Discussion
DSRCT is an aggressive tumor that develops in serous cavities, mainly in the abdomen/pelvis, and spreads generating multiple peritoneal implants. The age-adjusted incidence rate of DSRCT is 0,3 cases/million, with a peak incidence of 0,74 cases/million in those aged 20-24 years5 . In a series of 60 patients, 93% had intra-abdominal tumor and 90% had metastases at diagnosis6 . Extra-abdominal DSRCT is rare, affecting about 5-27% of cases and was reported in several sites, like parotid glands, pleura, tibia and the paratesticular region4,7-9 .
Although paratesticular DSRCT has been reported since 1992, primary DSRCT of the testis was first described by He and colleagues in 201310 . In our literature review we found 23 cases of paratesticular and 5 of testicular tumors, including the case here reported (Table 1) . Of the 5 testicular DSRCT, 2 cases presented with extension to the epididymis/spermatic cord and in another case the tumor invaded rete testis with infiltration to lymphovascular spaces10-12 . Of the paratesticular tumors, not one infiltrated the testis. In contrast, testicular DSRCT seems to invade paratesticular regions. The present case report is the fifth testicular DSRCT in the literature.
Translocation t(11;22)(p13;q12) is the hallmark of DSRCT and the fusion occurs in exon 7 of EWS gene and exon 8 of WT1 gene2,13,14 . This fusion results in a chimeric protein capable of acting as a transcription factor in more than 30 genes, such as the growth factor genes PDGF, EGFR and IGF-115,16 . Although the EWS-WT1 transcript is characteristic of DSRCT, it is still not known if the fusion is specific to this disease. Alaggio et al described 2 cases of intra-abdominal leiomyosarcomas positive for the EWS-WT1 fusion in children 9 and 11 years old. One of the cases presented as a single abdominal mass and both had a favorable course17 . Two cases that we reviewed presented unusual fusion with EWS in exon 9 and WT1 in exon 8, one a paratesticular DSRCT and the other testicular12,14 . Al-Ibraheemi described a series of 16 cases with DSCRT with atypical location; all of them presented the typical EWS-WT1 fusion, demonstrating that the molecular signature of DSRCT in atypical sites seems to be the same as of those in the abdomen, despite better outcomes18 .
Patients with abdominal DSRCT are usually diagnosed with advanced disease and have poor prognosis, with overall survival ranging from 12 to 33% in 5 years, even with multimodal treatment. Resectable and non-metastatic tumors have better outcomes, regardless of their location5,6,19,20 . Therefore, resectability is considered an independent prognostic factor. In a study by Wong et al, patients with non-metastatic, intra-abdominal disease at presentation who had undergone surgical resection of the primary tumor (n = 6) survived much longer than those who did not have surgery (n = 11), with median survival of 47 versus 16 months, respectively (p=0.0235)21 .
Some studies suggest that patients with extra-abdominal tumors have better outcomes compared to the typical abdominal tumors3,21 . Our review included 28 patients with testicular and paratesticular DSRCT. 6 of these were lost to follow-up. 12 out the remaining 22 (54%) were disease-free between 6 and 120 months after diagnosis. Differences of survival between testicular and paratesticular DSRCT was not significant due to the small number of cases and variable follow-up.
Survival improves considerably in non-metastatic testicular/paratesticular DSRCT. Of the 12 available patients, 9 were disease-free between 6-120 months after diagnosis and 3 died, resulting in a 75% disease-free survival.
In DSRCT with metastasis at diagnosis, regardless of testicular or para-testicular location, only 2 out of 8 cases were alive without evidence of disease 6 and 30 months after diagnosis. In our review, the most frequent sites of metastasis at the time of initial diagnosis or at the time of recurrence diagnosis were retroperitoneal lymph nodes (9 cases) and lungs (6 cases).
Resection surgery was possible in 93% of patients with paratesticular/testicular DSRCT, with orchiectomy reported in 23 of 28 cases, signaling the high resectability of these tumors when compared to abdominal DSRCT, in which less than 50% are completely resected6,20 .
Currently, the most used chemotherapy regimen is based on alkylating agents, anthracyclines and vinca alkaloids. However, several different regimens are reported in the literature6,21 . Our patient was treated with Irinotecan. Some authors have shown that topoisomerase inhibitors, such as Irinotecan, can be effective in DSRCT22-24 .
There is no consensus in the literature regarding the treatment of patients with DSRCT in the paratesticular or testicular regions due to the small number of cases. In non-metastatic cases the initial treatment is radical orchiectomy3,4,12,25-28 , but in patients with disseminated tumors we cannot say that primary-tumor-surgery improves survival. The administration of chemotherapy seems to be consensual due to the potentially aggressive behavior of the tumor. However, at least in paratesticular or testicular disease, it appears that radiotherapy can be avoided in tumors that are completely resected, although further studies are needed for definitive conclusions. In metastatic tumors multimodal treatment is mandatory, and the prognosis is poor regardless of the primary tumor location.
Efforts are being made to discover targeted therapies in DSRCT, however there is currently no drug that has a target effect in the EWS-WT1 fusion. Several agents, especially tyrosine kinase inhibitors, such as pazopanib, imatinib and sorafenib are being studied16 . A wide analysis of the genomic profile of DSRCT may provide data on whether other genetic alterations contribute to the growth and behavior of this tumor in different regions.