Testicular cancers were defined using the International Clas
Testicular cancers were defined using the International Classification of Diseases for Oncology (3rd ed.) topography (C62) and morphology codes (germ cell tumors: 9060/3–9062/3, 9064/3–9102/3; seminoma: 9060/3–9062/3, 9064/3; nonseminoma: 9065/3-9102/3; spermatocytic tumors: 9063/3; sex cord stromal tumors: 8640/3, 8650/3) . Nonseminomas were further classified as: embryonal carcinoma (9070/3, 9072/3), yolk sac tumors (9071/3), teratoma (9080/3, 9082–9084/3, 9102/3), choriocarcinoma (9100/3, 9101/3), and mixed germ cell tumors (9081/3, 9085/3). Primary testicular lymphomas were identified using a combination of topography (C62) and morphology codes for lymphoma. Incidence rates per 100,000 person-years, age-adjusted to the US 2000 standard population, and their 95% confidence intervals were calculated. Testicular cancer incidence rates were calculated by histologic subtype and age of diagnosis. Estimates of annual percent change (APC) were calculated for the 1999–2014 time period using the annual rates and weighted least squares regression . For temporal analysis, years of diagnosis were grouped into four periods: 1999–2002, 2003–2006, 2007–2010, and 2011–2014. Age of diagnosis was grouped into 8 categories: 50–54 years, 55–59 years, 60–64 years, 65–69 years, 70–74 years, 75–79 years, 80–84 years, and 85+ years. All statistical analyses were performed using the SEER*Stat statistical package (version 8.3.4).
Discussion The current study found that testicular lymphoma is the most commonly occurring testicular malignancy among men aged ≥ 70 years. Primary testicular lymphoma is a rare, clinically aggressive form of extranodal non-Hodgkin lymphoma (NHL) accounting for <5% of testicular cancers. The vast majority of cases are classified as histologically diffuse large B-cell lymphoma with high bilateral testicular involvement. There are limited data regarding specific risk factors for testicular lymphoma, however, Methoxy-X04 infection is a known risk factor for NHL, with lymphomas in HIV-infected patients presenting more commonly with extranodal primary sites, including the testis . The current study also found that the age-specific rates of spermatocytic tumors and sex-cord stromal tumors increased steadily with age in contrast to rates of seminoma and nonseminoma. Spermatocytic tumors, formerly called spermatocytic seminomas, are relatively indolent tumors that rarely metastasize and do not merit treatment apart from orchiectomy . Even though the highest rates of spermatocytic tumors occur among men ≥ 50 years, the incidence of spermatocytic tumors is always less than the incidence of seminoma, regardless of age. Sex-cord stromal tumors are extremely rare (approximately 2% of testicular cancer) and can appear sporadically or in combination with hereditary syndromes, such as Peutz–Jeghers syndrome . The etiology of sex cord stromal tumors is poorly understood, although associations with fumarate hydratase (FH) mutations, Klinefelter syndrome, hereditary leiomyomatosis, and renal cell carcinoma have been reported . Finally, the current study found an increase in the incidence of mixed germ cell tumors (MGCT) during the study period. Whether the increase reflects a true change in incidence is unclear, however, as the morphology code for MGCT was introduced with the release of ICDO-3 in 2001, thus, it is possible that the observed increase in MGCT is simply due to the more frequent usage of the MCGT specific code over time. Genetic susceptibility to TGCT exists, as evidenced by findings from genome wide association studies (GWAS). GWAS studies have identified at least 39 loci associated with TGCT susceptibility [, , , , , , ]. Genetic factors, however, cannot solely explain the steady increases observed in TGCT rates since the mid-20th century. Rather, increases in one or more environmental risk factors or decreases in protective factors are likely leading to the increasing incidence among genetically susceptible men.