed mullerian tumor. The cytologic features of Sertoli-Leydig-cell tumors have not been well described. Careful correlation of peritoneal cytologic findings, cell-block preparations, and immunocytochemistry with the cytohistologic features of these tumors is crucial for correct tumor classification.

Adolescent↗