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MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)-associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs), including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here, we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines.

Introduction: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes. Methods: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods. Results: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients. Conclusion: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Mediastinal germ cell tumors are rare and few large-scale studies on mediastinal germ cell tumors are reported. We aimed to investigate the clinical characteristics and survival outcomes of patients with mediastinum germ cell tumors in Japan. Methods: A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with mediastinal germ cell tumors in 2012–2013. The datasets were registered from 80 institutions. Results: The selection criteria were met by 123 patients, the majority of whom were male. The median age at diagnosis was 39 years (range 25–89 years) and the most common age groups at diagnosis was 30–39 years, followed by 40–49 years and ≥ 50 years. The histology of non-seminoma (55.3%) was slightly more frequent than that of seminoma (44.7%). The most common histological subtype in non-seminoma was yolk sac tumor, followed by mixed germ cell tumor. The 5-year survival of seminoma and non-seminoma were 96.4% and 57.3%, respectively (p < 0.001). Non-seminomatous mediastinal germ cell tumors, malignant teratomas, mixed germ cell tumors, and yolk sac tumors had comparable survival rates, while those with choriocarcinoma showed the worst prognosis. Conclusions: This is the first report showing the clinical characteristics and survival outcomes of mediastinal germ cell tumors in Japan using a real-world large cohort database. [ABSTRACT FROM AUTHOR]

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

Testicular germ cell tumors (TGCTs) can be treated with cisplatin-based therapy. However, a clinically significant number of cisplatin-resistant patients die from progressive disease as no effective alternatives exist. Curative cisplatin therapy results in acute and life-long toxicities in the young TGCT patient population providing a rationale to decrease cisplatin exposure. In contrast to genetic alterations, recent evidence suggests that epigenetics is a major driving factor for TGCT formation, progression, and response to chemotherapy. Hence, targeting epigenetic pathways with "epidrugs" is one potential relatively unexplored strategy to advance TGCT treatment beyond cisplatin. In this report, we demonstrate for the first time that targeting polycomb demethylases KDM6A and KDM6B with epidrug GSK-J4 can treat both cisplatin-sensitive and -resistant TGCTs. While GSK-J4 had minimal effects alone on TGCT tumor growth in vivo, it dramatically sensitized cisplatin-sensitive and -resistant TGCTs to cisplatin. We validated KDM6A/KDM6B as the target of GSK-J4 since KDM6A/KDM6B genetic depletion had a similar effect to GSK-J4 on cisplatin-mediated anti-tumor activity and transcriptome alterations. Pharmacologic and genetic targeting of KDM6A/KDM6B potentiated or primed the p53-dominant transcriptional response to cisplatin, with also evidence for basal activation of p53. Further, several chromatin modifier genes, including BRD4, lysine demethylases, chromodomain helicase DNA binding proteins, and lysine methyltransferases, were repressed with cisplatin only in KDM6A/KDM6B-targeted cells, implying that KDM6A/KDM6B inhibition sets the stage for extensive chromatin remodeling of TGCT cells upon cisplatin treatment. Our findings demonstrate that targeting polycomb demethylases is a new potent pharmacologic strategy for treating cisplatin resistant TGCTs that warrants clinical development. [ABSTRACT FROM AUTHOR]

Ovarian tumors can be divided into epithelial tumors, germ cell tumors, sex cordstromal tumors and metastatic tumors according to histological types. Their biological behaviors are different. Lymphangioma is a rare benign tumor that can occur anywhere in the body. Among them, ovarian lymphangioma is particularly rare. The case we reported is the case of ovarian lymphangioma. The patient was admitted to the hospital one month after the physical examination found the ovarian mass. After the examination, the patient was treated with laparoscopic surgery. The patient recovered well after the operation, and no recurrence was found after the follow-up. [ABSTRACT FROM AUTHOR]

Background: The role of high-dose chemotherapy followed by autologous hematopoietic cell transplantation in the management of patients with relapsed/refractory germ-cell tumors has not been established in prospective studies. Our aim was to estimate the benefits and harm of this treatment in men with relapsed/refractory germ-cell tumors. Methods: Electronic databases, conference proceedings, and trial registers until April 30, 2023, were searched. Randomized and non-randomized prospective controlled trials were included. Risk of bias assessments were performed using either RoB2 or ROBINS-I tools. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Time-to-event data were analyzed using the hazard ratio. The primary outcome was overall survival, and a meta-analysis was not conducted to assess it because non-randomized trials were judged to have a critical risk of bias. Categorical data were analyzed using a risk ratio. All results are presented with the corresponding 95% confidence interval. Results: Four out of 3,824 records met the inclusion criteria, and three out of four were used to assess primary and secondary outcomes. Based on the IT94 study (N = 263 participants), single high-dose chemotherapy followed by autologous hematopoietic cell transplantation may have little to no effect on overall survival [hazard ratio (HR) 0.98, 95%CI 0.68 to 1.42; p = 0.916]. Non-randomized trials (N = 43 participants) showed contrasting results, which may be explained by the number of cycles of high-dose chemotherapy administered in each study. Regarding secondary outcomes, information was only provided for event-free survival, response rate, and acute toxicities. Conclusions: Based on prospective data, there is insufficient evidence to support or refute the proposal that high-dose chemotherapy with autologous hematopoietic cell transplantation improves survival in men with relapsed/refractory germ-cell tumors. If this treatment is considered essential, the choice should be made by experienced clinicians at high-volume cancer centers. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Sacrococcygeal teratoma (SCT), a rare germ cell malignancy in newborns, necessitates prompt surgical intervention for complete resection. Long‐term follow‐up is crucial for monitoring recurrence and managing potential complications, regardless of histopathological findings, ensuring optimal outcomes and early intervention if needed. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH(-independent premature puberty in boys, characterized by elevated β-human chorionic gonadotropin (β-hCG) levels, can indicate a secreting germ cell tumor (GCT). These tumors are rare but more common in individuals with Klinefelter syndrome (KS). We present a case of a 7.3-year-old boy with precocious puberty. Physical examination revealed bilateral testicular volumes of 8 to 10 mL and Tanner stage 3 secondary sexual characteristics (genitalia G3, pubic hair P3). His skeletal age was 12 years. Biochemical tests showed suppressed gonadotropin levels, elevated testosterone, and increased β-hCG of 86.6 mIU/mL (86.6 IU/L, reference range: <5 mIU/mL, <5 IU/L). Imaging, including magnetic resonance imaging (MRI), chest x-ray, whole-body computed tomography (CT), and testicular ultrasound, were interpreted as normal except for a small pineal cyst. Karyotype testing confirmed KS. Over 10 months, β-hCG levels fluctuated between 1 to 105 mIU/mL (1-105 IU/L). When β-hCG was 3.6 mIU/mL (3.6 IU/L), a fluorodeoxyglucose positron emission tomography–CT (FDG PET-CT) scan revealed a mediastinal tumor. The tumor was surgically removed and identified as a mature teratoma. This case underscores the importance of karyotype testing and repeated imaging in boys with premature puberty and elevated β-hCG levels, even if β-hCG levels decrease spontaneously and remain low. [ABSTRACT FROM AUTHOR]

Germ cell tumors (GCTs) are categorized as gonadal or extra‐gonadal, based on the origin. Extra‐gonadal GCTs predominantly manifest within the central nervous system (CNS), mediastinum, retroperitoneum, and sacrococcygeal region. These malignancies are most frequently diagnosed in the pediatric, adolescent, and young adult demographics. Incidences of GCT within the nasal cavity are notably scarce, with only six cases documented. This report details the case of a 70‐year‐old man who presented with a left nasal mass ultimately diagnosed as immature teratoma. A remarkable aspect of this case was the detection of SMARCA4 (BRG1) loss through immunohistochemical analysis. In addition, methylation profiling aligned this case with CNS GCTs, specifically those classified as non‐germinomatous GCTs. This molecular characterization informed a tailored therapeutic strategy incorporating carboplatin and etoposide, alongside localized irradiation. This individualized treatment regimen achieved favorable outcomes, with the patient remaining recurrence free for over three years. This highlights the need for precise therapeutic approaches in the management of extragonadal GCTs, particularly those arising in atypical anatomical locations. The present case accentuates the significance of thorough diagnostic evaluations and customized treatment plans for rare GCT presentations. Further empirical and clinical investigations are warranted to enhance our understanding of and refine therapeutic protocols for such exceptional cases. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether 5‐year overall survival (OS) differs and to what extent between the American Joint Committee on Cancer stage III non‐seminoma testicular germ cell tumor (NS‐TGCT) patients and simulated age‐matched male population‐based controls, according to race/ethnicity groups. Methods: We identified newly diagnosed (2004–2014) stage III NS‐TGCT patients within the Surveillance Epidemiology and End Results database 2004–2019. For each case, we simulated an age‐matched male control (Monte Carlo simulation), relying on Social Security Administration (SSA) Life Tables with 5 years of follow‐up. We compared OS rates between stage III NS‐TGCT patients and simulated age‐matched male population‐based controls, according to race/ethnicity groups (Caucasian, Hispanic, Asian/Pacific Islander and African American). Both, cancer‐specific mortality (CSM) and other‐cause mortality (OCM) were computed. Results: Of 2054 stage III NS‐TGCT patients, 60% were Caucasians versus 33% Hispanics versus 4% Asians/Pacific Islanders versus 3% African Americans. The 5‐year OS difference between stage III NS‐TGCT patients versus simulated age‐matched male population‐based controls was highest in Asians/Pacific Islanders (64 vs. 99%, Δ = 35%), followed by African Americans (66 vs. 97%, Δ = 31%), Hispanics (72 vs. 99%, Δ = 27%), and Caucasians (76 vs. 98%, Δ = 22%). The 5‐year CSM rate was highest in Asians/Pacific Islanders (32%), followed by African Americans (26%), Hispanics (25%), and Caucasians (20%). The 5‐year OCM rate was highest in African Americans (8%), followed by Caucasians (4%), Asians/Pacific Islanders (4%), and Hispanics (2%). Conclusion: Relative to SSA Life Tables, the highest 5‐year OS disadvantage applied to stage III NS‐TGCT Asian/Pacific Islander race/ethnicity group, followed by African American, Hispanic and Caucasian, in that order. [ABSTRACT FROM AUTHOR]

To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications. This retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3 + AEs and post-RPLND complications on multivariable logistic regression analyses. One hundred and eighty-two men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was −6% (P = <.0001), while VAI, SAI, and FMI increased by +13% (P = <.0001), +11% (P = <.0001), and +6% (P = <.0001), respectively. Seventy-nine patients (43%) experienced at least one grade 3 + AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3 + AEs (P =.047). One hundred and 3 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least 1 grade 3 + post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications. In men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications. [ABSTRACT FROM AUTHOR]

Teratoma is a germ cell tumor composed of 2 or 3 germ cell layers, and it can occur in various parts of the human body. However, teratomas of the renal hilum are particularly rare, and those complicated by carcinoids are even more uncommon. Herein, we report the example of an asymptomatic 49-year-old woman in whom a tumor in the right renal hilum was unexpectedly discovered on imaging. Histological examination revealed a carcinoid tumor arising from a simple cyst composed of teratomatous tissue. Although the tumor was located in the renal hilum and touched the renal parenchyma, it appeared independent of the kidney and urinary tract. This report highlights the rare occurrence of teratomas with carcinoids and provides insights into their origins. [ABSTRACT FROM AUTHOR]

Evidence describing the use of plerixafor in the off‐label population of relapsed/refractory germ cell tumors (GCT) is limited. We aim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022. Depending on insurance approval, plerixafor was given either as "rescue" (after a first apheresis collection of < 5 × 106 CD34+ cells/kg) or as "preemptive" on Day 4 of granulocyte‐colony stimulating factor (G‐CSF) prior to the first apheresis collection, if the Day 4 peripheral blood CD34+ count was < 40 cells/μL. A total of 66% of patients who received preemptive plerixafor completed collection in 1 day, similar to good mobilizers who only needed G‐CSF (71%, p = 0.366). In contrast, all poor mobilizers in the rescue group required at least 2 days of collection and had lower CD34+ cell yields than the preemptive group (7.15 vs. 9.81 × 106/kg, p = 0.0055). A cost analysis revealed that preemptive plerixafor may save approximately $7000 per patient compared with a rescue approach. Preemptive plerixafor in GCT patients undergoing PBSC collection allows relatively poor mobilizers to collect in fewer days and with lower overall cost. Fewer apheresis procedures result in less risk to the patient, increased patient satisfaction, and the ability to schedule more patients within the constraints of staffing. [ABSTRACT FROM AUTHOR]

Non‐neuroendocrine tumors account for around 10% of all primary neoplasms of the sella. If meningiomas, craniopharyngiomas, and germ cell tumors are excluded, the remaining lesions include a broad spectrum of uncommon, benign, and aggressive, often diagnostically challenging lesions. This review aims to summarize the essential clinicopathological features of tumors of the posterior pituitary gland, infundibulum spectrum expressing thyroid transcription factor 1, and primary sellar atypical rhabdoid teratoid tumor, and provide the criteria for their diagnosis and management. [ABSTRACT FROM AUTHOR]

Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field are reported, these mainly focus on dedicated items such as a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best of our knowledge, a comprehensive overview is lacking. Here, we review the current state of liquid biopsy research for the most common non-central nervous system pediatric solid tumors. These include neuroblastoma, renal tumors, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, and liver tumors. Within this selection, we discuss the most important or recent studies involving liquid biopsy-based biomarkers, anticipated clinical applications, and the current challenges for success. Furthermore, we provide an overview of liquid biopsy-based biomarker publication output for each tumor type based on a comprehensive literature search between 1989 and 2023. Per study identified, we list the relevant liquid biopsy-based biomarkers, matrices (e.g., peripheral blood, bone marrow, or cerebrospinal fluid), analytes (e.g., circulating cell-free and tumor DNA, microRNAs, and circulating tumor cells), methods (e.g., digital droplet PCR and next-generation sequencing), the involved pediatric patient cohort, and proposed applications. As such, we identified 344 unique publications. Taken together, while the liquid biopsy field in pediatric oncology is still behind adult oncology, potentially relevant publications have increased over the last decade. Importantly, steps towards clinical implementation are rapidly gaining ground, notably through validation of liquid biopsy-based biomarkers in pediatric clinical trials. [ABSTRACT FROM AUTHOR]

The manifestation of a giant ovarian yolk sac tumor during late pregnancy is relatively rare. A yolk sac tumor is a highly malignant germ cell tumor that originates from primitive germ cells. It is characterized by yolk sac differentiation in vitro. The frequency of prenatal examinations should be appropriately increased for ovarian tumors discovered during pregnancy. Furthermore, regular follow-up ultrasound should be performed, and tumor markers should be dynamically detected. If needed, imaging examinations such as computed tomography and magnetic resonance imaging should be combined to comprehensively investigate disease progression. If the tumor diameter and tumor marker levels rapidly increase during pregnancy, the possibility of malignancy increases. Therefore, exploratory laparotomy should be immediately performed to further improve subsequent treatment modalities, early diagnosis, early treatment, and prognosis. Herein, we report the case of a 28-year-old pregnant woman whose pregnancy was terminated at 29 weeks and 5 days. She complained of lower abdominal pain for 2 days. A pelvic mass was detected for 1 week, accompanied by increased levels of tumor markers such as serum alpha-fetoprotein, cancer antigen 125, carbohydrate antigen 724, and human epididymis protein 4. Imaging revealed the presence of a pelvic mass. At 32 weeks and 3 days of pregnancy, a cesarean section was performed, with a transverse incision in the lower uterine segment. Furthermore, pelvic adhesiolysis, omentectomy, right adnexectomy, right pelvic lymph node dissection, and pelvic metastasis peritonectomy were performed. The postoperative pathological diagnosis was yolk sac tumors of the ovary (stage IIB). Postoperatively, a five-cycle chemotherapy regimen comprising bleomycin, etoposide, and cisplatin was administered. During postoperative follow-up, the patient's general condition was noted to be good, with the newborn and pregnant women ultimately achieving good outcomes. We reviewed the relevant literature to increase clinical doctors' understanding of ovarian malignancy during pregnancy, guide treatment selection, and facilitate early intervention for associated diseases. [ABSTRACT FROM AUTHOR]

Background and purpose: Imaging with conventional MRI plays a pivotal role in characterization of skull base bone-intrinsic lesions, yet some lesions are very challenging. The purpose of this study is to evaluate the role of diffusion and perfusion by T2* dynamic susceptibility contrast (DSC) in characterization of such lesions. Results: Lesions showed mostly correlated with approach: Chordomas had low perfusion and intermediate to high perfusion, while chondrosarcoma had ADC value > 1.6 × 10–3/cm2 and more perfused. Metastases had variable ADC values usually intermediate with high perfusion. Plasmacytomas had similar features yet with characteristic conventional morphology and single number. Lymphoma (primary bony) had high perfusion and lowest diffusion ADC (= 04–0.7 × 10–3/cm2). Giant cell tumors and hemangiopericytomas had lowest perfusion. Conclusion: The proposed imaging approach showed very good results and high accuracy in differentiation of skull base bony lesions. [ABSTRACT FROM AUTHOR]

Purpose: Testicular cancer survivors (TCS) exposed to chemotherapy have an increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype associated with immunosenescence. We seek to define whether the immunosenescent phenotype is associated with chemotherapy. Methods: Case–control study of TCS, disease‐free ≥3 months and stratified by primary treatment modality into orchiectomy only, chemotherapy, or bone marrow transplant (BMT). Each group was compared with age‐matched healthy controls (HC). We measured the relative proportions of lymphocyte subpopulations using flow cytometry, levels of C‐reactive protein, and relative expression of CDKN2A/p16INK4a quantified by qPCR. Results: We included 65 patients; 19 were treated with orchiectomy only, 35 received different doses of chemotherapy, and 11 underwent BMT. The chemotherapy and BMT groups had decreased naïve CD4 cells compared to HC. The chemotherapy group showed increased central and effector memory CD4 cells, as well as effector and terminally differentiated CD8 cells, compared to HC. Chemotherapy (chemotherapy 1.84 vs. HC 0.92; p < 0.01) and BMT (BMT 6.96 vs. HC 1.25; p < 0.005) groups had higher expression of CDKN2A/p16INK4a compared to HC. The orchiectomy group showed no significant difference with HC (orchiectomy 1.73 vs. HC 1.01; p = 0.17). CRP levels were higher in all groups when compared with HC; in the orchiectomy group, they were only marginally increased (chemotherapy 0.22 vs. HC 0.06; p < 0.01; BMT 0.26 vs. HC 0.06; p < 0.01; orchiectomy 0.09 vs. HC 0.07; p < 0.01). Conclusions: Among TCS, only patients exposed to cytotoxic agents developed an immunosenescent phenotype. This finding supports the attribution of this alteration to the cytotoxic treatment. [ABSTRACT FROM AUTHOR]

Background: In staging for testicular germ cell tumor (GCT), current guidelines lack consensus regarding the measurement of retroperitoneal lymph node metastasis, concerning the recommended plane and dimension. This exploratory study aimed to assess its impact on clinical stage (cS) and therapy. Methods: We retrospectively examined 154 cSI (retroperitoneal lymph nodes < 10 mm in axial short-axis diameter (SAD)) GCT patients, without adjuvant therapy and a follow-up ≥ 24 months. Retroperitoneal lymph nodes were measured in staging images in different dimensions (SAD and long-axis diameter (LAD)) and planes (axial, sagittal and coronal). Results: Overall survival was 100%, with 82% free of recurrence after a median follow-up of 83 months. All patients were classified as cSI, based on axial SAD (RECIST 1.1). However, significantly more patients would have been classified as cSIIA (0% vs. 38% vs. 52%) or even cSIIB (0% vs. 1% vs. 25%) according to axial LAD (SWENOTECA, German S3 guideline) or maximum LAD in any plane (EAU, ESMO, AJCC and onkopedia) (p < 0.001). Overtreatment was predicted in 0%, 31% and 61% of patients based on axial SAD, axial LAD and maximum LAD, while undertreatment was estimated at 18%, 10% and 2%, respectively, (p < 0.001). Conclusions: These findings indicate considerable variability in cS based on current lymph node staging recommendations, suggesting that axial SAD (RECIST 1.1) could be the most appropriate parameter for standardized guideline recommendations. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high‐dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. Methods: The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first‐line cisplatin‐based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression‐free survival and overall survival were analyzed using the Kaplan–Meier method. Medians with 95% confidence intervals were also calculated along with 2‐year probabilities. Results: The median age at HDCT was 30 years (range, 18–61 years). With a median follow‐up of 4.7 years (range, 1–14 years), the 2‐year progression‐free survival rate was 31% (95% confidence interval, 16%–47%), and the 2‐year overall survival rate was 35% (95% confidence interval, 19%–52%). At last follow‐up, nine patients (28%) remained without evidence of disease, including two platinum‐refractory patients and two patients who were receiving HDCT as third‐line therapy. There were three treatment‐related deaths. Conclusions: Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum‐refractory and third‐line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population. Patients who have relapsed primary mediastinal nonseminomatous germ cell tumors have poor outcomes with salvage chemotherapy. The authors report the results of high‐dose chemotherapy and peripheral blood stem cell transplantation, which permit more rapid succession to the subsequent cycle and potentially improved efficacy compared with historical regimens. [ABSTRACT FROM AUTHOR]

Background: Yolk 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 presentation: Here 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. Conclusions: This 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. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the clinical characteristics and outcomes of recurrent sacrococcygeal germ cell tumors (SC-GCTs). Materials and Methods: This study was conducted with patients diagnosed with SC-GCTs between 2002 and 2022. Epidemiology, diagnostic and treatment methods, anatomic/histopathological classifications and recurrence were evaluated. Results: This study included 55 patients (Female/Male: 45/10). According to Altman's-classification, 16 patients (29.1%) were Type I, 14 (25.5%) Type II, 12 (21.8%) Type III and 13 (23.6%) Type IV. Histologically, 69.1% of the lesions were mature teratomas, 14.5% were immature teratomas, and 16.4% were malignant teratomas. Eleven patients developed recurrent sacrococcygeal teratoma (recurrence age: 5 months-12 years). According to Altman's classification, 2/11 patients were Type II, 5/11 patients were Type III, and 4/11 patients were Type IV. The pathological results of the original tumors were mature teratoma in 4/11 patients, immature teratoma in 4/11 patients, and malignant teratoma in 3/11 patients. Malignant relapse with yolk sac tumor was detected in 6/11 patients, mature teratoma in 4/11 patients, and immature teratoma in 1/11 patients. Conclusion: The risk of malignancy increases with age and Altman's Type III and IV. Recurrent tumors may have different histopathological types from the original tumor. The risk of recurrence as a malignant tumor after immature teratomas was higher than mature teratomas. [ABSTRACT FROM AUTHOR]

• In germ cell tumors (GCT), especially seminoma and embryonal carcinoma activate cancer-associated fibroblasts (CAF), while teratoma play only a minor role in CAF formation. • CAF influence proliferation and expression of cisplatin resistance factors as well as organization of the extracellular matrix in GCT cells, putatively involving IGF signaling and LGALS3BP, LYVE1, and PTX3. • CAF influence monocyte / macrophage polarization via LGALS3BP, LYVE1, and PTX3. • Therapeutically interfering with CAF (IGF signaling) and / or macrophages in addition to the standard therapy might slow-down further progression of the GCT disease and re-shaping of the tumor microenvironment. • Thus, the vital interaction between GCT cells, CAF and macrophages is pivotal for shaping the tumor microenvironment, activating CAF, polarizing macrophages, and triggering GCT progression and response to a cisplatin-based therapy. Germ cell tumors (GCT) are the most common solid tumors in young men of age 15 - 40. In previous studies, we profiled the interaction of GCT cells with cells of the tumor microenvironment (TM), which showed that especially the 3D interaction of fibroblasts (FB) or macrophages with GCT cells influenced the growth behavior and cisplatin response as well as the transcriptome and secretome of the tumor cells, suggesting that the crosstalk of these cells with GCT cells is crucial for tumor progression and therapy outcome. In this study, we shed light on the mechanisms of activation of cancer-associated fibroblasts (CAF) in the GCT setting and their effects on GCT cells lines and the monocyte cell line THP-1. Ex vivo cultures of GCT-derived CAF were established and characterized molecularly and epigenetically by performing DNA methylation arrays, RNA sequencing, and mass spectrometry-based secretome analysis. We demonstrated that the activation state of CAF is influenced by their former prevailing tumor environment in which they have resided. Hereby, we postulate that seminoma (SE) and embryonal carcinoma (EC) activate CAF, while teratoma (TER) play only a minor role in CAF formation. In turn, CAF influence proliferation and the expression of cisplatin sensitivity-related factors in GCT cells lines as well as polarization of in vitro -induced macrophages by the identified effector molecules IGFBP1, LGALS3BP, LYVE1, and PTX3. Our data suggests that the vital interaction of CAF with GCT cells and with macrophages has a huge influence on shaping the extracellular matrix as well as on recruitment of immune cells to the TM. In conclusion, therapeutically interfering with CAF and / or macrophages in addition to the standard therapy might slow-down progression of GCT and re-shaping of the TM to a tumor-promoting environment. Significance: The interaction of CAF with GCT and macrophages considerably influences the microenvironment. Thus, therapeutically interfering with CAF might slow-down progression of GCT and re-shaping of the microenvironment to a tumor-promoting environment. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity. [ABSTRACT FROM AUTHOR]

Teratomas account for 18–20% of all intracranial germ cell tumors and mostly occur in the pineal region with only a few cases of pediatric sellar and suprasellar teratomas described in the literature. Here, we present a case of a child with an intracranial mature teratoma with pancreatic features causing vasospasm and subsequent stroke, found to be positive for CDKN2A—an independent variant associated with malignancy and small vessel disease leading to stroke. [ABSTRACT FROM AUTHOR]

Placental alkaline phosphatase (PLAP) in the spinal fluid is helpful for the diagnosis of intracranial germinomas. Bifocal lesions involving the pineal and pituitary regions have also been reported as characteristic findings of intracranial germinomas. We present a rare case of a 15-year-old boy with a pineal parenchymal tumor of intermediate differentiation (PPTID) with bifocal lesions negative for PLAP. Magnetic resonance imaging of the brain revealed bifocal mass lesions in the pineal and suprasellar regions and non-communicating hydrocephalus. We initially suspected a germinoma based on imaging findings, but all tumor markers, including PLAP, in the spinal fluid were negative. Based on these results, germinoma was considered less likely, and an endoscopic third ventriculostomy and endoscopic tumor biopsy were performed for diagnosis. The histopathological diagnosis was PPTID, corresponding to World Health Organization grade 3, in both pineal and suprasellar specimens. A craniotomy for tumor removal was performed, resulting in total resection. PLAP is known to have high sensitivity and extremely high negative predictive value for germinomas. Although bifocal lesions highly suggest germ cell tumors, there are exceptions, as in the present case. This case suggests that PLAP measurements are useful for differentiation, leading to appropriate treatment strategies. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) show promise as blood-based tumor markers for germ cell tumors (GCTs), with miRNA-371-3p being the most studied. The marginal benefit of including other candidate miRNAs to aid with the management of testicular GCTs remains unclear. Objective: To assess the performance of our combined miRNA assay (371a-3p and 372-3p) in patients with clinically localized testicular masses. Design, setting, and participants: This was a retrospective review of patients prospectively enrolled in an ongoing protocol collecting serum miR-371a-3p and miR-372-3p levels (together, Memorial Sloan Kettering Cancer Center [MSK] miRNA assay [MMA]) in patients with a suspected or diagnosed testicular GCT. Outcome measurements and statistical analysis: The coprimary outcomes of interest were sensitivity and specificity of miR-371a-3p and 372-3p, individually and together, to detect nonteratomatous GCTs in the orchiectomy specimen. Secondary outcomes included additional assay diagnostic parameters, the relationship of patient and disease factors with variations in miRNA levels, and temporal patterns of miRNA normalization after orchiectomy. Results and limitations: Sixty-two patients were included, 52 had a viable GCT at orchiectomy, and ten had no cancer or a non-GCT. Forty-six patients with a GCT had positive preorchiectomy MMA (sensitivity 88.5% [95% confidence interval {CI}: 79.8, 97.2]), and one patient had positive preorchiectomy MMA but no GCT (specificity 90.0% [95% CI: 71.4, 100]). The diagnostic performance of miR-371a-3-p and miR-372-3p was similar. The time for miRNA to decrease to undetectable levels varied, with some patients having positive levels up to 3 wk after orchiectomy. Conclusions: The biomarkers miR-371a-3p and miR-372-3p demonstrated high sensitivity and specificity for localized testicular GCTs, but causes of variation in relative miRNA levels and time to normalization for individual patients remain unclear. Patient summary: We studied the ability of the blood-based biomarkers miR-371a-3p and miR-372-3p to detect testicular cancer (germ cell tumors) in patients with small testicular masses. We found that together and individually these were sensitive and specific for testicular cancer.

Abstract Background Yolk 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 presentation Here 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. Conclusions This 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.

Background: Ovarian tumors rank as the third leading cause of mortality among female genital tract malignancies. This study examined the histopathological spectrum of ovarian neoplasms based on our center’s 2020 World Health Organization (WHO) classification. Materials and Methods: This descriptive study was carried out over 5 years at our tertiary healthcare hospital, including 406 cases of ovarian neoplasms. After proper fixation and gross examination, sections were routinely processed and examined. The histopathological spectrum of ovarian neoplasms was analyzed according to the 2020 WHO classification. Results: Out of the 406 cases studied, 329 (81.03%) were benign, 65 (16.01%) were malignant, and 12 (2.95%) were borderline. The cases included 326 (80.29%) surface epithelial tumors, 58 (14.28%) germ cell tumors, 19 (4.68%) sex cord-stromal tumors, and 2 (0.49%) metastatic tumors. The majority of ovarian tumors (n = 340, 83.74%) occurred in the 20–60 years age group. Conclusion: The study reveals that benign tumors were more prevalent than malignant ones, with serous tumors being the most common among the benign cases. We observed a higher incidence of malignancy in women over the age of 40. Therefore, early and accurate histological diagnosis is crucial for initiating an appropriate management plan.

Ovarian germ cell tumors account for 30 % of germ cell tumors of other localizations and 70 % of all ovarian neoplasms. The aim of this review is to study and systematize clinical manifestations, diagnosis and treatment of ovarian germ cell tumors in childhood and adolescence on the basis of current foreign and domestic studies.

Pineal gland tumors are significant despite being rare (

Many strands of research by different groups, starting from teratocarcinomas in the laboratory mouse, later moving the corresponding human tumors, contributed to the isolation and description of human pluripotent stem cells (PSCs). In this review, I highlight the contributions from my own research, particularly at the Wistar Institute during the 1980s, when with my colleagues we characterized one of the first clonal lines of pluripotent human embryonal carcinoma (EC) cells, the stem cells of teratocarcinomas, and identified key features including cell surface antigen markers that have since found a place in the study and exploitation of human PSC. Much of this research depended upon close teamwork with colleagues, many in other laboratories, who contributed different expertise and experience. It was also often driven by circumstance and chance rather than pursuit of a grand design. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to prospectively assess the extent to which magnetic resonance imaging (MRI) can differentiate malignant from benign lesions of the testis. Materials and Methods: All included patients underwent multiparametric testicular MRI, including diffusion-weighted imaging (DWI) and subtraction dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Subsequently, all patients underwent a histopathological examination via orchiectomy or testicular biopsy/partial resection. The Kolmogorov–Smirnov test, t-test, Mann–Whitney U test, Fisher's exact test, and logistic regression were applied for statistical analysis. Results: We included 48 male patients (median age 37.5 years [range 18–69]) with testicular tumors. The median tumor size on MRI was 2.0 cm for malignant tumors and 1.1 cm for benign tumors (p < 0.05). A statistically significant difference was observed for the type (type 0-III curve, p < 0.05) and pattern of enhancement (homogeneous, heterogeneous, or rim-like, p < 0.01) between malignant and benign tumors. The minimum apparent diffusion coefficient (ADC) value was 0.9 for benign tumors and 0.7 for malignant tumors (each ×103 mm2/s, p < 0.05), while the mean ADC was 0.05. The mean ADC value was significantly lower for malignant tumors; the mean ADC value was 1.1 for benign tumors and 0.9 for malignant tumors (each ×103 mm2/s, p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric MRI for differentiating malignant from benign testicular lesions were 94.3%, 76.9%, 91.7%, and 83.3%, respectively. The surgical procedures performed included orchiectomy (n = 33; 71.7%) and partial testicular resection (n = 11; 23.9%). Histopathology (HP) revealed malignancy in 35 patients (72.9%), including 26 with seminomas and 9 with non-seminomatous germ cell tumors (NSGCTs). The HP was benign in 13 (27.1%) patients, including 5 with Leydig cell tumors. Conclusions: Malignant and benign tumors differ in MRI characteristics in terms of the type and pattern of enhancement and the extent of diffusion restriction, indicating that MRI can be an important imaging modality for the accurate diagnosis of testicular lesions. [ABSTRACT FROM AUTHOR]

Undifferentiated embryonal sarcoma of the liver (UESL) is an extremely rare and aggressive malignancy in adults.1 Adults with UESL have a worse prognosis compared to pediatric population.2 Due to the rarity of this disease in adults, there has been a lack of information that assists in treatment decisions within this group. Improved understanding of UESL in adults might assist in understanding biological differences compared to pediatric cohorts as well as tailor treatments to improve their overall outcome. We described the management and outcome of a young adult managed at our center with metastatic relapsed UESL. For comparison, a PubMed search for adolescent and young adult (AYA) and adults with UESL was performed with the aim to review and address any distinct clinical features, different aspects of management and survival outcomes within this population. A 21-year-old male underwent right hepatectomy for a large 16 cm localized UESL with clear surgical margin and did not receive adjuvant chemotherapy. Seven months postsurgery, he relapsed with both local and metastatic disease and underwent chemotherapy with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide achieving a complete metabolic response. This was followed by Stereotactic Ablative Radiation Therapy and surgical resection of residual disease. He remains free of disease 3 years since his diagnosis. We subsequently reviewed 42 AYA and adults (aged >15) with UESL (median age, 33 years) between 1991 and 2022. Most patients presented with localized UESL and for those treated with surgery alone, 67% developed recurrences. Those receiving multimodality treatment, better outcomes, and reduced relapse rate was achieved. Twenty-seven patients developed recurrences, 13 with local recurrences and 14 with metastatic relapse. The median time to relapse was 12 months. We reported a successful outcome in multimodality treatment which resulted in long remission in a young adult with relapsed UESL. Combination of perioperative chemotherapy with locoregional treatment is important to improve long-term survival in adults with metastatic UESL. [ABSTRACT FROM AUTHOR]

Introduction: Urologists observed reduced cancer consultations and surgeries during the SARS-CoV-2 pandemic, raising concern about treatment delays. Testicular cancer serves as a particularly sensitive marker of this phenomenon, as the clinical stage of testicular cancer at presentation is predictive of cancerspecific survival. We aimed to investigate whether COVID-related restrictions to primary care access resulted in increased incidence of metastatic germ cell testis cancer. Methods: A retrospective chart review was conducted on all cases of testicular cancer managed surgically at our center from March 1, 2018, to February 28, 2023. Patients were categorized into temporal cohorts, representing before, during, and following the implementation of COVID-19 public health restrictions in the province of Newfoundland and Labrador. Results: Forty-one cases of testicular germ cell tumors were identified during the study period. The mean age at diagnosis was 40.8 years (standard deviation ±13.7). Demographics did not vary across the cohorts. Clinical stage 3 disease remained stable before and during the pandemic at 10.5% and 9.1% of cases, respectively. In the post-pandemic period, there was an increase to 27.3% (p=0.617). Surgical wait times remained stable across the pandemic (p=0.151). Conclusions: There was a 16.8% rise in clinical stage III disease from the pre-pandemic to postpandemic period. Our study failed to identify a statistically significant increase in metastatic testis cancer incidence upon lifting of pandemic restrictions. Further study is necessary to confirm suspicions that pandemic restrictions contributed to increased incidence of metastatic testis cancer. [ABSTRACT FROM AUTHOR]

We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3–189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3–54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST. • OYST tumor histology and residual lesions were independently associated with event free survival. • OYST histology, residual lesions and cycles to AFP normalization were independent risk factors for OYST overall survival. • Persistent and recurrent OYST demonstrated distinct molecular characteristics compared with primary OYST. • Persistent and recurrent OYST probably susceptible to immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

A mature cystic teratoma is a mass with heterogeneous appearance, consisting of adult tissue with two or three layers: endoderm, mesoderm, and ectoderm. It is a rare, benign transformation of somatic tissue most commonly found in the sacrococcygeal region and may resemble an uncomplicated spina bifida on prenatal ultrasonography. In this case report, we describe a female newborn with an extremely rare mature cystic teratoma in the thoracolumbar region. She presented prenatally with a preliminary diagnosis of meningomyelocele, diastematomyelia, and Chiari II malformation and a possible teratoma. However, a mass containing solid glandular tissues and bony calcifications approximately 3 × 4 cm in size was observed in the thoracolumbar region upon birth. During surgical resection, no nerve roots were found in the associated meningocele. The patient retained full lower body function postoperatively following surgical excision of the thecal sac and teratoma. [ABSTRACT FROM AUTHOR]

Purpose: Malignant intracranial germ cell tumors (GCTs) are rare diseases in Western countries. They arise in midline structures and diagnosis is often delayed. We evaluated imaging characteristics and early tumor signs of suprasellar and bifocal GCT on MRI. Methods: Patients with the diagnosis of a germinoma or non-germinomatous GCT (NGGCT) who received non-contrast sagittal T1WI on MRI pre-therapy were included. Loss of the posterior pituitary bright spot (PPBS), the expansion and size of the tumor, and the expansion and infiltration of surrounding structures were evaluated. Group comparison for histologies and localizations was performed. Results: A total of 102 GCT patients (median age at diagnosis 12.3 years, range 4.4–33.8; 57 males; 67 in suprasellar localization) were enrolled in the study. In the suprasellar cohort, NGGCTs (n = 20) were noticeably larger than germinomas (n = 47; p <.001). Each tumor showed involvement of the posterior lobe or pituitary stalk. A PPBS loss (total n = 98) was observed for each localization and entity in more than 90% and was related to diabetes insipidus. Osseous infiltration was observed exclusively in suprasellar GCT (significantly more frequent in NGGCT; p =.004). Time between the first MRI and therapy start was significantly longer in the suprasellar cohort (p =.005), with an even greater delay in germinoma compared to NGGCT (p =.002). The longest interval to treatment had circumscribed suprasellar germinomas (median 312 days). Conclusion: A loss of the PPBS is a hint of tumor origin revealing small tumors in the neurohypophysis. Using this sign in children with diabetes insipidus avoids a delay in diagnosis. [ABSTRACT FROM AUTHOR]

This review provides a rationale for using the Food and Drug Administration (FDA)-approved antibody-drug conjugates (ADCs) for implementing as therapy in recurrent refractory germ cell tumors similar to their position in the treatment of other types of chemoresistant solid tumors. Germ cell tumors (GCTs) originate from germ cells; they most frequently develop in ovaries or in the testes, while being the most common type of malignancy in young men. GCTs are very sensitive to cisplatin-based chemotherapy, but therapeutic resistance occurs in a considerable number of cases, which is associated with disease recurrence and poor patient prognosis. ADCs are a novel type of targeted antitumor agents that combine tumor antigen-specific monoclonal antibodies with chemically linked chemotherapeutic drugs (payload) exerting a cytotoxic effect. Several FDA-approved ADCs use as targeting moieties the antigens that are also detected in the GCTs, offering a benefit of this type of targeted therapy even for patients with relapsed/refractory testicular GCTs (rrTGCT) unresponsive to standard chemotherapy. [ABSTRACT FROM AUTHOR]

Malignant ovarian germ cell tumors (MOGCT) are rare in children. Surgery with or without chemotherapy is the primary treatment approach. This study aimed to analyze the impact of primary and delayed surgery on surgical morbidity and outcomes. Second-look surgery after inadequate surgical staging and the various components of surgical staging were also evaluated. Children below 15 years with MOGCT treated between 2006 and 2022 were analyzed. A comparison of patients undergoing primary, delayed, and second-look surgery was performed. 118 patients with a median age of 12 (0.11–15) years were eligible. Forty patients underwent primary, 51 delayed, and 27 second-look surgeries. Overall complications, including tumor rupture, blood loss, and adjacent organ removal, were significantly higher in the primary compared to the delayed surgery group (p = 0.0001). Second-look surgery conceded more blood loss (p = 0.0001), extended duration (p = 0.03), and complications (p = 0.004) than delayed surgery. The compliance with surgical guidelines was 100% for most components, with a positive yield rate of 10–80%. At a median follow-up of 5.2 years, the 5-year event-free survival (EFS) and overall survival (OS) for the entire cohort are 86% and 89%, respectively. The OS and EFS did not differ by the timing of surgery, although the second-look surgery demonstrated relatively inferior outcomes consequential to initial suboptimal surgery. MOGCT shows favorable outcomes. Delayed surgery after chemotherapy in appropriately selected patients minimizes the morbidity of surgery with similar outcomes compared to primary surgery. An optimal initial surgery is essential since second-look surgery produces significant morbidity. Prognosis Study, Level II evidence • Surgery with or without postoperative chemotherapy is the primary treatment approach in malignant germ cell tumors of the ovary in children. • Delayed surgery after chemotherapy in appropriately selected patients significantly reduces the morbidity of the surgery. [ABSTRACT FROM AUTHOR]

Testicular tumors represent a common form of solid tumor in young men, with choriocarcinoma of the testis being a rare, non-granulomatous germ cell tumor. It accounts for less than 0.3% of all testicular germ cell tumors. Pelvic and pulmonary metastases originating from testicular choriocarcinoma are exceptionally uncommon in men. This study describes a case of a 27-year-old male diagnosed with testicular choriocarcinoma, presenting initially with nausea, vomiting, and abdominal pain. Furthermore, this review encompasses cases of testiclar choriocarcinoma in individuals aged 30 years and below, both in China and internationally, over the past 20 years. [ABSTRACT FROM AUTHOR]

Background Objective Material and methods Results Discussion and conclusion Testicular germ cell tumor (TGCT) is the most common type of tumor in young men. Type II germ cell tumors including postpubertal‐type teratomas are derived from the germ cell neoplasia in situ (GCNIS), whereas prepubertal‐type teratomas arise independently of the GCNIS. The consomic mouse strain 129.MOLF‐Chr19 (M19) is a suitable murine model of such tumors, but its characterization remains incomplete.Here, we interrogated the suitability of testicular tumors in M19 mice as a model of human TGCT by analyzing their histological features and gene expression signature.Testes collected from M19 mice of different ages were categorized by macroscopic appearance based on size and the degree of suspected tumorigenesis. Histological sections from selected tumors were stained with Hematoxylin and Eosin, and expression of genes associated with tumorigenesis was determined in frozen tissue samples from a large range of tumors of different subclasses using RT‐qPCR and Fluidigm Dynamic Arrays.Macroscopically, testicular specimens appeared very heterogeneous concerning size and signs indicating the presence of a tumor. Histological analysis confirmed the development of teratomas with areas of cells corresponding to all three germ cell layers. Gene expression analyses indicated upregulation of markers related to proliferation, vascular invasive potential and pluripotency, and revealed a strong correlation of gene expression with tumor size and a significant intercorrelation of individual genes.TGCT in M19 mice is reminiscent of human testicular teratomas presenting with areas of cells derived from all germ layers and showing a typical gene signature. We thus confirm that these mice can serve as a suitable murine model of pure teratomas for preclinical research. [ABSTRACT FROM AUTHOR]

A chordoma is a slow growing, locally invasive, low-grade tumor belonging to the sarcoma family. It mainly affects the sacrum and skull base. We present a case of thoracic chordoma initially presented with epidural hematoma (EDH), which is a rare clinical entity. We reported this case, and also performed a PRISMA-driven systematic review to summary the similar cases in the literature. This review includes the clinical characteristics and outcome of thoracic chordoma. Our case involves a 60-year-old male who, despite no history of trauma, presented with acute paraparesis. An epidural hematoma was identified at T6 level, leading to a surgical intervention involving T4-6 laminectomy and fixation. Six months subsequent to surgery, the patient experienced progressive lower limb weakness and spasticity. Computed tomography (CT) exhibited erosion of T6 and an associated aggressive mass. Magnetic resonance imaging (MRI) revealed a large heterogenous soft tissue mass arising from the vertebral body and right pedicle of D6, protruding in the epidural space and compressing the spinal cord focally at this level. The mass measured approximately 5 × 4 × 3.5 cm. Magnetic resonance myelography indicated a filling defect at T5–6 level, confirming the intraspinal location of the soft tissue lesion. Complete excision of the mass confirmed the diagnosis of thoracic chordoma. Postoperative follow-up demonstrated notable improvement in the lower limb spasticity and paraparesis, and the patient started adjuvant radiotherapy. This case underscores the importance of maintaining a high index of suspicion when evaluating presentations resembling EDH. [ABSTRACT FROM AUTHOR]

Background: Compared to testicular germ cell tumors, the incidence of extragonadal germ cell tumors (EGCTs) is relatively low. While the lungs are a common site for metastasis of malignant germ cell tumors, primary pulmonary germ cell tumors are extremely rare. Objective: To enhance the understanding of the diagnosis and treatment of germ cell tumors, particularly extragonadal germ cell tumors (EGCTs). Methods: A Case Report of Recurrent Testicular Germ Cell Tumor in a Patient with Primary Pulmonary Germ Cell Tumor and a Review of the Literature. Clinical data: The patient was initially diagnosed with primary pulmonary germ cell tumor and received standard treatment. Five years later, the patient developed a recurrent testicular germ cell tumor. The pathological results from the two surgeries were different, indicating embryonal carcinoma in the first instance and seminoma in the second. Conclusion: For cases with a high suspicion of extragonadal germ cell tumors (EGCTs), early pathological biopsy is essential to confirm the histological subtype and to guide the selection of the most appropriate and sensitive treatment regimen. [ABSTRACT FROM AUTHOR]

Introduction: Necrotizing bronchial infection with severe infectious lymphadenitis is infrequently encountered and most commonly ascribed to Aspergillus, Histoplasma, and Mycobacterium species. We present a unique cause of severe airway destruction with lymphadenitis and bronchopleural fistula formation by the bacterium Gemella morbillorum. Case: A 24‐year‐old man presented with acute symptoms of vomiting, fever, and shoulder pain. A CT of the chest demonstrated a large subcarinal mass encasing the central bronchi. The workup for malignant, fungal, and granulomatous etiologies was unrevealing, while blood cultures identified G. morbillorum. Fiberoptic bronchoscopy revealed a perforation of the right middle lobar bronchus and the formation of a bronchopleural fistula, resulting in a large hydropneumothorax with empyema. Despite antibiotic therapy, surgical intervention to repair the fistula, and ventilatory support, the progression of the bronchopleural fistula led to fatal respiratory failure. Conclusion: In cases of severe mediastinal adenopathy in a young patient, bacterial lymphadenitis should be considered in the differential diagnosis with lymphoma, germ cell tumor, granulomatosis with polyangiitis, sarcoidosis, histoplasmosis, and inflammatory myofibroblastic tumor. [ABSTRACT FROM AUTHOR]

Simple Summary: Chordoma is a rare cancer that often occurs at the base of the skull. Treating skull base chordoma is challenging because the tumor is difficult to completely remove with surgery and has low radiosensitivity. This study compared two types of radiation modality: particle beam therapy (PT) and photon radiotherapy (RT). We found that PT provides better progression-free survival compared to photon RT. However, PT also has a higher risk of causing brain necrosis. Our findings suggest that PT is more effective for controlling skull base chordoma, but careful planning is needed to minimize side effects. [Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma. [Methods] A systematic review was conducted for skull base chordoma treated with PT or photon RT reported from 1990 to 2022. Data were extracted for overall survival (OS) and progression-free survival (PFS), late adverse events, age, gender, gross total resection (GTR) rates, tumor volume, total irradiation dose, and treatment modality. Random-effects meta-regression analysis with the treatment modality as an explanatory variable was performed for each outcome to compare the modalities. [Results] A meta-analysis of 30 selected articles found 3- and 5-year OS rates for PT vs. photon RT or combined photon RT/proton beam therapy (PBT) of 90.8% (95% CI: 87.4–93.3%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6543; 80.0% (95% CI: 75.7–83.6%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6787. The 5-year PFS rates for PT vs. photon RT or photon RT/PBT were 67.8% (95% CI: 56.5–76.7%) vs. 40.2% (95% CI: 31.6–48.7%), p = 0.0004. A random-effects model revealed that the treatment modality (PT vs. photon RT or photon RT/PBT) was not a significant factor for 3-year OS (p = 0.42) and 5-year OS (p = 0.11), but was a significant factor for 5-year PFS (p < 0.0001). The rates of brain necrosis were 8–50% after PT and 0–4% after photon RT or photon RT/PBT. [Conclusion] This study shows that PT results in higher PFS compared to photon RT for skull base chordoma, but that there is a tendency for a higher incidence of brain necrosis with PT. Publication and analysis of further studies is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Primary central nervous system germ cell tumors (GCT) are rare neoplasms in pediatrics. Treatment depends on the histological subtype and extent of the disease. Overall survival (OS) is above 90% for germinomas and 70%-80% for nongerminomatous GCT (NGGCT) in high-income countries (HIC) while data are usually lacking for patients in Low-Middle Income country (LMIC). Objective: This study aims to describe the experience of treating patients with CNS GCT in four of eight countries, members of the Asociacio'n de Hemato-Oncologı'a Pedia'trica de Centro Ame'rica (AHOPCA), and determine their 5-year OS. Design/methods: We conducted a retrospective chart review of patients treated for CNS GCT. Epidemiological and clinical characteristics, histology, treatment modalities, and outcomes were analyzed. Results: From 2001 to 2021, 48 patients were included: 22 from Guatemala, 18 from Nicaragua, three from the Dominican Republic, and five from El Salvador. Thirty-one (64.6%) were boys; the median age at diagnosis was 10.2 years (range: 1 to 17 years). Presenting symptoms were headaches (n = 24, 50%), visual disturbances (n = 17, 35.4%), vomiting (n = 12, 25%), nausea (n = 8, 16.7%), and diabetes insipidus (n = 7, 14.6%). Two patients with NGGCT presented with precocious puberty. Biopsy or tumor resection was performed in 38 cases (79.2%): 23 (88.4%) germinomas, 11 (78.6%) NGGCT, and four (50%) CNS GCT. Eight patientswere diagnosed and treated based on CSF tumor marker elevation; four germinomas (BHCG 11.32-29.41 mUI/mL) and four NGGCT (BHCG 84.43-201.97 mUI/mL or positive AFP > 10 UI/mL). Tumor locations included suprasellar (n = 17, 35.4%), pineal (n = 13, 27.1%), thalamus/basal ganglia (n = 5, 10.4%), other (n = 12, 25%), and one bifocal. Four (8.3%) had metastatic disease, and six had positive CSF; staging data were incomplete in 25 patients (52%). Patients were treated with varied chemotherapy and radiotherapy modalities. Nine patients had incomplete data regarding treatment. Five-yearOSwas 65% (68% for germinoma, 50.6% for NGGCT, and 85.7% for unclassified GCT). Conclusions: Germinoma was the most common histology, and there was a male predominance. More than half of patients had incomplete staging data and treatment was variable across the region. OS is lower compared to HIC. Standardized treatment protocols will aid in adequate staging and treatment planning, prevent complications, and improve survival. [ABSTRACT FROM AUTHOR]

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

Objective: Ovarian carcinomas are considered one of the deadliest malignancies, accounting for a significant number of cancer-related deaths than any other gynaecological malignancy. Advanced stage at diagnosis can be attributed to vague presenting symptoms, rarely bizarre, which usually point towards any disease but ovarian tumour. Here, we discuss a similar case, with presentations that compels us to think in favor of disseminated Koch’s, but turns out to be germ cell tumor (GCT) of the ovary; thereby pointing at the wide spectrum of bizarre signs and symptoms which should have ovarian malignancies as a differential during workup. Case report: A 21-year-old unmarried female came to our gynaecology outpatient department with complaints of pain lower abdomen, high-grade fever, shortness of breath and progressively increasing abdominal distension. After routine hematological and imaging workup, she was diagnosed with an ovarian tumour with ascites and bilateral pleural effusion. Fertility-sparing surgery was done after the patient was hemodynamically stable. The histopathology report was suggestive of mixed GCT. The patient was thereby referred to the department of medical oncology for adjuvant chemotherapy. Conclusion: Mixed GCTs are among the rare and inordinately malignant tumours of the ovary. Though they have their usual presentations, we ought to be heedful of their atypical presentations as well because these form grounds for early diagnosis and management. In our patients, the unusual feature was the high-grade fever with associated shortness of breath (due to pleural effusion), but the effusion was non-malignant and non-infectious in origin. In the literature there are not many cases of atypical clinical presentation; hence, this could be an area of further research. Besides, such case reports with bizarre manifestations widen our spectrum of diagnostic probabilities, thereby avoiding any gaps in management. Our workup should be comprehensive enough to diagnose the patient as early as possible because these tumors, though aggressive, have a very good prognosis due to excellent chemosensitivity. [ABSTRACT FROM AUTHOR]