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.