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Original Paper

Urologia

Urol Int 2009;82:448–452 DOI: 10.1159/000218536

Internationalis

Received: November 14, 2007 Accepted after revision: April 28, 2008

© Free Author Copy – for personal use only

Paratesticular Sarcomas in Brazil Fernando Korkes Marília G. Castro Maria F. Amary Roni C. Fernandes

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Godoy

Written permission to distribDivision of Urology and Department of Pathology, Medical School of Santa Casa of São Paulo, São Paulo, Brazil ute the PDF will be granted against payment of a permission fee, which is based on the number of accesses required. Please contact permission@karger.ch

Key Words Sarcoma ! Testis ! Scrotum ! Paratesticular

Abstract Purpose: Paratesticular sarcomas are rare and frequently reported as isolated case reports. Studies evaluating the relative frequency of the paratesticular sarcomas are limited, and to the best of our knowledge, this is the first study of paratesticular sarcomas in the Brazilian population. Patients and Methods: Medical records of all patients undergoing treatment for paratesticular sarcomas between 1993 and 2006 were retrieved from the archives of our institution. Results: Complete data from 12 patients (39 8 23 years, range 13–78) with paratesticular sarcomas were available, which represented 6.7% of all orchiectomies performed for testicular malignancies in the same period. At the time of diagnosis, 3 patients had retroperitoneal spread of the disease, all of which had elevated serum lactic dehydrogenase levels. The remaining 9 patients had normal serum markers. There were 6 rhabdomyosarcomas, 4 leiomyosarcomas, 1 liposarcoma and 1 undifferentiated sarcoma. Median follow-up was 31.4 months. Primary surgical excision by inguinal approach was performed in all cases (radical orchiectomy in 10 and preservation of the testis in 2). Retroperitoneal lymph node dissection was performed in 3 patients and excision of the hemiscrotum in 1. Eight patients received adjuvant chemotherapy. Mean overall survival time was 27.8 8 6.2 months after orchiectomy. Conclusion: Patients with paratesticular sarcomas are at high risk of disease progression, and systemic re-

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lapse remains a significant problem, determining poor prognosis. The high risk of local recurrence demands long-term follow-up, and intraoperative frozen section analysis might be of benefit. Elevated lactic dehydrogenase might also be a marker of retroperitoneal disease and poor prognosis. Improvement in survival systemic © Free Authorrequires Copy effective – for per sonaladjuvant use only therapy. Copyright © 2009 S. Karger AG, Basel ANY DISTRIBUTION OF THIS ARTICLE WITHOUT WRITTEN CONSENT FROM S. KARGER AG, BASEL IS A V Written permission to distribute the PDF will be granted against payment of a permission fee, which is

Introduction

Paratesticular sarcomas are rare and frequently reported as isolated case reports or small series of patients [1–3]. Optimal local and systemic treatment of these tumors remains controversial, since information is based on small retrospective studies with limited follow-up. Recent advances in the pathological classification make generalization regarding treatment and prognosis even more difficult. There are few cases reported in the literature with intermediate and long-term follow-up. For paratesticular rhabdomyosarcomas, large studies have been reported by pediatric international multi-institutional studies [4–6]. For leiomyosarcomas and liposarcomas, however, there are even fewer reports [7, 8]. As a further matter, studies evaluating the relative frequency of the paratesticular sarcomas are limited, and to the best of our knowledge, this is the first study of paratesticular sarcomas in the Brazilian population. Fernando Korkes Rua Pirapora, 167 04008-060 São Paulo – SP (Brazil) Tel. +55 11 3884 2244, Fax +55 11 3884 2233 E-Mail fkorkes@terra.com.br


Table 1. Clinicopathological features of 12 patients with paratesticular sarcomas

Age years

Initial presentation/time

Histology/grade

Surgery

Adjuvant therapy

24

right scrotal mass/4 months

rhabdomyosarcoma/high

orchiectomy

56 55

orchiectomy orchiectomy

21 16 17

right scrotal mass/18 months leiomyosarcoma/I left scrotal mass/2 months undifferentiated sarcoma/ high right scrotal mass/5 months rhabdomyosarcoma/high left scrotal mass/3 months rhabdomyosarcoma/high left scrotal mass/8 months rhabdomyosarcoma/high

orchiectomy orchiectomy orchiectomy

13

right scrotal mass/9 months

rhabdomyosarcoma/high

orchiectomy

19 78 74 57 43

right scrotal mass/1 month left scrotal mass/8 months right scrotal mass/4 months left scrotal mass/6 months left scrotal mass/3 months

rhabdomyosarcoma/high leiomyosarcoma/2 liposarcoma/1 leiomyosarcoma/2 leiomyosarcoma/high

orchiectomy orchiectomy orchiectomy nodulectomy nodulectomy

chemotherapy + retroperitoneal no lymph node dissection no chemotherapy + excision yes hemiscrotum chemotherapy chemotherapy no chemotherapy + retroperitoneal yes lymph node dissection chemotherapy + retroperitoneal no lymph node dissection chemotherapy no no no no no excision of hemiscrotum no no no

Patients and Methods Medical records of all men treated for paratesticular sarcomas between 1993 and 2006 were retrieved from the archives of our institution. Two histopathologists (M.F.A. and M.G.C.) reviewed all slides and immunohistochemical panels to confirm the diagnoses. Clinical data, histopathological findings, treatment modalities and oncological outcomes were reviewed. Men were treated with a multimodal approach, including surgery, radiotherapy and chemotherapy. Survival estimates were computed using the Kaplan-Meier method, and survivals were compared using the log-rank test.

Local Distant failure failure yes yes yes no no yes no yes no no no no

levels (range 445–563 ng/dl). The remaining 9 (75%) patients had normal serum markers.

Patient Demographics and Clinical Characteristics Median 8 SE age at diagnosis was 39 8 23 years (range 13–78). All men presented with painless scrotal swelling, and mean 8 SD history time was 5.7 8 4.6 months (range 1–18). At the time of diagnosis, 3 patients (25%) had retroperitoneal spread of the disease, all of which had elevated serum lactic dehydrogenase (LDH)

Tumor Characteristics Tumor characteristics are shown in table 1. Mean 8 SD tumor weight was 127 8 75 g (range 15–242). Surgical margins were negative in 9 (75%) patients. Median follow-up was 31.4 months (range 6–60). Only 2 patients were lost to follow-up. Leiomyosarcomas comprised one third of the paratesticular sarcomas. Mean 8 SD patient age was 58.3 81 4.8 (range 42–78), similar to other series [9]. Mortality rate was 50%, with both cases presenting pulmonary metastasis. Two patients underwent nodulectomy, and both of them had no evidence of disease at a follow-up of 8 and 48 months. Liposarcomas represented 8.3% of paratesticular sarcomas. Other series have shown a prevalence rate that ranges from 3 to 50% [10–12]. Most paratesticular liposarcomas are well differentiated and slow growing, but tend to recur if incompletely excised. Average age ranges within the 6th and 7th decades of life, and the present man was slightly older (74 years) [8, 10]. As is commonly seen in patients with this rare tumor, he presented with local disease and showed a good prognosis. For these cases, retroperitoneal lymphadenectomy does not seem to offer any additional therapeutic benefit and the role of chemotherapy is not well defined. Regardless of initial

Paratesticular Sarcomas in Brazil

Urol Int 2009;82:448–452

Results

Prevalence Complete data from 12 men with paratesticular sarcomas were available, which represented 6.7% of all orchiectomies performed for testicular malignancies during that period at our institution.

449


Color version available online

Color version available online

Fig. 1. Macroscopic aspect of paratesticular rhabdomyosarcoma

Fig. 2. Histology of paratesticular rhabdomyosarcoma: interlac-

therapy, the risk of local recurrence always requires longterm follow-up [10]. Rhabdomyosarcoma is the most frequent malignant tumor of paratesticular origin [13]. It is classified as embryonal, alveolar, pleomorphic and mixed. Embryonal form is most frequent in childhood and has the best prognosis (fig. 1, 2). Alveolar rhabdomyosarcoma occurs mainly in adolescents and young adults. The pleomorphic subtype occurs in adults and bears the worst prognosis [13]. At our institution, rhabdomyosarcomas represented 50% of all paratesticular sarcomas. It was found mainly in young men, with a mean 8 SD age of 18.3 8 3.9 years (range 13–24). The most common pathological variant was the embryonal rhabdomyosarcoma (83%, n = 5), followed by the pleomorphic subtype (17%, n = 1). Three of these men initially presented with metastatic disease and died after a mean period of 10 months after surgery, despite chemotherapy. Two are alive and cured, and 1 demonstrated retroperitoneal disease after 10 months of surgery. He is currently undergoing adjuvant chemotherapy.

possible. Radical orchiectomy with high ligation of the spermatic cord was required in 10 patients (83.3%). Retroperitoneal lymph node dissection for secondary tumor spread was performed in 3 patients, and excision of the hemiscrotum in 1, for local invasion. Eight patients (66.7%) received adjuvant chemotherapy. There were 2 local failures, and 6 patients developed distant metastases, including the lungs, liver, bones, peritoneum and lymph nodes.

associated with hydrocele and testis compression.

Treatment Modalities Primary surgical excision by the inguinal approach was performed in all cases. In 2 cases (16.7%), complete excision of the tumor with preservation of the testis was 450

Urol Int 2009;82:448–452

ing fascicles of atypical spindle cells. Hematoxylin and eosin. !25.

Oncological Outcomes Median follow-up was 31.4 months (range 6–60 months) and 2 patients were lost to follow-up. Mean 8 SD overall survival time was 27.8 8 6.2 months after orchiectomy (fig. 3). Six patients (50%) died at a mean follow-up of 22 months after surgery (range 4–48): 2 with leiomyosarcoma, 3 with rhabdomyosarcoma and 1 with undifferentiated sarcoma. For rhabdomyosarcoma, mean 8 SD overall survival was 11.4 8 2.1 months and for leiomyosarcoma it was 44.0 8 4.6 months. There was no difference in diseasespecific survival when comparing patients with rhabdomyosarcoma and leiomyosarcoma (p = 0.24).

Korkes/Castro/Romero/Godoy/Amary/ Fernandes/Perez


Paratesticular Sarcomas in Brazil

Urol Int 2009;82:448–452

Color version available online

Soft tissue sarcomas are aggressive tumors with a tendency towards local recurrence and systemic dissemination. Paratesticular are rare neoplasms that can arise from the epididymis, mesenchymal layers surrounding the testis and its true appendages or spermatic cord. It is often difficult, however, to localize the precise origin of these tumors [14] (fig. 1). Our study has some important findings. First, even in large institutions it is difficult to accumulate sufficient cases to document the natural history of paratesticular sarcomas and to draw conclusions about treatment results. At our institution, they represented 6.7% of orchiectomies performed for testicular cancer over a 13-year period. Furthermore, as this study is the first report of a Brazilian series, it might bring additional original data, since these neoplasms may vary according to environmental characteristics and changes [15]. When comparing it to the largest series available [12], our series had a higher frequency of leiomyosarcomas (33.3 vs. 19.0%), higher frequency of rhabdomyosarcomas (50 vs. 19%) and lower frequency of liposarcomas (8.3 vs. 44%). In our series, disease-specific mortality was higher, which can be explained by the lower frequency of better prognosis tumors such as liposarcomas [12]. Second, we could evaluate outcomes for different surgical approaches, as detailed in the Results section. Even though radical surgery is the first-line treatment for paratesticular sarcomas, 2 men with leiomysarcomas were

treated with nodulectomy and intraoperative frozen section analysis. This approach had been previously reported for paratesticular liposarcomas [16]. However, since conservative surgery is an exception for these tumors, little data is available [17]. These men do not show any sign of recurrence after 8 and 48 months of follow-up. Additionally, if frozen section analysis had been done in all surgeries, maybe we would not have as much as 25% positive margins. Even though it is not the scope of the present study to prove this statement, in our opinion, frozen section analysis should be considered a standard instrument when paratesticular sarcoma is suspected. If extensive resection is required to achieve negative histological margins, it should be undertaken and reconstructive techniques might be of value [18]. Additionally, adjuvant radiotherapy may also be considered to reduce local recurrence [18]. Third, LDH levels were shown to be a marker of retroperitoneal disease in the present group of men. None of the men with retroperitoneal metastasis had normal LDH levels, and all men with elevated LDH levels showed retroperitoneal evidence of disease at CT scan. LDH was also a poor prognostic marker in the present series, as all patients with elevated LDH at presentation died from disease after a mean period of 10 months. This finding is similar to that reported for soft tissue sarcomas [19]. Our study has several limitations. First, the number of patients is low and they were retrospectively evaluated, which limits the power for further conclusions. Furthermore, 2 patients were lost to follow-up. However, the strength of our study is to describe a series of men from a different region, since the few series available included men from North America and Europe [2, 12, 20]. The main goals in the treatment of soft tissue sarcomas are to perform wide en bloc excisions of all contaminated tissues and to combine adjuvant therapies. As previously reported, a policy of wide repeated resection of tissues at risk including excision of the hemiscrotum, when appropriate, can benefit the patients and lower the toxicity of high-dose radiation to the hemiscrotum and groin [21]. Retroperitoneal lymph node dissection can be used for both staging and treatment of paratesticular sarcomas [13]. Different from germ cell tumors, however, treatment guidelines for paratesticular sarcomas are not well established, since dissemination occurs by both hematogenous and lymphatic routes. Adjuvant loco-regional radiotherapy reduces the risk of local recurrence, and doxorubicin-based chemotherapy may improve time to local and distant failure and increase overall survival. The role of radio- and chemotherapy in paratesticular sarcomas, however, is not fully established [22].

Survival distribution function 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0

10

20

30 40 Months

50

60

70

Fig. 3. Kaplan-Meier estimation of disease-specific survival of 12

patients with paratesticular sarcoma.

Discussion

451


Conclusions

Patients with paratesticular sarcomas are at high risk of disease progression and systemic relapse remains a significant problem, determining poor prognosis. The high

risk of local recurrence demands long-term follow-up, and intraoperative frozen section analysis might be of benefit. Elevated LDH might also be a marker of retroperitoneal disease and poor prognosis. Improvement in survival requires effective systemic adjuvant therapy.

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14 Emerson RE, Ulbright TM: Morphological approach to tumours of the testis and paratestis. J Clin Pathol 2007;60:866–880. 15 Sesterhenn IA, Davis CJ Jr: Pathology of germ cell tumors of the testis. Cancer Control 2004;11:374–387. 16 Lopes RI, Leite KR, Lopes RN: Paratesticular leiomyosarcoma treated by enucleation. Int Braz J Urol 2006;32:66– 67. 17 Connolly SS, D’Arcy FT, Bredin HC, et al: Value of frozen section analysis with suspected testicular malignancy. Urology 2006; 67:162–165. 18 Enoch S, Wharton SM, Murray DS: Management of leiomyosarcomas of the spermatic cord: the role of reconstructive surgery. World J Surg Oncol 2005;3:23–24. 19 Bacci G, Ferrari S, Longhi A, et al: Prognostic significance of serum LDH in Ewing’s sarcoma of bone. Oncol Rep 1999;6:807–811. 20 Blyth B, Mandell J, Bauer SB, et al: Paratesticular rhabdomyosarcoma: results of therapy in 18 cases. J Urol 1990;144:1450–1453. 21 Catton C, Jewett M, O’Sullivan B, et al: Paratesticular sarcoma: failure patterns after definitive local therapy. J Urol 1999;161:1844– 1847. 22 Khoubehi B, Mishra V, Ali M, et al: Adult paratesticular tumours. BJU Int 2002;90: 707–715.

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Urol Int 2009;82:448–452

Korkes/Castro/Romero/Godoy/Amary/ Fernandes/Perez

© Free Author Copy – for personal use only ANY DISTRIBUTION OF THIS ARTICLE WITHOUT WRITTEN CONSENT FROM S. KARGER AG, BASEL IS A VIOLATION OF THE COPYRIGHT. Written permission to distribute the PDF will be granted against payment of a permission fee, which is based on the number of accesses required. Please contact permission@karger.ch


Paratesticular sarcomas in Brazil