Mixed Germ Cell Tumor Research Articles

Pulmonary metastases revealing a mixed germ cell tumor with a predominant yolk sac tumor component: A case report

Yolk sac tumor of the testis is rare in adults. Its diagnosis is histological, reproducing an extra-embryonic structure (endodermal sinus tissue). It can be present alone or associated with another component, thus forming a mixed germ cell tumor. Treatment involves orchiectomy and chemotherapy in extratesticular stages. Lymph node dissection is indicated if residual masses persist. These tumors are characterized by a poor prognosis at an advanced metastatic stage. However, we report the clinical case of a 69-year-old man who presented with pulmonary metastases from a mixed germ cell tumor of the testis with a predominant Yolk Sac Tumor component, treated by orchiectomy, chemotherapy, and lymph node dissection.

Bilateral Somatically Derived Germ Cell Tumors With 12p Gains Arising in High-grade Serous Carcinomas of the Ovary: A Case Report and Review of the Literature.

Epithelial ovarian neoplasms are commonly observed in older patients, while germ cell tumors (GCTs) typically present in young individuals. When GCTs are detected in patients over 35yrs old, they often have an associated epithelial component, a phenomenon known as somatically derived GCTs. We report a unique case of mixed GCT involving bilateral ovaries with a background of high-grade serous carcinoma, including a yolk sac tumor and choriocarcinoma in the mixed GCT component. Somatically derived GCTs are rare with only 45 cases of ovarian carcinoma with somatic yolk sac tumor reported to date. Pathologists face diagnostic challenges in identifying somatically derived GCTs, as they can mimic high-grade epithelial neoplasms. Somatically derived GCTs have poor outcomes, therefore, precise diagnosis is crucial for prognostic and therapeutic considerations.

PD-L1 expression in testicular germ cell tumors undergoing spontaneous regression.

Spontaneous regression of testicular germ cell tumors is a well-known phenomenon; however, the precise mechanisms of spontaneous regression are still unknown. Our study aimed to investigate programmed death-ligand 1 (PD-L1) expression in spontaneously regressed testicular germ cell tumors, exploring the link between the immune response and spontaneous regression. From a sample of 356 testicular germ cell tumors, we singled out 5 completely regressed and 6 partially regressed tumors. In four out of six cases with partial regression, a residual seminoma component was found, while in the remaining two cases, an embryonal carcinoma component was found. Comparisons were made with 20 pure seminomas and 20 mixed germ cell tumors (MGCTs). A semiquantitative immunohistochemical analysis of PD-L1 expression in tumor cells and intra/peritumoral lymphocytes was performed. There was no PD-L1 expression in tumors with complete regression. All partially regressed tumors showed expression in intra/peritumoral lymphocytes within the tumor remnants. Expression was significantly more frequent in pure seminomas compared to MGCTs (P = 0.004). A positive correlation was demonstrated between the seminoma component and the proportion of PD-L1 positive lymphocytes, with a Kendall's Tau-b coefficient of 0.626 (P < 0.001). Tumor cells showed PD-L1 expression in three MGCTs within the embryonal carcinoma component. Our results support an immunological mechanism of spontaneous tumor regression, with the strongest potential in testicular tumors containing seminoma components. However, further research is necessary to determine the role of PD-L1 ligand more precisely in the microenvironment of spontaneously regressed tumors.

Dysgerminomas: germ cell tumors exhibit high expression of PD-L1 and associated with high TILs and good prognosis

Ovarian germ cell tumors (OVGCTs) account for 28% of all diagnosed ovarian cancers, and malignant germ cell tumors specifically account for approximately 13% of diagnosed ovarian cancers in Saudi Arabia. Although most germ cell tumor patients have a high survival rate, patients who experience tumor recurrence have a poor prognosis and present with more aggressive and chemoresistant tumors. The use of immunotherapeutic agents such as PD-L1/PD-1 inhibitors for OVGCTs remains very limited because few studies have described the immunological characteristics of these tumors. This study is the first to investigate PD-L1 expression in ovarian germ cell tumors and explore the role of PD-L1 expression in tumor microenvironment cells and genetic alterations. A total of 34 ovarian germ cell tumors were collected from pathology archives. The collected tumor tissues included ten dysgerminomas, five yolk sac tumors, five immature teratomas, and one mature teratoma, and the remaining samples were mixed germ cell tumors. The tumors were analyzed using immunohistochemical analysis to determine PD-L1 expression, immune cell infiltration and cancer stem cell populations and their correlation with clinical outcome. Furthermore, the genetic alterations in different subtypes of germ cell tumors were correlated with PD-L1 expression and clinical outcome. Datasets for testicular germ cells (TGCTs) were retrieved from The Cancer Genome Atlas (TCGA) and analyzed using cBioPortal (cbioportal.org) and Gene Expression Profiling Interactive Analysis (GEPIA). Compared with yolk sac tumors, dysgerminomas highly express PD-L1 and are associated with high levels of tumor infiltrating lymphocytes (TILs) and stem cell markers. In addition, compared with PD-L1-negative yolk sac tissue, dysgerminomas/seminomas with high PD-L1 expression are associated with more genetic alterations and a better prognosis. Our findings will contribute to the knowledge about the potential benefits of ovarian cancer immunotherapy in specific subsets of germ cell tumor patients and the risk factors for resistance mediated by tumor microenvironment cells.

Radio-Histopathological Spectrum of Ovarian Specimens Following Cystectomy

Ovarian cysts can be benign or malignant and requires accurate diagnosis for efficient treatment. Objective: To characterize the radiological and histopathological spectrum of ovarian specimens following cystectomy. Methods: This retrospective study was conducted at Pakistan Atomic Energy Commission General Hospital, Islamabad from 1st April 2022 to 31st December 2022.Eighty patient’s samples from cystectomy patients who were suffering from ovarian cysts were included. Each patient underwent radiological examination before ovarian cystectomy through laparoscopic surgery except two cases of urgent laparotomy. Gross histopathological specimen examination was conducted. The data were analysed using SPSS version 26.0, wherein p value &lt;. 0.05 was considered as significant. Results: The mean age of the patients enrolled in this study was 35.5±5.9 years. Hemorrhagic cysts were having a reticular pattern of internal echoes with soli appearing area with concave margins and no internal flow, while endometrioma cysts were having homogenous low level internal echoes with non-solid component and tiny echogenic foci in the walls. While within the neoplastic cysts 4/8 werehaving cystic external surface and 1/8 presented with ovarian mass.The surface epithelial tumor presented of 2 cases with carcinoma detection on histopathology slides while in the germ cell tumor 1 cases each of strumaovarii, dysgerminoma and mixed germ cell tumor was observed. Conclusions: Surface epithelial tumors were the most common category of ovarian tumors and majority of the cysts were benign cystadenomas. Radiological imaging provides a precise non-invasive tool for categorizing various ovarian cysts and histopathological findings further confirms the exact category of tumors.

Epithelioid Trophoblastic Tumor Predominant Mixed Germ Cell Tumor of the Testis: A Case Report and Review of the Literature.

An epithelioid trophoblastic tumor is a rare form of gestational trophoblastic neoplasia that mostly affects the uterus and endocervix in female patients of the reproductive age group. The tumor is believed to arise from chorion leave-type intermediate trophoblast. The epithelioid trophoblastic tumor in men is extremely rare and mostly described in association with mixed germ cell tumors of the testis. It is more commonly identified at the metastatic sites than in the testis. The epithelioid trophoblastic tumor should be differentiated from placental site trophoblastic tumor and squamous cell carcinoma. The distinctive morphology and characteristic immunohistochemical staining pattern help differentiate epithelioid trophoblastic tumors from other neoplasms. Only 7 male patients with epithelioid trophoblastic tumors have been described to date. Of these 7 patients, 4 were in metastatic sites, 2 in the testis, and 1 in the lung without the involvement of the testis or retroperitoneum. The proportion of epithelioid trophoblastic tumors was only 5% in the 2 patients with testis involvement. Here, we report the third patient with a primary testicular epithelioid trophoblastic tumor in a young man. Further, this is the first report to document epithelioid trophoblastic tumor as dominant histology in a testicular germ cell tumor.

A mysterious malignant mixed germ cell tumor with successful term pregnancy- an enigma

A mysterious malignant mixed germ cell tumor with successful term pregnancy- an enigma

Embryoid Bodies and Related Proliferations in Ovarian Germ Cell Tumors.

We investigated the frequency and associated pathology of embryoid bodies in ovarian tumors by evaluating neoplasms in which they are known to occur: 100 immature teratomas, 125 malignant mixed germ cell tumors, and 6 polyembryomas. Three immature teratomas contained a single relatively well-formed embryoid body, whereas these and 11 others showed foci we categorized as embryoid body remnants consisting of microscopic aggregates of embryonal or yolk sac-type epithelium associated with spaces consistent with yolk sac or amniotic cavity but lacking a classic embryoid body structure. Teratomas with these foci were all high grade. A well-formed embryoid body was found in only 1 malignant mixed tumor, but embryoid body remnants were present in 25%, invariably associated with foci of immature teratoma (100%) and often with yolk sac tumor (97%), embryonal carcinoma (35%), or both (32%). These foci usually took the form of round to oval aggregates, often well-circumscribed, for which the term "polyembryoma background" has been proposed. The polyembryomas were typically grossly hemorrhagic and occurred in patients from 9 to 43 years of age. The embryoid bodies in them generally grew in lobules within an edematous to occasionally myxoid stroma. Four tumors contained liver-like cells, 4 numerous glands likely recapitulating the allantois, 3 syncytiotrophoblast cells, 2 prominent cysts, and 2 striking vascular proliferations. This study indicates that (1) typical embryoid bodies are rare in immature teratomas but about 14% of them have embryoid body remnants. (2) Embryoid body remnants are seen in 25% of malignant mixed germ cell tumors with a teratomatous component and often proliferate to form yolk sac tumor and embryonal carcinoma. (3) Well-formed embryoid bodies growing in a confluent manner (polyembryoma) are rare, and minor foci of teratoma, yolk sac tumor, or embryonal carcinoma are almost always present, indicating that these are fundamentally malignant mixed germ cell tumors but the polyembryoma component is dominant and distinctive which, in our opinion, justifies its own nomenclature. (4) Embryoid bodies are not a feature of other germ cell tumors.

Single-cell transcriptomic analysis reveals that the APP-CD74 axis promotes immunosuppression and progression of testicular tumors.

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

AB039. Malignant transformation of intracranial germinoma to non-germinomatous germ cell tumors-incidence, treatment strategy and outcome: a case report and literature review.

Intracranial germ cell tumors are rare neoplasms seen mainly in children and adolescents. Compared to non-germinomatous germ cell tumors (NGGCTs), germinomas typically respond well to chemo-radiotherapy and portend a better prognosis. We report here a patient with intracranial germinoma which showed complete remission following chemo-radiotherapy but re-presented with malignant transformation to NGGCT thirteen years later. We then performed a literature review to understand the treatment strategy and outcome of this rare phenomenon. Review of the patient's case note, followed by a literature review of the topic. A 13-year-old male presented with 6 weeks of polyuria and polydipsia. Imaging showed bifocal (suprasellar and pineal) lesions. Histology from an open biopsy diagnosed a germinoma. He underwent extended whole ventricular irradiation with local boost and chemotherapy, which led to complete resolution on imaging. Thirteen years later, he re-presented with headaches and diabetes insipidus. Imaging showed a new right frontal lesion with elevated serum beta-human chorionic gonadotropin (β-hCG) and alpha-fetoprotein (AFP). The tumor was excised with histology confirming a mixed tumor comprising germinoma, yolk sac, and choriocarcinoma. A literature review returned eight case reports of malignant transformation of intracranial germinoma to NGGCTs, covering eight patients (seven males, and one female; aged 5-23 years old). Four had the primary tumor located in the pineal region, three in the suprasellar region, and one at both sites. Recurrence with malignant transformation occurred at a median of 24.5 months after initial diagnosis (range, 5 months to 14 years). Five patients had recurrences intra-abdominally, all of whom had a ventriculoperitoneal shunt (VPS) inserted during the treatment of the initial tumor. Of the remaining three intracranial recurrences, two were at the same site while one at a distant site. The most common histology was yolk sac tumor (five patients), followed by two each of immature teratoma, choriocarcinoma, and embryonal carcinoma (some were mixed germ cell tumors). Of those with intra-abdominal recurrence, four died within 2 months of diagnosis. Those with intracranial recurrences survived longer, with a median survival of 15 months, and one longer than 27 months. Malignant transformation to NGGCTs is rare. Relapse can occur intracranially, or in cases where VPS was present, intraabdominally. Outcomes following transformation were poor despite aggressive treatment, with those intra-abdominal recurrences faring much worse.

A rare combination of double primary malignancies; mixed germ cell tumor of testis with papillary carcinoma of thyroid: a case report

Double malignancy occurring in multiple organs is relatively rare yet possible. The second primary lesion is identified either simultaneously with the primary lesion (synchronous) or after a while (metachronous). We report a case of synchronous double malignancy in a patient who had two separate carcinomas, a non-seminomatous germ cell tumor (NSGCT) and a papillary carcinoma of thyroid. These types of synchronous double malignancies can be dealt as independent carcinomas. This existence of two carcinomas at anatomically dissimilar sites with distinct histopathologies, being a rare combination, led us to report the case.

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.

A 10-year retrospective study of the risks and peculiarities in pediatric patients with (para)gonadal tumors and cysts.

Gonadal pediatric tumors are rare, ranking fourth (6%) among pediatric tumors, by Surveillance, Epidemiology, and End Results Program (https:∕∕seer.cancer.gov∕). They have vague symptoms, leading to late discovery, but early detection and identifying its risk factors result in favorable prognosis and reduction of its incidence respectively. A 10-year retrospective study identified peculiarities and risk factors in 210 children till age 17 with (para)gonadal tumors. Stress, pollution (agricultural chemicals, insecticides and metal mine), obesity, breastfeeding ≤5 months, malformations [mainly non-genetic related 67∕87 (77%), especially eye malformation - 64%], hormone, smoking, positive heredo-genetic history, rural residence area, abnormal birth weight, and menstruation disorders showed an increased gonadal malignancy risk; relative risk ratio (RR): 1.33, 1.30, 1.34, 1.11, 1.65, 1.16, 1.36, 1.10, 1.00, 1.08 and 1.15 folds, respectively. RR for histopathological subtypes: immature teratoma (IT) (pollution - 1.75, Rhesus positive - 3.41), dysgerminoma (menstruation disorders - 2.80), granulosa cell tumor (stress - 2.10, menstruation disorders - 2.80), mucinous cystadenomas (obesity - 2.84, no postnatal vaccine - 3.71), mature teratomas (stress - 2.35, malformations - 2.18) and serous cystadenomas (breastfeeding ≤5 months - 2.53), dependent variables being mixed germ cell tumors (GCTs) and cysts. Children presenting with bleeding (73%), abdominal distention (62%), elevated tumor markers (91%), (multilocular) solid tumor (88% and 100%), tumor size >10 cm (65%), GCTs (74%), death (100%), metastases (100%), viruses (77%), loss of appetite (68%), and weight (85%), had gonadal malignant tumors, especially mixed GCTs and IT. Avoiding these risk factors will prevent and reduce gonadal pediatric tumors. Investigating children presenting with the listed peculiarities, especially if exposed to the mentioned risk factors, will enable early gonadal tumor identification, successful patient management, and favorable prognosis.

A Rare Case of Mixed Germ Cell Tumor of Testies in Young Male Patient

A Rare Case of Mixed Germ Cell Tumor of Testies in Young Male Patient

Case Report of Mixed Germ Cell Tumor of Ovary in Young Female

Case Report of Mixed Germ Cell Tumor of Ovary in Young Female

P-381 Fertility preservation in patients with testicular cancer

Abstract Study question Do the clinical stage and histological characteristics of testicular cancer affect sperm quality? Summary answer Sperm concentration, motility and normal morphology significantly decreased in patients with testicular cancer. However, semen parameters were not significantly associated with tumor histology. What is known already Testicular cancer is rare in most countries, with an incidence ranging from ∼1/100,000 to 10/100,000, and represents about 1% of all cancers in men, but about 60% of all cancers in young males aged between 15 and 35 years. Additionally, the incidence of testicular cancer has doubled in the last 20-40 years. While it is clear that chemotherapy treatment can negatively impact infertility, it is increasingly recognized that male-factor infertility may play a significant role in the overall health status of men, and men with infertility may be at higher risk of developing testicular cancer. Study design, size, duration Retrospective data from 284 males, diagnosed with testicular cancer, undergoing to semen cryopreservation before surgery or chemo- or radiotherapy treatments, from January 2016 to June 2022 at Maternal and Child Department, Gynecology and Obstetrics Unit, Couple Sterility Center at Federico II, University of Naples, were included in the study. Participants/materials, setting, methods All patients signed their informed consent to cryopreservation. In order to have an internal control group coming from the same region, results of semen analysis from male partners of couples with certain female factors (bilateral tubal imperviousness or in case of egg donation) were included in the study. After semen collection and liquefaction, the semen specimens were cryopreserved following manufacturer’s protocol with media conteining TEST-yolk buffer. Main results and the role of chance Overall, taking in to consideration the semen cryopreservation, per WHO 2021 criteria, we observed that the majority of semen parameters of patients with testicular cancer resulted between 5°percentile and 25° percentile. The unique parameter over the 50°percentile was the semen volume. Comparing results from male partners of couples with certain female factors and testicular cancer patients several features were significant different. Especially, semen volume resulted significantly increased in cases respect to the control (p = 0,011). Instead, from microscopic evaluation semen concentration, percentage of total sperm motility and % of spermatozoa with normal morphology appeared significantly decreased in patients with testicular cancer (p = 0,000; p = 0,000; p = 0,002). Based on Histopathological Classification of Testicular Tumors the 59% (168/284) were classified as classic seminoma, 14% (41/284) mixed germ cell tumors including seminomatous and nonseminomatous cell tumors, 13% (38/284) nonseminomatous mixed germ cell tumors, 12% (35/284) nonseminomatous germ cell tumors including 4 cases of teratoma and 30 cases of embryonal carcinoma and 2 cases of cariocarcinoma. However, abnormal semen parameters were not significantly associated with tumor histology. Limitations, reasons for caution No information about semen quality after thawing and ICSI outcome could represent the main limitation for a complete information of the preservation program in these patients. Wider implications of the findings We presented our monocentric experience of oncofertility preservation program with especially attention to testicular cancer patients. Presented data emphasizes the importance of semen monitoring in young men and the fertility preservation in management of the patient. Trial registration number not applicable

Primary lung chordoma: a case report

BackgroundChordoma, a rare malignant tumor arising from notochordal tissue, usually occurs along the spinal axis. Only a few published reports of primary lung chordomas exist. Herein, we present a case of primary lung chordoma and discuss important considerations for diagnosing rare chordomas.Case presentationWe report a case of primary lung chordoma in a 39-year-old male with a history of testicular mixed germ-cell tumor of yolk sac and teratoma. Computed tomography revealed slow-growing solid lesions in the left lower lobe. We performed wedge resection for suspected germ-cell tumor lung metastasis. Histologically, large round or oval cells with eosinophilic cytoplasm were surrounded by large cells with granular, lightly eosinophilic cytoplasm. Tumor cells were physaliphorous. Immunohistochemistry was positive for brachyury, S-100 protein, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3, suggesting pulmonary chordoma. Re-examination of the testicular mixed germ-cell tumor revealed no notochordal elements. Although some areas were positive for brachyury staining, hematoxylin and eosin (HE) staining did not show morphological features typical of chordoma. Complementary fluorescence in situ hybridization (FISH) of the lung tumor confirmed the absence of isochromosome 12p and 12p amplification. Thus, a final diagnosis of primary lung chordoma was established.ConclusionsIn patients with a history of testicular mixed germ cell tumors, comparison of histomorphology using HE and Brachyury staining of lung and testicular tumors, and analyzing isochromosome 12p and 12p amplification in lung tumors using FISH is pivotal for the diagnosis of rare lung chordomas.

Clinical effects of neuroendoscopic infratentorial supracerebellar approach surgical technique for resecting pineal tumors: a retrospective study

ObjectivePineal tumors are relatively rare central nervous system lesions with a predilection for the pediatric population. This article aims to explore the clinical effects of neuroendoscopic infratentorial supracerebellar approach for resecting tumors in the pineal area. MethodsThis is a retrospective study that included patients who underwent neuroendoscopic infratentorial supracerebellar approach to resect nine tumors in the pineal area at the Department of Neurosurgery of the Second Hospital of Lanzhou University from December 2017 to October 2023. ResultsThe results of postoperative MRI revealed that all tumors were resected. Five patients received postoperative radiotherapy, three patients received radiotherapy along with chemotherapy, and one patient received neither radiotherapy nor chemotherapy. The pathological results showed that four patients were diagnosed with germinoma, two patients with teratoma, two patients with mixed germ cell tumors, and one patient with central neurocytoma. After surgery, one patient developed psychiatric symptoms, two patients developed binocular upward vision and diplopia, and one patient developed unstable walking and diplopia. With a follow-up of 1.7–4.8 years, all nine patients lived normally. Furthermore, none of them had tumor recurrence or death. ConclusionThe simple neuroendoscopic infratentorial supracerebellar approach has some safety and efficacy. It is suitable for tumors in the pineal region where the disease is mainly located below the Galen vein complex.

Assessment of Molecular Markers in Pediatric Ovarian Tumors: Romanian Single-Center Experience.

Pediatric ovarian tumors exhibit unique diagnostic and therapeutic challenges. This study evaluates the expression of SALL4 and OCT3/4 biomarkers in pediatric ovarian tumors and their associations with tumor subtype, stage, and clinical outcome. A retrospective analysis was conducted on 64 patients under 18 years old, examining demographic data, tumor characteristics, immunohistochemical staining, and clinical outcomes. Our results show that SALL4 was significantly expressed in adenocarcinoma, dysgerminoma (DSG), mixed germ cell tumors (GCTs), and immature teratoma, while OCT3/4 was highly expressed in DSG and mixed GCTs. Both markers are associated with a higher tumor grade and stage, indicating a more aggressive disease. The SALL4 positivity expression was correlated with high alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) levels, while OCT3/4 positivity significantly predicted the risk of subsequent metastasis. The mean progression-free survival (PFS) was notably shorter in patients with positive markers. These findings underscore the diagnostic and prognostic value of SALL4 and OCT3/4 in pediatric ovarian tumors, aligning with previous research and supporting their use in clinical practice for better disease management and patient outcomes.

GCT-15. CLINICAL AND MOLECULAR CHARACTERIZATION OF INFANTILE CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Abstract BACKGROUND The management of infantile central nervous system germ cell tumors (CNS-GCTs) presents unique challenges, including variable clinical presentations such as tumor size and propensity for hemorrhage. Moreover, data on the clinical and molecular features remain limited. METHODS We conducted a clinical and molecular analysis of CNS-GCTs in children aged 6 years or younger, registered with the Japan Children’s Cancer Group and the iGCT consortium. DNA methylation analysis was performed using the Illumina Methylation EPIC array to identify potential molecular prognostic indicators. RESULTS The cohort comprised 43 patients, with a median age at onset of 6.5 months (0–68 months). Notably, 23 patients (54%) were diagnosed before 1 year of age. The male-female ratio was 27:15. Most common tumor location was cerebellum (13 cases). The median AFP level was 538 ng/ml (0–206460). Pathologically, the tumors were predominantly diagnosed as teratomas and yolk sac tumors. Teratomas were more common in patients diagnosed before 1 year of age, while mixed GCTs were more frequent in those diagnosed after 3 years. Molecular analysis identified four cases as embryonal tumors, including three AT/RTs and one DICER1-mutant intracranial sarcoma. The 3-year overall survival rates varied significantly by diagnosis: mixed GCTs at 100%, teratomas at 90.6%, yolk sac tumors at 30.0%, and embryonal tumors at 0%. Notably, two patients with teratomas developed metachronous tumors more than 10 years post-diagnosis, with both secondary tumors exhibiting mutations in the MAPK pathway absent in the primary tumors. CONCLUSION Infantile CNS-GCTs exhibit distinct clinical and molecular profiles compared to those in older children and adults. Not all tumors classified as GCTs based on molecular characterization were GCTs; some were embryonal tumors, potentially impacting treatment strategy. The genetic analysis suggests that some metachronous GCTs may represent second primary tumors rather than recurrences.