Ovarian Mixed Germ Cell Tumor Research Articles

Malignant Germ cell Tumor of Ovary: An Unusual Combination and An Irony of Fate

Malignant mixed ovarian germ cell tumors are very rare malignant ovarian germ cell tumors, with a very high degree of malignancy. They are aggressive cancers affecting young adolescent girls. The commonest combination reported in literature is dysgerminoma and endodermal sinus tumors. Fertility sparing surgery followed by combination chemotherapy is the treatment of choice. The objectives of this case report are the advanced age of presentation, unusual histopathological combination, and the irony of infertility treatment. We report a rare case of 40-year-old woman with Malignant mixed germ cell tumor comprising of components of endodermal sinus tumor, immature teratoma, dysgerminoma and embryonal carcinoma. Patient was on hormonal therapy for the cause of infertility, presented with complains of lower abdominal pain, constipation and incomplete evacuation of bladder for 2months. Transvaginal ultrasonography and CT scan showed a large multicystic space occupying lesion with predominant solid component in midline abdominopelvic location. Tumor markers i.e., AFP, Prolactin and CA125 were raised. Total abdominal hysterectomy and bilateral salpingoophorectomy, pelvic and retroperitoneal node resection, peritonectomy and omentectomy was performed.

Role of staging surgery and adjuvant chemotherapy in adult patients with apparent stage I pure immature ovarian teratoma after fertility-sparing surgery

ObjectiveThe standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma, is unilateral salpingo-oophorectomy with complete staging...

Recurrent ovarian mixed germ cell tumor with unusual malignant transformation: a case report

BackgroundThe value of this report is the identification of late recurrence with an extremely unusual combination of malignant transformation. In particular, the retroconversion of immature to mature teratoma as well as a somatic-type malignant transformation were both observed postchemotherapeutically in our case.Case presentationWe report the case of a 20-year-old girl who completed fertility-sparing surgery and chemotherapy under the diagnosis of ovarian mixed germ cell tumor (immature teratoma and yolk sac tumor) and experienced subsequent recurrence 4 years after a second debulking surgery with a somatic type malignant transformation (teratoma with melanoma and leiomyosarcoma). Multiple metastases developed after a third debulking surgery, and the patient survived for 18 additional months.ConclusionsRecurrent disease after repeated cytoreduction and chemotherapy hints a poor outcome despite a generally excellent long-term survival rate among ovarian germ cell malignancies. It is important for clinicians to distinguish those at risk of poorer outcomes and establish individualized postoperative surveillance. Fertility-compromising surgery may be considered in selected patients.

Isolation of Streptococcus thoraltensis from an Abdominal Wall Abscess in a Young Female: A Case Report

Objective: Streptococcus thoraltensis is a recently described species, isolated from the intestinal and genital tracts of swine and from rabbit feces. We describe here a case of enterocutaneous fistula complicated by abdominal wall abscess formation attributable to S. thoraltensis. To our knowledge, this is the second reported human infection by this organism. Clinical features: Our patient is a 44-years-old diabetic female, with a previous history of ovarian mixed germ cell tumor treated with surgery and adjuvant chemoradiotherapy, presenting 18 years later with an enterocutaneous fistula complicated by abdominal wall abscess formation at the site of previous surgery. Culture from the drained pus and fistulous tract revealed Streptococcus thoraltensis. Outcome: The patient was treated conservatively with broad spectrum antibiotics and total parenteral nutrition. She suffered from disseminated intravascular coagulation and acute liver failure and passed away 4 weeks later. Conclusion: We report for the second time the isolation of streptococcus thoraltensis associated with a pathological process in humans. The infectious role of this newly identified organism pattern in human diseases is yet to be identified.

Frequent homozygosity in both mature and immature ovarian teratomas: a shared genetic basis of tumorigenesis

Although homozygosity is well documented in mature teratomas, the genetic zygosity of ovarian immature teratomas and mixed germ cell tumors is less well studied. Ten cases of mature cystic teratomas, eleven cases of grade 2 or 3 immature teratomas, and seven cases of mixed germ cell tumors with an immature teratoma component were investigated by short tandem repeat genotyping to interrogate their genetic zygosity. DNA genotyping was informative in eight mature teratomas, seven immature teratomas and six cases of mixed germ cell tumors. Out of the eight mature teratomas, five cases showed partial or complete homozygosity (63%) with two cases demonstrating complete homozygosity (25%). Of the immature teratomas, six cases showed partial or complete homozygosity (86%) with two cases demonstrating complete homozygosity (29%). For the mixed germ cell tumors, two cases showed partial homozygosity (33%) and none displayed complete homozygosity. Long-term clinical follow-up was available for five immature teratomas (mean follow-up 110 months) and five mixed germ cell tumors (mean follow-up 66 months). None of the five patients with pure immature teratoma had a recurrence; in contrast, four out of five mixed ovarian germ cell tumors recurred between 4 months to 8 years (P=0.048). In conclusion, both immature and mature teratomas harbor frequent genetic homozygosity suggesting a common cellular origin involving germ cells at the same developmental stage. The difference in the rate of homozygosity and tumor recurrence between pure immature teratomas and mixed germ cell tumors suggests that the two entities may involve different pathogenetic pathways and likely pursue different biological behaviors.

PET/CT diagnostic procedure from a rare case of ovarian mixed germ cell tumor

PET/CT diagnostic procedure from a rare case of ovarian mixed germ cell tumor

A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co‑occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC‑115, the MAPK1‑mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain‑associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease.

HCG 産生を伴う卵黄嚢腫瘍および成熟奇形腫からなる卵巣混合型胚細胞腫瘍の 1 例

hCG 産生を伴う卵黄嚢腫瘍および成熟奇形腫からなる卵巣混合型胚細胞腫瘍の 1 例

Ovarian mixed germ cell tumor with yolk sac and teratomatous components in a dog

Mixed germ cell tumors of the ovary have rarely been reported in veterinary species. A 3-year-old intact female Labrador Retriever dog was presented for lethargy, abdominal distention, and a midabdominal mass. An exploratory laparotomy revealed a large (23 cm in diameter) left ovarian tumor and multiple small (2-3 cm in diameter) pale tan masses on the peritoneum and abdominal surface of the diaphragm. Histological examination of the left ovary revealed a mixed germ cell tumor with a yolk sac component with rare Schiller-Duval bodies and a teratomatous component comprised primarily of neural differentiation. The abdominal metastases were solely comprised of the yolk sac component. The yolk sac component was diffusely immunopositive for cytokeratin with scattered cells reactive for α-fetoprotein and placental alkaline phosphatase. Within the teratomatous component, the neuropil was diffusely immunopositive for S100, neuron-specific enolase, and neurofilaments with a few glial fibrillary acidic protein immunopositive cells. Ovarian germ cell tumors may be pure and consist of only 1 germ cell element or may be mixed and include more than 1 germ cell element, such as teratoma and yolk sac tumor.

Overexpression of Karyopherin 2 in Human Ovarian Malignant Germ Cell Tumor Correlates with Poor Prognosis

BackgroundThe aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT).MethodsThe karyopherin 2 (KPNA2) expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2.ResultsKPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125), and the translation level (R = 0.6636, P<0.0001), was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS) of OMGCT (P = 0.02). The 5-year overall survival (OS) and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48) were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42)(P = 0.0151, P = 0.0109, respectively). The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62) was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28)(P = 0.0519, P = 0.0647, respectively).ConclusionsKPNA2 is a potential candidate molecular marker and important prognostic marker in OMGCT patients.

Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

IntroductionDevelopment of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically.Case presentationWe report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation.ConclusionThe presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma). In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

Clinical analysis of 15 cases of malignant ovarian germ cell tumors with lung metastasis

To investigate the clinical characteristics, diagnosis, treatment and prognosis of malignant ovarian germ cell tumors (MOGCT) with lung metastasis. Fifteen patients of MOGCT with lung metastasis treated in Peking Union Medical College Hospital from Jan. 1982 to Dec. 2010 was retrospectively analyzed. (1) Clinical characteristics: the average onset age of these 15 patients is (23 ± 11) years old (6 - 48 years). The majority of these patients presented with abdominal pain (8/15) or irregular vaginal bleeding (4/15) as their initial symptoms. The primary tumor located in the left ovary in 8 cases, right ovary in 6 cases, and both sides in only 1 case. Metastatic lesions were confined to the lung in 12 patients, while the other 3 patients were found to have multi-site distant metastasis. (2) DIAGNOSIS:all 15 cases included 9 pure non-gestational ovarian choriocarcinoma (NGOC), 3 MOGCT containing choriocarcinoma component (one mature teratoma with choriocarcinoma component, one endodermal sinus tumor with embryonal carcinoma and choriocarcinoma components, one choriocarcinoma with dysgerminoma component), 2 embryonal carcinoma, one immature teratoma. Only one patient in these 15 cases was correctly diagnosed before surgery. (3) Time of lung metastasis:of 12 MOGCT with choriocarcinoma component, 11 patients were found to have lung metastasis in the course of their primary treatment, only 1 had lung metastasis 2 months after the synthetic treatment finished. Three MOGCT patients without choriocarcinoma component were all found to have lung metastasis when tumor relapsed in the advanced stages of the disease. (4) TREATMENT:all 15 patients received multi-agent chemotherapy combined with surgery. The mean courses of chemotherapy for these patients were 16 courses (5 - 43 courses). (5) PROGNOSIS: of these 15 cases, complete remission was obtained in 10 patients of NGOC or mixed ovarian germ cell tumors with choriocarcinoma component, 3 patients (one NGOC, one endodermal carcinoma and one immature teratoma, respectively) died in the course of treatment as result of tumor progression, 2 progressed cases (one NGOC and one endodermal carcinoma respectively) abandoning therapy were lost to follow up. MOGCT with lung metastasis are more often to found in NGOC patients. These patients could obtain high complete remission rate after standard multi-agent chemotherapy combined with surgery. The prognosis of MOGCT with lung metastasis containing choriocarcinoma component are better than that of those without containing choriocarcinoma component.

A case of growing teratoma syndrome in mixed germ cell tumors of the ovary

Growing teratoma syndrome (GTS) is an increase in tumor size containing only mature teratoma component, during or after chemotherapy for germ cell tumors. A surgical resection is important to confirm diagnosis and is considered as the most appropriate therapeutic management. GTS is rare event in association with ovarian germ cell tumors. In this report, we present a case of GTS which occurred following the treatment of mixed ovarian germ cell tumor with immature teratoma and endodermal sinus tumor. The patient was given adjuvant chemotherapy consisting of six cycles of etoposide and cisplatin. Abdomen pelvis computed tomography performed after chemotherapy demonstrated no evidence of recurrence. She is on regular follow up and remained disease-free for 8 months following second surgery.

Ovarian mixed germ cell tumor in a patient with 45,X/46,X,+mar mosaic Turner's syndrome

We report a case that mixed germ cell tumor developed in an 18-year-old girl with 45,X/46,X,+mar mosaic Turner`s syndrome. Molecular biological studies showed that the patient`s DNA contained a fragment of Y chromosome. The patient underwent an operation and chemotherapy, and until now there is no evidence of recurrence. A presence of Y chromosome component should be evaluated in case a marker chromosome is found in a woman with Turner`s syndrome.

Malignant Mixed Ovarian Germ Cell Tumor with Embryonal Component

Background Malignant germ cell tumors of the ovary are relatively rare, making up less than 10% of all ovarian cancers. However, although they represent only a small fraction of ovarian cancers overall, they frequently affect adolescent women of reproductive age, making fertility sparing treatment of paramount importance. Malignant germ cell tumors are subdivided into dysgerminoma and nondygerminomatous tumors. The most common types of nondysgerminomatous tumors are yolk sac and immature teratoma. Mixed germ cell tumors with embryonal carcinoma, nongestational choriocarcinoma, and polyembryoma are less common. Embryonal carcinomas, though rare, are one of the most malignant cancers arising in the ovary. Case A 19-year-old female with abdominal pain and massive ascites was found to have a malignant mixed ovarian germ cell tumor with a large embryonal component which was treated via surgical resection and chemotherapy. Conclusions Malignant germ cell tumors frequently affect adolescent women of reproductive age. Management of these tumors requires consideration of fertility sparing surgical techniques and chemotherapy management. Using these techniques, the vast majority of patients will maintain their ovarian function and the ability to bear children after their recovery.

Morphologic, immunohistochemical, and fluorescence in situ hybridization study of ovarian embryonal carcinoma with comparison to solid variant of yolk sac tumor and immature teratoma

The prognosis and therapy for malignant ovarian germ cell tumors including embryonal carcinoma differ from those of other categories of ovarian tumors, making accurate diagnosis imperative for patient care. Because of its rarity, the protein markers and genomic alterations typifying primary ovarian embryonal carcinoma have not been fully characterized. The present study aims to establish a set of sensitive and specific protein markers useful for the diagnosis and delineation of ovarian embryonal carcinoma. Chromosomal 12p anomalies were analyzed by dual-color fluorescence in situ hybridization. In a series of 6 ovarian mixed germ cell tumors with a component of embryonal carcinomas, OCT4, CD30, SOX2, and glypican 3 expressions were analyzed immunohistochemically on formalin-fixed paraffin-embedded tissue specimens. The results were compared to 4 cases of mixed germ cell tumor that were originally mistaken for embryonal carcinoma. OCT4 marked the nuclei of 6 cases, among which 5 cases also showed glypican 3 expression indicative of an admixed yolk sac tumor component. SOX2 was positive in only 3 cases of embryonal carcinoma. In 1 case of mixed germ cell tumor containing embryonal carcinoma, embryoid bodies from a component of polyembryoma were demonstrated to be both OCT4 and CD30 positive. Two cases originally classified as embryonal carcinoma were OCT4 and CD30 negative and showed glypican 3 positivity. They were reclassified as solid variant of yolk sac tumor. Two other cases originally classified as embryonal carcinoma were OCT4 positive and CD30 negative and were classified as immature teratoma with neuroectodermal differentiation based on the immunohistochemical findings as well as morphologic features and were diagnosed as immature teratoma. Chromosome 12p alterations were identified in 5 of 6 cases of embryonal carcinomas. In summary, a panel of immunostains is more useful than a single biomarker in the differential diagnosis of ovarian germ cell tumors. Chromosome 12p fluorescence in situ hybridization combined with OCT4, CD30, and glypican 3 immunostains is useful in confirming the diagnosis of ovarian embryonal carcinoma.

Embryonic Stem Cell Transcription Factors and D2-40 (Podoplanin) as Diagnostic Immunohistochemical Markers in Ovarian Germ Cell Tumors

The embryonic stem cell transcription factors SOX2, NANOG, and OCT3/4 are involved in the regulation of germ cell tumor growth and differentiation. They, and D2-40 (podoplanin), an antigen expressed in seminomas, are emerging as useful diagnostic markers in testicular germ cell tumors. This study evaluates the use of these markers in ovarian tumors. Ovarian germ cell tumors (n=31) have distinct immunostaining profiles, depending on the type of differentiation as follows: dysgerminoma (SOX2-, NANOG+, OCT3/4+, D2-40+), embryonal carcinoma (SOX2+, NANOG+, OCT3/4+, D2-40-), immature teratomas (SOX2+, NANOG-, OCT3/4-, D2-40-), yolk sac tumors, and choriocarcinoma (SOX2-, NANOG-, OCT3/4-, D2-40-). In immature teratomas, SOX2 positivity was limited to neural and epithelial tissues, and OCT3/4 was positive only in scattered epithelial cells (<10% of cells). Nongerm cell tumors (n=57, including surface-epithelial stromal tumors and sex-cord stromal tumors) were negative for NANOG and D2-40. OCT3/4 was positive in 4 of 9 adult granulosa cell tumors (15% to 85% of cells). In a small number of surface-epithelial stromal tumors, SOX2 and/or OCT3/4 were variably positive (20% to 90% of cells). Of the markers, SOX2 and D2-40 discriminated between dysgerminoma and embryonal carcinoma. NANOG distinguished between either of these 2 tumors and nongerm cell tumors. The inclusion of these markers should therefore be considered in cases of pure or mixed ovarian germ cell tumors that are difficult to classify, and to exclude nongerm cell tumor mimics.

Mixed Ovarian Germ Cell Tumor in a BRCA2 Mutation Carrier

BRCA2 germ-line mutations confer an increased risk of developing breast and ovarian cancer. We report the occurrence of a mixed ovarian germ cell tumor (GCT) (50% embryonal carcinoma, 20%-25% choriocarcinoma, 10%-15% dysgerminoma, and 10%-15% immature teratoma) in a 33-year-old Ashkenazi Jewish woman, carrier of the BRCA2:6174delT mutation. The mutation is also present in the patient's father, who was diagnosed with breast cancer at age 59 and with prostate cancer at age 69. This is the first report of a GCT in a BRCA2 mutation carrier; there was one previous report of an ovarian dysgerminoma in a BRCA1 carrier. Molecular analysis of the proband's tumor DNA revealed there was no loss of heterozygosity of the wild-type allele in the tumor, as is usually the case for epithelial BRCA-related ovarian tumors. This suggests either that biallelic inactivation of BRCA2 is not required for GCT development or that this is a chance event unrelated to the presence of the mutation.

Yolk sac tumor of the ovary associated with endometrioid carcinoma with metastasis to the vagina: A case report

Mixed yolk sac tumors of the ovary are biologically aggressive even in early stage disease. A 41-year-old woman presented with a large pelvic mass and anterior vaginal wall tumor. At surgery vaginal biopsies were performed followed by an exploratory laparotomy with resection of the mass. Pathology of the ovary revealed a primary yolk sac tumor associated with poorly differentiated endometrioid and undifferentiated carcinoma with vaginal metastasis only. She was initiated on bleomycin, etoposide, and cisplatin, with three additional cycles of etoposide and cisplatin. Initially the patient experienced a complete response, however her disease recurred and she currently is dead of her disease. To our knowledge this is the first case of a mixed ovarian germ cell tumor with vaginal metastasis.

Analysis of ovarian teratomas for isochromosome 12p: evidence supporting a dual histogenetic pathway for teratomatous elements

Teratomas are the most common germ cell tumor (GCT) of the ovary and include several types with a range of clinical behavior. As in testicular teratomas, they may be benign, malignant or a component of a mixed GCT. In the testis, data support separate pathogeneses for prepubertal and postpubertal teratomas, with derivation of the former from a nontransformed germ cell and the latter from differentiation of a nonteratomatous, malignant GCT. The absence of cytogenetic abnormalities (including isochromosome 12p (i(12p)) in mature ovarian teratomas suggests that they may be analogous to prepubertal testicular teratomas, but there are no data regarding genetic changes in the teratomatous components of ovarian mixed GCTs. We therefore studied the teratomatous components of six mixed GCTs of the ovary using fluorescence in situ hybridization (FISH) for i(12p). Six mixed GCTs of the ovary occurred in patients 4–33 years of age; all had teratomatous and yolk sac tumor components and three also contained foci of embryonal carcinoma. Using FISH with 12p telomeric and 12 centromeric probes, five of six (83%) cases had detectable i(12p) in their nonteratomatous components, and four of six (66%) in the teratomatous component. One of the two cases without demonstrable i(12p) in the teratomatous portion of the mixed GCT also did not have identifiable 12p abnormalities in other elements of the mixed GCT. By comparison, five pure, mature ovarian teratomas and three pure, immature ovarian teratomas showed no evidence of either i(12p) or other forms of 12p amplification. These findings support that teratoma in mixed ovarian GCTs has a different pathogenesis compared to pure teratoma of the ovary. Furthermore, the findings of i(12p) in both the teratomatous and nonteratomatous components of ovarian mixed GCTs supports that the teratoma derives from other components, similar to the situation in the testis.