Adjunctive Surgery Is Often Without Oncological Benefit at Time of Postchemotherapy Retroperitoneal Lymph Node Dissection.

PURPOSE: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumors (GCTs) aims to resect all remaining metastatic tissue. Resection of adjacent visceral or vascular organs is commonly performed for complete resection. Resection of organs harboring only necrosis results in relevant overtreatment. The study aimed to describe the frequency of metastatic involvement of resected organs with teratoma or viable cancer and to analyze perioperative complications and relapse-free survival. MATERIALS AND METHODS: In a 2-center study, we reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 and identified 242 (20%) cases of adjunctive surgery during PC-RPLND. We analyzed the removed adjacent structures and the pathohistological presence of GCT elements in the resected organs: viable GCT, teratoma, or necrosis/fibrosis. Surgery-associated complications were reported according to the Clavien-Dindo classification. RESULTS: Viable GCT, teratoma, and necrosis were present in 54 (22%), 94 (39%), and 94 (39%), respectively, of all patients with adjunctive resection of adjacent organs. Vascular resections or reconstructions (n = 112; viable: 23%, teratoma: 41%, necrosis: 36%) were performed most frequently, followed by nephrectomies (n = 77; viable: 29%, teratoma: 39%, necrosis: 33%). Perioperative complications of grade ≥ IIIa occurred in 6.6% of all patients, with no difference between the viable GCT and teratoma/necrosis groups (P = .1). A total of 76 patients have been followed without a relapse for at least 36 months. Median follow-up of the whole cohort was 22 months (quartile 7 and 48). Patients with viable GCT/teratoma in the resected specimens had a significantly increased risk of recurrence by 5 years compared to patients with only necrosis (19% vs 59% vs 81%, P < .001). CONCLUSIONS: This study shows that 33% to 40% of all resections of adjacent organs do not harbor teratoma or viable GCT. This highlights the need for better patient selection for these complex patients.

Survival Benefit from Multimodal Treatment for Patients with Atypical Teratoid Rhabdoid Tumor in a Surveillance, Epidemiology, and End Results Database Analysis.

INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is among the most aggressive central nervous system malignancies. Although rare, this tumor typically afflicts young children and results in mortality within months. Here, we aim to determine key clinical features and treatment options that impact the survival of patients with ATRT. METHODS: From the year 2000 to 2019, 363 patients with ATRT were identified from the Surveillance, Epidemiology, and End Results database. Univariate analysis was used to identify variables that had a significant impact on the primary endpoint of overall survival (OS). Multivariable analysis was then used to identify independent predictors of survival. RESULTS: The median OS of the entire cohort was 13 months. Univariate analysis identified ages between 1 and 3 years, ages between 4 and 17 years, years of diagnosis between 2010 and 2019, and the receipt of treatment to have a significant impact on survival. In multivariable analysis, ages between 1 and 3 years and receipt of treatment were the only significant independent predictors of survival. The median OS was significantly greater in patients who received surgical treatment, chemotherapy, or radiation when compared to those who did not receive any treatment. In general, the receipt of any combination of therapies improved the median OS significantly. The receipt of triple therapy had the greatest impact on survival. DISCUSSION: This study highlights the survival benefit of a multimodal approach in the treatment of ATRT. The use of triple therapy, including surgery, radiation, and chemotherapy, was found to have the greatest survival benefit for patients. Overall, these findings may guide future care for patients with ATRT.

Growing teratoma syndrome in children and adolescents: Prevalence and surgical outcome.

INTRODUCTION: Patients affected by metastatic germ cell tumors may occasionally experience enlargement of masses with concurrent normalization of tumor markers during or after chemotherapy. This phenomenon is described as growing teratoma syndrome (GTS). The aim of the pre sent study is to assess the prevalence of GTS in the pediatric population and its implications in terms of surgical outcome. PATIENTS AND METHODS: The clinical notes of patients diagnosed with stage III and IV malignant germ cell tumors from January 2010 until December 2020 at our Institution were retrospectively reviewed. The prevalence of GTS, treatment strategies, survival, and outcome were analyzed. RESULTS: Thirty-three patients with high-stage malignant germ cell tumors were diagnosed in our institution in the analyzed period. Nine patients (28%) had radiologic evidence of enlargement of persistent masses with normal markers after chemotherapy; these patients were classified as GTS patients. All nine patients underwent resection of metastatic lymph nodes, and six had surgery on visceral metastases. In six patients, radical excision of all metastatic sites was achieved; five patients are alive and in complete remission, while one died because of peri-operative complications. Out of the three patients who could not achieve radical excision of the metastases, two died of progressive disease, and one is alive with progressive disease. CONCLUSIONS: Patients affected by GTS have a risk of progression of chemotherapy-resistant disease and death. Radical surgical excision is essential to achieve disease control and long-term survival.

New Findings in the Multidisciplinary Management of a Fetal Intrapericardial Teratoma: A Case Report.

INTRODUCTION: Fetal intrapericardial teratoma is a rare tumor that can be diagnosed by antenatal ultrasonography early in pregnancy. CASE PRESENTATION: A fetal intrapericardial teratoma was detected on routine ultrasonography in the second trimester of pregnancy. At 31 weeks gestation, a marked increase in tumor size, fetal ascites, and pericardial effusion were observed, indicating that preterm delivery would be inevitable. Corticosteroid prophylaxis (24 mg of betamethasone in two doses of 12 mg 24 h apart) initiated for prophylaxis of respiratory distress syndrome led to a reduction in fetal ascites and pericardial effusion. Betamethasone therapy (4 mg/per day) was continued with the aim to postpone the expected date of delivery. Gestation was extended for more than 2 weeks. At 33 weeks and 5 days gestation, the neonate was delivered by elective cesarean section with ex utero intrapartum treatment and immediately submitted to fetal cardiac surgery. The infant was discharged from the hospital in good health about 4 months later. CONCLUSION: The present report draws attention to improvement in fetal status and extension of gestation achieved with maternal low-dose corticosteroid therapy on antenatal ultrasound finding of fetal ascites and pericardial effusion due to intrapericardial teratoma.

Differentially expressed messenger RNA/proteins can distinguish teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection tissue.

BACKGROUND: Before postchemotherapy retroperitoneal lymph node dissection (pcRPLND), in patients with metastasized germ cell tumors (GCTs), those harboring necrosis (NEC) cannot be distinguished from those who have teratoma (TER), resulting in relevant overtreatment, whereas microRNA-371a-3p may be predictive for viable GCT. The purpose of this study was to explore messenger RNA (mRNA) and proteins to distinguish TER from NEC in pcRPLND tissue. METHODS: The discovery cohort consisted in total of 48 patients, including 16 each with TER, viable GCT, and NEC. Representative areas were microdissected. A NanoString panel and proteomics were used to analyze 770 genes and >5000 proteins. The most significantly and differentially expressed combination of both parameters, mRNA and its associated protein, between TER and NEC was validated using immunohistochemistry (IHC) in an independent validation cohort comprising 66 patients who were not part of the discovery cohort. RESULTS: The authors observed that anterior gradient protein 2 homolog (AGR2) and keratin, type I cytoskeletal 19 (KRT19) were significantly differentially expressed in TER versus NEC in mRNA and protein analyses (proteomics). The technical validation using IHC was successful in the same patients. These proteins were further validated by IHC in the independent patient cohort and exhibited significantly higher levels in TER versus NEC (p < .0001; area under the curve, 1.0; sensitivity and specificity, 100% each). CONCLUSIONS: The current study demonstrated that KRT19 and AGR2 mRNA and protein are overexpressed in TER versus NEC in pcRPLND tissue and might serve as a future diagnostic target to detect TER, for instance, by functional imaging, to avoid overtreatment. PLAIN LANGUAGE SUMMARY: The proteins and the corresponding genes called AGR2 and KRT19 can differentiate between teratoma and necrosis in remaining tumor masses after chemotherapy in patients who have metastasized testicular cancer. This may be a way to improve presurgical diagnostics and to reduce the current overtreatment of patients with necrosis only, who could be treated sufficiently by surveillance.

Radiotherapy for Atypical Teratoid/Rhabdoid Tumor (ATRT) on the Pediatric Proton/Photon Consortium Registry (PPCR).

PURPOSE: Atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system (CNS) are rare tumors with a poor prognosis and variable use of either focal or craniospinal (CSI) radiotherapy (RT). Outcomes on the prospective Pediatric Proton/Photon Consortium Registry (PPCR) were evaluated according to RT delivered. METHODS: Pediatric patients receiving RT were prospectively enrolled on PPCR to collect initial patient, disease, and treatment factors as well as provide follow-up for patient outcomes. All ATRT patients with evaluable data were included. Kaplan-Meier analyses with log-rank p-values and cox proportional hazards regression were performed. RESULTS: The PPCR ATRT cohort includes 68 evaluable ATRT patients (median age 2.6 years, range 0.71-15.40) from 2012 to 2021. Median follow-up was 40.8 months (range 3.4-107.7). Treatment included surgery (65% initial gross total resection or GTR), chemotherapy (60% with myeloablative therapy including stem cell rescue) and RT. For patients with M0 stage (n = 60), 50 (83%) had focal RT and 10 (17%) had CSI. Among patients with M + stage (n = 8), 3 had focal RT and 5 had CSI. Four-year overall survival (OS, n = 68) was 56% with no differences observed between M0 and M + stage patients (p = 0.848). Local Control (LC) at 4 years did not show a difference for lower primary dose (50-53.9 Gy) compared to ≥ 54 Gy (73.3% vs 74.7%, p = 0.83). For patients with M0 disease, four-year OS for focal RT was 54.6% and for CSI was 60% (Hazard Ratio 1.04, p = 0.95. Four-year event free survival (EFS) among M0 patients for focal RT was 45.6% and for CSI was 60% (Hazard Ratio 0.71, p = 0.519). For all patients, the 4-year OS comparing focal RT with CSI was 54.4% vs 60% respectively (p = 0.944), and the 4-year EFS for focal RT or CSI was 42.8% vs 51.4% respectively (p = 0.610). CONCLUSION: The PPCR ATRT cohort found no differences in outcomes according to receipt of either higher primary dose or larger RT field (CSI). However, most patients were M0 and received focal RT. A lower primary dose (50.4 Gy), regardless of patient age, is appealing for further study as part of multi-modality therapy.

Adjuvant chemotherapy does not improve outcome in children with ovarian immature teratoma: A comparative analysis of clinical trial data from the Malignant Germ Cell International Consortium.

BACKGROUND/OBJECTIVES: Surgery is the mainstay of therapy for children with ovarian immature teratoma (IT), whereas adults receive adjuvant chemotherapy, except those with stage-I, grade-1 disease. In Brazil, children with metastatic ovarian IT received postoperative chemotherapy. This practice variation allowed evaluation of the value of chemotherapy, by comparison of Brazilian patients with those in the United States and United Kingdom. DESIGN/METHODS: From the Malignant Germ Cell International Consortium data commons, data on ovarian IT patients from two recently added Brazilian trials (TCG-99/TCG-2008) were compared with data from US/UK (INT-0106/GC-2) trials. Primary outcome measure was event-free (EFS) and overall survival (OS). RESULTS: Forty-two Brazilian patients were included (stage I: 27, stage II: 4, stage III: 8, stage IV: 3). Twenty-nine patients had surgery alone, whereas 13 patients received postoperative chemotherapy. The EFS and OS for entire cohort was 0.80 (95% CI: 0.64-0.89) and 0.97 (0.84-0.99). There was no difference in relapse risk based on stage, grade, or receipt of chemotherapy. Comparing the Brazilian cohort with 98 patients in US/UK cohort (stage I: 59, stage II: 12, stage III: 27), there was no difference in EFS and OS across all stages, despite 87% of stage II-IV Brazilian patients receiving postoperative chemotherapy compared with only 13% of US/UK patients. The EFS and OS for Brazilian compared with US/UK cohort was stage I: 88% versus 98% (p = .05), stage II-IV EFS: 67% versus 79% (p = .32), stage II-IV OS: 93% versus 97% (p = .44); amongst grade-3 patients, there was no difference in EFS or OS. CONCLUSION: Addition of postoperative chemotherapy did not improve outcome in children with ovarian IT, even at higher grade or stage, compared with surgery alone.

[Prognostic comparison of active surveillance and adjuvant chemotherapy in the treatment of patients with stage â ovarian immature teratoma after fertility-sparing surgery].

Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group (n=40), the others were included in the adjuvant chemotherapy group (n=63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P>0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P<0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P=0.325, OS: P=0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.

Outcomes and prognostic variables of extracranial germ cell tumors in children and adolescents treated over a decade: A developing world perspective.

BACKGROUND: The purpose of this single-center study was to analyze the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multimodality regimen. METHODS: Retrospective study of children (<18 years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January 2009 to December 2018) treated on a uniform institution-based protocol consisting of both cisplatin- and carboplatin-based regimens. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk [LR]); stage IV ovarian, stage III-IV extragonadal GCTs received six cycles of chemotherapy (high risk [HR]), and the remaining received four cycles of chemotherapy (intermediate risk [IR]). RESULTS: A total of 297 children were treated with a female:male ratio of 1.72:1 and median age of 4 years. Forty-three children had pure teratomas. Gonadal GCTs (N = 180) were more common than extragonadal GCTs (N = 117) with ovary as primary site in 128 children (43%) and sacrococcygeal site being the commonest extragonadal location (N = 41; 14%). LR, IR, and HR disease were noted in 60 (20.2%), 125 (42%), and 112 (37.8%) patients, respectively. Three-fourths of ovarian tumors and half of testicular tumors operated prior to presentation needed upstaging. Forty-one patients relapsed and 43 children expired (disease-related: 33; toxic deaths: 9; unknown: 1). The 5-year event-free survival (EFS)/overall survival (OS) of malignant GCT (n = 254) was 72.50%/82.70%, respectively, with gonadal site (p = .001), LR and IR (p = .001) and nonmetastatic disease (p = .001) being favorable prognostic variables. CONCLUSIONS: The LR and IR GCTs in our cohort had an excellent outcome. A significant proportion of IR gonadal GCTs can be spared of systemic chemotherapy by adhering to strict surgical guidelines. In HR GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity, more so in a resource-limited setting.

Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report.

BACKGROUND: Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered. CASE PRESENTATION: Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). CONCLUSIONS: Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.

Clonal evidence for the development of neuroblastoma with extensive copy-neutral loss of heterozygosity arising in a mature teratoma.

Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole-exome sequencing identified extensive copy-neutral loss of heterozygosity (LOH) in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma. In addition, several truncating germline heterozygous variants in tumor suppressor genes, including RBL2 and FBXW12, became homozygous as a result of LOH. Collectively, we speculate that extensive LOH in teratoma cells may force heterozygous germline variants to become homozygous, which, in turn, may contribute to the development of neuroblastoma with the acquisition of additional chromosomal changes.

Outcomes of post-chemotherapy robot-assisted retroperitoneal lymph node dissection in testicular cancer: multi-institutional study.

OBJECTIVE: To evaluate the perioperative and oncological outcomes after post-chemotherapy robot-assisted retroperitoneal lymph node dissection (PC-RARPLND). MATERIALS AND METHODS: We retrospectively reported the perioperative and oncological outcomes of all the patients with testicular cancer who underwent PC-RARPLND at three tertiary teaching centers. Descriptive statistical measures were used to report demographic, clinical, intraoperative, postoperative and oncological outcomes. RESULTS: There were 43 consecutive patients who underwent PC-RARPLND at the participating institutions. Mean patient age was 29.2 years (± 8.2), BMI was 26.6 kg/m2 (± 6.2). The mean size of retroperitoneal mass was 4.1 cm (± 3.5). Full bilateral template dissection was performed in 38 (88.3%) patients. Nerve sparing was attempted in 19 (44.1%) patients. Mean operative time was 374 min (± 132) and estimated blood loss was 292 ml (± 445.6). The mean postoperative LOS was 2.8 days (± 5.9). There was a total of 12 complications in 10 patients (Clavien grade I = 5, II = 3, III = 3 and IV = 1). Postoperative pathology demonstrated 24 patients (55%) with necrosis/fibrosis, 16 (37%) with teratoma and 3 (7%) with viable tumor. Mean lymph node (LN) yield was 26.5 LNs (SD ± 16.1). Patients were followed for a mean of 30.7 months (± 24.7). No deaths were documented during follow-up and 2 pulmonary recurrences were identified. Antegrade ejaculation was preserved in 70.6% of patient who underwent nerve sparing. Limitations included retrospective nature and limited follow up. CONCLUSION: PC-RAPLND is safe and technically reproducible. It provides improved morbidity and less convalescence.

Syringic acid regulates suppression of the STAT3/JNK/AKT pathway via inhibition of human ovarian teratoma cancer cell (PA-1) growth-in vitro study.

Among the various gynaecological cancers, ovarian cancer (OC) is the third most severe cancer worldwide affecting women. Syringic acid (SRA) exhibits several hypoglycaemia, antioxidant, and anti-inflammatory properties. The study aimed to examine the proapoptotic activities of SRA on OC in PA-1 cells. SRA has been shown to decrease cell viability, increase the rate of cell apoptosis, and cause mitochondrial membrane potential to dissipate and induce over-accumulation of intracellular reactive oxygen species in PA-1 cells after 24 h of exposure. We examined the anticancer efficacy of SRA with its responsible molecular mechanism in the PA-1 cell lines of human OC. In a dose-dependent manner, SRA substantially suppressed cell proliferation and migration. SRA exhibited significant downregulation of cyclins including CDK2, CDK4, and Cyclin D1 responsible for cell-cycle regulation. The apoptosis-mediated anticancer activity was mainly mediated through caspase-3, caspase-8, caspase-9 and Bax upregulation, and Bcl-2 downregulation. We report that SRA significantly inhibits the expression of signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), P65, and protein kinase B (AKT) pathways. These findings depict the effective inhibition of STAT3, p38, and AKT expression by SRA, making it a potential therapeutic candidate for human OC.

Advanced germ cell tumor patients undergoing post-chemotherapy retroperitoneal lymph node dissection: Impact of residual teratoma on prognosis.

OBJECTIVES: To evaluate the histologic findings and clinical outcomes of post-chemotherapy retroperitoneal lymph node dissection for advanced germ cell tumor. METHODS: We analyzed the medical records of 66 patients who underwent post-chemotherapy retroperitoneal lymph node dissection between 2005 and 2019 at Tsukuba University Hospital. RESULTS: The proportions of necrosis, teratoma, and viable germ cell tumor in the specimens were 62.1%, 36.4%, and 1.5%, respectively. The 5-year progression-free and overall survival rates were 82.3% and 91.3%, respectively. The 5-year overall survival rate of patients with residual teratoma was significantly worse than that of patients with necrosis only (74.1% vs 100%). Overall, three patients died: one from cancer and two from teratoma with somatic-type malignancy. Of these, two patients relapsed after incomplete resection of residual teratoma. When limited to patients with completely resected teratoma, the 5-year overall survival rate was 91.7%, which did not differ from that for patients with necrosis only. Multivariate analysis showed that presence of teratoma in the primary site and decrease in retroperitoneal lymph node mass to less than 50% of the initial tumor size were independent factors for residual teratoma. However, the absence of these factors could not reliably predict necrosis only in retroperitoneal lymph node dissection specimens. CONCLUSIONS: In our series, 98% of post-chemotherapy retroperitoneal lymph node dissection pathology was either necrosis or teratoma, with viable germ cell tumor only found in 2% of patients. Residual teratoma was associated with poorer prognosis, especially in cases of incomplete resection.

[A Case of Stage â £ Cholangiocarcinoma with an Improved Quality of Life after Resection of a Symptomatic Giant Ovarian Teratoma].

An 82‒year‒old female presented to our hospital with abdominal fullness and loss of appetite. Abdominal computed tomography revealed a cholangiocarcinoma(Stage Ⅳ)with liver metastases and multiple lymph node metastases. In addition, we found a left ovarian teratoma(approximately 33 cm in diameter)occupying most of the abdominal cavity. She did not want an aggressive treatment for cholangiocarcinoma, but hoped to receive the best supportive care. She was treated with a fentanyl patch, although there was no symptomatic improvement. We explained that resection of the giant ovarian tumor may improve the symptoms. As a result, she accepted the surgery. The laparotomy was performed, and a left ovarian tumor(approximately 10,600 g in weight)was resected. Operation time was 2 hours and 35 minutes, and the amount of blood loss was small. No postoperative complications were observed. She started oral intake at POD 2. The abdominal symptom was relieved by the surgery, and she was discharged to her own home on POD 12. She was readmitted on POD 46 for general malaise, and died of advanced cholangiocarcinoma on POD 66. It was suggested that the QOL may be improved by resecting symptomatic benign tumors even in terminal cancer patients.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

Coexistence of the BRCA1 and KRAS mutations in a patient with salivary gland carcinoma arising in mediastinal mature teratoma.

Teratoma with malignant transformation is a rare type of malignant teratoma. In the present case, we describe a patient with salivary gland carcinoma (SGC) generating in mediastinal mature teratoma. Next-generation sequencing showed BRCA1 and KRAS somatic mutations, which might be associated with malignant transformation of the mediastinal mature teratomas. To our knowledge, the present case is the first report of coexistence of BRCA1 and KRAS mutations in mature cystic teratoma with malignant transformation to SGC. And the tumor showed a good response to chemotherapy with cisplatin and paclitaxel according to the transformed histology.

Atypical teratoid rhabdoid tumor: molecular insights and translation to novel therapeutics.

INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is a rare, often lethal brain tumor of childhood characterized by a complex epigenetic landscape amongst a simple genetic background. Recent molecular studies have defined key biologic events that contribute to tumorigenesis and molecular subtypes of ATRT. METHODS: Seminal studies on ATRT are reviewed with an emphasis on molecular pathogenesis and its relevance to novel therapeutics. RESULTS: In this review, we summarize the key clinicopathologic and molecular features of ATRT, completed and ongoing clinical trials and outline the translational potential of novel insights into the molecular pathogenesis of this tumor. CONCLUSIONS: SMARCB1 loss is the key genetic event in ATRT pathogenesis that leads to widespread epigenetic dysregulation and loss of lineage-specific enhancers. Current work is defining subtype-specific treatments that target underlying molecular derangements that drive tumorigenesis.

Effect of early radiotherapy initiation and high-dose chemotherapy on the prognosis of pediatric atypical teratoid rhabdoid tumors in different age groups.

PURPOSE: The optimal treatment strategy for pediatric atypical teratoid rhabdoid tumor (ATRT) is inconclusive. This study evaluated the prognostic value of early radiotherapy (RT) and high-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) in pediatric ATRT. METHODS: This pooled analysis included ATRT patients treated at our institution and from other studies who were identified by a search of the PubMed electronic database. The effect of patient demographics and treatment profiles on progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression. RESULTS: Overall, 34 patients from our institution and 436 patients from 35 published studies were included. In multivariable analysis, patients with gross total resection (GTR), early RT (time to RT interval < 2 months), and HDC/ASCR had both better PFS [hazard ratio (HR) 0.46, p[Formula: see text] 0.001; HR 0.64, p = 0.011; and HR 0.51, p = 0.005, respectively] and OS (HR 0.55, p = 0.002; HR 0.48, p = 0.004; and HR 0.42, p < 0.001, respectively). For patients aged < 3 years, both RT and HDC/ASCR were significant favorable factors for PFS (HR 0.32 and 0.46, respectively) and OS (HR 0.40 and 0.36, respectively), while early RT was not prognostic. For patients aged ≥ 3 years, early RT was significantly associated with better PFS (HR 0.51) and HDC/ASCR did not affect PFS, and neither was related to OS. CONCLUSION: Both early RT initiation and HDC/ASCR were important components in the treatment of pediatric ATRT. However, the optimal treatment strategies might differ by age.

Case report: meningitis as a presenting feature of anti-NMDA receptor encephalitis.

BACKGROUND: Meningitis is a very rare atypical presenting feature of anti-NMDA receptor encephalitis. In our case report, we describe an unusual clinical presentation of anti-NMDA receptor encephalitis with a biphasic pattern of meningitis followed by encephalitis and discuss potential mechanisms underlying this presentation. We aim to widen the differential diagnosis to be considered in a patient presenting with clinical meningitis and pyrexia. CASE PRESENTATION: This is a case of a 33-year old Caucasian woman who initially presented with a lymphocytic meningitis attributed to a viral infection. She subsequently developed fluctuating consciousness, agitation, visual hallucinations, dyskinetic movements, a generalized tonic-clonic seizure, and autonomic instability. Investigations revealed a diagnosis of anti-NMDA receptor encephalitis secondary to a previously unidentified ovarian teratoma. She made an excellent recovery with immunotherapy and removal of the teratoma. CONCLUSION: Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative pathogen and there is rapid development of an encephalitic phenotype.