Cases Of Germ Cell Tumors Research Articles

Metastatic germ cell tumors in serous cavities and cerebrospinal fluid: A single-center experience.

Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature. A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid. The most common primary site was the testis (n=10), followed by the ovaries (n=7), mediastinum (n=4), retroperitoneum (n=3), pineal gland (n=2), and sacrum/coccyx (n=1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0-134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty-four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months. Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.

Ovarian Germ Cell Tumors in North-Western India: A Comprehensive 3-Year Retrospective Study of 145 Cases at a Tertiary Cancer Hospital.

Germ cell tumors encompass a broad spectrum of neoplasms arising from germ cell lineage, demonstrating varying histological profiles and clinical presentations. These tumors encompass a range of benign and malignant entities. While global trends provide insights into their prevalence, specific regional variations, such as those within North-Western India, remain less explored. This study seeks to bridge this knowledge gap by examining the prevalence and characteristics of germ cell tumors within a tertiary cancer hospital. In this retrospective analysis, all cases of germ cell tumors diagnosed over a 3-year period in the specified tertiary cancer hospital were included. Cases with incomplete records or inadequate pathological data were excluded. Data encompassing histological subtypes, patient age distribution, clinical presentations, and histopathological features were collected and analyzed. The study comprised 145 cases of germ cell tumors. Teratomas were the most prevalent subtype, with mature teratomas accounting for the majority. The highest incidence occurred within the 21-30-year age group with a mean age of 24.77years. Abdominal mass (56%) and abdominal pain (34%) were the prominent clinical presentations. Benign cases constituted the majority 85.5%. Solid tumors (p < 0.00001) and tumors more than 10cm (p .029028) were found to have a high propensity to be malignant, which was proven to be statistically significant. This study comprehensively explains germ cell tumors' prevalence, clinical features, and histopathological subtypes in a tertiary cancer hospital in North-Western India. The predominance of teratomas, particularly mature ones, aligns with global trends. The age distribution and clinical presentations reflect common patterns. The diverse histopathological appearances underscore the heterogeneous nature of germ cell tumors. This study offers valuable insights for clinical management and further regional research.

Clinicopathological Analysis of Adnexal Masses Presenting in a Tertiary Healthcare Centre, Karnataka, India: A Retrospective Observational Study

Introduction: The ovaries, fallopian tubes, and the broad ligament make up the anatomical adnexa. Adnexal masses represent a commonly occurring issue in gynaecology. The majority of ovarian malignancies are detected at advanced stages. The clinical manifestations of adnexal masses vary, with many cancers either showing no symptoms or presenting with vague signs. In the reproductive age group, the most typical manifestation is a benign functional cyst. Aim: To conduct a clinico-pathological analysis of adnexal masses among women presenting at a tertiary healthcare centre. Materials and Methods: A retrospective observational study was conducted in the Department of Obstetrics and Gynaecology at Akash Institute of Medical Science and Research Centre, Devanahalli, Karnataka, India, from November 2022 to April 2024. The diagnosis of adnexal mass was based on clinical symptoms, abdominal examination, bimanual examination, and trans-abdominal ultrasound. The CA-125 and other tumour markers were sent depending on the risk of malignancy. All tissues were sent for histopathological examination. The data were collected and tabulated in a Microsoft excel sheet, and percentages were calculated. Results: This study included 38 cases, in which benign ovarian and para-ovarian cysts were the most common findings, observed in 21 cases (55.3%). There were six cases of benign serous cystadenoma (15.8%), three cases of teratoma (7.9%), two cases of high-grade serous carcinoma (5.3%), one case of germ cell tumour (2.6%), one case of mucinous cystadenoma (2.6%), two cases of endometriotic cysts (5.3%), one case of adnexal cystic degeneration of a fibroid (2.6%), and one rare case of primary fallopian tube carcinoma (2.6%). The most common presenting complaint was abdominal pain, reported in 21 cases (55.3%). Conclusion: Adnexal masses can present in a variety of forms, ranging from benign cysts to infections and cancers. A thorough history and clinical examination are essential for accurate diagnosis. Investigations support the diagnosis, and histology confirms it.

Clinico-epidemiological Profile and Outcome of Testicular Germ Cell Tumors: A Retrospective Study from a Tertiary Cancer Centre of North-East India

Introduction: Testicular Germ Cell Tumor (GCT) is a disease of young adults and is also highly curable. But in India, most of the patients present in an advanced stage and succumb to the disease as compared to the Western nations where patients present at an earlier stage and are mostly cured. Also, there is a scarcity of literature on testicular GCT from the Indian subcontinent. We present our experience from the Tata Memorial Centre of North-east India. Methods: This retrospective study was conducted at Tata Memorial Centre - BBCI, Guwahati for the period of 5 years from January 2018 to December 2022. The study focused on epidemiology, clinical presentation, and treatment outcomes. Results: Seventy-two cases of testicular GCTs were studied (28 cases were seminoma, and 44 were non-seminoma). Most common presenting stage was stage I in seminoma (53.6%), and stage III (77.2%) in non-seminoma. As per the International Germ Cell Cancer Collaborative Group (IGCCCG) classification, 25%, 35%, and 40% of patients were good-risk, intermediate-risk, and poor-risk in non-seminoma. In patients with seminoma, 54% and 46% were in good and intermediate-risk, respectively. Seventy-two percent and 21% had achieved a radiologic complete response (CR) and partial response (PR) with conventional chemotherapy in patients with seminoma. Radiologic CR and PR rates were 20% and 61% among non-seminoma patients. The median recurrence-free survival (RFS) was 43 months. RFS was better in seminoma versus non-seminoma, stage I versus stage III, and good-risk versus high-risk group. Conclusion: Most of our patients presented with an advanced stage of the disease and a high nodal burden. In patients with non-seminoma GCT, the best response to conventional chemotherapy was a partial response. The use of an alternative chemotherapy regimen to improve outcomes for such patients can be further explored.

Extracranial Germ Cell Tumors in Children: Ten Years of Experience in Three Children's Medical Centers in Shanghai.

The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant germ cell tumors (MGCTs) in order to optimize therapeutic options. The clinical data of children with extracranial GCTs in three children's medical centers in Shanghai were retrospectively analyzed. In total, 1007 cases of extracranial GCTs diagnosed between 2010 and 2019 were included in this study, including teratomas (TERs) 706 (70.11%) and MGCTs 301 (29.89%). There were twice as many TER cases as MGCT cases. Approximately 50% of children with GCTs were <3 years old (43.39% for TERs, 67.13% for MGCTs). GCTs in children of different ages show differences in tumor anatomical locations and pathological subtypes. The 5-year event-free survival (EFS) and overall survival (OS) of all patients with MGCTs were 82.33% (95% CI, 77.32%, 86.62%) and 94.13% (95% CI, 90.02%, 96.69%), respectively. The multivariate Cox regression analysis identified a primary site in the mediastinum and alpha fetoprotein (AFP) levels ≥10,000 ng/mL as independent adverse prognostic factors (p < 0.0.0001, χ2 = 23.6638, p = 0.0225, χ2 = 5.2072.). There were no significant differences in OS among children receiving various chemotherapy regimens, such as the BEP, PEB, JEB and other regimens (VBP/VIP and AVCP/IEV) (p < 0.05). The clinical features of GCTs in Chinese pediatrics are similar to those reported in children in Europe and America. The age distribution of pathological types and primary sites in GCTs reflect the developmental origin of type I and type II GCTs transformed from mismigration primordial germ cells (PGCs). Optimizing the current platinum-based chemotherapy regimens and exploring the treatment strategies for MGCTs of the mediastinum are future research directions.

Epidemiology, Management, and Survival Outcomes of Germ Cell Cancer in Southern Portugal: A Population-Based Study (2008-2012)

IntroductionBuilding on previous suboptimal survival results, we aimed to perform a study of the epidemiological status, management, and outcomes of germ cell tumors (GCT) in the Portuguese population. Materials and MethodsRetrospective populational study of GCT cases diagnosed between 2008 and 2012 in southern Portugal. Joinpoint regression was used to compute average annual percentage change (AAPC) in incidence rate. ESMO/EAU guidelines served as references to evaluate compliance. Association between compliance with guidelines and hospital GCT case load was performed by generalized estimating equation. Survival was calculated by Kaplan–Meier and prognostic factors by Cox models. ResultsThe study included 401 GCT male cases. The AAPC was 5.4% (IC 95% 3.3-7.4, P < .001) from 1999 (an earlier cohort published) to 2012. The median time to diagnosis was 63 days (Q25 = 33 days; Q75 = 114 days; IQR = 81 days). For stage II/III the median time to start chemotherapy was 34 days (Q25 = 22 days; Q75 = 56 days; IQR = 22 days). In 86% cases there was noncompliance with guidelines for the orchiectomy report, 6% for staging, 38% for tumor markers evaluation, 20% for treatment and 25% for chemotherapy dose intensity. The 5-year overall survival was 93.8% (95% CI, 91.3%-96.4%). Hospitals that managed ≤ 3 GCT cases/ year had higher odds for noncompliance with guidelines of blood markers, treatment and dose intensity. None of GCT healthcare access and management factors studied were associated with prognosis. ConclusionsThe burden of GCT is rising in Portugal. Although survival has improved, efforts must be made to nationally enhance training and expertise in GCT and support region adapted models of centralization of care.

Analysis of microsatellite instability (MSI) in pediatric gonadal and extra-gonadal germ cell tumors.

Gonadal and extragonadal pediatric germ cell tumors (GCTs) are rare neoplasms with different clinical behavior. Although surgery and cisplatin-based chemotherapy are resolutive in most cases, some patients do not respond to chemotherapy and have a worse outcome. Microsatellite instability (MSI) was correlated to resistance to chemotherapy and sensitivity to immunotherapy in different neoplasms. A series of 21 pediatric GCTs were tested by immuno-histochemistry and PCR to evaluate MSI status. Next generation sequencing was applied to further evaluate cases with discordant results between immunohistochemistry and PCR. Twenty-one cases of pediatric GCT were included in the series. The mean age ranged between 1 and 10 years. Nine cases were gonadal GCTs and the remaining 12 were extra-gonadal GCTs. By immunohistochemistry, one case showed a deficit of Mismatch repair (MMR) proteins. This case was a 1-year-old children affected by gonadal yolk sac tumor. However, all cases resulted microsatellite stable (MSS) by PCR and NGS. MSI was not detected in our series of pediatric GCTs, as well as the data present in literature about adult patients with GCTs. Molecular techniques could have a role to confirm the MSI status in case of dMMR by immunohistochemistry.

Associations between birth defects and childhood and adolescent germ cell tumors according to sex, histologic subtype, and site.

Studies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics. Birth defect-GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population-based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. The odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status were estimated by using unconditional logistic regression. All defects were considered collectively and by genetic and chromosomal syndromes and nonsyndromic defects. Stratification was by sex, tumor histology (yolk sac tumor, teratoma, germinoma, and mixed/other), and location (gonadal, extragonadal, and intracranial). Birth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0% and 2.7% vs. 0.2%, respectively; both p < .001). In multivariable models, GCT risk was increased among children with birth defects (OR, 1.7; 95% CI, 1.3-2.4) and syndromic defects (OR, 10.4; 95% CI, 4.9-22.1). When stratified by tumor characteristics, birth defects were associated with yolk sac tumors (OR, 2.7; 95% CI, 1.3-5.0) and mixed/other histologies (OR, 2.1; 95% CI, 1.2-3.5) and both gonadal tumors (OR, 1.7; 95% CI, 1.0-2.7) and extragonadal tumors (OR, 3.8; 95% CI, 2.1-6.5). Nonsyndromic defects specifically were not associated with GCTs. In sex-stratified analyses, associations were observed among males but not females. These data suggest that males with syndromic birth defects are at an increased risk of pediatric GCTs, whereasmales with nonsyndromic defects and females are not at an increased risk. We investigated whether birth defects (such as congenital heart disease or Down syndrome) are linked to childhood germ cell tumors (GCTs), cancers that mainly develop in the ovaries or testes. We studied different types of birth defects (defects that were caused by chromosome changes such as Down syndrome or Klinefelter syndrome and defects that were not) and different types of GCTs. Only chromosome changes such as Down syndrome or Klinefelter syndrome were linked to GCTs. Our study suggests that most children with birth defects are not at an increased risk of GCTs because most birth defects are not caused by chromosome changes.

Clinical and pathological characteristics of extra-cranial germ cell tumors: A 30-year single-center experience in Saudi Arabia.

To investigate the clinical and pathological characteristics of extracranial germ cell tumors (GCTs) in children aged 0-168 months treated at the National Guard Hospital, Jeddah, Saudi Arabia from 1990 to 2020. In this retrospective analysis, the data for all cases of GCTs were collected from 1990 to 2020. Statistical analyses were carried out using JMP software. The data was divided into 4 main categories: demographics, pathological/clinical features, recurrence, treatment and outcome. The study included 50 patients, with a mean age at diagnosis of 56.52 months. The median follow-up duration was 30 months. Most tumors were in the gonads, and among the extragonadal tumors, the sacro-coccyx was the most frequent site of the disease.The most common histological subtype of GCTs is yolk sac tumor, accounting for 28% of cases. Of the 50 patients, 46% received chemotherapy, and 54% underwent surgery without chemotherapy. Ten (20%) patients experienced recurrence after treatment. At the last follow-up, 96% of the patients were alive, and only 2 of the patients died due to advanced disease. Our findings were comparable to international data, but improvement in surveillance is required for long-term survivors.

COT-12 ANALYSIS OF 5-ALA STRONGLY POSITIVE FINDINGS USING IMAGE J FOR MALIGNANT BRAIN TUMOR

Abstract For brain tumor surgery using 5-ALA during surgery, we analyze the brightness using image analysis software Image J, we report the results to date for strongly positive findings. Thirty-nine patients who were suspected of having malignant glioma before surgery and who were strongly positive for 5-ALA during surgery were included. (21 malignant glioma, 14 metastatic brain tumor, 3 meningioma, and 1 germ cell tumor.) Intraoperative 5-ALA-positive findings were analyzed with image analysis software Image J (Wayne Rasband: NIH), brightness was measured with histograms, and maximum brightness was compared. The average maximum brightness titer was 106.38 (50-225) in 21 cases of malignant glioma. The brightness titer was 84.5 (28-121) in 14 cases of metastatic brain tumor, 80 (59-97) in meningioma, and 43 in 1 case of germ cell tumor. No clear correlation was found between brightness, tumor grading, and MIB-1 LI. In addition, a clear difference in luminance was observed between the tumor and the ventricle in one case.By analyzing brightness with Image J, it will be possible to obtain informations about tumors from different perspectives.

A North-West London Experience of the Impact of Treatment Related Toxicity on Clinical Outcomes of Elderly Patients with Germ Cell Tumors.

Simple SummaryGerm cell testicular cancer is seen in men aged 15–35. Incidence of this cancer in the elderly aged > 45 is less than 10%. The aim of our retrospective study is to understand the treatment-related toxicity in the elderly population, the chemotherapy regimens used, and its tolerability in this age group. Incidence of non-seminomatous germ cell cancer was 42% and incidence of seminoma was 58% in this cohort of patients. We used chemotherapy regimens, similar to those used in the younger population; platinum-based regimens were the backbone of the treatment algorithm. Outcomes were similar to the population group aged 15–35, and around 96% of the population were alive 5 years after and beyond. Toxicity was more common in this age group, and careful consideration should be made for dose modification and appropriate use of supportive therapies.Background/Aim: The occurrence of germ cell tumour (GCT) in the elderly is rare, with scarce data available. The aim of this study was to understand the clinical outcomes of patients with GCT in patients aged > 45 years. Materials and Methods: A retrospective study was conducted in a large tertiary cancer centre in north-west London. Between 1 January 2003 and 31 March 2022, 108 cases of GCT in men aged > 45 years were identified and treated at the Mount Vernon Cancer Centre. The median age at diagnosis was 54 years (range = 45–70 years). Results: The 5-year survival rate of all patients was 96%, and the toxicity profile was similar to the younger age group. Conclusion: Older patients with GCT are able to tolerate chemotherapy; however, care must be taken to prevent life-threatening complications using appropriate dose modification.

Role of Lactate Dehydrogenase in Identifying Relapse for Patients With Stage I Testicular Cancer on Surveillance.

Tumor markers alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase assume a key role in the management of testicular germ cell tumors. While alpha-fetoprotein and human chorionic gonadotropin have modest sensitivity and specificity for germ cell tumors, lactate dehydrogenase has weak sensitivity and specificity. We explored the utility of lactate dehydrogenase in identifying relapse among stage I seminomatous and nonseminomatous germ cell tumors on surveillance. Patients with a history of stage I testicular germ cell tumors were identified from a prospectively maintained database at the Princess Margaret Cancer Centre from December 1980 to May 2021 and surveyed according to established institutional algorithm guidelines. The utility of lactate dehydrogenase elevation to independently detect germ cell tumor relapse was examined. Among 1,014 seminoma and 676 nonseminomatous germ cell tumor patients, 176 and 176 patients relapsed with a median time to relapse of 13.6 and 8.9 months, respectively. Imaging alone was the most common mode of relapse detection in 144 and 74 of seminoma and nonseminomatous germ cell tumor patients, respectively. Lactate dehydrogenase was elevated in 49 cases of seminoma and 38 cases of nonseminomatous germ cell tumors at relapse, but was never the sole relapse indicator. Among 350 seminoma and 311 nonseminomatous germ cell tumor patients who never relapsed, 210 and 233, respectively, had at least 1 elevated lactate dehydrogenase value. Lactate dehydrogenase alone did not independently contribute to early relapse detection in stage I seminoma or nonseminomatous germ cell tumor. Elevated lactate dehydrogenase values were documented in a high proportion of nonrelapsing seminoma and nonseminomatous germ cell tumor cases.

Abstract 2497: Inherited copy number variants that increase risk of developing pediatric germ cell tumors with a particular focus on the X chromosome

Abstract Pediatric malignant germ cell tumors (GCTs) are heterogeneous but are grouped together due to the presumed common cell of origin, the primordial germ cell (PGC). Little is known about etiology; however, evidence supporting in utero origins of pediatric and adult GCT suggests that disruptions in normal germ cell development are likely to be highly relevant. Germline copy number variants (CNVs) are a plausible source of inherited genetic variation and have not been thoroughly evaluated to date. CNVs on the X chromosome are of particular interest because individuals with both Klinefelter syndrome (47, XXY) and Turner syndrome (45, X) are at increased risk of pediatric GCT, suggesting that alterations in X chromosome dosage contribute to etiology. A family study of adult testicular cancer where at least one member had bilateral cancer identified a significant linkage peak at Xq27 (hLOD=4.7). In addition, somatic copy number gains of chromosome X are frequently seen in adult testicular germ cell tumors. Given these findings in adult GCT, similar aberrations may also be relevant risk factors for the pediatric group. Pediatric GCT samples were obtained from a Children’s Oncology Group study and state biobank programs in Michigan and California. Genotyping array data were generated using the Illumina HumanCoreExome Beadchip (Illumina, San Diego). CNV calls were made for 2,002 GCT cases and 1,402 controls with high quality intensity data using Genvisis, which has specialized algorithms to make CNV calls on the X chromosome. Klinefelter syndrome cases (n=27) were excluded from the analyses. No study sample had classic Turner syndrome; however, one female case had a giant 51Mb deletion of Xq. Analyses were performed for females-only, males-only, and everyone together. We identified two regions that are study-wide significant on chromosome X at Xq27.1 and Xp11.2 and one nominally significant near Xq28. The most significant finding was identified in females-only and is located within a region that encodes genes within the SPANX family. Evidence suggests these genes affect germ cells; however, supporting data is reported in spermatozoa rather than oocytes. The events in our study were large (240kb), had similar breakpoints, and appear to be flanked by repetitive DNA that might lead to recurrent events at the same region. The variant was present in the control samples within gnomAD at a low allele frequency (0.18%). In our study, both deletions and duplications were noted: 11 female cases (1 or 2 expected based on gnomAD allele frequencies) and 0 female controls (0-1 expected). The finding was not replicated in males (6 male cases and 5 male controls harbored similar CNVs). We are in the process of validating these in silico and potentially via quantitative PCR. Findings may shed light on disruptions in normal development that may increase risk of GCT. Citation Format: Shannon S. Cigan, John J. Meredith, John Zaharick, Erica Langer, Anthony J. Hooten, John A. Lane, Nathan Pankratz, Jenny N. Poynter. Inherited copy number variants that increase risk of developing pediatric germ cell tumors with a particular focus on the X chromosome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2497.

Germ cell tumors with neuroglial differentiation do not show molecular features akin to their central nervous system counterpart: experience from extra-gynecological sites.

Teratomas with secondary somatic malignancy showing neuroglial differentiation (central nervous system (CNS)-type tumors) arising from a glial or neuroepithelial component is a very uncommon event and primarily described in the ovary. We aimed to describe the morphological spectrum and molecular features of CNS type of neuroepithelial tumors arising from the germ cell tumors (GCT) in the extra-gynecological sites. All cases of teratoma and mixed GCT arising from the non-gynecological sites over 7years were screened for CNS type of neuroepithelial tumors. Detailed histological and immunohistochemical analysis was performed. IDH1 and 2 sequencings were performed in the glial tumors. Fluorescent in situ hybridization (FISH) was performed for EWSR1 rearrangement, 19/19q co-deletion, CDKN2A homozygous deletion, EGFR amplification, and C19MC amplification, wherever required. Out of 302 GCTs examined, the neuroglial tumor was detected in 15 cases. It included nine cases of glial tumors (including one pilocytic astrocytoma (grade I), two diffuse astrocytomas (grade II), one oligodendroglioma (grade II), one gemistocytic astrocytoma (grade II), three anaplastic astrocytomas (grade III), and one case of glioblastoma (grade IV)) and six cases of the embryonal tumor with multilayered rosettes (ETMR). None of the gliomas showed IDH mutation by immunohistochemistry or sequencing. The ETMR cases did not show Lin28 expression or C19MC amplification. To conclude, the spectrum of neuroglial tumors arising from teratoma in the extragonadal sites is vast and most commonly includes glial neoplasms and embryonal tumors. Our findings indicate that the genotype and pathogenesis of tumors with neuroglial differentiation in teratoma are distinct from their CNS counterpart.

GCT-09. Transcriptome and methylome profiles of CNS germ cell tumors and their comparison with testicular counterpart

BACKGROUND: The pathophysiology of CNS germ cell tumors (GCTs) has yet to be fully unraveled, resulting in the paucity of treatment options. The biological comparison with its testicular counterpart has not been interrogated. METHODS: In total, 84 cases of CNS GCT were investigated for methylation and transcriptome analyses, and an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs was conducted. RESULTS: Transcriptome analysis revealed germinoma and non-germinomatous GCTs (NGGCTs) were clearly separated. On transcriptome, germinoma was characterized by primitive cell state, closely related to primordial germ cell (PGC) with meiosis/mitosis potentials. NGGCT had a feature of more differentiated cell state directed toward organogenesis. Germinoma was subdivided into two clusters on integrated transcriptome and methylation analysis, and they are different in the age distribution and tumor cell content. CNS and testicular GCTs were divided based on histology, either germinoma/seminoma or NGGCT/non-seminomatous GCTs on methylation. Expression analysis mainly clustered them depending on the site of origin and histology. CONCLUSIONS: Expression profiles of CNS GCTs distinctly reflect the histological variabilities. Germinoma may be clustered into two groups, with possible differentiation in treatment intensity in the future. GCTs at CNS and gonads seem to have a mutual cell-of-origin and similar genomic backgrounds, which potentiates site-agnostic treatment development.

Clinicopathological Evaluation of Childhood Sacrococcygeal Germ Cell Tumors: A Single-Center Experience

ObjectiveWe aimed to evaluate the cases of sacrococcygeal germ cell tumors diagnosed in our hospital between 2006 and June 2021.Materials and MethodsWe evaluated 38 sacrococcygeal germ cell tumors cases in our series in terms of age, sex, clinical complaints, localization, macroscopy, tumor size, histopathological diagnosis, surgical, postoperative complications, treatment, recurrence, and prognosis.ResultsThe cases ranged from 1 day to 16 years of age; 14 cases were diagnosed with routine ultrasonographic examination during prenatal period while the rest of the cases most frequently presented with complaints of constipation. In terms of localization, 6 cases were type 1, 11 cases were type 2, 6 cases were type 3, and 15 cases were type 4. In the pathological evaluation, 25 cases were mature teratoma, 8 cases were immature teratoma, and 5 cases were pure yolk-sac tumor. In terms of complications, temporary colostomy was performed as a result of rupture during birth in 2 cases, disseminated intravascular coagulation at birth in 1 case, and colon injury in 2 cases. There was a recurrence in 2 of our cases. Thirty-seven of our cases were alive and 1 died. Alpha-fetoprotein level was high in 28 of our cases.ConclusionIn our series, type 4 cases were observed more frequently, contrary to the literature. We recommend to use a routine ultrasonography to patients who come to the clinic with complaints of constipation and inability to urinate and if a mass is detected, asking for alpha-fetoprotein for further follow-up. Sacrococcygeal germ cell tumors are ultimately a disease that can be successfully treated with multidisciplinary approach, accurate diagnosis in the antenatal and postnatal period, appropriate surgical intervention, and regular follow-up.

The value of CXorf67 and H3K27me3 for diagnosing germ cell tumors in central nervous system

Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r2=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.

CYTOLOGICAL EVALUATION OF NECK LYMPH NODES FOR METASTATIC DISEASE

Background: Fine needle aspiration cytology (FNAC) is a simple, rapid and cost effective procedure with minimal complications for evaluating enlarged neck nodes, but also gives clue. Neck lymph nodes are a common site of metastasis for various carcinomas, usually from the upper aerodigestive tract and salivary gland or carcinoma of unknown primary. Objectives: To study different cytomorphological patterns of metastatic neck nodes. To evaluate the diagnostic utility of FNAC in diagnosis of metastatic lesions of lymph node. Methods: It is a one year prospective study comprised of all aspirates 139 lymphnodes of 968 patients. FNACs conducted in the Department of Pathology, Vydehi Institute of Medical Sciences, Bangalore, between January 2019 to December 2019. A total of 70 out of 139 peripheral neck nodes in patients diagnosed with metastatic neck lymph node on FNAC were included in the study. Results: Out of 70 cases included in our study, metastasis to the neck lymph nodes were most common in the age group 51 to 60 years (38.6%) followed by 61 to 70 years (28.6%). Male preponderance was noted with male to female ratio of 1.7:1. On cytological examination, squamous cell carcinoma was found to be the most common tumor metastasizing to the neck nodes, accounting for 37 (52.9%) cases followed by each 10 (14.3%) cases each of undifferentiated carcinoma and thyroid carcinoma, 9 (12.9%) cases of adenocarcinoma, 3 (4.3%) cases of parotid gland carcinoma and 1 (1.4%) case of germ cell tumor of testis. Conclusion: FNAC is an early and reliable tool for the diagnosis of metastatic neck nodes. Any enlarged neck node should be investigated to rule out metastasis.

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors.

Terminal deoxynucleotidyl transferase (TdT) is aunique type of DNA polymerase predominantly expressed in precursor lymphoid cells and acute lymphoblastic leukemia. It participates in the junctional diversity of T-cell receptors and immunoglobulins. Recently, aberrant TdT expression was found in seminomas. Here, we evaluated the expression of TdT in our cohort of germ cell tumors (GCTs) with two anti-TdT antibody clones. We included 173 cases of testicular GCTs, 5 ovarian dysgerminomas, and one gonadoblastoma in the study. Tissue microarrays containing representative tumor samples were constructed and subsequently stained with anti-TdT monoclonal rabbit antibody EP266 (Dako) and TdT rabbit polyclonal antibody (Cell Marque). Expression was assessed with the H-score. No specific nuclear reaction was observed for the polyclonal anti-TdT antibody. The H-score values varied between the histological subtypes for the EP266 antibody. Positive nuclear staining was consistently seen in germ cell neoplasia in situ , seminoma, dysgerminoma, and embryonal carcinoma. Pure tumors had higher TdT H-scores than the mixed ones. Teratomas, yolk sac tumors, and choriocarcinomas were almost uniformly negative. Our study confirms that aberrant expression of TdT by testicular and ovarian GCTs exemplifies apotential diagnostic pitfall in histopathological diagnostics.

BOT-3 Prognostic Factors of CNS Germ Cell Tumors; Molecular and Histopathological Analyses on 154 Cases from the iGCT Consortium

Background: Germ cell tumors (GCTs) preferentially occurs in pediatric and young adult age groups. Chemo- and radiation therapies cause long-term sequelae in their later lives. We searched for clinical and histopathological features to predict the prognosis and affect treatment response, with a future goal of treatment stratification.Methods: A total of 154 GCT cases were included in the analysis. Total of 114 germinoma cases underwent measurement of tumor cell content on H-E specimen, and 82 GCT cases underwent 450K methylation analysis. 12p gain was determined on methylation-based copy number computation and FISH. Association with progression-free and overall survival (PFS/OS) was investigated. Results: The tumor cell content was widely distributed from <5% to 90% in the specimens, with a median value of 50%. Patients with a higher tumor cell content (>=50%) showed shorter PFS than those with a lower tumor cell content (<50 %) (p=0.03). In the multivariate analysis with tumor location, tumor cell content was the sole statistically significant prognostic factor (p=0.04). 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs, particularly in cases with malignant components. The presence of 12p gain correlated with shorter PFS and OS, even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS. The 12p copy number status was shared among histological components in mixed GCTs. Whole-genome amplification was suggested by FISH.Conclusions: We found that tumor cell content significantly affected the prognosis of germinomas. 12p gain predicts the presence of malignant components of NGGCTs, and poor prognosis of the patients. Furthermore, 12p is likely to be an early event in the tumorigenesis of CNS GCT. These potentially open the possibility of leveraging these pathological and molecular factors in the future clinical trials when stratifying the treatment intensity.