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Item Multi-Observer Study on the Assessment of Pediatric Gonadal Tumors Using Higher Harmonic Generation Microscopy as Compared to Conventional Histology(MDPI, 2025-05-12) Spies, Sylvia; Nazarian, Elina; Bremmer, Felix; Gonzalez, Ivan A.; Lobo, João; Reyes-Múgica, Miguel; Zambrano, Eduardo; Hulsker, Caroline C. C.; Mavinkurve-Groothuis, Annelies M. C.; de Krijger, Ronald R.; Groot, Marie Louise; Pathology and Laboratory Medicine, School of MedicineBackground/objectives: Pediatric gonadal tumors are rare tumors, and germ cell tumors (GCTs) are the most common subgroup. GCTs are heterogeneous tumors and have different subtypes that can be either benign or malignant. Therefore, extensive sampling of the resected tumor is required to obtain an accurate diagnosis. Higher harmonic generation microscopy (HHGM) is an innovative imaging technique that enables rapid visualization of fresh tissue without the need for preparation or staining. This makes it particularly valuable for sample selection, as the tissue can be reused for further analysis. This study aims to evaluate the accuracy of pathologists detecting normal gonadal tissue, germ cell tumors, and other pediatric gonadal tumors in HHGM images. Methods: Twenty-eight samples of twenty-two patients with a germ cell tumor or other gonadal tumor were imaged with the HHG microscope and subsequently processed for histology. Overview images of the samples were made in 10 s per mm2, and high-quality images in 1 min per mm2. A multi-observer study was performed with five expert pathologists. Results: Pathologists were able to differentiate between tumor and non-tumor tissue with an accuracy of 75% (21/28) on the HHGM images versus an accuracy of 89% (25/28) on the corresponding histology. Discrepancies mainly concerned teratoma cases for HHGM as well as H&E, indicating that sampling errors of these heterogeneous tumors affected the outcomes of this study adversely. Conclusions: Although the sample size was limited by the rarity of these tumors, our data show that HHGM is a promising technique for the rapid assessment of pediatric gonadal tumor samples, particularly in evaluating their representativeness.Item Outcomes of adolescent males with extracranial metastatic germ cell tumors: A report from the Malignant Germ Cell Tumor International Consortium(Wiley, 2021) Shaikh, Furqan; Stark, Daniel; Fonseca, Adriana; Dang, Ha; Xia, Caihong; Krailo, Mark; Pashankar, Farzana; Rodriguez-Galindo, Carlos; Olson, Thomas A.; Nicholson, James C.; Murray, Matthew J.; Amatruda, James F.; Billmire, Deborah; Stoneham, Sara; Frazier, A. Lindsay; Pediatrics, School of MedicineBackground: Adolescents with extracranial metastatic germ cell tumors (GCTs) are often treated with regimens developed for children, but their clinical characteristics more closely resemble those of young adult patients. This study was designed to determine event-free survival (EFS) for adolescents with GCTs and compared them with children and young adults. Methods: An individual patient database of 11 GCT trials was assembled: 8 conducted by pediatric cooperative groups and 3 conducted by an adult group. Male patients aged 0 to 30 years with metastatic, nonseminomatous, malignant GCTs of the testis, retroperitoneum, or mediastinum who were treated with platinum-based chemotherapy were included. The age groups were categorized as children (0 to <11 years), adolescents (11 to <18 years), and young adults (18 to ≤30 years). The study compared EFS and adjusted for risk group by using Cox proportional hazards analysis. Results: From a total of 2024 individual records, 593 patients met the inclusion criteria: 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS rate was lower for adolescents (72%; 95% confidence interval [CI], 62%-79%) than children (90%; 95% CI, 81%-95%; P = .003) or young adults (88%; 95% CI, 84%-91%; P = .0002). The International Germ Cell Cancer Collaborative Group risk group was associated with EFS in the adolescent age group (P = .0020). After adjustments for risk group, the difference in EFS between adolescents and children remained significant (hazard ratio, 0.30; P = .001). Conclusions: EFS for adolescent patients with metastatic GCTs was similar to that for young adults but significantly worse than for that children. This finding highlights the importance of coordinating initiatives across clinical trial organizations to improve outcomes for adolescents and young adults. Lay summary: Adolescent males with metastatic germ cell tumors (GCTs) are frequently treated with regimens developed for children. In this study, a large data set of male patients with metastatic GCTs across different age groups has been built to understand the outcomes of adolescent patients in comparison with children and young adults. The results suggest that adolescent males with metastatic GCTs have worse results than children and are more similar to young adults with GCTs. Therefore, the treatment of adolescents with GCTs should resemble therapeutic approaches for young adults.Item Practice Makes Perfect: The Rest of the Story in Testicular Cancer as a Model Curable Neoplasm(American Society of Clinical Oncology, 2017-11-01) Tandstad, Torgrim; Kollmannsberger, Christian K.; Roth, Bruce J.; Jeldres, Claudio; Gillessen, Silke; Fizazi, Karim; Daneshmand, Siamak; Lowrance, William T.; Hanna, Nasser H.; Albany, Costantine; Foster, Richard; Cedermark, Gabriella Cohn; Feldman, Darren R.; Powles, Thomas; Lewis, Mark A.; Grimison, Peter Scott; Bank, Douglas; Porter, Christopher; Albers, Peter; De Santis, Maria; Srinivas, Sandy; Bosl, George J.; Nichols, Craig R.; Medicine, School of MedicineItem Prediction Model for Brain Metastasis in Patients With Metastatic Germ‐Cell Tumors(Wiley, 2025) Salous, Tareq; Ashkar, Ryan; Althouse, Sandra K.; Cary, Clint; Masterson, Timothy; Hanna, Nasser H.; King, Jennifer; Einhorn, Lawrence H.; Adra, Nabil; Medicine, School of MedicineBackground: Brain metastasis (BM) is an independent adverse prognostic factor in metastatic germ cell tumors (mGCT). We aimed to establish an effective and practical BM prediction model. Patients and methods: Between January 1990 and September 2017, 2291 patients with mGCT who were treated at Indiana University were identified. Patients were divided into two categories: BM present (N = 154) and BM absent (N = 2137). Kaplan-Meier methods were used to analyze progression free survival (PFS) and overall survival (OS). Logistic regression was used to determine a predictive model for whether BM was present. The data was separated into training and validation datasets with equal numbers of events in each. Results: The 2-year PFS and OS for patients with versus without BM: 17% versus 65% (p < 0.001) and 62% versus 91% (p < 0.001) respectively. Among the 154 patients with BM, 64 (42%) had radiation only (whole-brain radiotherapy or gamma knife), 22 (14%) had BM-surgery only, 14 (9%) had both radiation and BM-surgery. 54 patients (35%) did not receive local therapy for BM. Stepwise selection was used to determine the best model with p < 0.15 as the entry and staying criteria. The model with the largest ROC AUC was used moving forward. The model was tested in the validation dataset. A model was generated including age at diagnosis ≥ 40, choriocarcinoma predominant histology, pre-chemotherapy hCG≥ 5000, presence of pulmonary metastases size < 3, or ≥ 3 cm, and presence of bone metastasis. Patients with score of 0, 1, 2, 3, 4, 5, 6, 7, 8 points had a 0.6%, 1.4%, 3.5%, 8.2%, 18.3%, 36%, 58%, 78%, 90% probability of having BM, respectively. Conclusions: The prediction model developed in this study demonstrated discrimination capability of predicting BM occurrence in mGCT and can be used to identify high-risk patients.Item Primary Teratoma of the Lesser Sac: Lesser Sac Teratoma(Hindawi, 2012) Hardesty, Brandon M.; Ulbright, Thomas M.; Touloukian, Christopher; Einhorn, Lawrence H.; Medicine, School of MedicineGerm cell tumors predominantly involve the gonads but may rarely be found outside of the gonads, primarily in midline structures. We describe the case of a 27-year-old male with an asymptomatic 8 cm teratoma located within the lesser sac of his omentum. This is the fourth case of a teratoma located within the lesser sac of the omentum, which provides the opportunity to make some comparisons. Finally, we discuss some of the etiologic theories behind extragonadal germ cell tumors and how they relate to teratomas in the lesser sac.