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- MATERIALS AND METHODS
Malignant mesothelioma of the tunica vaginalis is a rare disease, with less than 80 cases reported within the last 30 years. Approximately 15% of tunical mesotheliomas are malignant, with an overall frequency of 5% of all mesotheliomas developing in the tunica vaginalis.29, 39 However, a worldwide increase of mesotheliomas has been observed.48 More than 60% of cases have developed in patients older than 45 years, with the highest incidence during the fifth to seventh decades of life. Malignant mesotheliomas of the tunica vaginalis have also been reported in younger patients, but the reasons for the development of the disease have remained unclear in those cases.
Exposure to asbestos or asbestos-containing materials has been demonstrated to be a risk factor for the development of mesothelioma. A positive history of asbestos exposure was found in 34.2% of patients with mesotheliomas of the tunica vaginalis. These results were consistent with those described by Jones et al., who reported a positive occupational history in 41% of 27 reviewed cases.25 Furthermore, the frequency of asbestos exposure among patients with mesotheliomas of the tunica vaginalis is comparable to that among patients with pleural mesotheliomas.57 Therefore, patients known to be exposed to asbestos or asbestos-containing materials (shipyard workers, car brake workers, and engineering and building maintenance workers) are at risk for the development of a tunical disease and should be monitored.
One of the major difficulties in managing malignant mesothelioma of the tunica vaginalis is making an accurate preoperative diagnosis. Because there are no characteristic clinical symptoms or tumor markers available, the majority of the cases (97.3%) were diagnosed intraoperatively. A correct preoperative diagnosis was available in only 2 cases (2.7%). Most frequently, a rapidly growing hydrocele (56.3%) or suspected testicular tumor (32.8%) were reported as indications for surgery. Rapid growth of the scrotum should be suspicious for the presence of a tunical or testicular disease. Ultrasonography of the scrotum can provide further information for use in the determination of tumor excrescences of the tunica vaginalis, although there are limitations. Because papillary lesions can be smaller than 0.5 cm, it may be difficult to identify these lesions, even with the use of a high-resolution ultrasound probe (7.5MHz).13 In addition, mesotheliomas can be solitary or multifocal and, especially in case of a solitary lesion, may be missed during sonography. However, preoperative ultrasound can give substantial information for the determination of inhomogenous hydrocele fluid, hypoechogenecity of the fluid, or exophytic tumors. In case of suspicion, cytoanalysis of the hydrocele fluid can be diagnostic and is therefore recommended. By immunohistochemical staining methods, the presence of malignant mesothelioma may be determined, which is a major therapeutic advantage prior to surgical intervention.58
In case of suspected mesothelioma of the tunica vaginalis, exploration of the testis should be performed through an inguinal incision. If a tumor is found intraoperatively, resection of the hydrocele wall is not adequate due to the increased risk of local recurrence, which was found to be three times higher in patients after hydrocele wall resection than in patients undergoing radical orchiectomy. A reason for the worse outcome after mere resection of the tunica may be the implantation of tumor cells at the incision site or an incomplete resection due to invasive tumor growth.23 These cells may be the origin of local recurrence or tumor dissemination. Although local recurrence was seen more often after hydrocele wall resection than after radical orchiectomy, no significant difference in the effect of the primary treatment on patients' survival could be determined. In accordance with others, radical orchiectomy via an inguinal incision should be the first-line therapy.5, 9, 44
Because mesotheliomas of the tunica vaginalis were mostly found intraoperatively or at final pathology, as in our case, incomplete resection of the tunica vaginalis was commonly reported as the primary therapy. A radical approach could not have been taken due to the lack of informed consent by the patients. To diminish the risk of local recurrence in these cases, a hemiscrotectomy within due course and safe cut margins should be performed as second-line therapy.
Besides the importance of primary orchiectomy, the necessity for inguinal or iliac lymph node dissection as primary therapy is still under discussion. The presence of primary metastasis was reported in 15% of cases, and dissemination to the retroperitoneal lymph nodes was most often seen (in 8.5% of cases). Positive inguinal or iliac lymph nodes were found in 5.1% and 3.4% at diagnosis. The presence of positive lymph nodes at diagnosis were significantly correlated with shorter survival. However, 35.3% of these patients underwent staging lymphadenectomy without any tumor found. Retroperitoneal lymph nodes are the first station of lymphatic drainage in testicular diseases, but 8.5% of the cases had metastatic disease to the inguinal and/or iliac lymph nodes. The lymphatic drainage of the scrotum is to the horizontal tract of the superficial inguinal lymph nodes. Depending on the localization of the mesothelioma on the serosa (the parietal or visceral layer of the tunica vaginalis), the site of infiltration of the subtunical tissue and/or the scrotal skin which was seen in more than 35% of cases, the presence of positive inguinal or iliac lymph nodes may be possible. Staging by thoracal and abdominal CT scan should be performed after orchiectomy, and a limited lymph node dissection of the suspected region is recommended in cases of suspected dissemination. If there is no suspicion of metastasis, staging lymphadenectomy is not supported due to the low risk of positive lymph nodes.
The development of tumor recurrence was frequently observed, with more than 60% developing within the first 2 years. There were also late recurrences after 10 and 15 years of follow-up. Thus, clinical examinations and CT scan or retroperitoneal ultrasound should be performed every 3 months for the first 2 years. Later on, patients should be controlled on a yearly basis until 5 years of follow-up have been provided. In accordance with Eden et al., chest radiology should be performed for pulmonary symptoms or in cases of recurrent disease.13 Due to the possibility of late tumor recurrence reported in 2.7%, lifelong follow-up can be recommended and should be offered to the patient.
Although organ metastasis was rarely reported, adjuvant therapy may be useful for some patients. However, these treatments should be considered investigational, because the efficacy of adjuvant treatments has not yet been established due to the limited number of reported cases. Most of the patients with disseminated mesothelioma received chemotherapy, radiotherapy, or combined radiotherapy and chemotherapy, although malignant mesotheliomas are considered rather chemoresistant.59
Patients undergoing adjuvant chemotherapy had a reduction in tumor volume of 20%, but no complete remission was reported. Although there were some reports of symptomatic improvement, 80% of the patients died of disease progression after chemotherapy. Recently, Ong and Vogelzang reviewed the results of chemotherapeutic trials involving patients with malignant pleural mesotheliomas.59 These data must be interpreted cautiously, because pleural mesotheliomas are commonly sarcomatous or biphasic in comparison to the mostly epithelial mesothelioma of the tunica vaginalis. However, the response rates of either single or combined chemotherapy did not reach more than 30% in pleural tumors. Promising results were reported only for methotrexate and edatrexate, although these data need further confirmation.59 Due to the limited experience with chemotherapy for tunical mesothelioma, conclusions regarding the effect of chemotherapy must be drawn with caution. However, the given data seem to support that chemotherapy should not be recommended as primary adjuvant therapy for disseminated malignant mesothelioma of the tunica vaginalis.
Similarly, the efficacy of adjuvant radiotherapy has not yet been clearly determined. Complete remission for 12 months was reported in 50% of cases and transient partial remission in 10% of cases (1 patient). Finally, 40% of patients died due to disease progression after radiotherapy. Because of the small number of treated patients, the efficacy of the treatment must be interpreted cautiously, but radiotherapy was more effective than chemotherapy. We believe that the indication for adjuvant radiotherapy should be considered for patients with locally extended mesothelioma after resection of the tumor with safe cut margins, and also for patients with disseminated disease who are in good physical condition.
There has also been limited experience with combined chemotherapy and radiotherapy in the treatment of malignant mesothelioma of the tunica vaginalis. There were only 6 patients reported with no complete remission achieved after combination therapy, but 2 survivals for 4.5 and 13 years. This may present a major improvement in survival as compared with a median survival of less than 2 years. However, in cases of pleural mesothelioma, no significant difference in survival was seen with radiotherapy alone compared with combined therapy.60 This suggests that combined chemotherapy and radiotherapy may be effective in treating disseminated disease, although the numbers are too small for any final conclusions to be drawn.