Malignant Mesothelioma of the Tunica Vaginalis Testis

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1 Case Report Malignant Mesothelioma of the Tunica Vaginalis Testis A Case Illustrating Doppler Color Flow Imaging and Its Potential for Preoperative Diagnosis James Boyum, BA, Neil F. Wasserman, MD Malignant mesothelioma of the tunica vaginalis testis is a rare aggressive neoplasm with fewer than 100 cases reported in the world literature. Because of its nonspecific symptoms, wide age distribution, and absence of tumor markers, most cases have been diagnosed intraoperatively. 1 A small number of case reports have illustrated the typical sonographic appearance of this tumor, but in only 1 case has imaging led to a preoperative diagnosis. 2 Color Doppler images have been documented with the advancement of imaging technology, but all of these cases lacked appearances specific for malignancy. We describe a case of malignant mesothelioma of the tunica vaginalis with typical sonographic and previously unreported color Doppler characteristics. Case Report Abbreviations CEA, carcinoembryonic antigen; CK, cytokeratin; CT, computed tomography; PET, positron emission tomography Received March 16, 2008, from the Medical School (J.B.) and Department of Radiology (N.W.), University of Minnesota, Minneapolis, Minnesota USA; and Department of Radiology, Veterans Affairs Medical Center, Minneapolis, Minnesota USA (N.W.). Revision requested March 18, Revised manuscript accepted for publication April 24, Address correspondence to Neil F. Wasserman, MD, Department of Radiology, 114, Veterans Affairs Medical Center, 1 Veterans Dr, Minneapolis, MN USA. A 60-year-old man with a history of recurrent epididymitis had progressive left scrotal swelling of 2 months duration. There was no trauma, fever, discharge, or pain. The patient had no known asbestos exposure. He had a 20- year smoking history but no history of tuberculosis, sarcoidosis, primary malignancy, or lymphoma. Physical examination revealed a transilluminating left hemiscrotal fluid collection measuring 7 to 8 cm in diameter. The left testicle was not palpable. Urinalysis and complete blood count study results were normal. α-fetoprotein and β-chorionic gonadotropin levels were within the normal range. Chest radiographic findings were unremarkable. Scrotal sonography was performed with an iu22 ultrasound machine (Philips Medical Systems, Bothell, WA) using a 12-MHz gray scale, 5-MHz Doppler transducer, which revealed a slightly enlarged left testicle and a normal-sized right testicle. There was a large left hydrocele with internal echoes present in the left scrotum. A cm heterogeneous noncalcified polypoid mass was located at the superior aspect of the left scrotal wall adjacent to the testicle (Figure 1A). Two similar addi by the American Institute of Ultrasound in Medicine J Ultrasound Med 2008; 27: /08/$3.50

2 Malignant Mesothelioma of the Tunica Vaginalis Testis tional polypoid masses appeared to arise from the tunica vaginalis (Figure 1B). The paratesticular mass showed increased vascularity with Doppler interrogation (Figure 2). This finding was suspicious for malignancy. Multiple scrotal calcifications ( pearls ) were seen bilaterally (Figure 3). The patient underwent a left hydrocelectomy and scrotal exploration. Pathologic examination indicated biphasic-type malignant mesothelioma. A subsequent left radical orchiectomy and hemiscrotectomy were performed, which Figure 1. A, Transverse scrotal sonogram showing a nonhomogeneous nodule seemingly arising from the superior pole of the left testicle (arrowhead). B, More inferior transverse scrotal sonogram showing 2 similar nodules arising from the tunica vaginalis (arrowheads). A small scrotolith is also present (arrow). Note a portion of a large hydrocele containing echogenic material. A revealed a 4-cm paratesticular tumor arising from the tunica vaginalis and extending into peritesticular fibrous tissue and the spermatic cord. The tumor also surrounded the epididymis. There was no evidence of involvement of vascular, lymphatic, or neural elements or the vas deferens. The biphasic nature comprised a glandular component and a closely associated spindled cell component (Figure 4). The glandular element showed slitlike glandular spaces lined by cuboidal to lowcolumnar cells. Both the glandular and spindled components showed minimal atypia with frequent mitotic figures. Immunohistochemical analysis showed that both components had positive findings for cytokeratin (CK) and vimentin. The epithelial cells had positive findings for CK5 and CK6 and showed focal positivity for calretinin with rare CD15 positivity. Epithelial membrane anti- Figure 2. A and B, Longitudinal color Doppler scrotal sonograms showing vascularity within 2 different nodules. A B B 1250 J Ultrasound Med 2008; 27:

3 Boyum and Wasserman gen, carcinoembryonic antigen (CEA), placental leukocyte alkaline phosphatase, and mucicarmine stains yielded negative findings. These pathologic results were diagnostic of malignant mesothelioma of the tunica vaginalis. Staging chest radiography and computed tomography (CT) of the abdomen and pelvis showed a normal chest but an enlarged left paraaortic lymph node just inferior to the left renal hilum (Figure 5). Retroperitoneal lymph node biopsy results were positive for malignant mesothelioma. The patient underwent retroperitoneal lymph node dissection. Metastatic disease was found in 3 of 16 nodes. The patient began adjuvant chemotherapy and was followed with Figure 3. A and B, Some of the multiple bilateral scrotoliths (pearls) showing acoustic shadowing (arrows). A serial CT scans. Positron emission tomography (PET) was performed 21 months after the initial diagnosis because of a palpable supraclavicular lymph node that had positive findings for malignant mesothelioma on excisional biopsy. Intense radioisotope uptake was noted in a left medial retroclavicular mass and left external iliac nodes (Figure 6). Shortly thereafter, repeated CT showed numerous enlarged mediastinal lymph nodes and pulmonary nodules. Repeated PET performed 2 months later confirmed the suspicion of widely metastatic disease involving the mediastinum and lungs. The patient underwent additional chemotherapy treatment. Discussion Malignant mesothelioma of the tunica vaginalis is a rare primary tumor arising from the serosal membranes of the abdominal peritoneum that evaginate with testicular descent during embryogenesis. Most cases of malignant mesothelioma develop from the pleural or peritoneal cavities, but mesothelioma of the tunica vaginalis accounts for 0.2% to 5% of all cases. 1 3 To our knowledge, only 98 cases have been reported. The mean age at diagnosis is 60 years, with a wide range from 7 to 91 years. 1,4,5 A positive history of asbestos exposure exists in 12.5% to 41% of patients and remains the only consistently reported risk factor, 1,4,6,7 although trauma and a B Figure 4. Micropathologic specimen (original magnification 20) showing mixed stromal and epithelial elements of biphasictype malignant mesothelioma. Similar pathologic findings were shown subsequently in a retroperitoneal lymph node and other lymph nodes. J Ultrasound Med 2008; 27:

4 Malignant Mesothelioma of the Tunica Vaginalis Testis Figure 5. Axial CT at the level of the left kidney showing an enlarged left para-aortic lymph node (N) that had subsequent positive percutaneous biopsy findings for malignant mesothelioma. Note the inferior vena cava (I) and renal cyst (C). The right kidney is congenitally absent. Figure 6. Positron emission tomography performed 21 months after the radical orchiectomy showing uptake of a left supraclavicular lymph node (arrow). long-standing hydrocele have been suggested. 8,9 Patients with malignant mesothelioma of the tunica vaginalis typically have an enlarging or recurrent hydrocele and less frequently a scrotal mass. 1 A correct preoperative diagnosis has proven difficult and infrequent. Almost all reported cases have been diagnosed intraoperatively or postoperatively, but for patients with hydrocele, aspiration cytologic analysis has led to an accurate preoperative diagnosis in 3 cases Macroscopically, mesothelioma of the tunica vaginalis is a paratesticular tumor that typically appears as multiple firm tan-to-white nodules or papillary excrescences studded on the internal surface of the hydrocele sac that range in size from several millimeters to several centimeters. 2,7 The tumor also presents with local invasion of adjacent structures in one-third of patients with malignant mesothelioma. The subtunical connective tissue and testis are involved in 50% of these cases, whereas the epididymis, scrotal skin, and vascular structures are involved less frequently. 6 Histologically, malignant mesothelioma is classified into 3 types: epithelial, biphasic, and sarcomatoid. The epithelial subtype occurs in 60% to 75% of cases, and the biphasic subtype occurs in 25% to 37% of cases. 1,13 Pure sarcomatous mesothelioma is exceedingly rare. 14 The differential diagnosis of paratesticular mesothelioma includes both benign and malignant conditions. Mesothelial hyperplasia, welldifferentiated papillary mesothelioma, papillary serous neoplasms, rete and epididymal carcinoma, adenomatoid tumors, and adenocarcinoma may exhibit similar morphologic characteristics and may mimic malignant mesothelioma. Mesothelial hyperplasia is differentiated microscopically from malignant mesothelioma by its lack of nuclear pleomorphism, mitotic activity, and areas of stromal invasion that are characteristic of malignancy. 15 Well-differentiated (benign) papillary mesothelioma is a newly distinct pathologic entity of the paratesticular region and for many years was considered the first case of malignant mesothelioma. 16 Histologically, the lesion shows bland entrapped superficial mesothelial cells. 17 Most lesions occur in the peritoneum, but 6 paratesticular cases have been documented. One of the 6 progressed to malignancy, making it necessary that all cases be treated surgically J Ultrasound Med 2008; 27:

5 Boyum and Wasserman Immunohistochemical analysis is effective in diagnosing papillary serous neoplasms, which express CEA and antihuman epithelial antigen Ber-Ep4 markers that are usually negative in paratesticular nesotheliomas. 4 Adenomatoid tumors, or benign mesothelioma, are difficult to distinguish from malignant mesothelioma. They often arise from the epididymis, although they can be intratesticular or originate in the tunica. Adenomatoid tumors may be oval or cystic on sonography, but confidently differentiating them from malignant mesothelioma has required histologic examination. 18 Metastatic adenocarcinoma usually is identified with CEA, CK20, and BerEp4 markers. A tumor that has negative findings for these markers and positive findings for calretinin, thrombomodulin, epithelial membrane antigen, and CK7 is typical of malignant mesothelioma. 4 The role of imaging in the evaluation and diagnosis of malignant mesothelioma has been limited. Only recently has a preoperative diagnosis of mesothelioma of the tunica vaginalis been suspected on sonography and confirmed with sonographically guided fine-needle aspiration. 2 Variable sonographic appearances of malignant mesothelioma contribute to the difficulty in making a diagnosis with imaging. Typically, a simple or complex (low-level echoes) hydrocele is present, which can be associated with the following: (1) multiple extratesticular nodular masses of variable echogenicity, ranging from a few millimeters to several centimeters in size 2,19 21 ; (2) a single hypoechoic mass located in the epididymal head, 22,23 in the parietal tunica layer inside the hydrocele space, 24 within the scrotal sac, 25,26 or intratesticularly 27 ; (3) multiple extratesticular papillary projections of mixed echogenicity 5,28 ; (4) focal irregular thickening of the tunica vaginalis 2,29,30 ; and (5) a simple hydrocele as the only sonographic finding. 1,31,32 Imaging characteristics on color Doppler sonography for evaluating malignant mesothelioma of the tunica vaginalis have recently been described. In each case, the location of the malignant mesothelioma was atypical. Wolanske and Nino-Murcia 27 were the first to describe the color Doppler sonographic features, documenting an intratesticular mass that was hypovascular compared with the surrounding testicular tissue. Two other cases have been reported, both describing hypovascular masses within the epididymis. 22,23 Our case differs from previous reports in that it illustrates hypervascularity within a paratesticular nodule arising from the tunica vaginalis. Because most paratesticular masses are benign, they are not expected to show hypervascularity on color Doppler imaging. In our case, we think that the vascularity of the nodule may have been indicative of the malignant nature of the tumor. This finding may be especially useful if found in a typical paratesticular nodule arising from the tunica vaginalis, as with our case. In the other documented cases of malignant mesothelioma on Doppler imaging, the relative absence of vascularity should not be dismissed. The locations of the masses make their vascularity difficult to show if the abnormalities are deep to the transducer, as may happen with large hydroceles. Very slow flow may also escape detection. Although not performed in our case, it would be well to perform power Doppler imaging in all cases showing similar nodules. The interpretation on color Doppler imaging may also be affected by other intratesticular and epididymal conditions that can cause hypervascular findings. If imaging alone suggests malignant mesothelioma, sonographically guided fine-needle aspiration should be used to confirm the diagnosis when possible. 2 Surgical exploration and biopsy can be performed through an inguinal incision when fine-needle aspiration yields negative findings or is not an option. 2 A radical orchiectomy is the initial treatment once the diagnosis of malignant mesothelioma has been established. 1 Overall tumor recurrence occurs in 53% of patients, most occurring within 2 years. Local recurrence is common because of the aggressive nature of the tumor, ranging from 35.7% after a simple hydrocelectomy to 10.5% after a scrotal orchiectomy. 1 If a hydrocelectomy is performed initially, it should be followed with a hemiscrotectomy. 33 The high incidence of local recurrence and risk of dissemination with resection of the hydrocele wall illustrate the importance of an accurate preoperative diagnosis with a subsequent radical orchiectomy. 32 J Ultrasound Med 2008; 27:

6 Malignant Mesothelioma of the Tunica Vaginalis Testis Metastatic disease is present in 15% of patients on initial diagnosis. The retroperitoneal lymph nodes are most often involved, followed by inguinal and iliac lymph nodes. 17 Distant metastasis commonly involves the lungs, liver, and, rarely, bone. 7,17,32 Staging with thoracic and abdominal CT scans should be performed with lymph node dissection of any suspicious regions. A PET scan may be helpful, as it was in our case. Adjuvant radiotherapy and chemotherapy have been used but frequently fail. 1 Prophylactic lymphatic radiation, 34 prophylactic retroperitoneal lymph node dissection, 35 and aggressive local resection of a tumor 33 for recurrence have all been proposed as additional therapies. Median survival is less than 2 years, and 40% of patients will die of the malignancy. 1 The coexisting finding of scrotoliths (scrotal pearls) is interesting and was reported in only 1 article in the literature. 36 The etiology of a scrotal pearl is unclear. Some think that it originates as a fibrinous deposit in the tunica vaginalis or as a remnant of a detached torsed appendix testis or appendix epididymis. 37,38 Scrotal calculi are often found in association with a secondary hydrocele. The appendix epididymis and appendix testis may calcify and are recognized by their characteristic position and shape. The tunica vaginalis may occasionally calcify more extensively, producing a linear plaque with acoustic shadowing. Calcification in or adjacent to the epididymis may result from epididymitis, granulomatous disease, including sperm granulomas (sperm extravasation with granuloma formation), and hematomas. Any of these may produce a solitary echogenic area within the epididymis but do not migrate freely in the paratesticular region. It is tempting to postulate a common fibrous proliferative origin between the many scrotoliths and multiple mesothelial tumors in our case, but the association is more likely coincidental. In conclusion, malignant mesothelioma of the tunica vaginalis is a rare aggressive neoplasm that is challenging to diagnose preoperatively. Paratesticular papillary excrescences or nodularities on sonography associated with a hydrocele are the typical sonographic appearances. Color Doppler imaging showing a vascular paratesticular mass or nodules may be a new diagnostic sign for distinguishing malignant mesothelioma from other more common benign paratesticular masses, such as adenomatoid tumors. A preoperative diagnosis of malignancy is important because timely and proper surgical treatment is paramount to increasing survival in patients with this devastating disease. References 1. Plas E, Riedl CR, Pflüger H. Malignant mesothelioma of the tunica vaginalis testis: review of the literature and assessment of prognostic parameters. Cancer 1998; 83: Bruno C, Minniti S, Procacci C. Diagnosis of malignant mesothelioma of the tunica vaginalis testis by ultrasoundguided fine-needle aspiration. J Clin Ultrasound 2002; 30: Murai M. Malignant mesothelioma in Japan: analysis of registered autopsy cases. Arch Environ Health 2001; 56: Winstanley AM, Landon G, Berney D, Minhas S, Fisher C, Parkinson MC. The immunohistochemical profile of malignant mesothelioma of the tunica vaginalis: a study of 20 cases. Am J Surg Pathol 2006; 30: Fields JM, Russel SA, Andrew SM. Case report: ultrasound appearances of a malignant mesothelioma of the tunica vaginalis testis. Clin Radiol 1992; 46: Gupta NP, Anjani KA, Swapan S, Ashok KH, Manju N. Malignant mesothelioma of the tunica vaginalis testis: a report of two cases and review of literature. J Surg Oncol 1999; 70: Jones MA, Young RH, Scully RE. Malignant mesothelioma of the tunica vaginalis: a clinicopathologic analysis of 11 cases with review of the literature. Am J Surg Pathol 1995; 19: Abe K, Kato N, Miki K, et al. Malignant mesothelioma of testicular tunica vaginalis. Int J Urol 2002; 9: Gürdal M, Erol A. Malignant mesothelioma of tunica vaginalis testis associated with long-lasting hydrocele: could hydrocele be an etiological factor? Int Urol Nephrol 2001; 32: Japko L, Horta AA, Schreiber K, et al. Malignant mesothelioma of the tunica vaginalis testis: report of the first case with preoperative diagnosis. Cancer 1982; 49: Gupta SC, Gupta AK, Misra V, Singh PA. Pre-operative diagnosis of malignant mesothelioma of tunica vaginalis testis by hydrocele fluid cytology. Eur J Surg Oncol 1998; 24: Ahmed M, Chari R, Mufi GR, Azzopardi A. Malignant mesothelioma of the tunica vaginalis testis diagnosed by aspiration cytology: a case report with review of literature. Int Urol Nephrol 1996; 28: J Ultrasound Med 2008; 27:

7 Boyum and Wasserman 13. Yamanishi T, Masami W, Ito H, Matsuzaki O, Nagao K, Shimazaki J. Malignant mesothelioma of the tunica vaginalis testis. Eur Urol 1984; 10: Shimada S, Ono K, Suzuki Y, Mori N. Malignant mesothelioma of the tunica vaginalis testis: a case with a predominant sarcomatous component. Pathol Int 2004; 54: Chetty R. Well differentiated (benign) papillary mesothelioma of the tunica vaginalis. J Clin Pathol 1992; 45: Barbera V, Rubino M. Papillary mesothelioma of the tunica vaginalis. Cancer 1957; 10: Tolhurst SR, Lotan T, Rapp DE, et al. Well-differentiated papillary mesothelioma occurring in the tunica vaginalis of the testis with contralateral atypical mesothelial hyperplasia. Urol Oncol 2006; 24: Barry P, Chan KG, Hsu J, Quek ML. Adenomatoid tumor of the tunica albuginea. Int J Urol 2005; 12: Tyagi G, Munn CS, Kiser LC, Wetzer SM, Tarabulcy E. Malignant mesothelioma of tunica vaginalis testis. Urology 1989; 34: Reynard JM, Hasan N, Baithun SI, Newman L, Lord MG. Malignant mesothelioma of the tunica vaginalis testis. Br J Urol 1994: 74: Pfister M, Daez D, Celeste F. Sonographic appearance of malignant mesothelioma of the tunica vaginalis testis in a child. J Clin Ultrasound 1992; 20: Mak CW, Cheng TC, Chuang SS, Wu RH, Chou CK, Chang JM. Malignant mesothelioma of the tunica vaginalis testis. Br J Radiol 2004; 77: Ascoli V, Facciolo F, Rahimi S, Carnovale C, Nardi F. Concomitant malignant mesothelioma of the pleura, peritoneum, and tunica vaginalis testis. Diagn Cytopathol 1996; 14: Iczkowski KA, Katz F, Zander DA, Clapp WL. Malignant mesothelioma of tunica vaginalis testis: a fatal case with liver metastasis. J Urol 2002; 167: Eden CG, Bettochi C, Coker CB, Yates-Bell AJ, Pryor JP. Malignant mesothelioma of the tunica vaginalis. J Urol 1995; 153: Jalon AG, Gil P, Azua-Romeo J, Borque A, Sancho C, Rioja LA. Malignant mesothelioma of the tunica vaginalis: report of a case without risk factors and review of the literature. Int Urol Nephrol 2003; 35: Black PC, Lange PH, Takayama TK. Extensive palliative surgery for advanced mesothelioma of the tunica vaginalis. Urology 2003; 62: Amin R. Case report: malignant mesothelioma of the tunica vaginalis testis an indolent course. Br J Radiol 1995; 68: Smith JJ, Malone MJ, Geffin J, Silverman ML, Libertino JA. Retroperitoneal lymph node dissection in malignant mesothelioma of tunica vaginalis testis. J Urol 1990; 144: Pelzer A, Akkad T, Herwig R, et al. Synchronous bilateral malignant mesothelioma of tunica vaginalis testis: early diagnosis. Urology 2004; 64: Bushby LH, Miller FNAC, Rosario S, Clarke JL, Sidhu PS. Scrotal calcification: ultrasound appearances, distribution and aetiology. Br. J Radiol 2002; 75: Linkowski GD, Avellone A, Gooding GAW. Scrotal calculi: sonographic detection. Radiology 1985; 156: Wang MT, Mak CW, Tzeng WS, Chen JC, Chang JM, Lin CN. Malignant mesothelioma of the tunica vaginalis testis: unusual sonographic appearance. J Clin Ultrasound 2005; 33: Fujisaki M, Tokuda Y, Sato S, et al. Case of mesothelioma of the tunica vaginalis testis with characteristic findings on ultrasonography and magnetic resonance imaging. Int J Urol 2000; 7: Adler BD, Kelsey PJ. Malignant mesothelioma of the tunica vaginalis testis. Australas Radiol 1992; 36: Sawada K, Inoue K, Ishihara T, Kurabayashi A, Moriki T, Shuin T. Multicystic malignant mesothelioma of the tunica vaginalis with an unusually indolent course. Hinyokika Kiyo 2004; 50: Wolanske K, Nino-Murcia M. Malignant mesothelioma of the tunica vaginalis testis: atypical sonographic appearance. J Ultrasound Med 2001; 20: Berti E, Schiaffino E, Minervini MS, Longo G, Schmid C. Primary malignant mesothelioma of the tunica vaginalis testis: immunohistochemistry and electron microscopy. Pathology 1997; 29: J Ultrasound Med 2008; 27:

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