Germ Cell Tumors Research Articles

074. Pulmonary Lacunae Due to Chemotherapy-Induced Pneumothorax in Metastatic Breast Cancer: A Rare Case Report and Review of Literature

Background: Chemotherapy plays a major role in treating breast cancer patients who develop hematogenous spread or disseminated metastase. Spontaneous pneumothorax is a rare complication of chemotherapy and is commonly associated with chemosensitive tumours such as germ-cell tumours, lymphomas, and sarcomas and rarely with lung and gynaecological malignant disease. Pneumothorax seems to occur 2–7 days after chemotherapy treatment and can be unilateral or bilateral. To present the rare case of a A 56-year-old woman with breast cancer on chemoterapy who had secondary pneumothorax after undergo chemotherapy and treated with chest tube insertion. Methods: Clinical and imagery review of a secondary pnuemothorax after several chemoterapy outlined in case report also review of literature. Results: The patient underwent a chest tube insertion and hospitalized 10 days. She was discharged and responds well to therapy. Conclusion: This is the case of secondary penumothorax due to chemoterapy in breast cancer patient. The mechanisms involved in chemotherapy-related pneumothorax have been proposed because of tumor necrosis inducing the formation of a fistula. Our patient underwent chest tube insertion and other pharmacology therapy to decreased patient her complaint.

Driver mutations associated with signatures of platinum sensitivity in germ cell tumors

We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance. Prevalence was calculated for platinum-resistant alterations (PRAs; KRAS, TP53, and KIT mutations, and MDM2 amplification) and high copy number amplifications (CNA ≥ 6 copies). Tumors were designated as chemo-naïve (PreC, N = 66) or post-chemotherapy (PostC, N = 17). A transcriptomic signature associated with platinum sensitivity (PSS, high suggests increased sensitivity) was applied. KIT mutations were observed in 14.5% of primary versus 1.8% of met and 0% of lymph. TP53 mutations were identified in 10% of primary GCTs versus 17% of met and 16.7% of lymph. MDM2 CNAs were similar between sites. PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.

Phase II Trial of Pathology-based Tripartite Treatment Stratification for Patients with CNS Germ Cell Tumors: A Long-term Follow-up Study.

A previous Phase II clinical trial, conducted from 1995 to 2003, evaluated CNS germ cell tumors (GCTs) using a three-group treatment stratification based on histopathology. The primary objective of the study was to assess the long-term efficacy of standardized treatment regimens, while the secondary objective focused on identifying associated long-term complications. Total 228 patients were classified into three groups for treatment: germinoma (n=161), intermediate prognosis (n=38), and poor prognosis (n=28), excluding one mature teratoma case. Treatment involved stratified chemotherapy regimens and varied radiation doses/coverage. Clinical data was retrospectively analyzed at a median follow-up of 18.5 years. The treatment outcomes for germinoma, with or without syncytiotrophoblastic giant cell, were similar. The 10- and 20-year event-free survival rates for the germinoma, intermediate, and poor prognosis groups were 82/76/49% and 73/66/49%, respectively. Overall survival (OS) rates were 97/87/61% at 10 years and 92/70/53% at 20 years. Germinomas in the basal ganglia, treated without whole-brain radiation therapy (WBRT), frequently relapsed but were effectively managed with subsequent WBRT. Deaths in germinoma cases had varied causes, whereas deaths in the poor prognosis group were predominantly disease-related. Nineteen treatment-related complications were identified in 16 patients, with cumulative event rates of 1.9% at 10 years and 11.3% at 20 years. OS rates at 1 and 2 years post-relapse for tumors initially classified as germinoma, intermediate, and poor prognosis were 94/88/18% and 91/50/9%, respectively. Initial treatment intensity is crucial for managing non-germinomatous GCTs, while long-term follow-up for relapse and complications is imperative in germinomas. Irradiation extending beyond the immediate tumor site is essential for basal ganglia germinomas. Addressing relapse in non-germinomatous GCT remains a significant challenge.

Stereotactic Radiosurgery for Choriocarcinoma Brain Metastases: Illustrative Case Presentation and Systematic Review

BackgroundChoriocarcinoma (CC) is a rare and aggressive form of germ cell tumor. There is limited evidence reporting outcomes in patients with primary CC and brain metastases (BM). To date, only a few single case reports have documented the use of SRS for CC BM. MethodsWe retrospectively assessed patients who were treated with SRS for pure CC BM from 1998-2024. Lesion follow-up sizes and local tumor control status were evaluated after SRS treatment using RECIST criteria. A comprehensive literature search was performed for CC BM in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. ResultsIn our series, 3 patients with 7 CC BM underwent SRS. Two were male with testicular CC and one was female with gestational CC. The median diameter of the lesions was 8 mm with a median volume of 0.14 cm3 at treatment. The MRIs at 3 and 6 months demonstrated reductions in median diameters to 6 mm and 4 mm, respectively. At the last follow-up visits, one lesion had local progression at 15 months after SRS and one lesion had sustained complete response. Our systematic review yielded 249 articles. After screening, a total of 18 reports were identified for CC BM. Among these, only three single cases documented the use of SRS for CC BM. ConclusionSRS is a feasible and viable approach for CC BM, particularly in cases where immediate surgical management is not necessary. This is yet the largest report evaluating the outcome of CC BM treated with SRS.

Optimal Treatment Strategies for Early-Stage Primary Mediastinal Germ Cell Tumors

Data on optimal therapy for patients with primary mediastinal germ cell tumors consist overwhelmingly of single-institution studies with small sample sizes. The objective of this study is to assess the association of survival outcomes with surgery vs non-operative management for patients with early-stage primary mediastinal germ cell tumors. Overall survival of all patients with seminomas and non-seminomatous primary germ cell tumors in the mediastinum who received 1) chemotherapy, or 2) surgery with or without chemotherapy (referred to as 'surgery' for simplicity) for early-stage disease from 2004-2015 in the National Cancer Database was assessed using Kaplan-Meier analysis, propensity score-matched analysis, and multivariable Cox proportional hazards analysis. Among patients with seminomas, chemotherapy alone was used in 120 (80.5%) patients and surgery was used in 29 (19.5%) patients. There was no significant difference in 5-year survival between surgery and chemotherapy in unadjusted and propensity score-matched analysis. Among patients with non-seminomatous tumors, chemotherapy alone was used in 91 (46.7%) patients and surgery was used in 104 (53.3%) patients. Surgery was associated with improved 5-year survival when compared to chemotherapy in unadjusted, and multivariable-adjusted, and propensity score-matched analysis. In this national analysis, multimodality treatment involving surgery was associated with improved survival when compared to chemotherapy alone for early-stage primary mediastinal non-seminomatous germ cell tumors. For seminomas of the mediastinum, chemotherapy was associated with similar long-term outcomes when compared to multimodality treatment involving surgery.

P221 Complete resection of post-chemotherapy residual tumor could improve the prognosis in Non-Seminomatous Germ Cell Tumors (NSGCT)

P221 Complete resection of post-chemotherapy residual tumor could improve the prognosis in Non-Seminomatous Germ Cell Tumors (NSGCT)

O09 Correlation between Fibroblast Activation Protein inhibitor (99mTc-FAPi/SPECT) and histology in patients submitted to Retroperitoneal Lymph Node Dissection (RPLND) with residual post-chemotherapy disease in Non-Seminomatous Germ Cell Tumors (NSGCT)

O09 Correlation between Fibroblast Activation Protein inhibitor (99mTc-FAPi/SPECT) and histology in patients submitted to Retroperitoneal Lymph Node Dissection (RPLND) with residual post-chemotherapy disease in Non-Seminomatous Germ Cell Tumors (NSGCT)

Pancancer analysis of the interactions between CTNNB1 and infiltrating immune cell populations.

Recently, evidence has indicated that CTNNB1 is important in a variety of malignancies. However, how CTNNB1 interacts with immune cell infiltration remains to be further investigated. In this study, we focused on the correlations between CTNNB1 and tumorigenesis, tumor progression, mutation, phosphorylation, and prognosis via gene expression profiling interaction analysis; TIMER 2.0, cBioPortal, GTEx, CPTAC, and GEPIA2 database analyses; and R software. CTNNB1 mutations are most found in uterine endometrioid carcinoma and hepatocellular carcinoma. However, no CTNNB1 mutations were found to be associated with a poor prognosis. In addition, CTNNB1 DNA methylation levels were higher in normal tissues than in tumor tissues in cancer except for breast invasive carcinoma, which had higher methylation levels in tumor tissues. The phosphorylation level of the S675 and S191 sites of CTNNB1 was greater in the primary tumor tissues in the clear cell renal cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, and breast cancer datasets but not in the glioblastoma multiform dataset. As for, with respect to immune infiltration, CD8 + T-cell infiltration was negatively correlated with the expression of CTNNB1 in thymoma and uterine corpus endometrial carcinoma. The CTNNB1 level was found to be positively associated with the infiltration index of the corresponding fibroblasts in the TCGA tumors of colon adenocarcinoma, human papillomavirus-negative head and neck squamous cell carcinoma, mesothelioma, testicular germ cell tumor, and thymoma. We also identified the top CTNNB1-correlated genes in the TCGA projects and analyzed the expression correlation between CTNNB1 and selected target genes, including PPP4R2, RHOA, and SPRED1. Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.

P209 Ureteric involvement and obstructive uropathy caused by retroperitoneal lymph nodes in patients with testicular germ cell tumor as seen on post-chemotherapy computed tomography scan – no-brainer or enigma

P209 Ureteric involvement and obstructive uropathy caused by retroperitoneal lymph nodes in patients with testicular germ cell tumor as seen on post-chemotherapy computed tomography scan – no-brainer or enigma

Mature mediastinal teratoma with adhesions to the pericardium: A rare case report.

Mature mediastinal teratoma (MMT) is a benign tumor that is composed of well-differentiated tissues from all three germ cell layers. Malignant tumors have a distinct feature of adhering to the surrounding organs. Therefore, adhesion of MMT to the adjacent tissues, as a benign tumor, is rare and considered a surgical challenge. It leads to incomplete tumor resection to avoid damage to the surrounding tissues. MMT is a germ cell tumor that contains well-differentiated tissues from ectodermal, mesodermal, and endodermal germ cell layers. MMT comprises approximately 3%-12% of mediastinal tumors in adults and 60%-70% of mediastinal germ cell tumors. Complete surgical resection is the standard treatment. When adhesion to the surrounding tissues is present, residual tissues could be retained to reduce the injury of the peripheral blood vessels and nerves. We are reporting a rare case of MMT with adhesions to the pericardium and discussing the diagnostic and surgical challenges.

O04 Differentially expressed miRNA signatures as diagnostic and prognostic molecular biomarkers for seminomatous and non-seminomatous testicular germ cell tumors

O04 Differentially expressed miRNA signatures as diagnostic and prognostic molecular biomarkers for seminomatous and non-seminomatous testicular germ cell tumors

High-coverage targeted lipidomics revealed novel profile of serum lipid dysregulation in adult growth hormone deficiency.

Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Despite extensive research efforts in recent decades, the lipid metabolism pattern of AGHD has yet to be thoroughly characterized. In this study, we used lipidomics analysis of fasting serum samples from 30 AGHD patients due to intracranial germ cell tumors (iGCTs) and 30 age-, gender-, and body mass index (BMI)-matched healthy controls to investigate the serum lipidomic pattern of AGHD patients due to iGCTs. We meticulously quantified 534 serum lipids from 29 classes using high-coverage targeted lipidomics technology in conjunction with a robust bioinformatics pipeline. Our results revealed an AGHD-specific dynamic change in serum lipidomic profile, manifested by higher overall levels of many lipid subclasses, including triacylglycerols (TAGs), diacylglycerols (DAGs), phosphatidylglycerols, phosphatidylethanolamines (PE), phosphatidylcholines (PC), phosphatidylinositols, ceramides, and bis(monoacylglycerol)phosphates than in healthy controls, and a distinct lowering level in alkyl PE (PE-O) and alkyl PC (PC-O). AGHD individuals with non-alcoholic fatty liver disease showed specific changes in higher TAG and DAG subclass levels. Alterations in lipid profiles may contribute to metabolic dysregulation in AGHD patients. TAGs, PCs, and PE-fatty acids positively correlated with BMI, fasting insulin, insulin resistance index, and adverse lipid parameters. In contrast, ether-linked PE-O, PC-O, and LysoPE-O showed a negative correlation. This study has significantly expanded the current understanding of lipid dysregulation in AGHD patients due to iGCT. These findings can potentially guide future research and the development of monitoring and intervention strategies.

Mediastinal Germ Cell Tumors: Update From the WHO Classification of Tumors: 5th Edition

Mediastinal Germ Cell Tumors: Update From the WHO Classification of Tumors: 5th Edition

P212 Incidence of gonadal and extragonadal germ cell tumours in patients with and without Klinefelter’s Syndrome

P212 Incidence of gonadal and extragonadal germ cell tumours in patients with and without Klinefelter’s Syndrome

P211 Evaluation of the M371 test under real life conditions for the diagnosis of testicular germ cell cancer

P211 Evaluation of the M371 test under real life conditions for the diagnosis of testicular germ cell cancer

Refractory testicular germ cell tumors are highly sensitive to the targeting of polycomb pathway demethylases KDM6A and KDM6B

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.

Metastatic Mesothelioma of the Tunica Vaginalis Presenting as Scrotal and Abdominal Nodules: A Case Report and Review of the Literature.

Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

Bilateral Somatically Derived Germ Cell Tumors With 12p Gains Arising in High-grade Serous Carcinomas of the Ovary: A Case Report and Review of the Literature.

Epithelial ovarian neoplasms are commonly observed in older patients, while germ cell tumors (GCTs) typically present in young individuals. When GCTs are detected in patients over 35yrs old, they often have an associated epithelial component, a phenomenon known as somatically derived GCTs. We report a unique case of mixed GCT involving bilateral ovaries with a background of high-grade serous carcinoma, including a yolk sac tumor and choriocarcinoma in the mixed GCT component. Somatically derived GCTs are rare with only 45 cases of ovarian carcinoma with somatic yolk sac tumor reported to date. Pathologists face diagnostic challenges in identifying somatically derived GCTs, as they can mimic high-grade epithelial neoplasms. Somatically derived GCTs have poor outcomes, therefore, precise diagnosis is crucial for prognostic and therapeutic considerations.

A case report of intrapulmonary mature teratoma with aspergilloma

Introduction: Teratomas are benign germ cell tumors composed of components from the ectoderm, mesoderm, and endoderm. While germ cell tumors account for 10-20% of anterior mediastinal masses, intrapulmonary teratomas (IPTs) are extremely rare. They typically occur in the third decade of life and may present as metastasis from gonadal tumors. This study reports a rare case of a mature IPT in the right middle lobe of the lung, initially misdiagnosed as pulmonary tuberculosis and aspergilloma. Case Presentation: A 17-year-old female presented with a 4-year history of cough with sputum and two episodes of hemoptysis. Despite negative tuberculosis tests, she was treated with anti-tubercular drugs and multiple antibiotics. Imaging revealed a 5.5-cm cavitary mass in the right middle lobe containing an aspergilloma. Surgical resection was performed, and the pathology confirmed a mature teratoma with aspergilloma colonization. The patient recovered well postoperatively and showed no signs of recurrence. Discussion: Teratomas are germ cell tumors rarely found in the lungs, with fewer than 100 cases reported globally. Diagnosis is challenging due to overlapping symptoms with other conditions such as tuberculosis. In this case, the presence of an aspergilloma further complicated the diagnosis. Complete surgical resection led to the patient's recovery. Conclusion: Mature IPTs with aspergilloma are extremely rare, and should be considered in the differential diagnosis of cavitary lung lesions. Early diagnosis and surgical resection are crucial for successful treatment.

Pulmonary metastases revealing a mixed germ cell tumor with a predominant yolk sac tumor component: A case report

Yolk sac tumor of the testis is rare in adults. Its diagnosis is histological, reproducing an extra-embryonic structure (endodermal sinus tissue). It can be present alone or associated with another component, thus forming a mixed germ cell tumor. Treatment involves orchiectomy and chemotherapy in extratesticular stages. Lymph node dissection is indicated if residual masses persist. These tumors are characterized by a poor prognosis at an advanced metastatic stage. However, we report the clinical case of a 69-year-old man who presented with pulmonary metastases from a mixed germ cell tumor of the testis with a predominant Yolk Sac Tumor component, treated by orchiectomy, chemotherapy, and lymph node dissection.