Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.

Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications

Mediastinal germ cell tumors (MGCTs) share histologic, molecular and biomarkers features with testicular GCTs; however, nonseminomatous MGCTs are usually more aggressive and have poorer prognosis than nonseminomatous TGCTs. Most nonseminomatous MGCT cases show early resistance to platinum-based therapies and seldom have been associated with the onset of one or more concomitant somatic malignancies, in particular myeloid neoplasms with recent findings supporting a common, shared genetic precursor with the primary MGCT. Genomic, transcriptomic and epigenetic features of testicular GCTs have been extensively studied, allowing for the understanding of GCT development and transformation of seminomatous and nonseminomatous histologies. However, MGCTs are still lacking proper multi-omics analysis and only few data are reported in the literature. Understanding of the mechanism involved in the development, in the progression and in their higher resistance to common therapies is still poorly understood. With this review, we aim to collect all molecular findings reported in this rare disease, resuming the similarities and disparities with the gonadal counterparts.

Burned-Out Testicular Tumors in Adolescents: Clinical Aspects and Outcome

Purpose: Testicular germ cell tumors are the fourth most common neoplasm in adolescents, accounting for 8% of all tumors in the age group 15–19 years. On rare instances, the primary testicular lesion is not clinically or radiologically evident while nodal or visceral metastases represent the clinical manifestations of the disease. This phenomenon is described as “burned-out testicular tumor.” In this paper, the authors report a single-institution experience with burned-out testicular tumors in adolescents and discuss their clinical implications.Patients and Methods: All the patients diagnosed with metastatic testicular germ cell tumors at Bambino Gesù Children Hospital between January 1, 2010, and June 30, 2020, were included in the study. Patients were categorized into two groups: “primary testicular” and “burned out.” All the patients were staged and treated according to the AIEOP–TCGM 2004 protocol.Results: Eleven patients were classified as “primary testicular,” and five patients were classified as “burned out.” “Burned-out” tumors were associated with the presence of systemic symptoms compared to “primary testicular” tumors (80 vs. 0%; p = 0.0027) and higher aFP, hCG, and LDH levels (p &lt; 0.00001). The “burned-out” population had a statistically significant higher incidence of relevant toxicity than the “primary testicular” population (80 vs. 18%; p = 0.0357) and a worse outcome in terms of both mean overall survival (15 vs. 43 months; p = 0.0299) and mean event-free survival (12 vs. 38 months; p = 0.0164).Conclusion: “Burned-out” testicular tumors seem to be a well-distinct clinical entity with a high treatment-related toxicity and poor prognosis. Further studies are needed to clarify the “burned-out phenomenon” and to identify more effective therapeutic strategies for these patients.