Pure Mature Teratoma Research Articles

Treatment Course and Outcomes of Intracranial Teratomas in Pediatric Patients: A Retrospective 15-Year Case Series Study

Introduction: There is no standard treatment paradigm for intracranial teratomas, a rare subset of primary intracranial non-germinomatous germ cell tumors (NGGCT), which comprise less than 1% of pediatric brain tumors. This case series retrospectively analyzes treatment and outcomes of pediatric intracranial teratomas from a single institution. Methods: Authors reviewed a comprehensive pathology database at Stanford’s Lucile Packard Children’s Hospital for intracranial teratomas in pediatric patients treated from 2006 to 2021; their demographics, treatment, and clinical course were analyzed. Results: Among 14 patients, median follow-up time was 4.6 years and mean age at diagnosis was 10.5 years. Ten had elevated tumor markers and underwent chemotherapy as initial treatment for NGGCT. Ultimately, these patients all required surgery for progressive or residual disease. Two patients did not undergo radiation. After biopsy or resection, 8 patients had pure mature teratoma, five had mixed germ cell tumor with teratoma component, and one had immature teratoma. The patient with immature teratoma died during chemotherapy from septic shock. No patients experienced recurrence. Common sequelae were endocrine (42.8%) and eye movement (50.0%) abnormalities. Discussion/Conclusion: We highlight the variable treatment course and outcome for pediatric patients with intracranial teratomas. Elevated tumor markers at presentation, along with imaging findings, favor chemotherapy initiation for presumed NGGCT. Resection of residual tumor is recommended even if tumor markers return to normal. Prognosis remains excellent; no patients had recurrence with a median follow-up of 4.6 years.

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.

Congenital Benign Metastasizing Teratoma? A Case Report and Literature Review

Abstract A case is presented of a patient with completely resected congenital immature gastric teratoma containing yolk sac tumor, with locoregional recurrence and peritoneal seeding 25 months later as pure mature teratoma. To the knowledge of the author, this is the first case of its type to progress purely as mature teratoma.

Outcome of men with relapses after adjuvant BEP for clinical stage I nonseminoma.

510 Background: Clin. stage I (CSI) non-seminoma (NS) is disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant (adjuv) chemotherapy with BEP after which relapses are rare. Little is known about the outcome of patients (pts) relapsing after such treatment. Methods: Data from 51 pts with CSI NS and relapse after adjuv BEP from 18 centers/11 countries was collected and retrospectively analyzed. Primary endpoints were OS and PFS calculated from start of treatment of relapse. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results: 23 pts received one cycle adjuv BEP and 28 pts two. Median time to relapse was 13 months, with the earliest relapse two months after start of adjuv BEP and the latest relapse recorded after 26 years. According to IGCCCG, 84% of pts classified as good prognosis at relapse. With a median follow up of 50 months 5y PFS was 64% (95% CI 52-80%) and 5y OS 79% (95% CI 68-92%). Treatment upon relapse was diverse, the majority of pts received combination- chemotherapy and surgery. 10 pts (20%) had pure mature teratoma at relapse treated with surgery alone. None of these pts experienced a second relapse. If teratoma relapses were excluded, 5y PFS dropped to 58% (44-77%) and 5y OS to 76% (63-92%). Relapses later than three years after adjuv therapy occured in 15/51 pts. (29%) and were associated with a statistically significant higher risk of death from germ-cell cancer (p=0.02). 15/51 pts (29%) experienced a subsequent relapse. Excluding pts with teratoma only, subsequent relapses occured in 15 of the remaining 41 pts (37%). At last follow-up, 41/51 (80%) pts were alive and disease-free, 8/51 (16%) had died from progressive disease and one pt each had died from therapy-related or other causes. Conclusions: Outcome of pts with relapse after adjuv BEP seems to be better compared to pts with relapse after metastatic disease, but worse compared to de novo metastatic pts. There is a substantial rate of late and subsequent relapses. Pts and care-takers need to be informed about this and therapy intensification at first relapse might be considered. However, considering the low rate of relapses, OS in general for CSI NS pts receiving adjuv BEP is excellent.

Mature and Immature Teratoma: A Review of Pathological Characteristics and Treatment Options

Testicular teratoma is a sub-type of Non-Seminomatous Germ Cell Tumour (NSGCT) and often occurs in two distinct age groups. Adult testicular teratomas are often mixed and are malignant. Teratoma can be divided histologically into mature and immature. Pure mature teratoma of the testis is rare. Intratubular Germ Cell Neoplasia (ITGCN) is a common feature associated with teratoma. Teratoma is frequently chemoresistant and clinical management of these tumours includes radical inguinal orchidectomy followed by Retroperitoneal Lymph Node (RPLND) dissection if indicated. Long-term oncological outcomes for mature and immature testicular teratoma are equivocal.

Kommentar zur retroperitonealen Lymphadenektomie – laparoskopisch vs. robotisch

Retroperitoneal lymph node dissection (RPLND) in high risk clinical stage I nonseminomatous germ cell tumors (NSGCT) plays a limited role in modern uro-oncology due to the superior therapeutic efficacy of even one cycle of PEB (cysplatin, etoposide, bleomycin) chemotherapy. There might be an indication for the rare case of pure mature teratoma with unfavorable prognostic risk factors. If RPLND is performed for clinical stage I NSGCT it always has to be performed in a nerve-sparing technique and within the well-defined boundaries of an anatomically adequate template in order to avoid unnecessary adjuvant systemic chemotherapy. In this aspect, laparoscopic RPLND is inferior to open RPLND as basically all patients with lymph node positive disease receive adjuvant chemotherapy. The evidence for robotic-assisted RPLND is too weak to draw any clinically useful conclusions. Currently, it is an experimental procedure.Postchemotherapy RPLND (PC-RPLND) remains a surgery for tertiary referral centres due to the complexity of the surgical intervention and the high probability of adjunctive visceral and/or vascular surgery. In accordance with international guidelines it remains a domain for an open surgical approach. Laparoscopic PC-RPLND is reserved for small residual masses with the option of a unilateral modified template resection in very experienced laparoscopic centres. With regard to robotic-assisted PC-RPLND there is no evidence in the literature with regard to morbidity and complications, short-term and long-term oncological results being in favor of this experimental approach.

Histopathological and molecular features of late relapses in non‐seminomas

• To describe the histopathological types of late relapses of germ cell tumours and to search for molecular markers associated with chemotherapy resistance. • Samples from 14 patients with late relapse from a non-seminoma were analysed. • Archival tumour tissue was gathered at intial diagnosis (n= 9) and at relapse (n= 9), mostly after previous treatment with chemotherapy. • In addition to routine histopathology, tumours were analysed for microsatellite instability and screened for mutations in the KRAS and BRAF genes. • Relapse occurred after 76.5 months (median, range: 24-209 months). • The histology in relapse was pure yolk sac tumour in four of the nine patients analysed. • Three had a non-germ cell malignancy, one was a mixed non-seminoma and one was a pure mature teratoma. • One sample with non-germ cell malignancy originated from a yolk sac tumour without any evidence of teratoma. • In four of 12 evaluable patients, high-level microsatellite instability was observed. • All patients were KRAS wild-type but four showed a BRAF mutation at V600E. • Many late relapses of germ cell tumours show pure yolk sac histology. • Non-germ cell malignancies do not necessarily develop from teratoma but can also arise from yolk sac histology. • The biology underlying chemotherapy resistance in late relapse could be related to a high incidence of microsatellite instability and BRAF mutation V600E, which were found in half of the patients.

Intracranial teratomas in children: the role and timing of surgical removal

In this study, the authors report their experience with the surgical treatment of intracranial teratomas with an emphasis on the indications for delayed resection after oncological treatment. The authors retrospectively reviewed the cases of 14 children with intracranial teratomas. The mean age at diagnosis was 10.5 years (range 2 days-18 years), and 11 patients were male. The final histological analysis revealed pure mature teratoma in 5 cases, mixed teratoma with germinoma in 3 cases, and nongerminomatous malignant germ cell tumor in 6 cases. Thirteen patients underwent tumor resection, and these patients were divided into 2 subgroups according to the timing of surgery. In Group A, 10 patients underwent resection as the primary treatment because no tumor markers were detected in 4 patients, a teratomatous component was revealed on biopsy sampling in 3 patients, and a large tumor volume in 3 patients. In Group B, 3 patients underwent removal of residual pure mature teratoma after oncological treatment. Seven of the 8 patients (87.5%) with pure mature teratomas or with mixed teratoma and germinoma are currently alive (mean follow-up of 9 years); the eighth patient died of postoperative meningitis. Two of the 6 patients (33%) with mixed nongerminomatous malignant germ cell tumors died of tumor progression regardless of the timing of surgery. The results of this study support the belief that microsurgical removal is the only effective treatment for intracranial teratomas. Surgery may be performed as the primary therapy when there is evidence of a noninvasive teratoma, and as a secondary therapy if there is only a partial response to neoadjuvant therapy or if progression is observed in mixed malignant germ cell tumors.

Mature and Immature Extracranial Teratomas in Children: The UK Children's Cancer Study Group Experience

The purpose of this article is to describe the features, treatment, and risk factors for relapse of children with mature teratoma (MT) and immature teratoma (IT) to assist future treatment plans. Patients were younger than 16 years of age and referred to the UK Children's Cancer Study Group centers with biopsy-proven extracranial MT and IT and no prior chemotherapy. Complete excision, with the coccyx in sacrococcygeal patients, and follow-up, including serum alpha-fetoprotein monitoring for early detection of malignant yolk sac tumor (YST) recurrence, were recommended. Carboplatin, etoposide, and bleomycin (JEB) were given for YST relapse, whereas relapsed MT and IT were treated at clinicians' discretion, usually surgically. Pathology was reviewed and treatments, outcome, and prognostic features assessed. There were 351 patients, 227 with MT, 124 with IT. Tumor sites were: testis (n = 53), ovary (n = 130), sacrococcygeal region (n = 98), thorax (n = 23), and other (n = 47). Surgical resection was incomplete in 26% of MT and 40% of IT patients; 5-year event-free survival was 92.2% and 85.9%, respectively, and 5-year overall survival was 99% and 95.1%. Poorer outcome occurred with incomplete resection, tumor rupture, nongonadal site (particularly sacrococcygeal), young age, higher stage and grade, and gliomatosis peritonei, but not with cyst fluid aspiration/spillage, tumor enucleation, nodal gliomatosis, or microfoci of YST in the tumor (Heifetz lesions). JEB was effective for YST recurrence, but not for MT or IT. Treatment remains primarily surgical, with JEB chemotherapy for YST relapse. No definite response followed JEB for pure MT and IT. Adjuvant chemotherapy after surgery for sacrococcygeal patients is not advocated.

Interphase Fluorescence In situ Hybridization Analysis of Chromosome 12p Abnormalities Is Useful for Distinguishing Epidermoid Cysts of the Testis from Pure Mature Teratoma

The distinction of epidermoid cyst of the testis from teratoma is of critical importance because the former is benign and the latter is a malignant tumor that may have associated metastasis of either teratomatous or non-teratomatous germ cell tumor types. Chromosome 12p abnormalities are seen in the vast majority of testicular germ cell tumors of adults and are present in all histologic subtypes. In this study, we investigated the clinical utility of interphase fluorescence in situ hybridization (FISH) analysis of chromosome 12p abnormalities for distinguishing epidermoid cysts of the testis from pure mature teratoma. Sixteen testicular epidermoid cysts and 17 testicular teratomas were investigated for isochromosome 12p [i(12p)] and 12p overrepresentation using interphase FISH analysis. Neither i(12p) nor 12p overrepresentation were observed in 16 epidermoid cyst cases, whereas i(12p) was detected in 76% of teratomas and 12p overrepresentation was identified in 29% of teratomas. Overall, 88% of testicular teratomas had chromosome 12p abnormalities. FISH identification of i(12p) and/or 12p overrepresentation in routinely processed surgical specimens is a useful ancillary diagnostic tool in distinguishing testicular epidermoid cysts from teratoma.

Organ-Sparing Surgery for Testicular Lesions

Introduction and objectives Intratesticular lesions represent a special medical problem whose diagnosis often requires an histological evaluation. Aim of this study was to critically review the evidences supporting the role of organ-sparing surgery for benign and malignant intra-parenchimal tumors of the testis. Methods Analysis of published full-length papers that were identified with Medline and Cancerlit from January 1995 to January 2006. A description of a personal approach for organ-sparing procedure has also been provided. Results Although most of the intra-parenchimal benign tumors often have specific ultrasound features, they cannot be safely differentiated from malignant lesion. Therefore, a histological evaluation is needed and an organ-sparing surgery might be performed. If a benign testicular tumor is confirmed, a retroperitoneal lymph node dissection (RPLD) is not needed, unless patients share bad prognostic parameters such as old age, high mitotic activity, high volume tumour and vascular invasion. In case of malignant lesion, an organ sparing approach should be performed with certain precautions in case of solitary testis, volume lesion <2 cm and normal pre-operative testosterone levels. Furthermore, a surgical experience is needed. In solitary testis and biopsy-documented testicular intraepithelial neoplasia (TIN) in the remaining testicular parenchima, adjuvant Radiotherapy (RT;18-20 Gy) is indicated. However, patients should be awared of the irreversible infertility associated with RT. Conclusions The organ-sparing approach is the standard surgical approach to confirm benign intratesticular lesions. In solitary testes, the approach can be recommended with precautions. Further studies are needed to evaluate the role of an organ-sparing approach for the treatment of certain subtypes of malignant disease (e.g. pure mature teratoma), in presence of contralateral normal testis.

Clinical stage I mature teratoma of the testis--retroperitoneal lymphadenectomy or surveillance?

Pure teratomas are considered to be less aggressive and less likely to metastasize than other nonseminomatous germ cell tumors. Therefore, patients with mature teratomas are considered to be candidates for surveillance protocols. We report on the clinical history and treatment of 44 patients with a primary pure testicular teratoma. In all, 35 patients (79.5%) presented with clinically low-stage disease [n = 26, clinical stage I (59.1%); n = 9, clinical stage IIA/B (20.4%)] and underwent radical orchiectomy followed by retroperitoneal lymphadenectomy (RPLND); nine patients (20.5%) presented with clinically advanced disease (clinical stage IIC to stage IV). Archival tumor blocks were available for pathological reevaluation and serial sections were obtained in all cases. The frequency of lymph node metastases in patients with clinical stage I disease was 19.2%; in patients with clinical stage IIA/B the risk was 66%. Pathohistological diagnosis of mature teratoma was confirmed in all cases; however, 17/20 patients demonstrated scars or calcifications in the adjacent parenchyma, indicating a burned-out tumor and 3/20 demonstrated microfocal germ cell tumor elements. None of the clinical stage I patients relapsed during follow-up; relapse rate among patients with stage IIA/B disease was 33%. Our data demonstrate the malignant potential of pure testicular mature teratoma. Based on our results, metastases in testicular mature teratoma seem to result from metastazising non-germ-cell components undergoing early regression as demonstrated by the high frequency of burnedout tumors. We recommend serial sections of the orchiectomy specimen in all cases of pure mature teratoma for deciding on adequate management: RPLND in cases with associated scars, calcifications or microfocal malignant germ cell components, and surveillance in cases with pure mature teratomas.

The Role of Retroperitoneal Lymphadenectomy in Mature Teratoma of the Testis

Pure testicular teratoma is rare in adulthood with an incidence of 5%. Pure teratoma is considered less aggressive and less likely to metastasize than other nonseminomatous germ cell tumors. Therefore, patients with mature teratoma have been considered candidates for surveillance protocols. We report our experience with 44 cases of primary pure testicular teratoma. We retrospectively identified 44 patients (5.7%) with primary pure teratoma of the testis of the 772 treated for testicular germ cell tumors at our institutions. Archival tumor blocks were available for pathological reevaluation and serial sections were obtained in all cases. A total of 35 patients (79.5%) who presented with clinical low stage disease, including stage I in 26 (59.1%) and stage IIA/B in 9 (20.4%), underwent radical orchiectomy followed by retroperitoneal lymphadenectomy. Nine patients (20.5%) who presented with clinically advanced disease (stages IIC to IV) were treated with primary chemotherapy and secondary retroperitoneal lymphadenectomy of residual masses. The frequency of lymph node metastases was 19.2% in clinical stage I disease and 66% in stage IIA/B. Histopathological diagnosis of mature teratoma was confirmed in all cases. However, of 20 patients 16 (80%) had scars or calcifications in the adjacent parenchyma, indicating a burned out tumor, and 4 (20%) had microfocal embryonal carcinoma. None of the patients with clinical stage I disease had relapse during followup and the relapse rate in those with stage IIA/B disease was 33%. Median followup was 97 months (range 24 to 250). Overall 43% of patients with pure teratoma presented with metastatic disease. Our data demonstrate the malignant potential of pure testicular mature teratoma. Based on our results metastases in testicular mature teratoma seem to result from metastasizing nongerm cell components undergoing early regression, as demonstrated by the high frequency of burned out tumors. We recommend that serial sections be taken of the orchiectomy specimen in all cases of pure mature teratoma to determine adequate management: retroperitoneal lymphadenectomy in cases of associated scars, calcifications or microfocal malignant germ cell components and surveillance in cases of pure mature teratoma.

Late recurrence of testicular cancer.

The aim of this study is to draw attention to important points concerning the clinical management of late relapses in testicular cancer. From 1972 to 1982 The Norwegian Radium Hospital (NRH) has treated 1,008 patients with testicular cancer. Fifteen (1.5%) of these patients relapsed 36 months or more after their primary treatment. The patients' medical records were reviewed in this retrospective study, and all available histological sections were reevaluated. Six patients had pure seminoma initially and relapsed after an average of 54.5 months. Five of them had subjective symptoms due to recurrent tumor. Four patients relapsing in the supradiaphragmatic lymph nodes only are alive with no evidence of disease after an observation time of 17 to 30 months after treatment. Nine nonseminoma patients relapsed after an average of 85 months (36 to 194 months). Eight of these were aware of subjective signs or symptoms due to recurrent tumor leading to the diagnosis of the relapse. Four of these patients are alive with no evidence of disease after an observation time of 4 to 46 months after treatment. Two of these patients relapsed with pure mature teratoma. Late relapses do occur although they are rare events. Seminoma patients relapsing in the lymph nodes only have a good prognosis, and nonseminoma patients have a slightly poorer prognosis. Active follow-up for relapse detection is not justified. All testicular cancer patients should instead be informed of typical signs and symptoms that can be related to a relapse and encouraged to seek medical help for further investigation.