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Primary malignant teratoma of the thyroid: case report and literature review of cervical teratomas in adults.

A case of primary malignant teratoma of the thyroid in a gravid 37-year-old female is reported and the literature on cervical teratomas in adults reviewed. The patient was treated by total thyroidectomy and left radical neck dissection followed by cervical and mediastinal radiotherapy and chemotherapy. She fied of recurrent tumor and related complications 9 months after discovery of the lesion. This is the 6th case of primary teratoma of the thyroid and the 9th case of cervical teratoma reported in a adult. These tumors are characteristically large, rapidly growing and highly malignant. The longest survival reported is 10 months. The differentiation of this lesion from carcinosarcomas of the thyroid is discussed.

Adolescent

[Mature benign teratomas with malignant tumors and malignant monodermal ovarian teratomas. Anatomo-clinical presentation of 10 cases].

The clinicopathologic features are presented of 8 malignant neoplasms occurring in adult teratomas, and of 2 malignant monodermal teratomas found in a continuous series of 1029 cases of ovarian adult teratomas. The age of the patients was 44--76 years. The first 8 observations included 6 epidermoid carcinomas, 1 undifferentiated carcinoma and 1 strumal carcinoid. In the epidermoid carcinomas malignancy was recognized peroperatively only in three instances. One tumor had infiltrated the broad ligament on one side and another the urinary bladder. The neoplasm appeared as a mass which thickened the wall of a typical dermoid cyst. Four patients died of the tumor from 3 months to 1 year after operation; one is alive more than 19 years later and one is lost to follow-up. The crucial factor in prognosis is the integrity of the ovarian capsule. The undifferentiated carcinoma, which had infiltrated the pelvic walls, could only be incompletely resected and caused death within 3 1/2 months. The strumal carcinoid was discovered by chance during laparotomy for a far-advanced adenocarcinoma of the pancreas which led to death within 2 months. The two cases of malignant monodermal teratoma comprised 1 thyroid papillary carcinoma and 1 carcinoid. Both patients are alive more than 8 and 5 years after operation. The carcinoid manifested itself by persistant diarrhea which ceased soon after operation and did not recur subsequently.

Adult

Why are ovarian teratomas benign whilst teratomas of the testis are malignant?

A mechanism is suggested to account for the fact that most ovarian teratomas are benign (dermoid cysts) whereas testicular teratomas are almost always malignant. The mechanism advanced assumes that malignancy is cause by a recessive mutation, and then shows that the known facts of germ-cell development will produce the homozygous (malignant) state in the male but the heterozygous counterpart in the female. It is proposed that the benign nature of ovarian teratomas is a reflection of this heterozygous genotype.

Cell Differentiation

Teratomas, neoplasia and differentiation: a biological overview. I. The natural history of teratomas.

In this paper I have attempted to outline the natural history of spontaneously occurring teratomas and associated tumours, but without introducing any preconceptions or assumptions as to their histogenesis or mechanisms of internal differentiation. The justification for this omission is that there is presently no direct evidence in respect of either process in human tumours of this type, with the exception of recent work by LINDER et al. (1975a, b). The various histopathological classifications of teratoid lesions have not been discussed in detail either, because for the most part they have been evolved to serve a specific prognostic purpose on either an empirical basis or on certain histogenetic assumptions. In either case there is an inevitable tendency to emphasize extremes of morphological appearance at the expense of possible continuities of structure and behaviour across the spectrum of teratoid lesions. The purpose of this paper, on the contrary, has been to discern features common to these tumours whenever and wherever they occur. Thus, human teratomas are uniquely puritissular lesions composed, potentially at least, of virtually every recognizable (and probably some as yet unrecognizable), type of embryonic, foetal and adult cell and tissue, together with, in some cases, frankly malignant cells of no obvious derivation or differentiation. In spite of the occasional appearance of structures resembling pre-somite embryos (embryoid bodies), there is no compelling evidence that human teratomatous histogenesis recapitulates embryogenesis in any strict fashion. Histologically, the overwhelming impression is of a more or less random association of cells and tissues at different stages of development and differentiation that proceed up to but not beyond organogenesis. Such teratomas are found at a number of well-defined sites, of which the sacrococcyx is the most prominent in infancy and the gonads during adult life. Both gonadal and extragonadal sites are also associated with apparently homogeneous neoplasms containing cells with features reminiscent of early stages of germinal differentiation which evoke, in many cases, a marked stromal and lymphocytic response, the so-called germinomas. In 'mixed' tumours, which are recognized in an increasing proportion of cases, there is karyological evidence of a conjoint rather than separate origin of teratomatous and germinomatous elements in at least some tumours, challenging a long held belief in their invariably separate character (e.g. HALLEY, 1963).

Animals

Tumors of the thymus and thymic region: III. Clinicopathological studies on teratomas and tumors of Germ Cell type.

In a series of 82 patients with tumors of the thymus and thymic region there were 11 with teratomas and germinal tumors. Four of these patients had benign cystic teratomas, 4 had malignant teratomas, 1 had an embryonal carcinoma, and 2 had seminomas. The benign teratomas were removed by simple extirpation without complications. The malignant teratomas were highly invasive, and despite extensive operations and postoperative radiotherapy, 3 of the 4 patients died within 9 months. One patient with predominantly seminomatous differentation of the teratoma was alive and well more than 3 years after the operation. The patient with an embryonal carcinoma died after 4 months. One of the 2 patients with seminoma remained alive 20 years after radical excision and postoperative radiotherapy. The other, who had a huge seminoma, died during operation. The prognosis in patients with seminomas or with predominantly seminomatous structures in teratomas seems to be good after combined radical excision and radiotherapy, although nonradical resection followed by raditherapy may be justified in high-risk patients.

Adult

[Vitelline components in teratomas and serum alpha-1 fetoprotein].

Serum alpha1-fetoprotein (AFP) had been determined in 31 patient with (mostly malignant) teratomas before or immediately after operation, and later in the evolution of 3 other cases with clinical evidence of recurrence or metastases. Without knowledge of these serum AFP levels, histological slides of the same 34 teratomas were reexamined, especially for the presence of yolk sac components. Two pure yolk sac tumors and 6 teratomas containing yolk sac structures were associated with serum AFP levels above 500 ng/ml. Teratomas without yolk sac structures were associated with normal serum AFP levels (i.e. 10-500 ng/ml) in 14 cases, and high serum levels (i.e. above 500 ng/ml) in one case. Histologic analysis of the 14 cases with slightly elevated AFP levels did not reveal tissue possibly responsible for the low but nevertheless abnormal AFP synthesis. High AFP levels, which are easily detectable by counter-current immunoelectrophoresis, are, however, highly specific for the yolk sac tumor or the yolk sac component of teratomas, and hence suggest that this extra-embryonic structure should be distinguished from other teratoma components.

Adolescent

Teratomas in children and young adults.

A review of all teratomas seen at the University of Wisconsin Hospital between 1965 and 1977 revealed that sacrococcygeal and presacral teratomas were most common. In these cases survival was best in infants less than one year old, with the exception of two cases of malignant medulloepithelioma. Testicular teratomas were predominant in the young adult male, and survival was poor. Pathology and treatment of teratomas are discussed, with an accompanying discussion of congenital anomalies associated with teratomas.

Adolescent

Teratoma Formation and Genomic Profiling Using Multi-Omics Approaches.

Teratoma formation is the gold standard assay for evaluating the developmental pluripotency of human and mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Following subcutaneous injection into immunodeficient mice, pluripotent stem cells spontaneously differentiate into derivatives representing all three embryonic germ layers-ectoderm, mesoderm, and endoderm. Beyond serving as a functional assay for pluripotency, teratomas provide a unique three-dimensional model system for studying early human development and lineage specification in vivo. This chapter describes comprehensive protocols for teratoma formation in immunodeficient mice, tissue processing for multiple downstream genomic applications, and multi-omics profiling approaches. We detail methods for embryonic stem cell culture, teratoma generation via subcutaneous injection, tissue dissection and processing for chromatin immunoprecipitation followed by sequencing (ChIP-Seq), RNA sequencing (RNA-Seq), single-cell multiome profiling combining chromatin accessibility (ATAC-Seq) and gene expression (scRNA-Seq), and histological analysis using hematoxylin and eosin (H&E) staining. Additionally, we provide bioinformatics workflows for analyzing the resulting genomic datasets to characterize the epigenetic and transcriptional landscapes of teratoma-derived tissues. These methods enable comprehensive molecular characterization of developmental processes and provide valuable resources for stem cell biologists studying pluripotency, differentiation, and early embryonic development.

Teratoma

Ovarian teratomas in early childhood.

The ovary is second only to the sacroccygeal area as the commonest anatomic site for the occurrence of teratomas (including dermoid cysts) in infancy and childhood. While virtually all sacrococcygeal teratomas are present at birth or appear within the first 24 mo of life, ovarian teratomas are quite rare within the first 24 mo of life and seldom appear before 6 yr of age. Teratomas comprise half the surgically significant lesions of the ovary in infancy and childhood and carry a mean malignancy incidence of approximately 14% in this age group. Seven cases of ovarian teratoma in the first 2 yr of life have been reported. All of these have been seen in the second 12 mo of life. They differ from those occurring after 2 yr of age in the lesser incidence of abdominal pain, the higher incidence of an abdominal mass and the absence of reported malignancy.

Age Factors

Alternative explanations of the differing behaviour of ovarian and testicular teratomas.

There are several aspects of the biology of teratomas which may be important in the aetiology of malignant versus non-malignant forms. Firstly, the ages when malignant teratomas form in the ovary (children) and testis (adult) follow by a similar span of years the time of oogenesis (fetus) and spermatogenesis (onset at puberty) and, specifically, follow by less than a decade the periods of active mitosis and meiosis during which interconnection of germ cells by intercellular bridges occurs. Secondly, ovarian teratomas may be viewed as parthenogenically activated oocytes, while testicular teratocarcinomas may represent post-meiotic fusion events more comparable to fertilisation; the malignant potential in the latter case could relate to fundamental differences in male and femal germ plasm. Thirdly,, the fact that malignant teratomas are easily produced by transplanting early embryos to extrauterine sites, while there is loss of malignancy with differentiation within a tumour or when malignant cells are injected into pre-implantation embryos and contribute cells to a variety of normal tissues, suggests that the malignant potential of teratomas has to do with gene control rather than mutational events.

Adolescent

[Diagnosis and treatment of mediastinal teratomas].

Among 221 operated patients with primary tumors and cysts of the mediastinum teratomas were observed in 54 (24.4%). The diagnosis of mediastinal teratodermoids should be complex. Clinically in benign teratomas the localization and character of the process were determined precisely in 94%, histogenesis--in 35%, in malignant teratomas--the proper localization was determined in 90%, the tumor character--in 78%, histogenesis--in 26%. For malignant tumors the combination therapy with intensive telegamma therapy prior to and after surgery was employed. Resectability in malignant teratomas made 73%, the postoperative mortality--in 5.5%. A five-year survival following radical surgery in patients with malignant teratoma was 37%. In inoperable teratoblastomas it seems rational to use intensive split course telegamma therapy with a total focal dosage of 5,500-6,500 rad.

Adult

A study on the melanin-laden dendritic cell (melanocyte) in ovarian cystic teratoma.

To confirm the existence and to analyse the distribution of the melanocyte in cystic teratoma of the ovary, 51 cases were collected, among which 47 were found suitable for gross and histological examinations. The tissue components of cystic teratoma where the melanocyte was seen more or less associating were; the squamous, cuboidal and columnar cell epithelia especially the epidermal epithelium, the brain tissue principally the leptomeninx, and the interstitium. The frequency of melanocytes' association in the respective tissue was shown and compared between each other. One thing which was quite interesting for us was the relationship between the existence of brain tissue and the development of melanocyte in cystic teratoma. The melanocyte appeared in the above tissues, especially the interstitium, of cystic teratoma more frequently when the brain tissue was coexisting in the same tumor. These findings seem to be of meaningful suggestions concerning the melanocytogenesis not only of cystic teratoma of the ovary, but also in a physiological condition in man.

Adolescent

Malignant presacral teratoma in children.

Malignant presacral teratoma is a rare tumor seen predominantly in young female children. The introduction of planned multidisciplinary treatment has improved the outlook for patients with this once dismal disease. Six female children were seen at Memorial Hospital with the diagnosis of malignant presacral teratoma. Five children were age 17 mo to 3 yr and the sixth child was 13 yr old at diagnosis. Presenting symptoms included masses in the buttock or groin, constipation, difficulty voiding, and local pain. Pathological features were varied and complex but three had predominantly endodermal sinus features. One child had the malignant presacral teratoma develop 18 mo after successful resection of a benign sacrosoccygeal teratoma in the newborn period. Treatment varied in the six cases since all were referred after failure of treatment elsewhere. All children had surgery, irradiation, and multiple drug chemotherapy. Four of the six children are surviving disease-free, 3 more than 24 mo off treatment. Evolution of treatment up to the present protocol management is discussed.

Antineoplastic Agents

[Sacrococcygeal teratomas in children treated at the Oncological Clinic of the Mother and Child Institute in Warsaw].

During the years, 1962 through 1975, 27 children with sacrococcygeal teratomas were seen at the Oncological Department of the National Research Institute for Mother and Child in Warsaw. 13 teratomas were benign and 14 were malignant. Surgical removal through a sacral approach was the basis of the treatment. In the presacral tumors with great diameter two-phase method was performed (the first phase--trans-abdominal excision of the tumor and the second phase--excision of remnant tumor's pedicle with coccygeal bone resection). Monodrug chemotherapy (Cyclophosphamide, Actinomycin D) in malignant tumors was without effect. In the group of benign teratomas are alive 11 children, in the group of malignant teratomas only one child survived. Some profits are expected from the multidrug chemotherapy ( Methotrexate , Cyclophosphamide, Actinomycin D) associated with radiotherapy, this can make operable primarily inoperable tumors.

Antineoplastic Combined Chemotherapy Protocols

Sacrococcygeal teratomas in infants and children: relationship of histology and prognosis in 40 cases.

Histological grading of teratomas is a useful method for evaluating patient prognosis. Although this has been repeatedly shown with ovarian teratomas, those of the sacrococcygeal area have not been scrutinized to a comparable extent. We believe that histologic grade and clinical behavior correlate closely in congenital sacrococcygeal teratomas. Correlation with clinical staging is less clear. There are some taxonomical and conceptual problems posed by the congenital nature of these tumors. The worst prognosis is dictated by the presence of yolk sac tumor areas, which was seen in seven of 40 teratomas examined. Although a neuroectodermal component is common, and was here proved to have metastasizing capacity, its inherent tendency may be toward spontaneous self-limiting differentiation. Vitelline differentiation, however, seems to imply irreversible progression and a uniformly bad prognosis.

Child, Preschool

Parthenogenic origin of benign ovarian teratomas.

To determine the origin of benign cystic teratomas of the ovary, chromosome-banding studies were done on normal tissues and teratomas from five patients. The normal tissues were heterozygous (+/-) for 17 chromosome polymorphisms at or near the centromere, whereas the teratomas were uniformly homozygous (+/+ or -/-). These findings and those employing electrophoretic variants indicate that ovarian teratomas are parthenogenic tumors that arise from a single germ cell after the first meiotic division.

Aminohydrolases

Teratomas of the neck in adults.

True teratomas of the neck in adults are unusual neoplasms. Their clinicopathologic aspects are distinctly different from the counterpart tumor of the neonate and infant. While the latter is almost always a benign tumor, adult teratomas are both histologically and clinically malignant neoplasms. To our knowledge, we report the tenth case of a teratoma of the neck in an adult.

Aged