Epidemiology and Management  of Pediatric Testicular Tumors: History
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Pediatric testicular tumors are rare and represent 1% to 2% of all solid tumors in children. Germ-cell tumors are the most frequent etiology; most are benign in the pre-pubertal population, whereas post-pubertal testicular tumors are similar to those that occur in adults, with potential malignancy. 

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1. Epidemiology of Pediatric Testicular Tumors

Pediatric testicular tumors are rare and represent 1% to 2% of all pediatric solid tumors. In patients < 14 years old, the incidence is estimated at 0.5 to 2 per 100,000 children [1][2]. Testicular tumors have a bimodal distribution: the first peak is seen in boys < 3 years of age, most being benign, and the second occurs after puberty, from age 15 to 19 years, with a higher proportion of malignant neoplasms. This observation highlights two distinct patterns of disease leading to different approaches to treatment.
Among all prepubertal intra-testicular tumors, 90% are germ-cell tumors (GCTs) and 10% to 15% are epidermoid cysts [3][4][5]. Reports suggest that benign GCTs are frequent, approximately 40% to 50% being teratomas. Most teratomas show mature elements, but immature teratomas in this age group have been reported [6]. Epidermoid cysts are always benign. Malignant GCTs are mainly represented by yolk-sac tumors, with a frequency ranging from 8% to 30% [4]. Among non-GCTs, Leydig cell tumors are more frequent, representing approximately 5% of the etiologies, followed by juvenile stromal granulosa cell tumors. The incidence of prepubertal testicular tumors peaks in the first three years of life [7]. As compared with yolk-sac tumors, teratomas usually develop in younger children, with a median age of approximately 8 to 13 months and 16 to 17 months, respectively [4][8]. Among prepubertal testicular malignancies, the 5-year relative survival is 97% for children with localized tumors and 73% for those with distant disease [9].
Between ages 4 to 11 years, the diagnosis of a testicular GCT is rare. In contrast, in post-pubertal adolescents 15 to 19 years old, the incidence increases and represents 12% of all cancers in adolescents [10]. In this population, tumors are more likely to be malignant and include immature teratomas, mixed non-seminomatous malignant GCTs and embryonal carcinomas [11]. In young adults, 95% of testicular cancers are malignant GCTs, and 50% of these are seminomas. The 2016 World Health Organization classification system redefines testicular GCTs into two main groups: those derived from germ-cell neoplasia in situ, which are representative of post-pubertal lesions, and those not derived from germ-cell neoplasia in situ, which characterize prepubertal neoplasms [12].
One specific tumor type is the gonadoblastoma, which includes both germ-cell and sex-cord stromal-cell tumor types and occurs almost exclusively in the setting of differences in sexual differentiation [13]. In patients presenting a scrotal mass, a para-testicular mass should also be accounted for in the differential diagnosis. Para-testicular rhabdomyosarcoma is the most frequent para-testicular malignant mass in children; it represents 5% of all testicular and para-testicular malignancies. The para-testicular tumor spectrum remains wide and also includes benign lesions such as hemangiomas, leiomyomas, fibromas, lipoblastomas [14], cystic lymphangiomas and the rare malignant melanotic neuroectodermal tumor of infancy [15]. A classification of testicular tumors in children is presented in Table 1.
Testicular tumor markers are a major tool in evaluating pediatric testicular tumors; these include alpha-fetoprotein (AFP) and beta-human chorionic gonadotrophin (BHCG). Serum AFP levels are normally higher in children than in adults and are reduced to normal levels by age 1 (<10 ng/mL). Therefore, for children < 1 year old with testicular tumors, AFP level may be elevated in those with benign tumors, whereas for children > 1 year, a normal AFP level often indicates a benign tumor. Elevated serum AFP level is strongly associated with >90% of yolk-sac tumors, whereas immature teratomas may present a slightly elevated serum AFP level [16]. AFP should be measured before any therapeutic intervention and after surgery to assess an appropriate decrease in level.
BHCG is elevated in choriocarcinomas, embryonal carcinomas or seminomas, which are extremely rare in prepubertal boys but could be seen in adolescents. Thus, it is not useful in the diagnostic work-up of prepubertal boys with a testicular tumor but is useful in adolescents presenting a testicular mass [8]. Lactate dehydrogenase is also useful because high levels are associated with bulky disease and increasing levels after therapy may signify disease recurrence.

2. Management of Pediatric Testicular Tumors

For decades, TSS has been reported to control pediatric testicular benign tumors, with potential psychologic, cosmetic and functional advantages. The size of the tumor is an important factor in choosing the therapeutic option, with significantly smaller lesions in children after TSS versus radical orchidectomy [1]. Actually, a cut-off tumor size of <2.5 cm is generally considered a good candidate for TSS [1]. TSS has shown reliability and feasibility with no atrophy and rare cases of recurrence [17][18]. A recent systematic review [19] approved this strategy in selected cases of prepubertal testicular tumors.
However, tumor size only does not seem a sufficient criterion to differentiate benign from malignant neoplasms. Imaging, especially US, when combined with clinical data and tumor marker levels, is a reliable protocol for the differential diagnosis of benign and malignant lesions. However, intra-operative frozen section analysis seems to more accurately predict the pathological diagnosis [20], which suggests that it should be systematically performed during TSS to confirm the benign diagnosis and that microscopically margin-negative resection has been achieved. In the case of microscopic positive margins in a malignant or potentially malignant tumor, orchidectomy should be performed [8]. Orchidectomy with the inguinal approach should be considered if normal testicular parenchyma is no longer detectable on preoperatively high-resolution US and/or with AFP level > 100 ng/mL in a child > 12 months, considering high suspicion of yolk-sac tumor [8], or with AFP level > 23 ng/mL in a child < 8 months with a tumor > 2.5 cm because of increased frequency of immature teratomas [21].

This entry is adapted from the peer-reviewed paper 10.3390/cancers14133180


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