Yolk Sac Tumor Research Articles

[Clinical analysis of 12 cases of ovarian yolk sac tumor].

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Abstract 2856: Multi-omics approaches for biomarker discovery and target therapy in pediatric germ cell tumors

Abstract Pediatric germ cell tumors (GCT) are rare and heterogeneous, presenting various histologies. There are no specific markers for diagnosing GCT, and 30% of patients are resistant to standard cisplatin-based chemotherapy, which can be related to epithelial-mesenchymal transition (EMT). Therefore, this study aims to elucidate markers for classifying GCTs, evaluate the molecular mechanisms related to drug resistance, and search for new therapeutic approaches. The expression of miRNAs was assessed for 42 GCT-pediatric patients through miRNA Panel - Nanostring technology. Whole Exome Sequencing (WES) was performed for 16 GCT-pediatric patients to assess somatic mutations. In silico analysis of epithelial-mesenchymal transition (EMT) markers was performed using the cBioPortal database. The expression of EMT markers was evaluated in vitro in parental and cisplatin-resistant models (NTERA-2R). Xenograft model-derived NTERA-2R was established and EMT markers were also assessed. We identified specific miRNA expression signatures for each histology, including 34 miRNAs for dysgerminomas, 13 for embryonal carcinomas, 25 for yolk sac tumors, and one for immature teratoma. We identified 26 miRNAs that were commonly expressed in malignant tumors, with six miRNAs (miR-302a-3p, miR-302b-3p, miR-371a-5p, miR-372-3p, miR-373-3p, miR-367-3p) showing significant overexpression. MiR-302b-3p had a significant association with all the evaluated clinical features. WES analysis showed that Single Base Substitution signature 39 was observed in 68.75% of samples and SBS22 in 12.5%. Copy number alterations were identified in 4, 7, 8, 10, 12, 21, and 22 chromosomes, with amplification of CDKN1B, KRAS, CCND2, ETV6, and KDM5A genes and deletions of KIT and PTEN genes. Somatic mutations in NYAP2, RHBDF2, MTOR, KIT, ATM, KRAS, and PIK3CA were frequent among the samples. KIT (Asp816Val, Ala829Pro) and KRAS (Gln61Leu) mutations were classified with potential clinical significance and were validated. In silico analysis showed that different histologies had distinct expression profiles for EMT markers. Patients with SNAILlowSLUGlow expression had higher PFS than those with SNAILhighSLUGhigh (p=0.006). The median PFS of patients with SLUGlow was 46.4 months, while SLUGhigh was 28.0 months (p=0.022). In vitro analysis using NTERA-2R showed overexpression of EMT markers. The same result was obtained in the xenograft model derived from NTERA-2R. Our study offers vital insights into pediatric GCTs' molecular landscape, using in silico, in vitro, in vivo analyses, and genetic assessments, highlighting three points: 1) The miRNA signatures for each histology may have robust diagnostic and prognostic potential, besides clinical implications as biomarkers. 2) KIT and KRAS genes are possible therapeutic targets of pediatric GCTs. 3) EMT is related to cisplatin resistance and SLUG is a potential molecular target. Citation Format: Ana Flavia Souza Peres, Ingridy Izabella Vieira Cardoso, Janaina Mello Soares Galvao, Ana Glenda Santarosa Vieira, Marcela Nunes Rosa, Isabela Cristiane Tosi, Daniel Antunes Moreno, Ana Carolina Laus, Andre van Helvoort Lengert, Silvia Aparecida Teixeira, Adriane Feijo Evangelista, Rui Manuel Reis, Luiz Fernando Lopes, Mariana Tomazini Pinto. Multi-omics approaches for biomarker discovery and target therapy in pediatric germ cell tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2856.

Primary Co-Occurrence of Gonadal and Extragonadal Central Nervous System (CNS) Germ Cell Tumors (GCTs): Case Report and Review of the Literature

Background: The primary co-occurrence of gonadal and extragonadal central nervous system (CNS) germ cell tumors (GCTs) has rarely been reported in the literature, and a common opinion on the underlying etiopathogenetic mechanism is lacking. Objective: We aim to investigate the pathophysiological mechanisms and genetic pathways underlying the primary co-occurrence of gonadal and CNS GCTs. Methods: We reviewed data from 29 consecutive patients with a diagnosis of CNS GCT, evaluated in our Hospital over the past 23 years, and searched for those who had at least a primary gonadal co-occurrence of GCT. A systematic review of the literature according to the PRISMA guidelines was also conducted. For a comprehensive and detailed search, PubMed, Ovid MEDLINE, and Ovid EMBASE databases have been consulted. Boolean operators and MeSH terms were used to find studies. Only articles published between 2000 and 2023 were considered. Results: Including our Institutional case report, a total of 7 patients with both testicular NGGCTs and CNS GCTs were identified (5 patients with metachronous tumors and patients with synchronous presentation). The average age at tumor diagnosis was 17 years. The cerebral histotypes reported were mixed GCTs (3 cases; 43%), pure germinomas (3 cases, 43%), and one yolk sac tumor (14%). Two out of seven cases (29%) were syndromic, one suffering from Down Syndrome and the other from Testicular Dysgenesis Syndrome. Regarding the etiology and molecular mechanism of GCT development, several gene mutations have been reported in the literature. Particularly, genetic alterations in the MAPK and/or PI3K/AKT/mTOR pathway, together with mutations of the KIT gene, have been shown to guarantee survival and transformation of mismigrated totipotent primordial germ cells, while suppressor genes allow their resistance against apoptotic death. Aberrant chromosomes have also been reported to be responsible for oncogenic transformation. It is also known that CNS and testicular GCTs share some genetic/epigenetic profiles. Conclusions: The primary co-occurrence of testicular NGGCT and extragonadal CNS GCTs is extremely rare. Genetic factors seem to play a paramount role in their etiopathogenesis. Additional research is needed to elucidate molecular mechanisms of oncogenesis in such patients.

P53 Overexpression May Represent an Early Marker of Clinicopathologic Progression in Vasculogenic Mesenchymal Lesions of Germ Cell Tumor Origin.

Vasculogenic mesenchymal lesions (VMLs) of germ cell tumor origin are thought to originate in postpubertal-type yolk sac tumor componentsand include a spectrum of lesions from teratoma with vasculogenic stroma (TVS), to low and high-grade vasculogenic mesenchymal tumors (VMTs). VMLs exhibit rudimentary to well-developed neoplastic vessels within primitive mesenchyme, being considered a neoplastic reiteration of embryonic vasculogenesis in the splanchnic mesoderm of the yolk sac. They occur in patients with primary mediastinal germ cell tumors after chemotherapy, and a subset progresses to "somatic-type" sarcomas [including angiosarcoma (AS)], with high-grade VMTs likely portending a higher risk. Recently, we encountered a low-grade VMT that progressed to metastatic AS during follow-up. In this case, both the low-grade VMT and the subsequent AS demonstrated p53 overexpression, suggesting that p53 alterations may precede histopathologic transformation. To test this hypothesis, we evaluated neoplasms representing the entire spectrum of VMLs using p53 immunohistochemistry (IHC; clone DO-7, Dako). Overexpression was defined as nuclear positivity in > 80% of neoplastic cells. Because the distinction between high-grade VMT and AS can be subjective in some cases, they were grouped together in a single category. Thirty-nine VMLs were assessed: 16 high-grade VMT/AS, 19 low-grade VMT, and 4 TVS. Patient age ranged from 19 to 46 years (mean, 30 years; male = 97%). Four high-grade VMT/AS and one low-grade VMT showed p53 overexpression (5/39 VMLs, 13%; 4/16 high-grade VMT/AS, 25%). These tumors included 1 unequivocal AS and 1 high-grade VMT/AS with progression to rhabdomyosarcoma. The only low-grade VMT with p53 overexpression demonstrated progression to AS. Another high-grade VMT that progressed to sarcoma demonstrated p53 overexpression in the sarcoma component, but it was excluded because the VMT was not represented in the material availableat the time of the study. Lesions with intratumoral grade heterogeneity (classified based the highest grade), demonstrated more pronounced p53 overexpression in the high-grade components. P53 overexpression is associated with disease progression in a subset of VMTs and may precede morphologic transformation to sarcoma. Routine evaluation of VMTs with p53 IHC seems justified, with overexpressors likely requiring an close clinical surveillance.

Alpha-fetoprotein producing endometrioid carcinoma arising in an adenomyoma of the uterus.

We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that "endometrioid carcinoma with yolk sac tumor differentiation" or "endometrioid carcinoma with a primitive phenotype" may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium.

Retroperitoneal Sarcomatoid Yolk Sac Tumor in a Chemotherapy-Naive Patient With Testicular Postpubertal Type Teratoma: A Rare Case Report With Emphasis on Molecular Features.

Sarcomatoid yolk sac tumor is a very rare histologic type of testicular germ cell tumor and is mainly reported in testicular germ cell tumor patients who receive chemotherapy. Herein, we report an extremely rare concurrent retroperitoneal sarcomatoid yolk sac tumor in a man with a testicular postpuberal teratoma before he received chemotherapy. A 37-year-old man initially presented with a persistent abdominal pain. Subsequent imaging studies revealed a 9.6-cm retroperitoneal mass, and 2 testicular masses (3.1 cm and 0.9 cm in greatest dimension, respectively). His serum tumor markers were within normal ranges. His radical orchiectomy demonstrated a postpubertal type teratoma with an adjacent scarring nodule. Later, his retroperitoneal tumor showed spindle tumor cells embedded in predominantly myxoid and focally fibrous stroma with diffuse and strong immunoreactivity for keratin AE1/AE3, SALL4 and glypican 3. No tumor necrosis or brisk mitotic figures were observed. A diagnosis of sarcomatoid yolk sac tumor was rendered. Fluorescence in situ hybridization analysis of his retroperitoneal sarcomatoid yolk sac tumor revealed polysomy 12 and MYC amplification, whereas no evidence of isochromosome 12p [i(12p)], and DNA sequencing showed 6 mutations per megabase (muts/Mb), and the somatic alterations included ARAF amplification and ATR I774Yfs*5. Considering its rarity, sarcomatoid yolk sac tumor may pose diagnostic challenges. Therefore, relevant clinicoradiologic information and ancillary work up, including immunohistochemistry and molecular studies, may be helpful for the accurate classification. Our tumor further raises awareness of this rare event, expands the spectrum of its clinical presentation, and explores the molecular features.

46, XX disorder of sexual development associated with mixed germ cell tumor of the prostate: a rare case report

BackgroundExtragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis.Case presentationA 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels.DiscussionA case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment.

Identification of a panel of microRNA biomarkers for the management of patients with refractory germ cell tumor of the testis.

521 Background: In 1946, nearly 90% of patients diagnosed with metastatic Testicular Germ Cell Tumor (TGCT) succumbed to the disease within a year. In the present day, over 90% of such patients are successfully cured. However, there is a remaining 10% of patients have tumors that consist of chemotherapy-resistant forms of TGCT, such as yolk sac tumors and teratomas. This underlines the need for developing biomarkers that can guide the choice between additional chemotherapy and surgical intervention. MicroRNAs (miRNAs), non-coding RNA molecules that control post-transcriptional modifications, have shown promise in identifying TGCTs. Research has particularly highlighted the overexpression of miR-371a-3p and miR-375-3p in TGCTs. Nevertheless, these miRNAs are not effective in distinguishing between teratomas and other TGCT types. The Cancer Genome Atlas (TCGA), a publicly accessible database, offers clinical and miRNA data on various tumors, including TGCTs. Our objective is to leverage TCGA to identify miRNAs that can be used to classify TGCTs containing teratomas from those that do not. Methods: Between 2001 and 2013, TCGA gathered a total of 135 primary TGCT samples. We group these tumors into those without teratomas and those with any teratomatous components. We used EdgeR, a Bioconductor package designed for differential expression analysis of RNA that accounts for both biological and technical variation. A false discovery rate of less than 1e-8 was applied. A heatmap was generated to display the hierarchical clustering of differentially expressed miRNAs. Results: Based on the above cut-off, a panel of 50 miRNAs of differentially expressed miRNA were used to generate a hierarchical clustering that showed clear clustering between the two groups. Notably, tumor suppressor miRNAs such as hsa-mir-203a, hsa-mir-199, and hsa-mir-152, which are usually downregulated in non-teratoma TCGT, are overexpressed in teratomas. Other miRNA including hsa-mir-146a and hsa-mir-3607, which are downregulated tumor suppressors for non-TCGT are also downregulated in teratomas but not in teratoma-free TGCT. Conclusions: Despite the high cure rate for TGCTs, tumors containing chemotherapy-resistant teratomas still contribute to elevated mortality rates. Utilizing TCGA data, we identified a set of miRNAs that are effective in distinguishing between teratoma-containing and teratoma-free TGCTs. This miRNA panel has the potential to inform decisions related to surgical treatment plans and provide further insight into the biology of the disease.

Primary extragonadal yolk sac tumor of the orbit: A rare case and review of literature

Germ cell tumors usually arise from primordial cells in gonads, mainly testes, and ovaries. Extragonadal involvement of orbit is very unusual. We report one case of primary yolk sac tumor of orbit in a 3-year-old male child presented as a left lateral orbital mass. Its clinical presentation may mimic many common pediatric orbital tumors causing misdiagnosis which affects ocular morbidity and mortality. Awareness about this rare entity to clinicians is helpful in the early diagnosis and proper management of young kids.

Assessing the risk to develop a growing teratoma syndrome based on molecular and epigenetic subtyping as well as novel secreted biomarkers

In germ cell tumors (GCT), a growing teratoma during chemotherapy with decreasing tumor markers was defined as ‘growing teratoma syndrome’ (GTS) by Logothetis et al. in 1982. So far, its pathogenesis and specific treatment options remain elusive.We aimed at updating the GTS definition based on molecular and epigenetic features as well as identifying circulating biomarkers. We selected 50 GTS patients for clinical characterization and subsequently 12 samples were molecularly analyzed. We further included 7 longitudinal samples of 2 GTS patients. Teratomas (TER) showing no features of GTS served as controls.GTS were stratified based on growth rates into a slow (<0.5 cm/month), medium (0.5–1.5) and rapid (>1.5) group. By analyzing DNA methylation, microRNA expression and the secretome, we identified putative epigenetic and secreted biomarkers for the GTS subgroups. We found that proteins enriched in the GTS groups compared to TER were involved in proliferation, DNA replication and the cell cycle, while proteins interacting with the immune system were depleted. Additionally, GTSrapid seem to interact more strongly with the surrounding microenvironment than GTSslow. Expression of pluripotency- and yolk-sac tumor-associated genes in GTS and formation of a yolk-sac tumor or somatic-type malignancy in the longitudinal GTS samples, pointed at an additional occult non-seminomatous component after chemotherapy. Thus, updating the Logothetis GTS definition is necessary, which we propose as follows:The GTS describes a continuously growing teratoma that might harbor occult non-seminomatous components considerably reduced during therapy but outgrowing over time again.

Yolk Sac Tumor in Ascitic Fluid – Cytodiagnosis of a Rare Case

Abstract Yolk sac tumor (YST) is a germ cell tumor of gonads presenting in children and young adults. It is rare to find metastasis of the YST in effusion fluid. We report a case of a YST in a 17-year-old female diagnosed on cytological examination of ascitic fluid and confirmed histologically after resection as YST. This case not only highlights the rare possibility of metastasis of the YST in ascitic fluid cytology but also emphasizes the diagnostic dilemma it causes in diagnosing such cases in body fluids. Detailed clinical history including the age of the patient, along with serum alpha-fetoprotein (AFP) levels is essential to a make a preoperative diagnosis. Histopathology with AFP immunohistochemistry confirms the diagnosis of such lesions.

Clinicopathological Evaluation of Extragonadal Germ Cell Tumors - A Retrospective Study from a Regional Cancer Center in India

Introduction: Extragonadal germ cell tumors (EGGCTs) are tumors arising at extragonadal ana-tomical locations. The biological behavior and prognosis of these tumors differ from their gonadal counterparts. Our study aims to analyze their histological subtypes, the outcome, and the prognosis of these lesions at various age groups.Material and Methods: We carried out a retrospective analysis of all patients with EGGCTs diag-nosed from January 2017 to December 2019. Results: Our study included 61 cases of EGGCTs. These cases were divided into neonatal (birth to six months), prepubertal (more than six months to 12 years), and post-pubertal group (&gt;12 years). The most frequently affected group was prepubertal (44.2%). The age ranged from birth to 45 years with a male-to-female ratio of 1:1.03. The frequently involved site was sacrococcyx (36%) followed by mediastinum (31.1%). The common histologic subtype was mature teratoma (39.3%), followed by yolk sac tumor (YST) (18%), mixed germ cell tumor (18%), immature teratoma (14.7%), and germinoma (9.8%). Four cases of teratoma had somatic malignancies. There were 48 stage I, 8 stage II, and 2 stage III tumors. Statistical analysis revealed a significant association of age group concerning primary site (p=0.004), histological type (p=0.002), and clinical stage (p=0.034). In a median follow-up of 30 months, an Overall Survival (OS) of 93.2% and Event Free Survival (EFS) of 90.4% were noted across all age groups. OS of 100% (neon tal), 96% (prepubertal) and 88.0% (post-pubertal) revealing a declining trend (p=0.324) with increasing age was noted. The important prognostic factors include histological subtype (mixed germ cell tumors and teratomas with somatic malignancies had reduced overall survival) and stage (I vs II and III) for OS and stage alone for EFS (P&lt;0.0001). Conclusion: Our study highlights the clinicopathological characteristics, prognostic parameters, and the outcome of GCTs occurring at extragonadal sites and emphasizes the role of pathologists in the detailed reporting of these lesions.&#x0D;  

Ovarian Yolk Sac Tumors: Is Fertility Preservation Possible?

Abstract Yolk sac tumors make up 14% to 20% of all malignant ovarian germ cell tumors. Serum alpha-fetoprotein (AFP) levels are elevated in a significant number of patients and are useful for monitoring the response to treatment and for post-treatment surveillance. Surgery is required for diagnosis, staging, and treatment. The first case is a 12-year-old girl presented with abdominal pain. The ultrasonography (US) showed a huge pelvic tumor. AFP level was high (1000 mg/ml). Right salpingo-oophorectomy and pelvic lymphadenectomy were done. Histopathology reported yolk sac tumor of ovary. She received 3 courses of bleomycin, etoposide, cisplatin (BEP). The second case is a 25-year-old G1AB1 presented with pelvic pain and distension. The US showed a huge pelvic tumor in the right abdominopelvic region. AFP level was high (1000 mg/ml). Right salpingo-oophorectomy, omentectomy, and appendectomy were done. Histopathology reported yolk sac tumor of ovary. The patient received four cycles of BEP protocol; AFP level decreased to 10 mg/ml after the four cycles of chemotherapy. The third case is a 21-year-old girl presented with abdominal pain. The US showed a huge pelvic tumor in the right adnexa. AFP level was high (8700 mg/ml). Right salpingo-oophorectomy and pelvic lymphadenectomy were done. Yolk sac tumor is rare in children and it could be cured usually. In this study, we described three patients with ovarian yolk sac tumors and their fertility preservation treatments.These cases has reminded that in young age with high AFP levels and rapidly growing ovarian mass, diagnosis of the yolk sac tumor has to be kept in mind.

Rudimentary and Incipient-Yolk Sac Tumour- Testis

Yolk sac tumour of testis configures as a germ cell neoplasm comprised of cellular articulations or structures simulating embryonic or foetal yolk sac, allantois and extra-embryonal mesenchyme. Testicular yolk sac tumour is pre-eminently comprised of prepubertal subtype which is non-concordant to germ cell neoplasia in situ, emerges as a ‘pure’ neoplasm and demonstrates multiple gains within chromosome 1q, 20q or 22 and losses within chromosomes 1p, 4 or 6q. Postpubertal subtype is concurrent to germ cell neoplasia in situ (GCNIS), preponderantly configures as a component of ‘mixed tumour’ and occurs due to testicular dysgenesis syndrome, subfertility or as single nucleotide polymorphism (SNP) variants within KITLG, SPRY4 or DMRT1 genes and expounds gain of isochromosome 12p. Upon microscopy, neoplasm may configure distinctive configurations as microcystic or reticular pattern, macrocystic pattern, myxomatous pattern, sarcomatoid or spindle shaped cellular pattern, solid pattern, glandular or alveolar pattern, endodermal sinus or perivascular pattern, hepatoid pattern, papillary pattern, parietal pattern or poly-vesicular vitelline pattern. Yolk sac tumour appears immune reactive to alpha fetoprotein (AFP), glypican 3, SALL4, pancytokeratin, villin or CK7. Neoplastic cells appear immune non-reactive to OCT3/4, CD30, CD117, placental alkaline phosphatase (PLAP), podoplanin (D2-40), inhibin, GATA3 or p63. Testicular yolk sac tumour requires segregation from neoplasms as teratoma, seminoma, embryonal carcinoma, rete testis with hyaline globules and microcystic leydig cell tumour. Tumefaction preponderantly depicts elevated levels of serum alpha fetoprotein (AFP). Testicular yolk sac tumour may be optimally subjected to surgical manoeuvers as orchiectomy.

Analysis of GATA3 and FOXA2 expression suggests that downregulation of genes involved in the maintenance of a mature yolk sac tumor phenotype may underlie sarcomatoid transformation.

In the post-chemotherapy setting, germ cell tumors of the testis (GCTT) that resemble non-specific sarcomas and co-express cytokeratins and glypican-3 (GPC3) are diagnosed as "sarcomatoid yolk sac tumor postpubertal-type (YSTpt)". The diagnosis of sarcomatoid YSTpt is clinically relevant but challenging due to its rarity, non-specific histology, and negative α-fetoprotein (AFP) staining. Recently, FOXA2 has emerged as a key-gene in the reprogramming of GCTT (activating the transcription of several genes, among which GATA3), and immunohistochemical studies showed that GATA3 and FOXA2 have a higher sensitivity for non-sarcomatoid YSTpt than GPC3 and AFP. We found that sarcomatoid YSTpt did not express FOXA2 [0: 14/14 (100%)] and showed focal expression of GATA3 [0: 12/14 (85.7%), 1 + : 2/14 (14.3%)], thus suggesting that these markers are not useful in diagnosing this tumor. Furthermore, we proposed a potential mechanism of sarcomatoid transformation in the post-chemotherapy setting of GCTT, mediated by the downregulation of FOXA2 and GATA3.

Diagnosis and management of mediastinal extragonadal germ cell tumors

SummaryExtragonadal germ cell tumors (EGCT) are rare and comprise only 2–3% of all testicular germ cell tumors. The majority of EGCT are located in the mediastinum, followed by the retroperitoneum. Although histologically similar to germ cell tumors (GCT), EGCT have distinct histological patterns which result in a biologically aggressive variant of GCT with the need for interdisciplinary care in highly specialized centers. The majority of mediastinal EGCT harbor teratoma or yolk sac tumor elements. Treatment usually consists of a combination of systemic cytotoxic therapy and aggressive postchemotherapeutic surgery. First-line treatment for extragonadal seminomas and nonseminomas consists of three and four cycles of PEB or PEI, respectively. In patients with significantly elevated markers, a personalized approach based on adequate marker decline can be used, and in poor-risk patients, first-line high-dose chemotherapy might be discussed. Postchemotherapeutic surgery remains an integral part of the multidisciplinary treatment for nonseminomatous EGCT and it is of utmost importance that all residual masses, independent of size and location, are resected completely. Residual masses in seminomatous EGCTs rarely harbor vital cancer and might be followed by serial imaging studies or FDG-PET/CT. The prognosis of nonseminomatous EGCT is poor, with 5‑year overall survival rates of 17%, 60–70%, and 90% for poor, intermediate, and excellent prognosis, respectively. Prognosis for seminomatous EGCT is excellent, with 5‑year overall survival rates of 95% and 88% for good and intermediate prognosis, respectively. Salvage chemotherapy consists of high-dose chemotherapy or targeted therapy in very selected patients.

10121-BT-8 CLINICOPATHOLOGICAL ANALYSIS OF CENTRAL NERVOUS SYSTEM GERM CELL TUMORS -387CASES IN THE JCCG COHORT AND THE IGCT CONSORTIUM COHORT

Abstract BACKGROUND Central nervous system germ cell tumors (CNS GCTs) are rare primary tumors that tend to occur in East Asian boys. In Japan, the Japan Children's Cancer Group (JCCG) and the CNS GCT Genome Analysis Consortium (iGCT Consortium) have been accumulating clinical and pathological data on CNS-GCT cases. METHODS Statistical analyses were performed on 178 cases in the JCCG's Solid Tumor Observational Study (2016-2022) and 209 cases in the iGCT Consortium (2011-2021) for age, gender, site of origin, and pathological diagnosis. RESULTS There were 306 primary cases and 44 recurrent cases, 296 (77%) males and 90 (23%) females, with a median age of 13 years, 11 years for JCCG and 16 years for iGCT Consortium, with differences between these two cohorts. The most common pathological diagnosis was germinoma in 200 cases (52%). Non-germinomatous germ cell tumors (NGGCTs) in 167 cases (43%), of which 69 cases (18%) were mixed GCT with germinoma, 34 cases were immature teratoma, mature teratoma in 32 cases (8%), yolk sac tumor in 20 cases (5%), mixed GCT without germinoma in 5 cases (1%), choriocarcinoma in 5 cases (1%), embryonal carcinoma in 2 cases (0.5%). The median age of patients with germinoma was 15 years, while with other histological types was 12 years. The pineal gland was the most common site (208 cases, 56%) and 114 cases (31%) occurred in the neurohypophysis. 38 cases of them were bifocal. Tumor development in the basal ganglia occurred in 40 cases (11%), and multiple lesions were seen in 37 cases (10%). In the neurohypophysis, the male-to-female ratio was 1:1, while in the pineal region was 11:1. In the neurohypophysis, 67% had germinoma and 9% had teratoma, whereas, in the pineal regions, 50% had germinoma and 19% had teratoma. CONCLUSIONS CNS GCT is closely correlated with age, sex, site of origin, and histology.

Right ovarian Endodermal sinus tumor and left ovarian Gonadoblastoma in a young female of Turner’s syndrome: a case report.

Gonadal dysgenesis includes variety of clinical condition due to abnormalities of sex chromosomes. The most frequent of this condition is Turner’s syndrome, affecting 1 in every 2000 to 2500 live births. Gonadoblastoma is a benign lesion mostly detected in individuals with dysgenetic gonads with Y chromosome and has potential for malignant transformation; or may be associated with malignant germ cell tumors, most commonly dysgerminoma or occasionally immature teratoma, endodermal sinus tumor, embryonal carcinoma, or choriocarcinoma. We report a 22-year-old girl with primary amenorrhea and physical stigmas of Turner’s syndrome presented with huge abdominopelvic mass and abdominal pain. She underwent laparotomy with TAH with BSO with appendectomy with omentectomy with resection of portion of terminal ileum with ileoileal anastomosis with resection of sigmoid colon with colorectal anastomosis and right pelvic lymph node dissection. Patient had anastomotic site leak with sepsis with multi organ dysfunction syndrome and could not be revived. Final histopathology was consistent with endodermal sinus tumor in right ovary and gonadoblastoma in left ovary. Her karyotype analysis revealed 45, X0. Endodermal sinus tumor is a highly malignant gem cell tumor with poor prognosis. Gonadoblastoma associated with endodermal sinus tumor in Turner’s syndrome is very rare and challenging for the clinical management.

Retroperitoneal sarcomatoid yolk sac tumor in a chemotherapy-naïve patient with testicular teratoma

Abstract Introduction/Objective Sarcomatoid yolk sac tumor (SYST) is a rare histologic subtype of yolk sac tumor. In patients with testicular germ cell tumor, it is most frequently seen at the metastatic sites in the post-chemotherapy setting. SYST is rarely reported in chemotherapy-naïve testicular cancer patients in the existing literature. Herein, we report a rare concurrent retroperitoneal SYST in a chemotherapy-naïve testicular teratoma patient. Methods/Case Report A 37-year-old male presented with a 3.4 cm right testicular mass and a radical orchiectomy was performed, which demonstrated a pT1 teratoma with a separate adjacent regression fibrous nodule. His staging computed tomography revealed a heterogeneously enhancing and lobulated retroperitoneal mass measuring 9.6 cm in the greatest dimension. One month later, the mass enlarged to 26.3 cm. Fine needle aspiration biopsy revealed malignant spindle cell neoplasm with myxoid features, which displayed immunoreactivities for AE1/AE3, SALL4 and glypican 3, while was negative for OCT3/4, myogenin, SMA, desmin, S100 and CD34. Based on these findings, it was most compatible with SYST. The subsequent resection specimen showed a mass with soft fleshy to rubbery and friable gelatinous cut surfaces, and thorough tissue sections revealed the same histologic and immunophenotypic features as the prior biopsy. Therefore, a final diagnosis of SYST was rendered. Four cycles of cisplatin, etoposide, and ifosfamide (VIP) were administered, and the patient tolerated it well at his 6-month follow-up. Results (if a Case Study enter NA) NA Conclusion Here we presented a rare concurrent retroperitoneal SYST in a chemotherapy-naïve male patient who initially presented with a testicular teratoma. Due to its rarity, SYST may cause a diagnostic dilemma, and our case could raise awareness of this uncommon event and potentially expand the tumor spectrum.

Treated Non Seminomatous Germ Cell Tumor of Testes Post Resection of Teratomatous Lung Nodule

Background: Testicular tumors are relatively rare, accounting for only 1% of all malignancies in men. Among the different types of testicular tumors, germ cell tumors are the most common. They are very sensitive to chemotherapy and are curable even when metastatic. Cure rates approximates 90%-95% in good risk and early stage tumors. Earlier on, metastatic testicular cancer was usually incurable and fatal, but newer treatments including high-dose chemotherapy and stem cell rescue have changed the scenario. Case Presentation: This case report presents a case of a 30-year-old male with a large testicular tumor, diagnosed as a mixed germ cell tumor consisting of a yolk sac tumor, teratoma with immature elements, and seminoma with germ cell neoplasia in situ. After undergoing radical orchiectomy, the patient experienced a postoperative decline in alpha-fetoprotein levels and was placed on surveillance. Subsequent imaging revealed the development of a lung nodule, accompanied by an increase in alpha-fetoprotein levels. The patient received chemotherapy with three cycles of BEP (bleomycin, etoposide, platinum), resulting in a partial response. Due to the patient's COVID-19 infection, the final cycle of chemotherapy was modified. Further imaging showed a marginal decrease in the size of the lung nodule, prompting surgical resection. The lung nodule was found to be a post-pubertal teratoma without significant immature elements. Following surgery, the patient's alpha-fetoprotein levels decreased to a baseline nadir. Close follow-up continues, demonstrating no evidence of disease recurrence. Conclusion: This case emphasizes the importance of a multidisciplinary approach, including surgery and chemotherapy, in managing testicular germ cell tumors with metastasis, leading to favorable outcomes and long-term disease control.