Pure Immature Teratoma Research Articles

Laparoscopic-Assisted Fertility-Sparing Surgery for Growing Teratoma Syndrome of the Ovary: Experience From a Tertiary Center

Study ObjectiveThe main objective is to evaluate the feasibility of laparoscopic fertility-sparing surgery in women with growing teratoma syndrome. DesignRetrospective cohort study. SettingChinese tertiary university hospital. PatientsPatients with growing teratoma syndrome who underwent fertility-sparing surgery between January 2015 and August 2023. InterventionsBaseline characteristics and surgical outcomes were evaluated, including clinical information, surgical procedures, operative time, intraoperative blood loss, complications, length of hospital stay, and follow-up information. Measurement and Main ResultsTwenty-six patients with ovarian growing teratoma syndrome underwent fertility-sparing surgery: 12 had laparoscopic surgery and 14 underwent laparotomic surgery. In the laparoscopic group, the median age of the patients during initial management of immature teratoma or mixed malignant ovarian germ cell tumor was 14.0 years (interquartile range: 13.0-24.5 years). Eleven patients were nulliparous. The primary ovarian tumor was pure immature teratoma in 10 patients and mixed ovarian germ cell tumor in 2 patients. Complete laparoscopic tumor resection was achieved in 11 patients. Patients in laparoscopic group had shorter median operative time (76.5 vs 180.0 minutes, p = 0.001), lower estimated blood loss (20.0 vs 400.0 ml, p < 0.001), decreased postoperative hospital stay (2.0 vs 7.0 days, p < 0.001), compared with laparotomic surgery. There was no conversion to laparotomy and no perioperative complications. Histological examination confirmed mature teratoma in all cases. During a median follow-up of 21.9 months (interquartile range: 7.6-44.9 months), 11 patients were alive without disease and 1 was alive with disease. One pregnancy was achieved postoperatively. ConclusionLaparoscopic fertility-sparing surgery may represent a feasible option in well-selected patients with ovarian growing teratoma syndrome. Surgery should be performed in gynecologic oncology centers by experienced staff trained in endoscopic procedures. More research and long-time follow-up are needed to determine the oncological outcomes and safety of laparoscopic surgery in this population.

Oncological and reproductive outcomes of cystectomy compared with unilateral salpingo-oophorectomy as fertility-sparing surgery in patients with apparent early-stage pure immature ovarian teratomas

<h3>Objectives:</h3> To compare the oncological and reproductive outcomes of patients with apparent early-stage pure immature teratomas (IMTs) of the ovary treated with cystectomy or unilateral salpingo-oophorectomy (USO). <h3>Methods:</h3> We retrospectively reviewed the medical records of patients with apparent early-stage pure IMTs who received fertility-sparing surgery (FSS) between January 1984 and December 2019. FSS was defined as preservation of the uterus and at least one adnexa. Recurrence rates were compared between patients receiving cystectomy and USO. Reproductive outcomes and menstrual histories were assessed by telephone interview. <h3>Results:</h3> A total of 124 patients were included, of whom 41 underwent cystectomy and 83 underwent USO. After a median follow-up of 70.6 months (range: 6.2–410.6 months), eight patients suffered recurrences (3 in the cystectomy group and 5 in the USO group). The median times to recurrence were 5.1 and 5.0 months in the cystectomy and USO groups, respectively (P=0.764). All patients with recurrence were successfully salvaged by surgery, except for one death. Univariate analysis showed no difference in disease-free survival and overall survival between the groups (P=0.781, 0.155). Of the 111 patients contacted by telephone, 97 resumed menstruation following the surgery. Of the 31 patients desiring pregnancy, 26 achieved 28 successful pregnancies. USO (83.3%), like cystectomy (85.7%), resulted in excellent pregnancy rates. <h3>Conclusions:</h3> A USO is the standard treatment for women with early stage pure IMTs who want to preserve fertility. However, a cystectomy may be a suitable fertility-sparing therapy when a cystectomy is the only surgical option.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre

BackgroundPrimary mediastinal germ tumours (PMGCT) constitute, a mere 3–4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19–25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DesignWe have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010–2019) from a tertiary-care oncology centre. ResultsThe study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. ConclusionPMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Oncological and Reproductive Outcomes of Cystectomy Compared with Unilateral Salpingo-Oophorectomy as Fertility-Sparing Surgery in Patients with Apparent Early Stage Pure Immature Ovarian Teratomas.

To compare the oncological and reproductive outcomes of patients with apparent early stage pure ovarian immature teratomas (IMTs) treated with unilateral salpingo-oophorectomy (USO) or cystectomy. We retrospectively reviewed the medical records of patients with apparent early stage pure ovarian IMTs who received fertility-sparing surgery (FSS) between 1984 and 2019. FSS was defined as preservation of the uterus and at least one adnexa. Recurrence rates were compared between patients receiving USO and cystectomy. Reproductive outcomes and menstrual histories were assessed by telephone interview. A total of 124 patients were included, of whom 83 underwent USO and 41 underwent cystectomy. After a median follow-up of 70.6 months (range: 6.2-410.6 months), eight patients suffered recurrences (5 in the USO group and 3 in the cystectomy group). The median times to recurrence were 5.0 and 5.1 months in the USO and cystectomy groups, respectively (P=0.764). All patients with recurrence were successfully salvaged by surgery, except for one death. Univariate analysis showed no difference in disease-free survival and overall survival between the groups (P=0.781, 0.155). Of the 111 patients contacted by telephone, 97 resumed menstruation following the surgery. Of the 31 patients desiring pregnancy, 26 achieved 28 pregnancies. USO (83.3%), like cystectomy (85.7%), resulted in excellent pregnancy rates. A USO is the standard treatment for women with early stage pure IMTs who want to preserve fertility. However, a cystectomy with adjuvant chemotherapy may be a suitable fertility-sparing therapy when a cystectomy is the only surgical option.

ASO Author Reflections: Ovarian Cystectomy for Apparent Early-Stage Pure Immature Ovarian Teratomas.

ASO Author Reflections: Ovarian Cystectomy for Apparent Early-Stage Pure Immature Ovarian Teratomas.

Role of complete staging surgery and adjuvant chemotherapy in adults with apparent stage I pure immature ovarian teratoma after fertility-sparing surgery: Experience at a tertiary center in China

Objective: The standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma (IMT), is unilateral salpingo-oophorectomy with complete staging surgery (CSS) followed by platinum-based chemotherapy. However, the role of CSS and adjuvant chemotherapy remains controversial.

Can we replace adjuvant chemotherapy with surveillance for stage IA-C immature ovarian teratomas of any grade? an international multicenter analysis

BackgroundThe role of surveillance after surgery for stage IA-C grade 2 (G2) or grade 3 (G3) immature teratomas (ITs) is controversial with many guidelines advocating adjuvant chemotherapy. Here, we investigate the safety of surveillance in stage IA-C G1-3 ITs. MethodsClinicopathological data were analysed on postpubertal patients with stage I pure ITs in Multicenter Italian Trials in Ovarian Cancer centres and at Charing Cross Hospital, UK, between January 1985 and January 2018. ResultsOf 108 stage I patients, 66 (61.1%), 3 (2.8%) and 39 (36.1%) were International Federation of Gynecology and Obstetrics IA, IB, IC, respectively, with 31 (28.7%), 41 (38%) and 36 (33.3%) having grade 1 (G1), 2 and 3 disease, respectively. After surgery, 27 patients (25%) had adjuvant chemotherapy and 81 (75%) surveillance. There was no significant increase in the risk of malignant (G2-3 IT) relapse (9/81 vs 2/27; p = 0.72) or in disease-free survival (DFS) or overall survival in the surveillance vs chemotherapy groups. The median time to relapse was 17.8 months (range: 3–47) with no significant difference between surveillance or chemotherapy groups. The median follow-up was 64.3 months (Interquartile range (IQR) 22.2–101.7). Chemotherapy induced cures in all except for one patient who did not follow the surveillance protocol due to pregnancy and died of disease. Univariate and multivariate analyses revealed that only tumour grade (hazard ratio [HR] = 3.11; p = 0.02) and complete surgical staging (HR = 0.2; p = 0.01) were independent prognostic factors for decreased DFS. ConclusionThe present study suggests that in the adult setting careful surveillance appears to be an acceptable alternative to adjuvant chemotherapy for stage IA-C ITs of any grade, properly staged and with negative postoperative tumour markers.

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...

A unique uterine cervical \u201cteratocarcinosarcoma\u201d: a case report

BackgroundTeratocarcinosarcoma (TCS) is a rare aggressive tumor of the nasal cavity and paranasal sinuses and has both epithelial and two or more mesenchymal components. In other organs, 5 cases of ovarian tumors closely resembling TCS have been reported; however, there has been no published case of cervical TCS. Herein, we describe a unique case of cervical tumor that had carcinosarcomatous and teratomatous features, resembling a sinonasal TCS.Case presentationA 45-year-old woman presented to our hospital for evaluation of a cervical lesion. The gynecologist found a large polypoid mass, whose biopsy showed glandular components of probable germ cell origin based on the immunohistochemical features. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy. The cervical polypoid mass was found to consist of both epithelial and mesenchymal tissues, including immature glandular structure resembling fetal enteric tubules, neuroepithelial cells, hyaline cartilage, and rhabdomyosarcoma cells. This tumor was diagnosed as TCS of the uterine cervix. Following the surgery, the patient received radiotherapy and has been free of disease for 13 months.ConclusionThis is the first case report of cervical TCS. The tumor is thought to be histogenetically less associated with HPV infection, and its teratomatous components with an absence of cytogenetic abnormalities (including isochromosome 12p (i(12p)) suggest a analogous histogenesis compared to pure mature or immature teratoma.

Experience of applying cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for ovarian teratoma with malignant transformation and peritoneal dissemination.

ObjectivesThe prognosis of ovarian teratoma with malignant transformation and peritoneal dissemination (PD) is poor. This condition is rare but associated with a high recurrence rate even after aggressive debulking surgery and adjuvant chemotherapy. In the present paper, we describe our experience of using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for this condition.MethodsThe data of ten female patients having ovarian teratoma with malignant transformation and PD between June 2007 and June 2017 were collected and reviewed retrospectively. CRS-HIPEC was performed according to the standard protocol. Patient characteristics, pathological reports, tumor markers, perioperative operative parameters, postoperative events, and disease status during the follow-up period were recorded.ResultsThe primary ovarian neoplasms were pure mature cystic teratoma with malignant transformation (n=6, including 5 of mucinous adenocarcinoma), mixed germ cell tumor with mature cystic teratoma and yolk sac tumor (YST) (n=1), pure immature teratoma (n=1), immature teratoma with growing teratoma syndrome (GTS) (n=1), and immature teratoma mixed YST with GTS (n=1). The mean levels of tumor markers, including carcinoembryonic antigen, cancer antigen 19-9 (CA19-9), and CA125, were markedly elevated. The recurrence rate was 10%. The median and mean disease-free survival (DFS) after CRS-HIPEC were 22.3 and 36.2 months, respectively, and the 5-year DFS rate is 88%.ConclusionCRS-HIPEC is a safe therapeutic option for reducing the recurrence rate in selected patients with PD originating from ovarian teratoma with malignant transformation.

The genetic landscape of 87 ovarian germ cell tumors

BackgroundOvarian germ cell tumors (OGCT) are rare gynecological neoplasms, mostly affecting children and young women. The underlying molecular genetic background of these tumors is poorly characterized. MethodsWe analyzed somatic copy number aberration (CNA) profiles in 87 OGCT tumors and performed whole exome sequencing (WES) on 24 OGCT tumor and matched germline samples to further elucidate their molecular genetic landscape. ResultsThe overall mutation rate was very low in OGCT compared to other human cancers, with an average of 0.05 mutations per Mb, consistent with their embryological origin. We identified recurrent mutations in KIT and KRAS, while CNA profiling revealed frequent focal amplifications affecting PIK3CA and AKT1 in yolk sac tumors, recurrent focal deletions affecting chromosomal regions 1p36.32, 2q11.1, 4q28.1, 5p15.33, 5q11.1 and 6q27, as well as gains in chromosome 12p that were present in all tumors, except for pure immature teratomas. ConclusionWe here present the first whole exome sequencing data and to our knowledge the largest CNA study in OGCT. We confirmed that earlier reported KIT mutations were frequent in dysgerminomas and mixed forms with a dysgerminoma component, whereas chromosome 12p gains were present in all histological subtypes except pure immature teratomas. We detected recurrent KRAS mutations, recurrent focal deletions and an enrichment in the PI3K/AKT/PTEN pathway in yolk sac tumors. Several of these aberrations involve targetable pathways, offering novel treatment modalities for OGCT.

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.

Pure Immature Teratoma of the Ovary in Adults: Thirty-Year Experience of a Single Tertiary Care Center.

ObjectiveThe aim of this study was to evaluate clinicopathologic characteristics, treatment outcome, and reproductive function in women diagnosed with ovarian immature teratoma (IT). Our standard chemotherapy regime is currently etoposide/cisplatin (EP), creating a unique opportunity to evaluate this protocol in ovarian ITs.Materials and MethodsThis study is a retrospective analysis. Twenty-seven women older than 18 years with ovarian IT stages IA to IIIC were identified and included in this study. Patients were treated at 1 institution, Health Sciences Center, Women’s Hospital, Winnipeg, Manitoba, Canada, between 1983 and 2013.ResultsThe median age at diagnosis was 27.0 years (range, 18–36 years). Twenty-two (82%) presented with an International Federation of Gynecology and Obstetrics stage I disease, 3 (11%) had stage II, and 2 patients (7%) had stage III disease. The histologic grade distribution was grade I in 9 patients (33%), grade II in 3 patients (11%), and grade III in 15 patients (56%). Initial management was surgical for all patients: 3 (11%) hysterectomy and bilateral salpingo-oophorectomy, 1 (4%) cystectomy only, and 23 (85%) unilateral salpingo-oophorectomy. Twenty-one patients (78%) received adjuvant therapy. The median follow-up was 60 months (range, 36–72 months). One patient recurred (histological grade III) 6 months after surgery and had a complete clinical response to 4 cycles of EP chemotherapy. Twelve patients reported an attempt to conceive resulting in 10 pregnancies (8 after chemotherapy).ConclusionsOvarian IT is a curable disease. Fertility-sparing surgery should be offered. Adjuvant treatment with cisplatinum-based chemotherapy, typically with bleomycin, etoposide, and cisplatin, is still considered the standard in stages greater than stage IA grade I. Etoposide/cisplatin as a primary chemotherapy regime for early- or advanced-stage disease is an effective treatment with minimal adverse effects and high tolerability. This is the first published study examining EP as a primary treatment modality for IT. Further studies are needed to strengthen these findings.

Protocol for the Examination of Specimens From Pediatric and Adult Patients With Extragonadal Germ Cell Tumors

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the ‘‘Surgical Pathology Cancer Case Summary (Checklist)’’ portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents.

Oct4 Expression in Immature Teratoma of the Ovary

Immature teratoma of the ovary is an uncommon tumor comprising 1% of ovarian malignancies. The amount of immature neuroepithelium in the teratoma is an important prognostic factor. Although the current grading system based on this criterion is widely accepted, the biological significance of immature neuroepithelium is poorly understood. In this study, we used immunohistochemistry to evaluate the expression of Oct4 (also known as Oct3 or POU5F1), a transcription factor expressed in primordial germ cells and embryonic stem cells, along with that of PAX6, a transcription factor contributing to neurogenesis, and CD56, a known marker for tumors of neural origin, in 18 cases of pure immature teratoma of the ovary. Oct4 was expressed in the immature neuroepithelium of all 7 grade-3 cases and 2 grade-2 cases. It was not expressed in 4 grade-2 cases and all 5 grade-1 cases. These tumor cells lacked CD30 or α-fetoprotein expression, which supported the diagnosis of pure immature teratoma. PAX6 was expressed in the immature neuroepithelium of all immature teratomas, but not in Oct4-positive cells. CD56 was expressed in neural components of various maturities including PAX6-positive immature neuroepithelium, but not in Oct4-positive cells. These data suggest that the expression of these markers probably reflects the differentiation status of neural tissue in immature teratomas. The finding that Oct4 expression was exclusively detected in immature neuroepithelium of high-grade immature teratomas indicates that Oct4 might serve as a promising biomarker for the diagnosis of highly malignant cases of immature teratoma.

Is adjuvant chemotherapy indicated in stage I pure immature ovarian teratoma (IT)? A multicentre Italian trial in ovarian cancer (MITO-9)

Objective . Conservative surgery followed by platinum-based chemotherapy is considered the standard approach for stage I immature ovarian teratoma (IT), except for stage IA G1. Nevertheless the use of chemotherapy in stage IA G2–3 and IB–IC is controversial. The aim of this study was to evaluate the outcome of patients with IT in order to define the role of chemotherapy in stage I disease. Methods . Twenty-eight patients with stage I IT treated in MITO centers were retrospectively reviewed. Grade, stage, age, surgical and postoperative treatment were analyzed using χ 2 test and T test looking for association with recurrence. Results . Median age was 25.5. Twenty-four patients underwent fertility-sparing surgery. FIGO stages were 19 IA, 2 IB, and 7 IC. Nine patients had grade 1 tumor, 12 grade 2, and 7 grade 3. Nine patients received adjuvant chemotherapy. Overall recurrence rate was 21.4% (2 in chemotherapy group and 4 in the group without treatment). No patients with G1 had recurrence, whereas 25% of G2 and 42.9% of G3 relapsed. Recurrence rate was not significantly different according to stage, grade or adjuvant chemotherapy, whereas it was greater in the group not operated in a MITO center, not staged and of age lower than 20 years, with statistical significance. At recurrence 4 patients presenting with mature teratoma were treated with surgery alone, whereas 2 recurring with IT were treated with surgery plus chemotherapy. After a median follow-up of 59 months all patients are NED. Conclusions . Our study suggests that chemotherapy may be withheld for primary therapy and utilized only for recurrence.

Risk of late relapse after surveillance for stage I mixed (M) or non seminomatous (NS) testicular germ cell tumors (TGCT)

14576 Background: Surveillance is an alternative to retroperitoneal lymph node dissection or adjuvant chemotherapy for stage I M or NS TGCT. It has been shown to be associated with a low mortality rate of about 1%, similar to that of the other therapeutic options. However, there are few reports of long-term results. The aim of this retrospective study was to investigate late relapses in this setting. Methods: Screening of the computerized database from 1984 to 2005 for patients (pts) treated for a relapse of a M or NS TGCT at 10 years or more after an orchidectomy. Results: From 1994 to 2006, the files of 5 pts were retrieved. Two pts were referred from other institutions whereas 3 pts had initially been included in the surveillance program of the Institution out of a total of 88 from 1984 to 1996. (3.4% CI 95% 0.7–9.6). Initial histology was available in 4pts: it was pure mature and immature teratoma in one pt and mixed GCT with seminoma in 3 pts. There was no vascular invasion in any of the tumors. Relapse occurred between 10 and 13 years after orchidectomy (median 11 years). The diagnosis of relapse was made based on a systematic 10-year follow-up CT scan in one pt. The 4 other pts who relapsed presented with symptoms: abdominal and back pain due to retroperitoneal involvement in 2 pts, walking disability due to a spinal cord compression in one pt and acute respiratory distress syndrome due to massive metastatic lung involvement in one pt respectively. All 4 pts had bulky retroperitoneal masses. According to the IGCCCG classification, the prognosis was poor in 2 pts and intermediate in 2pts. One pt died of disease despite cisplatin-based chemotherapy. Conclusion: These data demonstrate that there is a small but clinically significant risk of late relapse of stage I M or NS GCT after orchidectomy alone and support the need for long-term surveillance and patient information. No significant financial relationships to disclose.

Significance of p53 expression in immature teratomas.

Twenty-nine pediatric immature teratomas were reviewed to determine the frequency and clinical significance of p53 expression. Tumors were stained for p53 expression by immunohistochemistry and results were correlated with the presence of other germ cell tumor elements and with outcome. Sequencing of p53 for mutations was performed on positive cases. Eighteen cases showed widespread positive p53 staining of the immature teratoma elements, 9 showed staining only in very occasional cells, and 2 cases showed no staining. Of the 18 positive cases, 5 recurred. All five were pure immature teratomas at diagnosis. Four recurred as immature or mature teratoma and one as a sarcoma; all except one showed frequent cells positive for p53 in the recurrent tumor. Another 5 of the 18 diffusely positive cases contained immature teratoma as well as other malignant germ cell elements at diagnosis; none of these recurred. None of the remaining eight cases with frequent positive cells, the nine cases with occasionally positive p53 staining, or the two cases with no staining recurred or demonstrated other germ cell tumor elements. We conclude that p53 expression is not unusual in immature teratoma and diffuse p53 immunopositivity is associated with recurrence or the presence of malignant elements in approximately 50% of cases. In only 1 of 29 cases tested was p53 immunopositivity associated with mutations in the p53 gene; hence, overexpression in the majority of cases is presumed to reflect increased half-life of the protein from undetermined stabilizing factors. Expression of p21, a p53 target gene, was only focal, suggesting impaired transcriptional activation by p53. The finding of frequent p53-positive cells in immature teratoma should prompt a search for malignant elements within the tumor and affected patients should be followed closely for evidence of recurrence.

Surgical Resection Alone Is Effective Treatment for Ovarian Immature Teratoma in Children and Adolescents: A Report of the Pediatric Oncology Group and the Children’s Cancer Group

This study was conducted to evaluate the routine use of chemotherapy, with its attendant long-term effects, in children and adolescents after the surgical removal of ovarian immature teratoma. Forty-four girls who underwent laparotomy for complete removal of an ovarian tumor containing pure immature teratoma between 1995 and 1996 served as subjects. Patients were classified as having stage I cancer when disease was found in the ovary only with negative peritoneal washings. Among the patients who had adequate staging, no stage II disease was observed. Follow-up for the first 2 years included frequent measurements of serum levels of α-fetoprotein (AFP) and diagnostic imaging studies of the chest and pelvis. Thereafter, patients returned annually for regular physical examinations. At diagnosis, the age range of the subjects was 1.5 to 20 years. Four girls were lost to follow-up, two shortly after surgery and two within 2 years. Nineteen patients were followed for more than 5 years, and four had undergone surgery less than 2 years earlier. Histologic examination found no embryonal carcinoma, choriocarcinoma, or germinoma. Fifteen patients were classified as having grade 1 tumors, 12 had grade 2 tumors, and 2 had grade 3 tumors. On central pathology review, 13 patients were found to have tumors containing microscopic foci of a yolk sac tumor that was previously undetected. Unilateral salpingo-oophorectomy was the treatment selected in 28 patients (64 percent). Only one hysterectomy was necessary. Lymph node samples, obtained from 16 patients, showed mature gliomatosis in three patients. Three subjects had positive peritoneal washings, all of which contained only mature teratomatous or immature glial cells. The 13 patients with ovarian immature teratoma plus yolk sac tumor were slightly older (median, 12 years) than those with pure teratoma (median, 10 years) and were more likely to have larger tumors. Fifty-five percent of the girls with immature teratoma had grade 1 disease, compared with only 8 percent of those whose teratoma contained a yolk sac tumor. Conversely, 46 percent of the children with immature teratoma plus yolk sac tumor were classified as having grade 3 disease, compared with 6 percent of those without yolk sac tumor. Ten of the 13 girls (80 percent) with yolk sac components had measurable levels of AFP, compared with only 10 of 31 of the girls (34 percent) with no yolk sac tumor elements. Furthermore, the median level of AFP was 252 among children with yolk sac tumor, compared with 25 among those without yolk sac tumor. Ovarian immature teratoma containing yolk sac tumor was less likely to rupture during removal than immature teratoma (8 vs. 32 percent). No patients died. There was one malignant recurrence in a 12-year-old girl who had a large ovarian immature teratoma with yolk sac tumor, an initial serum AFP level of 1045 ng/ml, and peritoneal washings and lymph nodes positive for gliomatosis. A sharp rise in her serum AFP level at 18 weeks signaled a recurrence. Two nodules containing grade 2 immature teratoma with yolk sac tumor were found in her liver. She was disease free 57 months after four courses of cisplatin, etoposide, and bleomycin therapy. Two other patients required additional surgical procedures. Both girls underwent exploratory laparotomy for a pelvic mass. One contained ovarian mature cystic teratoma and mature glial implants. The other was composed of multiple mature glial implants on the peritoneal surfaces and on the surface of the remaining ovary, which was removed. Both patients had normal serum AFP levels that did rise, and both continue to be well without additional symptoms. Normal adolescent follicular cysts were frequently observed among the entire study group. Am J Obstet Gynecol 1999;181:353–358

DNA Content of Ovarian Immature Teratomas and Malignant Germ Cell Tumors

Objective.Ovarian germ cell tumors (GCT) show greater histologic and biologic heterogeneity than their testicular counterparts and remain poorly understood. Ploidy analysis was performed on ovarian GCT registered on Pediatric Oncology Group germ cell tumor protocols 9048 and 9049 to distinguish biologically distinct subsets of immature teratomas and malignant ovarian germ cell tumors.Methods.Tumors from 22 patients (mean age 12 years) were analyzed and classified according to the submitting diagnosis; when pure samples of different histologic subtypes within a single tumor were possible, these were analyzed separately. Archival tissue was disaggregated and Feulgen stained; DNA index (DI) was determined by static image analysis utilizing internal normal cells as diploid controls.Results.26 histologic subtypes from 22 patients were analyzed. The tumors of 18 patients were composed of a single histologic subtype according to the submitting institution, including 6 dysgerminomas, 8 immature teratomas (IT), and 4 endodermal sinus tumors (EST). Two tumors contained both IT and EST components that were separately analyzed. Two tumors were classified as mixed germ cell tumors; 1 showed multiple intermingling subtypes unable to be separately analyzed and the second showed three histologic subtypes separately analyzed (IT, EST, embryonal carcinoma). From a total of 15 malignant histologic GCT subtypes in 14 patients, all but 2 demonstrated a DI of 1.4–2.4 (mean 1.85). Two diploid malignant GCT (1 EST, 1 dysgerminoma) were both associated with gonadoblastoma. Overall, 11 IT subtypes were analyzed and 9 were diploid (2 grade 1, 5 grade 2, and 2 grade 3). Two tumors originally submitted and classified as pure IT (grades 2 and 3) were aneuploid with a dominant diploid and a secondary aneuploid peak (both DI 1.7). On central review, both of these tumors demonstrated the presence of subtle patterns of EST that were unrecognized by the submitting institution and were much too small for separate analysis. Analysis of the 3 patients containing sufficient IT and EST to be separately analyzed all showed a diploid IT component and an aneuploid EST component.Conclusions.Analysis of ploidy data suggests that polyploidization is a consistent finding in malignant ovarian GCT arising in normal patients, similar to the data for adult testicular GCT. Immature teratomas in this pediatric population, however, are most commonly diploid, regardless of grade. The development of EST within an IT is associated with the development of an aneuploid clone. Therefore, the finding of such a clone in an IT may be of diagnostic utility, as EST may be difficult to recognize. Last, the development of a malignant GCT in patients with gonadal dysgenesis may be pathogenetically different from those arising in normal patients, in that polyploidization is not required.