Yolk Sac 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.

Diagnostic incidence and pitfalls of rete testis hyperplasia and hyaline globules in a multi-institutional study of 348 testicular germ cell tumors.

The concept of rete hyperplasia with hyaline globules simulating testicular yolk sac tumor was first reported in a mostly retrospective review over 30 years ago. Nonetheless, we continue to encounter examples where this scenario resulted in misdiagnosis. Herein, we sought to investigate the incidence of rete hyperplasia/hyaline globules in germ cell tumors and their associated subtypes and hypothesize an etiology. A consecutive series of 348 germ cell tumor orchiectomies was evaluated for the presence of rete hyperplasia and hyaline globules, with clinicopathologic features recorded. The incidence of rete hyperplasia and/or hyaline globules in our cohort was 30%, with 56% of specimens with rete hyperplasia containing concomitant hyaline globules. Hyaline globules were more often identified in specimens with nonfocal rete hyperplasia (78%) vs focal rete hyperplasia (22%). Absence of a yolk sac tumor component was seen in over half (61%) of orchiectomies with concurrent rete hyperplasia/hyaline globules (n = 105), inclusive of tumors with "pure" subtypes (ie, pure seminoma, pure teratoma, or pure embryonal carcinoma). Of these 105 specimens, rete invasion was seen in only 48%; notably, Paneth cell-like metaplasia was identified in efferent ductules/epididymis in 13%. Rete hyperplasia and hyaline globules are not uncommon findings in the setting of germ cell tumors (including occurrences in various pure/mixed germ cell tumors) and can show striking overlap with yolk sac tumor. We hypothesize that these histologic pitfalls evolve secondary to testicular obstruction by the tumor mass. Recognition of and distinguishing this morphologic mimicry is fundamental to guide appropriate clinical management.

Comparison of clinical characteristics of testicular tumor between children and adult population: a retrospective analysis

ObjectiveTesticular tumor (TT) is a uncommon disease posing serious health problem. There are differences in some aspects between adult and pediatric TT. The study was to compare their differences of clinical and histological characteristics through the analysis of the long-term experiences in TT patients from two institutions.Materials and methodsThe clinical data of hospitalized patients was collected and analyzed retrospectively from January 2014 to January 2024 at a pediatric and an adult institution, respectively. The data included composition, gender, age, initial presentation, tumor size, tumor markers, pathological diagnosis.ResultsA total of 195 hospitalized patients were included. There were 135 children and 60 adult with TT, respectively. Of these children, patients were aged from 1 month to 14 years, with a mean age of 2.32 years. More cases (37.04%) were diagnosed at age younger than 1 years. 69 cases were left-sided, 65 cases were right-side and only 1 case was bilateral. Pediatric TTs mainly included 82 prepubertal teratomas, 37 had prepubertal yolk sac tumors and 3 mixed malignant germ tumors. Testicular surgeries included testicular-sparing surgery (TSS) (n = 73), radical orchiectomy (n = 60), and testicular biopsy (n = 2). There were 24 patients receiving postoperative chemotherapy. Adult TTs mainly contained 17 seminomas, 10 prepubertal teratomas,7 postpubertal teratomas, 6 stromal tumors and 3 embryonal carcinomas. The average age was 34.08 years. There were 29 right-sided, 27 left-sided and 4 bilateral tumors. TSS (n = 26), radical orchiectomy (n = 33), and testicular biopsy (n = 1) were performed in these TT patients. Only 6 patients received postoperative chemotherapy. The most common symptom was a painless scrotal mass at initial diagnosis in both groups. In addition, we found that significant differences were explored between histological type and age, tumor size (P < 0.05). Yolk sac tumor and seminoma were the most common malignant TT in pediatric and adult population, respectively. After two year follow-up, two children with yolk sac tumor and 4 adults with seminoma died of their diseases.ConclusionsThe majority of pediatric cases were benign compared to adult. The most common type was prepubertal teratoma and yolk sac tumor. Pediatric TTs often occurred under the age of 1 year. Seminomas and prepubertal teratomas were commonly found in adult TTs, especially for young adult. We found that pediatric tumor type was associated with age and tumor size. TSS should be considered for benign TTs based on frozen biopsy findings in children.

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.

Mediastinal Teratoma with Angiosarcomatous Overgrowth in a Background of Vasculogenic Mesenchymal Tumor

Abstract Introduction/Objective Vasculogenic mesenchymal tumor refers to neoplastic reiteration of embryonic vasculogenesis. It is most commonly associated with nonseminomatous germ cell tumors of the mediastinum, in particular yolk sac tumor. In rare instances these lesions progress to angiosarcoma. Herein, we describe a case of angiosarcoma in a background of vasculogenic mesenchymal tumor in the setting of a mediastinal teratoma. Methods/Case Report A 33-year-old male, with a past medical history of anxiety, and right orchiectomy for testicular torsion, presented with shortness of breath, chest pain, and left arm swelling. Imaging studies demonstrated a mediastinal mass. Biopsy of the mass showed a germ cell tumor most compatible with a teratoma in the limited specimen. The patient received two rounds of chemotherapy and additional treatments were discontinued due to poor tolerance. Subsequent imaging showed continued increase in the size along with mass effect causing moderate to severe compression of the superior vena cava. Subsequently, the patient underwent resection of the mass. Grossly the mass was predominantly encapsulated with areas of capsular disruption. Sectioning revealed heterogeneous cut surfaces with fleshy, cystic, and necrotic areas. Morphologically the tumor was composed predominantly of teratomatous elements with areas of anastomosing atypical vascular channels within a hypocellular stroma suggestive of vascular genic mesenchymal as well as areas reminiscent of Masson lesion. Focally within these areas were malignant spindle cell proliferations compatible with angiosarcoma. The patient had an elevated AFP; however, no yolk sac tumor component was identified after thorough sampling. Final diagnosis of teratoma with angiosarcoma in a background of vasculogenic mesenchymal tumor was rendered after expert consultation. Results (if a Case Study enter NA) NA Conclusion Somatic-type malignancy and sarcomatous overgrowth are known to occur in mediastinal germ cell tumors; however, classification of the sarcomatous overgrowth can be challenging. Vasculogenic mesenchymal tumor is an exceedingly rare sarcomatous overgrowth that can rarely progress to angiosarcoma.

Metastatic Germ Cell Tumors Often Represent Continuous Evolving Processes (Somatic Transformation) toward SALL4-Positive Dominant Yolk Sac Tumors and Teratomas

Abstract Introduction/Objective SALL4 has been used to diagnose primary and metastatic germ cell tumors (GCT). However, it is not well established if SALL4 represents an evolving biomarker for GCT during the metastatic processes. Methods/Case Report We studied the fetal expression of SALL4 and a small series of metastatic GCT by comparing SALL4 expression (in all levels of GCT) with OCT3/4 expression (mainly in the early chain of germ cell tumors such as seminoma and embryonal carcinoma). Results (if a Case Study enter NA) First, we found SALL4 expression in Wolffian ducts and their surrounding stromal cells of 4 early embryos (5-7 weeks of gestation), implying that SALL4 may be involved in the early genital structure development. Then we identified 6 cases with metastatic GCT and compared SALL4 with OCT3/4 stains. The original tumors were all positive for both OCT3/4 and SALL4, but 4 out of 6 subsequently metastatic GCT stained positive only for SALL4 but not for OCT3/4. Particularly in case 5, the first two biopsies for metastatic GCT were positive for both biomarkers, but the last metastatic GCT to the gallbladders was positive only for SALL4. Conclusion Our pilot study raises the possibility that metastatic GCT may represent some evolving process to epithelial differentiated neoplasms (via somatic transformation) namely yolk sac tumor and teratoma along the germ cell differentiation chain. Therefore, SALL4 staining becomes a necessary step to avoid the pitfall of misdiagnosing unusual metastatic tumors with a known and unknown history of GCT particularly in male patients.

Expression of Heat Shock Protein 90 in Testicular Cancer: A Retrospective Cohort Study.

The HSP90 marker is believed to play a constructive role in facilitating neoplastic transformation mainly via interaction with multiple pro-survival proteins. Welldesigned studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors. The current study aimed to investigate the expression of HSP90 in various types of testicular cancer and highlight its expression in embryonal testicular cancer. Immunohistochemical staining for HSP90 in 84 male patients, with nonmetastatic testicular cancer, who underwent orchiectomy from 2000 to 2023, was retrospectively performed at the Laboratory Department of General Hospital of Nikaia in Greece. A total of 84 males, with a mean age of 36.2 years, who have undergone high-cord radical orchiectomy, were included in this study. Out of the included males, 28.57% had embryonal carcinoma, 23.81% had seminoma, 19.05% had yolk sac tumor, 11.9% had mature teratoma, 9.52% had immature teratoma, and 7.14% had choriocarcinoma. HSP90b was positive in all embryonal carcinoma, seminoma, and choriocarcinoma cases, while it was positive in 75% of the yolk sac tumor, 75% of mature teratoma, and 75% of immature teratoma specimens. HSP90 was found negative in all choriocarcinoma, mature teratoma, and immature teratoma specimens, while it was positive in 25% of yolk sac tumor, 8.33% of embryonal carcinoma, and 10% of seminoma cases. Concerning the expression of HSP90b, a statistically significant relationship was found between excised tumor specimens and normal parenchyma specimens, especially in sac cases (p <0.001). Regarding HSP90a expression, a statistically significant relationship (OR=21.5, p =0.021) was found between excised tumor specimens and normal parenchyma specimens, especially in embryonal carcinoma cases (p <0.001). HSP90b is highly expressed in the majority of the types of testicular tumors, both in tumor and normal parenchyma specimens, while HSP90a staining is negative in resected specimens. Further well-designed studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors.

Enhancing the accuracy of preoperative and intraoperative evaluation of malignant ovarian germ cell tumors with a focus on fertility preservation in young women.

To analyze and improve the accuracy of preoperative assessment and intraoperative frozen-section analysis (FSA) for malignant ovarian germ cell tumors (MOGCTs), especially in the context of fertility preservation. A retrospective review of 48 women aged under 40 years, diagnosed with MOGCTs, and treated at Chonnam National University Hospital between July and December 2022 was conducted. The results of preoperative magnetic resonance imaging (MRI), measurement of serum tumor markers (α-fetoprotein [AFP], β-human chorionic gonadotropin, lactate dehydrogenase [LDH], cancer antigen [CA] 125, CA 19-9, CA 72-4, carcinoembryonic antigen), and intraoperative FSA were compared with the final pathology diagnosis. MRI demonstrated a sensitivity of 95.5%, whereas FSA showed a sensitivity of 72.9% for all MOGCTs. Sensitivities varied according to the subtype, but were consistently higher in MRI (100% for dysgerminoma, 88.9% for immature teratoma, 100% for endodermal sinus tumor, 100% for others). However, there were differences in FSA according to subtype (100% for dysgerminoma, 50.0% for immature teratoma, 100% for endodermal sinus tumor, 25.0% for others). Serum tumor markers also provided diagnostic insights, particularly LDH for dysgerminoma (82.4%) and AFP for immature teratoma (75.0%) and endodermal sinus tumor (100%). Preoperative MRI and serum tumor marker measurement may be effective in guiding fertility-sparing surgical decisions. MRI could outperform FSA in terms of accuracy, especially for immature teratoma.

CLINICOHISTOPATHOLOGICAL STUDY OF TESTICULAR TUMOURS IN DR. HASAN SADIKIN GENERAL HOSPITAL BANDUNG

Objective: The purpose of this research was to describe the clinical and histopathological characteristics of testicular tumours at Hasan Sadikin General Hospital (RSHS) between 2017-2021. Material &amp; Methods: This research was a cross-sectional descriptive study examining the clinical and histopathological profiles of testicular tumours. The secondary data sources included medical records from the Department of Urology, Anatomic Pathology, Medical Records, and Hospital Information System (SIRS). The collected data covered age, ethnicity, clinical symptoms, site, stage, annual prevalence rate, and analyzed using Microsoft Excel. Results: There were 42 patients who had primary testicular tumour. The highest prevalence of testicular tumours at RSHS was in 2019 consist of 12(29%) patients and the lowest in 2020 were 6(14%) patients. Most patients were &gt;35 years old amounting 19(45%) patients, Sundanese ethnicity were 29(69%) patients, and testicular enlargement revealed in 27(64%) patients. Majority patients were in stage 0/IB 36(86%) patients and occurred in unilateral testis which 34(80%) patients, with 3(7%) patients metastasized. The most common histopathological type was seminoma 18(43%) cases followed by prepubertal-type yolk sac tumour 9(21%) patients. Seminomas, and the fibroma-thecoma group were mostly in patients over 35 years old, while prepubertal-type yolk sac tumour was more commonly in children under 15 years old. Conclusion: Prevalence of testicular tumours increased from 2017 to 2019, then started to decrease in 2020. Histopathologically, seminoma was the most common type. These tumours were most commonly found in older individuals (&gt;35 YO) and unilateral, diagnosed in stage 0/IB, and were mostly presented with enlargement of testis. Keywords: Testicular tumours, clinical features, histopathology

Primary yolk sac tumor of the endometrium combined with situs inversus totalis: a case report and literature review

BackgroundYolk sac tumor (YST) is a highly malignant germ cell tumor, a majority of which originate from the gonads and are extremely rare from endometrium.Case presentationHere we present a case of a 42-year-old woman suffered from primary pure yolk sac tumor of the endometrium complicated with situs inversus totalis. The patient presented at our hospital with irregular vaginal bleeding. Imageological examination showed a space-occupying lesion in the cervix and the serum Alpha-fetoprotein (AFP) level was significantly high (more than 1210ng/ml). Then she underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection. The subsequent postoperative pathological diagnosis was yolk sac tumor arising from the endometrium. Next, the patient was treated with 6 cycles of chemotherapy with Pingyangmycin, etoposide and cisplatin regimen and was alive without evidence of recurrence or distant metastases for 13 months.ConclusionsThis rare disease needs to be differentiated from endometrial epithelial neoplasia and the significant increase in AFP is helpful for diagnosis. Combined with previous literature reports, comprehensive staging laparotomy or maximum cytoreductive surgery complemented by standard chemotherapy can usually achieve a good efficacy.

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.

A single center experience on PI3K/AKT/MTOR signaling defects: Towards pathogenicity assessment for four novel defects.

Phosphoinositide 3 kinases (PI3K) are lipid kinases expressed in lymphocytes/myeloid cells. PI3K/AKT/mTOR signaling defects present with recurrent infections, autoimmunity, lymphoproliferation, and agammaglobulinemia. To characterize the PI3K/AKT/mTOR pathway defects and perform pathway analyses to assess novel variant pathogenicity. We included 12 patients (heterozygous PIK3CD (n = 9) and PIK3R1 (n = 1) (activated PI3K delta syndrome (APDS) with gain-of-function mutations) and homozygous PIK3R1 variant (n = 2)), performed clinical/laboratory/genetic evaluation, and flow cytometric PI3K/AKT/mTOR pathway analyses. Median age at onset of complaints was 17.5 months (3 months to 12 years) and at diagnosis was 15.7 years (2.5-37) in APDS. Median diagnostic delay was 12.9 years (1.6-27). Recurrent respiratory tract infections (90%), lymphoproliferation (70%), autoimmune/inflammatory findings (60%), and allergy (40%) were common in APDS. Recurrent viral infections were present in 4/10 and malignancy (non-Hodgkin lymphoma and testicular yolk sac tumor) was present in 2/10 in APDS. Low CD4+ T cells(5/8) with increased CD4+ effector memory (8/8) and CD4+ TEMRA cells (6/8) were present in the given number of APDS patients. We diagnosed tubulointerstitial nephritis, Langerhans cell histiocytosis, and late-onset congenital adrenal hyperplasia in APDS. Allergic findings, lymphoproliferation/malignancy, and high IgM were present in the APDS but not in PIK3R1 deficiency. Low IgM/IgG/CD19+ B cell counts were characteristic in patients with PIK3R1 homozygous loss-of function mutations. Differential diagnosis with combined immunodeficiency and diseases of immune dysregulation make molecular genetic analysis crucial for diagnosing mTOR pathway defects. It is easy to differentiate APDS and homozygous PIK3R1 defects with specific laboratory features. Additionally, mTOR pathway functional analysis is a definitive diagnostic and pathogenicity assessment tool for novel APDS mutations.

The expression of programmed cell death ligand 1 (PD-L1) involves in the clinicopathologic characteristics and prognostic implications of testicular germ cell tumor (TGCT): a systematic review and meta-analysis.

Testicular germ cell tumor (TGCT) is a type of tumor with relatively lower incidence but being more prevalent in young men. The expression of programmed cell death ligand 1 (PD-L1) serves as a potential biomarker for predicting the survival outcomes of other tumors. Some studies discovered higher prevalence of PD-L1 in TGCT patients who achieved favorable treatment outcomes, while other studies showed lower or absent expression of PD-L1 in TGCT with the better prognosis as well. Therefore, in order to address this controversy and clarify the association between the expression of PD-L1 and pathological features and prognosis of TGCT, this meta-analysis was conducted. A comprehensive literature search was performed using following search terms: "testis", "testicle", "testicular", "cancer", "carcinoma", "tumor", "neoplasm", "programmed cell death ligand 1", "programmed death ligand 1", "PD-L1", "PDL1", "B7 homolog 1", "B7-H1", "B7H1" and "CD274". Relevant studies were retrieved according to the inclusion criteria from reputable databases including PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI). These studies investigated the expression of PD-L1 in both tumor cells and tumor infiltrating immune cells (TIICs) in TGCT. The overall proportion of PD-L1 positivity was assessed using R programming. Pooled hazard ratio (HR) and odds ratio (OR) with corresponding 95% confidence interval (CI) were calculated using Revman software to evaluate the involvement of PD-L1 expression in TGCT. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality assessment of included studies. Sensitivity analysis and publication bias evaluation were subsequently performed. A total of eight eligible studies compromising 1,589 patients diagnosed with TGCT were finally included in this study. PD-L1 positivity was detected in 31% and 41% of TGCT patients' tumor cells and TIICs, respectively. The pooled data demonstrated a significant association between elevated PD-L1 expression levels in TIICs and a favorable prognosis characterized by the reduced disease progression and relapse events (HR =0.21, 95% CI: 0.13-0.33). Furthermore, PD-L1+ TIICs exhibited higher prevalence rates in seminoma (OR =2.11, 95% CI: 1.57-2.84) and embryonal carcinoma (OR =6.23, 95% CI: 2.42-16.02) patients. Notably, PD-L1 expression in TIICs displayed a tendency to increase in TGCT patients with lower stages or without lymph node metastasis. PD-L1 expression was observed in choriocarcinoma tumor cells, while yolk sac tumor and teratoma tumor cells exhibited lower or absent expression of PD-L1. Conversely, PD-L1 expression in TIICs was associated with seminoma and embryonal carcinoma, which was more commonly observed in TGCT patients with lower stages and better prognosis, thereby providing a theoretical foundation for the application of immunotherapy in relapsed/refractory TGCT patients.

Association of serum alpha-fetoprotein (AFP) with indirect prognosis in gastric cancer

Aims: Alpha-fetoprotein (AFP) is a glycoprotein secreted from the yolk sac and hepatocytes during fetal life. Elevated levels in adults are considered markers for yolk sac tumors, hepatocellular carcinoma and gastric cancer. There is still no consensus on the definition of AFP-secreting gastric cancers, but AFP-secreting gastric cancers have been reported to have a worse prognosis. In this study, AFP levels in gastric cancers with high AFP were compared with pathology results and evaluated in terms of indirect prognosis. Methods: Patients with gastric cancer operated in the General Surgery Clinic of Ankara Bilkent City Hospital between 2019 and 2023 were retrospectively screened. Among the screened patients, those whose information could not be reached and those with incomplete information were excluded and 126 patients were included in the study. Serum AFP levels of these patients were compared with pathology results, stages and tumor sizes. Results: The mean age of the patients in our study was 66±11 years, 42 (33.6%) were female and 84 (66.7%) were male. Of the 126 patients analyzed in the study, 107 (84.9%) were AFP-negative and 19 (15.1%) were AFP-positive. There was no significant difference in AFP levels between all patients in terms of liver metastasis, peritoneal metastasis, disease stage, perineural invasion and tumor location. However, serum AFP levels were significantly higher in patients with lymphovascular invasion and lung metastases (p=0.042; p=0.024). In the analysis for serum AFP level in the presence of lymphovascular invasion, ROC value was 2.35 ng/ml, sensitivity 58.2%, specificity 55.9%, area under the curve (AUC) 0.618, 95% confidence interval (95% CI) 0.512-0.723 and p=0.028. Conclusion: Lymphovascular invasion is a poor prognostic factor in gastric cancer. In this study, a significant correlation was found between serum AFP value and lymphovascular invasion. In gastric cancers without AFP secretion, a serum AFP value above 2.35 ng/ml may be indirectly associated with poor prognosis because it predicts lymphovascular invasion.

Spectrum of Somatic Malignancy in Testicular Germ Cell Tumors—A Histopathological Review of 25 Cases with Clinical Outcome

Abstract Introduction Germ cell tumors (GCTs) are the commonest testicular malignancy in young males. These tumors are highly chemoresponsive, however become resistant to conventional therapy when a somatic-type malignancy (SM) develops, which happens in ∼3 to 6% of the cases. Methods We reviewed the histologic profile of all cases of testicular/retroperitoneal GCT with SM, diagnosed over a period of 12 years in our institute. Correlation of histologic profile with clinical outcome was done wherever feasible. Results A total of 25 cases of testicular/retroperitoneal GCT with SM were identified for review. The histological spectrum of SMs included carcinoma (n = 9), sarcoma (n = 9), embryonic-type neuroectodermal tumor (ENET) (n = 4), and other rare histological types (n = 3). SMs were frequently seen at the resected metastatic sites (n = 13) and in postchemotherapy setting (n = 12); 14 cases had concurrent GCT and SM at the time of diagnosis/initial resection and 9 cases presented as late relapses (more than 2 years after initial presentation). Four patients were treated with metastasectomy and lymph node dissection, six patients were treated with combined resection and chemotherapy, and nine patients were treated with only adjuvant chemotherapy. The patients with SM confined to testis and those treated with multimodality approach had relatively better outcome. Conclusion GCTs with SM are a highly heterogeneous group of tumors with varying histologic types and management strategies. Strict adherence to histological diagnostic criteria, differentiating these tumors from close mimics such as glandular and sarcomatoid yolk sac tumors, teratomatous overgrowth, and a new second primary somatic tumor are important due to implications in management and prognosis.

Management and Outcomes of Children with Malignant Germ Cell Tumor.

To assess the clinico-pathological features, management and outcomes, amongst extracranial malignant germ cell tumors (MGCTs) in children treated primarily at a tertiary care center in a resource-challenged nation. The prospectively maintained data for children below 14 y of age treated for extracranial MGCT from May 1994 to January 2023 was analyzed for patient characteristics, management, event-free survival (EFS) and overall survival (OS) and factors effecting survival. Events was defined as death, recurrence and progression. Multivariate logistic regression analysis was performed to identify the factors independently predicting unfavorable outcomes. One hundred and seventy-seven children (37% males) with a median (IQR) age at presentation of 30 mo (range 2-168 mo) were included. The cohort consisted of 87 (49%) extra-gonadal and 90 (51%) gonadal cases. Disease was metastatic at presentation in 48 (27%) with lungs being the most common site. Neoadjuvant chemotherapy (NACT) was given to 119 (67%) and finally 162/177 (92%) had undergone resection of the primary tumor. Endodermal sinus tumor (EST) was the commonest histological subtype in 141 children (73%). Twenty-two (12%) patients had died giving a 5-y OS of 84.7% (95% CI 78.3- 91.1). Recurrence occurred in 25 patients, and an additional 5 patients had progression giving a 5-y EFS of 69.9% (95% CI 62.5- 77.3). Stage III (p = 0.05), Stage IV (p = 0.006) and extra-gonadal site (p = 0.05) were significantly associated with poorer EFS. Children with MGCT have a favorable outcome with 5-y OS of 84.7% and EFS of 69.9%. Stage III and IV disease and extra-gonadal sites were independent predictors of a poor outcome.

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.

Association between glutathione S-transferases M1 expression and treatment outcome in germ cell tumor patients.

Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.

Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Impact of microscopic deposits of yolk sac tumor on recurrence of mature sacrococcygeal teratoma.

Sacrococcygeal teratomas (SCT) with malignant histology frequently recur and are treated aggressively, but risk factors and surveillance protocols are less established for mature tumors. In particular, prior studies have not investigated whether microscopic deposits of yolk sac tumor (YST) in otherwise mature teratomas lead to higher recurrence rates. We reviewed patients with mature SCTs resected at our institution from 2011 to 2021 and analyzed tumor characteristics, treatment, and outcomes. We identified 56 patients with mature SCT, of which 9 (16%) demonstrated microscopic YST. Following surgery, 7/56 (13%) patients developed local recurrence at a mean of 1.2 ± 0.7 years, while no patients developed metastases. Recurrence was more likely in patients with microscopic YST [5/9 (56%) vs. 2/47 (4%), p = 0.021] and positive margins [6/24 (35%) vs. 1/32 (3.1%), p = 0.030]. A solid tumor component tended to increase recurrence risk as well [6/29 (21%) vs. 1/27 (4%), p = 0.053]. Five patients demonstrated malignant recurrence and were all detected by a rising alpha-fetoprotein (AFP), while two patients demonstrated recurrence of mature teratoma and were detected on surveillance magnetic resonance imaging (MRI). Microscopic foci of YST may increase recurrence risk for patients with mature SCT. Such patients might benefit from closer postoperative surveillance with serial AFP measurements and MRI.