i(12p) in a malignant ovarian tumor

We have found one or more copies of i(12p) in an ovarian germ cell tumor, histologically a yolk sac tumor. This chromosome marker is characteristically associated with germ cell tumors in males. This report indicates that further investigation is necessary to establish the role of the i(12p) marker in the pathogenesis of germ cell tumors also in females.     

Microdissection-based analysis of mature ovarian teratoma

The genotypic features of mature ovarian teratomas (MOTs) are controversial. Early studies detected a homozygous genotype in MOTs suggesting that these tumors are composed of germ cells that have undergone meiosis I. Other studies, however, revealed a heterozygous genotype in a substantial proportion of MOTs suggesting an origin either from premeiotic germ cells or from a somatic cell line. In view of the complex morphology of MOTs and to increase the sensitivity of teratoma genotyping, we applied tissue microdissection before genetic analysis of teratomatous tissue. This approach allowed selective analysis of different heterotopic tissue elements as well as the lymphoid tissues within MOTs the origin of which is unknown. After DNA extraction, the tissue samples were polymerase chain reaction amplified using a random panel of highly informative genetic markers for different chromosomes to evaluate heterozygosity versus homozygosity. In all seven cases that were analyzed, heterotopic tissues consistently revealed a homozygous genotype with several markers; in two cases, heterozygosity was detected with a single marker, indicating a meiotic recombination event. Lymphoid aggregates within MOTs were heterozygous and derived from host tissue rather than from teratomatous growth. However, well differentiated thymic tissue was consistently homozygous, suggesting lymphoid differentiation capability of MOTs. We conclude that potential pitfalls in genotyping of teratomas including meiotic recombination and host cell participation can be avoided by a microdissection-based approach in combination with a panel of genetic markers.     

i(12p): Specific chromosomal marker in seminoma and malignant teratoma of the testis?

A similar small marker chromosome, frequently present in duplicate, was seen in direct preparations and short-term cultures of each of ten seminomas, one combined seminoma and teratoma, and one malignant teratoma of the testis. In the four most favorable tumors (seminomas) this chromosome was identified as an i(12p). The findings may point to a chromosomal change that is specific for malignant testicular tumors.     

Mosaicism in Pallister i(12p) syndrome

The clinical diagnosis of Pallister syndrome in a 1-day-old white boy was confirmed by the presence of i(12p) in 100% of cells on direct bone marrow analysis. This is the second Pallister syndrome case in which cytogenetic diagnosis was made in bone marrow cells during the neonatal period. Other tissues analyzed in our patient included peripheral blood PHA-stimulated cultured lymphocytes and postmortem skin and lung cultured fibroblasts with 3%, 98.5%, and 97.5% of cells containing the i(12p), respectively. Serial skin fibroblast cultures re-established from frozen cells were analyzed sequentially over time for the isochromosome. There was slight reduction in the proportion of i(12p) cells until passage 15 with plateauing of the proportion of i(12p) cells at about 80% until culture senescence. Our review of such cytogenetic analyses suggests that in vivo and perhaps also in vitro isochromosome loss best explains the intra- and inter-tissue specific chromosomal mosaicism in the i(12p) syndrome. In any event, our results indicate that confirmation of the diagnosis in the neonatal period is possible by direct cytogenetic analysis of bone marrow.     

Glioblastoma multiforme in a mature ovarian teratoma with recurring brain tumours

AIMS: We report a case study to highlight the occurrence of glioblastoma multiforme in an ovarian teratoma. METHODS AND RESULTS: A 10-year-old girl presented with a left frontal lobe primitive neuroectodermal tumour which was successfully treated. After 6 uneventful years, she developed glioblastoma multiforme located posterior to the site of the initial tumour. Six years later, she presented with a mature cystic teratoma containing glioblastoma multiforme. CONCLUSIONS: Glioblastoma in an ovarian teratoma is an exceptional event, which might have an initial clinical presentation as a metastatic brain tumour. Alternatively, recurring glial tumours may occur in a genetically predisposed person; the role of radiation and chemotherapy in this context remains to be elucidated.     

Centromere-telomere (12;8p) fusion, telomeric 12q translocation, and i(12p) trisomy

The concurrence of a short arm isochromosome and a translocation of the entire long arm of the same chromosome to a telomere of another chromosome, implying trisomy for 4p, 5p, 7p, 9p, 10p or 12p, has been described in 13 patients. We have now used fluorescence in situ hybrization (FISH) to better characterize one of these rearrangements in which 12q was translocated to 8pter, whereas 12p was converted into an isochromosome. An alphoid centromere-12 repeat gave a strong signal on the i( 2p) and a weak but distinct signal at the breakpoint junction of the der(8), whereas the pantelomeric probe revealed three clear hybridization sites on the der(8): one at each end and another at the breakpoint junction. These findings suggest that the prime event was a post-fertilization centric fission of chromosome 12 leading to the 12q translocation via a real centromere telomere fusion and the i(12p). Alternatively, the crucial event may have been a centromere telomere recombination. An interstitial telomere has been documented by means of FISH at the breakpoint junction of the sole derivative usually present in 20 constitutional translocations including eight with a jumping behavior. In addition, six other telomeric translocations defined by banding methods, including another case of 12q translocation/i(12p), have also been jumping ones. These telomeric translocations have been de noro events and their proneness to exhibit a jumping behavior appears to be independent of the involved chromosomes, size of the translocated segments, and concomitant abnormalities.     

Necrotic mature ovarian teratoma associated with anti-N-methyl-D-aspartate receptor encephalitis

A 20-year-old female with a diagnosis of autoimmune encephalitis against N-methyl-D-aspartate receptor was found to have a 13 mm teratoma in the left ovary. The tumor had undergone massive coagulative necrosis within a normal ovary, a previously unreported feature. Necrosis of a mature cystic teratoma is very rare in the absence of ovarian torsion. It is proposed that necrosis may have induced a massive liberation of neuronal antigens. The vast majority of the tumors associated with this newly described condition are ovarian teratomas containing neural tissues. In this paper, we review their different histopathological aspects that may explain the relative incidence of various tumor types associated to this form of encephalitis. Anti N-methyl-D-aspartate receptor encephalitis has now become the most frequent autoimmune disorder associated with ovarian teratoma.     

Squamous cell carcinoma in situ arising in ovarian mature cystic teratoma

Mature cystic teratoma is a benign neoplasm, but malignant transformation of one component may occur in 2% of cases. Although very different types of carcinomas may be arise from mature cystic teratoma, invasive squamous cell carcinoma is the most frequent type of malignancy found, comprising about 80% of all malignancies arising from dermoid tumours. Although invasive squamous cell carcinoma is relatively frequent, it is surprising that so few cases of squamous cell carcinoma in situ in mature cystic teratoma have been reported. We describe a case of squamous cell carcinoma in mature cystic teratoma without an invasive component.     

Risk effect of maternal age in Pallister i(12p) syndrome

Pallister syndrome is consequent to mosaicism for i(12p). The isochromosome is found mainly in skin fibroblast cultures, but rarely also in cultured peripheral blood lymphocytes. Maternal age for reported cases of Pallister syndrome was significantly older (p less than 0.005) compared to maternal age for the general population, and similar to maternal age in cases of Down syndrome (p less than 0.5). Paternal age in cases of Pallister syndrome was that expected in the general population from the age of their spouses (p less than 0.9). These data complement the maternal age effect seen in other aneuploidy conditions and suggest, as is found in mosaic cases of Down syndrome, that the chromosomally normal cell line in Pallister syndrome arises post-conception from a zygote already aneuploid consequent to meiotic nondisjunction.     

Uniparental origin of i(12p) in human germ cell tumors

We present molecular data to demonstrate that the isochromosome 12p, specific for human germ cell tumors (GCTs), is of uniparental origin. Eight GCT-derived cell lines, containing one or more copies of i(12p) and/or other 12p anomalies, were analyzed with different 12p-derived polymorphic markers. The results from Ma-90, a near-diploid cell line with only one i(12p) in addition to two copies of a normal chromosome 12, clearly show an allelic 12p ratio of approximately 3:1, indicating that both 12p arms are of identical parental origin. These results were further substantiated by data obtained from the other i(12p)-positive GCT-derived cell lines. Therefore, we conclude that the i(12p) in GCTs constitutes a genuine isochromosome with genetically identical arms. The isochromosome most likely originates from a misdivision of the centromere rather than from a translocation or a non-sister chromatid exchange as proposed by others. We also found that supernumerary 12p copies, as observed in i(12p)-negative GCTs, are of uniparental origin. These observations seem to point to an important role for certain 12p-derived sequences in the development of human GCTs. © 1993 Wiley-Liss, Inc.     

A case of ovarian mature cystic teratoma presenting as a pedunculated ileal tumor

We report on a 34-year-old Japanese woman who presented with a pedunculated ileal tumor and who was finally diagnosed as having a right ovarian mature cystic teratoma penetrating and protruding into the ileum. She had undergone laparoscopic left ovarian cystectomy, whose specimen was diagnosed as dermoid cyst when she was 27 years old. The colon fiberscope revealed an ileal polyp, diagnosed as mature teratoma. Because of adhesion to the necrotic nodule between the tumor and the right ovary, ileocecal resection and right ovarian cystectomy were performed. The ileal tumor contained tissues of skin, neuroglia, ganglion, choroid, retina, smooth muscle, as well as fibrous and adipose tissues, cartilage, bone, mucous epithelium, and bronchial structures with bronchial glands. The necrotic nodule showed abscess, granulation tissue, foreign body reaction, hairs, normal ileal epithelium, and the ovary with ovums.     

Sebaceous adenoma arising within an ovarian mature cystic teratoma in Muir-Torre syndrome

This is the first reported case of a sebaceous adenoma arising within an ovarian mature cystic teratoma in a patient with Muir-Torre syndrome. The pathologic findings and a literature review are presented, including the importance and possible benefits of an early diagnosis of Muir-Torre syndrome. It is proposed that the presence of a sebaceous adenoma in an ovarian cystic teratoma may serve as a useful trigger to consider further history and investigations, with the goal of identifying an important genetic cancer predisposition syndrome.     

Pseudomyxoma peritonei: unusual origin from an ovarian mature cystic teratoma

Pseudomyxoma peritonei (PMP) is classified into pathologically and prognostically distinct categories, such as disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis. There is overwhelming evidence that DPAM arises from a mucinous adenoma of the appendix. The one exception to this is the presentation of a mature ovarian cystic teratoma as PMP where the appendix is normal. This report describes such a case and discusses the presentation, histopathology, and treatment options.     

A case of de novo i(12p) with 12q whole-arm translocation mosaicism

We report a dup(12p) due to a de novo i(12p) in a girl with mosaicism for 12q whole-arm translocations onto 7p, 7q, and 11q terminal regions. The dup(12p) syndrome was confirmed by clinical, cytogenetic, and LDH-dosage studies.     

Squamous cell carcinoma arising in a mature cystic ovarian teratoma with bladder invasion: a case report

Background

Malignant transformation in a mature cystic ovarian teratoma is rare. Except in cases with high index of suspicion or overt metastasis, oophorectomy is the mainstay of treatment for ovarian teratoma.

Method

A 46-year-old perimenopausal woman who had salpingo-oophorectomy following a clinical diagnosis of benign ovarian tumour that was subsequently reported histologically as mature cystic ovarian teratoma with malignant transformation is presented.

Results

She was referred to our facility based on the histopathology report and haematuria two weeks after surgery. Cystoscopic biopsy done was reported as metastatic squamous cell carcinoma most probably from the ovary. Patient was thereafter referred for radiotherapy but was lost to follow-up after the first course.

Conclusion

Adequate evaluation prior to surgery in suspected ovarian teratoma with malignant transformation is critical to determine extent of surgery and adjuvant therapy. Prognosis in advanced disease condition such as the case presented is generally poor although radical pelvic surgery with resection of the adjacent involved bladder before radiotherapy would probably have improved her prognosis.     

Bronchial carcinoma in an ovarian cystic teratoma (dermoid)

An ovarian cystic teratoma (dermoid) in which a squamous cell carcinoma had developed from bronchial epithelium via a process of basal cell hyperplasia, squamous metaplasia, and malignant change in situ is described. It is suggested that this sequence of changes may be due to the carcinogenic action of a constituent of the cyst contents.     

Chromosome 12q heterozygosity is retained in i(12p)-positive testicular germ cell tumor cells

Restriction fragment length polymorphism analysis is used to demonstrate that formation of the i(12p) chromosome, characteristic of testicular germ cell tumors, does not lead to loss of heterozygosity of various loci on the q arm of chromosome 12. This result suggests that during the etiology of these tumors, aneuploidization precedes the formation of the i(12p) marker chromosome.