Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

Targeting CLDN6 in germ cell tumors by an antibody-drug-conjugate and studying therapy resistance of yolk-sac tumors to identify and screen specific therapeutic options.

BACKGROUND: Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients present with a remaining (resistant) yolk-sac tumor (YST(-R)) component, resulting in poor prognosis due to lack of novel treatment options besides chemotherapy and surgery. The aim of this study was to identify novel targets for the treatment of YST by deciphering the molecular mechanisms of therapy resistance. Additionally, we screened the cytotoxic efficacy of a novel antibody-drug-conjugate targeting CLDN6 (CLDN6-ADC), as well as pharmacological inhibitors to target specifically YST. METHODS: Protein and mRNA levels of putative targets were measured by flow cytometry, immunohistochemical stainings, mass spectrometry of formalin-fixed paraffin-embedded tissues, phospho-kinase arrays, or qRT-PCR. Cell viability, apoptosis and cell cycle assays of GCT and non-cancerous cells were performed using XTT cell viability assays or Annexin V / propidium iodide flow cytometry, respectively. Druggable genomic alterations of YST(-R) tissues were identified by the TrueSight Oncology 500 assay. RESULTS: We demonstrated that treatment with a CLDN6-ADC enhanced apoptosis induction specifically in CLDN6+ GCT cells in comparison with non-cancerous controls. In a cell line-dependent manner, either an accumulation in the G2 / M cell cycle phase or a mitotic catastrophe was observed. Based on mutational and proteome profiling, this study identified drugs targeting the FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling pathways as promising approaches to target YST. Further, we identified factors relevant for MAPK signaling, translational initiation and RNA binding, extracellular matrix-related processes as well as oxidative stress and immune response to be involved in therapy resistance. CONCLUSIONS: In summary, this study offers a novel CLDN6-ADC to target GCT. Additionally, this study presents novel pharmacological inhibitors blocking FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling for the treatment of (refractory) YST patients. Finally, this study shed light on the mechanisms of therapy resistance in YST.

Primary orbital yolk sac tumor presenting as fungating mass.

Primary yolk sac tumor of the orbit is a rare entity. Orbital involvement is usually seen in young children and proptosis is the commonest presentation. Aggressive orbital involvement and presentation as a fungating mass is rarely seen. We report a case of primary orbital yolk sac tumor with an aggressive presentation that responded well to systemic chemotherapy.

Buccal Mucosa Vaginoplasty Through an Anterior Sagittal Transrectal Approach (ASTRA) for Management of Yolk Sac Tumor in a 3-Year-Old Girl.

Vaginal yolk sac tumors are rare pediatric malignant tumors and the most common form of vaginal germ-cell tumors in children. They are almost exclusively found in females under 3 years of age. Treatment involves local excision either with or without chemotherapy. Herein, we describe a case of a 3-year-old girl with vaginal Yolk sac tumor, who underwent buccal mucosa vaginoplasty through an anterior sagittal transrectal approach , as an effective oncological procedure, with preservation of reproductive function.

Primary vaginal endodermal sinus tumor in infants and children: experience from a tertiary center.

BACKGROUND: The objective of the study was to analyze the clinical features, treatment, and outcomes of primary vaginal endodermal sinus tumor (EST) in infants and children treated in a tertiary center. METHODS: Clinical data of patients with pathologically confirmed primary vaginal EST in our hospital from January 1997 to December 2017 were retrospectively reviewed and analyzed. RESULTS: A total of 21 patients were included in this study. The median age at diagnosis was 11 months (range, 4-44 months). The most common manifestations were abnormal vaginal bleeding, and a polypoid mass protruding from the vagina. Chemotherapy based on PEB (cisplatin, etoposide, bleomycin) regimen was given, and serum alpha-fetoprotein (AFP) levels dropped to normal levels after 2 to 4 cycles of chemotherapy (median, 2 cycles). After 3 to 13 cycles of chemotherapy, with a median of 5 cycles, 20 patients achieved complete remission (95.2%). The median follow-up time was 80 months (range, 4-281months). At the time of the last follow-up, 19 cases were alive without disease, and the survival rate was 90.5%. CONCLUSION: Vaginal EST is a very rare malignant germ cell tumor and is sensitive to chemotherapy. Conservative surgery combined with PEB chemotherapy is an effective way of treatment. Serum AFP and imaging examinations can monitor the treatment response and recurrence.

Imaging Findings and Clinical Analysis of Primary Intracranial Pure Yolk Sac Tumors in Children and Adolescents: A Retrospective Study from China.

BACKGROUND AND PURPOSE: Primary intracranial pure yolk sac tumor is very rare. Our aim was to summarize the characteristics of primary intracranial pure yolk sac tumors from the clinical and imaging aspects in a retrospective study. MATERIALS AND METHODS: We studied 5 patients with primary intracranial pure yolk sac tumors in Guangzhou Women and Children's Medical Center from January 2015 to June 2021. A comprehensive literature search was performed on the electronic database of the China National Knowledge Infrastructure (1990 to June 2021). Clinical data based on age, sex, treatment, CT, and MR imaging findings were collected and analyzed. RESULTS: A total of 25 patients were included in the study, 21 boys and 4 girls. Twenty-one patients underwent plain MR imaging and an enhanced examination, 9 patients underwent DWI, and 12 patients underwent plain CT and/or an enhanced examination. The tumors were posterior fossa in 9 cases and supratentorial in 16 cases. All tumors showed marked enhancement after enhanced scanning by MR imaging or CT. The signal on DWI was similar to that of the cerebral cortex, and the ADC map was similar to or slightly higher than that of the cerebral cortex. Among the cases, 13 were followed up from 2 months to 5 years. There was no recurrence or metastasis in 9 patients with postoperative chemotherapy or chemoradiotherapy followed up for 1.5-5 years. Four patients died 2 months to 1.5 years after only an operation, or chemoradiotherapy but no operation. CONCLUSIONS: There are some relatively specific imaging findings of primary intracranial yolk sac tumors that could assist in their diagnosis. Surgery combined with radiation therapy and/or chemotherapy can achieve a better prognosis.

Addressing the diagnostic and therapeutic dilemmas of ovarian immature teratoma: Report from a clinicopathologic consensus conference.

Ovarian immature teratoma is a rare subtype of germ cell tumour that can be pure or associated with non-teratomatous germ cell tumour elements and is graded based on extent of the immature neuroectodermal component. Immature teratoma (IT) can also be associated with somatic differentiation in the form of sarcoma, carcinoma, or extensive immature neuroectodermal elements and may produce low levels of serum alpha-fetoprotein. Variable interpretation of these issues underlies diagnostic and management dilemmas, resulting in substantial practice differences between paediatric and adult women with IT. The Malignant Germ Cell International Consortium (MaGIC) convened oncologists, surgeons, and pathologists to address the following crucial clinicopathologic issues related to IT: (1) grading of IT, (2) definition and significance of 'microscopic' yolk sac tumour, (3) transformation to a somatic malignancy, and (4) interpretation of serum tumour biomarkers. This review highlights the discussion, conclusions, and suggested next steps from this clinicopathologic conference.

Pitfalls in the diagnosis of yolk sac tumor: Lessons from a clinical trial.

Though outcomes for patients with recurrent/refractory malignant germ cell tumors (mGCTs) are poor, therapies targeting mTOR and EGFR inhibition have shown promise in vitro. We hypothesized that the combination of sirolimus and erlotinib will show activity in patients with recurrent/refractory mGCTs. Patients were enrolled in a prospective phase II clinical trial; central review of existing pathology specimens was performed. Of the five patients evaluated, two had their diagnoses revised to pancreatic acinar cell carcinoma and alpha-fetoprotein (AFP)-secreting gastric adenocarcinoma, respectively. Although mGCTs are common AFP-secreting neoplasms, recurrence or refractoriness to standard regimens should prompt histologic reevaluation for other diagnoses.

Laparoscopic Trachelectomy for Cervix Yolk Sac Tumor in 11-Month-Old Girl: The Youngest Case.

BACKGROUND: Yolk sac tumor (YST) is a malignant entity that often occurs in girls less than 3 years of age and is the most frequent type of primary extragonadal germ cell tumor. CASE: We describe the case of an 11-month-old girl who was referred to our center for vaginal bleeding with evidence of a uterine mass on ultrasonography. Preoperative investigations confirmed YST of the uterine cervix without metastasis. After 4 cycles of systemic chemotherapy, the patient was treated with laparoscopic trachelectomy (fertility-sparing surgery) without perioperative complications. SUMMARY AND CONCLUSION: After 12 months of follow-up, no residual mass was seen. The laparoscopic technique for trachelectomy for uterine cervix YST seems to be feasible and safe in children under 1 year of age.

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.

Establishment and characterization of an ovarian yolk sac tumor patient-derived xenograft model.

OBJECTIVE: The lack of appropriate preclinical models of ovarian yolk sac tumor (OYST) is currently hindering the pursuit of new methods of treatment and investigation of the pathogenesis of the disease. We developed and characterized an OYST patient-derived xenograft (PDX) model in this study. METHODS: Tumor fragments from a patient with an OYST were implanted subcutaneously into BALB/c Nude mice. Engrafted xenografts were compared with the original tumor according to histology, immunohistochemistry, humanized identified, and drug efficacy testing with in vivo treatment programs. RESULTS: There was a high degree of histologic and immunohistochemical (IHC) resemblance between the established PDX model and its corresponding human tumors. Bleomycin, etoposide, and cisplatin (JEB) chemotherapy regimens were effective in clinical patients and were effective in the OYST PDX model; therefore, the effect of PDX intervention was consistent with clinical outcomes of OYSTs. CONCLUSION: We have successfully established an OYST PDX model. This OYST model preserves the basic molecular features of the primary human tumor, thereby providing a valuable method to preclinically evaluate new treatments and explore disease pathogenesis.

Yolk Sac Tumour of the Ovary in Pregnancy Treated With Surgery and Chemotherapy: A Case Report.

BACKGROUND: Ovarian carcinoma diagnosed in pregnancy is rare. Treatment should take both mother and fetus into consideration. CASE: We present the case of a patient diagnosed with a stage IC1 yolk sac tumour of the ovary at 15 weeks gestation, who underwent surgical staging and adjuvant chemotherapy during pregnancy. Intrauterine growth restriction was diagnosed and the patient delivered by cesarean at 36 weeks gestation for obstructed labour. CONCLUSION: Yolk sac tumour of the ovary in pregnancy with concomitant chemotherapy is uncommon. Adverse outcomes, including restricted fetal growth, are possible and their identification may help guide timing of delivery.

Vaginal Yolk Sac Tumor: A Case Series and Review of the Literature.

OBJECTIVE: To report diagnosis, treatment, and outcomes of vaginal yolk sac tumor (YST) cases at a single institution and review literature on vaginal YST to outline advancements in diagnosis, treatment, and survival. DESIGN: Retrospective chart review of female patients less than 21 years of age with pathologic diagnosis of vaginal YST treated at a large children's hospital, and summary of a 100-year review of the literature on vaginal yolk sac tumor. SETTING: Children's Healthcare of Atlanta, a tertiary center in Atlanta, GA. PARTICIPANTS: Female patients less than 21 years of age diagnosed with vaginal YST. RESULTS: Two cases of vaginal YST at our institution are outlined. Both patients presented within the first 2 years of life with vaginal bleeding and were treated successfully with chemotherapy alone. After review of the literature, 137 cases of vaginal YST were found. The mean age at diagnosis was 11 months, and all patients presented with vaginal bleeding. Before 2000, more radical treatments were pursued, and 40% resulted in death. Since the year 2000, treatment has shifted toward chemotherapy and more conservative surgical management, with 51% of vaginal YST cases treated with chemotherapy alone with 92% of patients alive at time of publication. CONCLUSION: Our cases contribute to the limited literature demonstrating the efficacy of conservative management of rare cases of vaginal YST with chemotherapy alone. This case series and review of the literature provide mounting evidence that vaginal YST should be in the differential diagnosis in young girls with vaginal tumors, and conservative management of vaginal YST has excellent outcomes.

Malignant germ cell tumour in an infant vagina.

The mother of a 9-month-old female infant complained that her child was unable to pass urine at the same time noticing a mass protruding from the vaginal orifice.The infant had a single episode of vaginal bleeding.The primary concern of the mother was the inability of the daughter to micturate. Malignant germ cell tumour arising from an infant vagina is rare and accounts for about 3% of all paedriatic malignancies. These are also referred to as endodermal sinus tumours or yolk sac tumours, and are mostly the commonest form of infant vaginal malignancies encountered. A diagnosis of endodermal sinus tumour was established based on the histology and raised α-fetoprotein levels.These tumours had Schiller-Duval bodies which are primarily blood vessels surrounded by primordial germ cells and were periodic acid shift (PAS) positive diastase resistant hyaline globules which also stain positive with α- fetoprotein which is an important diagnostic feature. Tumours with high α-fetoprotein levels have a poorer prognosis. However, they respond satisfactorily to chemotherapy.

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.

A yolk sac tumor of the pancreas and derived xenograft model effectively responded to VIP chemotherapy.

BACKGROUND: Yolk sac tumors (YSTs) of the pancreas are extremely rare, and no drug responsiveness data are available regarding YSTs. METHODS: We report a pancreatic YST in a 70-year-old woman, and its chemotherapeutic responsiveness based on clinical records and evaluation of a patient-derived xenograft (PDX) line of the YST. RESULTS: The YST was an 11-cm, solid mass located in the pancreatic tail. Histologically, the tumor showed medullary proliferation of tumor cells, with a variety of growth patterns including microcystic/reticular, endodermal sinus, and hepatoid patterns. Immunohistochemically, the tumor cells were positive for Sall4, glypican-3, and alpha-fetoprotein. We administered VIP (etoposide, ifosfamide, cisplatin) chemotherapy for a recurrent liver tumor, and obtained complete pathological remission. A drug-response assay using the PDX line from this YST revealed that both VIP and gemcitabine effectively inhibit tumor growth. CONCLUSIONS: These results suggest that differential diagnosis of YST from adenocarcinoma is important for selecting appropriate chemotherapy.

Yolk Sac Tumors of the Head and Neck in Aicardi Syndrome.

OBJECTIVES: To understand that yolk sac tumors (YSTs) of the head and neck (H&N) are exceedingly rare and typically carry a poor prognosis. To acknowledge the possibility of increased incidence in patients with Aicardi Syndrome and the ramifications this has on early diagnosis and treatment in this population. METHODS: To date, four germ cells tumors of the H&N have been reported in patients with Aicardi Syndrome. This report presents the second known case of a H&N YST in a patient with Aicardi syndrome. In both cases, the patient was initially misdiagnosed given unconvincing radiologic evidence. However, tissue diagnosis and elevated alpha-fetoprotein (AFP) levels were suggestive of a YST. RESULTS: In contrast to the poor prognosis previously described, both patients with Aicardi syndrome had an excellent chemotherapeutic response exhibited by normalization of AFP levels and imaging. CONCLUSIONS: Rare germ cell tumors of the H&N, such as YSTs, have now been documented in several patients with Aicardi syndrome, indicating a possible association given the rarity of these tumors in the population. YSTs should be considered in the differential diagnosis of H&N masses in these patients, with emphasis on early tissue diagnosis and treatment.

Metástasis retroperitonal gigante de un tumor del saco de Yolk / Giant retroperitonal metastasis from a Yolk sac tumor

RESUMEN Paciente con antecedentes de cirugía de tumor testicular, con biopsia de tumor de saco de Yolk y con diagnóstico de un tumor metastásico retroperitoneal irresecable. Un año más tarde de este último diagnóstico es remitido a nosotros, con un aumento considerable de dicha lesión y se logra su exéresis satisfactoriamente. Se realizó una revisión de la literatura, las indicaciones y técnicas en el tratamiento de la metástasis retroperitoneal de un tumor del saco de Yolk y se presentan los resultados de un paciente diagnosticado e intervenido en el Hospital Clínico Quirúrgico "Hermanos Ameijeiras", en el año 2016. La diseminación metastásica retroperitoneal del tumor del saco de Yolk es poco frecuente, muy poco reportado a nivel mundial y con pocas experiencias en su tratamiento. Se realizó una técnica de resección de una lesión gigante con quimioterapia adyuvante posoperatoria. No hubo complicaciones relacionadas con el proceder(AU)

ABSTRACT Patient with a history of testicular tumor surgery, with a Yolk sac tumor biopsy and with a diagnosis of an unresectable retroperitoneal metastatic tumor. One year after this last diagnosis, he was referred to us, with a considerable increase in this lesion and his excision was successfully achieved. A review of the literature, indications and techniques for the treatment of retroperitoneal metastasis from a Yolk sac tumor was performed, and the results of a patient diagnosed and operated on at the "Hermanos Ameijeiras" Clinical Surgical Hospital, in the year 2016. Retroperitoneal metastatic spread of Yolk sac tumor is infrequent, very little reported worldwide and with few experiences in its treatment. A giant lesion resection technique was performed with postoperative adjuvant chemotherapy. There were no complications related to the procedure(AU)