|Year : 2015 | Volume
| Issue : 3 | Page : 670
Paraneoplastic nephritic syndrome and concurrent solitary mediastinal lymph node metastasis from mesothelioma of testis diagnosed by endobronchial ultrasound: Unusual manifestations of an extremely rare tumor
Michael Doris1, Elvira-Markela Antonogiannaki2, Stamatis Katsenos2
1 Interventional Bronchoscopy Unit, "Ygeia" Hospital, Athens, Greece
2 Department of Pneumonology and Interventional Bronchoscopy, Army General Hospital of Athens, Athens, Greece
|Date of Web Publication||9-Oct-2015|
Department of Pneumonology and Interventional Bronchoscopy, Army General Hospital of Athens, 158 Mesogion and Katehaki Avenue, 115 25 Athens
Source of Support: None, Conflict of Interest: None
Malignant mesothelioma is most commonly found in the pleura, peritoneum and pericardium, whereas mesothelioma of the tunica vaginalis testis is exceedingly rare. The usual sites of metastasis are inguinal nodes, retroperitoneal lymph nodes and lung. Herein, we describe a patient with mesothelioma of testis, who presented with paraneoplastic glomerulopathy and asymptomatic solitary mediastinal lymphadenopathy on serial computed tomography imaging after radical orchiectomy. A diagnosis of metastatic lymph nodal disease was set by using convex-probe endobronchial ultrasound (EBUS) with transbronchial needle aspiration. We also briefly discuss clinical, etiological, pathological and therapeutical aspects of the disease, and highlight the paramount importance of real-time EBUS as the preferred method in the diagnostic approach of mediastinal lesions.
Keywords: Malignant mesothelioma, mediastinal lymphadenopathy, metastasis, nephritic syndrome, real-time endobronchial ultrasound, tunica vaginalis of the testis
|How to cite this article:|
Doris M, Antonogiannaki EM, Katsenos S. Paraneoplastic nephritic syndrome and concurrent solitary mediastinal lymph node metastasis from mesothelioma of testis diagnosed by endobronchial ultrasound: Unusual manifestations of an extremely rare tumor. J Can Res Ther 2015;11:670
|How to cite this URL:|
Doris M, Antonogiannaki EM, Katsenos S. Paraneoplastic nephritic syndrome and concurrent solitary mediastinal lymph node metastasis from mesothelioma of testis diagnosed by endobronchial ultrasound: Unusual manifestations of an extremely rare tumor. J Can Res Ther [serial online] 2015 [cited 2020 Nov 29];11:670. Available from: https://www.cancerjournal.net/text.asp?2015/11/3/670/146104
| > Introduction|| |
Malignant mesothelioma of the tunica vaginalis testis is an exceedingly rare tumor representing only 0.3-5% of all mesotheliomas.  The first case was described by Barbera and Rubino in 1957, and until date, there have been <100 cases reported. , It is generally an aggressive tumor with poor clinical outcome. Even after intensive multimodal treatment approach, high recurrence rates have been noted. The most common metastatic sites include inguinal, and retroperitoneal lymph nodes as well as the lung parenchyma. , Testicular mesothelioma can be metastasized to the mediastinum presenting as an asymptomatic solitary lymph node enlargement without initially involving anatomic structures lined by mesothelium; such as pleura, pericardium and peritoneum. To the best of authors' knowledge, our presented case is the first ever reported case of solitary mediastinal lymph node metastasis; caused by mesothelioma of testis, and diagnosed by convex-probe endobronchial ultrasound (EBUS) easily and more precisely.
| > Case report|| |
A 73-year-old non-smoker male was referred to our department, for evaluation of mediastinal lymphadenopathy and bilateral swelling of lower extremities. In particular, a right hilar lymph node enlargement was visible on the chest, and computed tomography (CT) obtained as a routine work-up in association with abdominal CT imaging for detection of metastatic disease after resection of a testicular mesothelioma [Figure 1]. Three years earlier, the patient presented with a right scrotal mass. A radical inguinal orchidectomy was then carried out, and the pathological report showed the presence of a malignant well-differentiated tubulopapillary mesothelioma of the tunica vaginalis testis.
|Figure 1: Contrast-enhanced chest computed tomography showing right hilar lymphadenopathy|
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On his current admission, the clinical examination was unremarkable except the presence of marked bilateral peripheral edema and elevated systolic blood pressure (150 mmHg). Blood biochemistry tests showed decreased levels of albumin (2.0 g/dl) and total protein (5.1 g/dl) as well as increased total cholesterol, and triglyceride levels (357 mg/dl and 420 mg/dl respectively). Proteinuria (4.5 g/day) was also noted without microscopic hematuria. The patient underwent a percutaneous renal biopsy showing minimal change disease with neither immunoglobulins nor complement deposits. The diagnosis of paraneoplastic nephrotic syndrome was made by exclusion of other causes since antibodies against hepatitis B and C viruses, human immunodeficiency virus, antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative as well as serum levels of C3 and C4 complement components were normal. Oral prednisone at a dose of 1 mg/kg/day and furosemide at a dose of 40 mg/day were initiated. A convex-probe EBUS (BF-UC160F-OL8, Olympus, Tokyo, Japan) was subsequently performed showing an enlarged right hilar lymph node 2.5 cm in diameter (station 10) [Figure 2]. Transbronchial needle aspiration (TBNA) using a dedicated 22-gauge needle (NA-201SX-4022, Olympus) was carried out from the 10R lymph node, and histological examination demonstrated a neoplastic lesion [Figure 3]. Particularly, by immunohistochemical staining, the cells were found to be consistently positive for cytokeratin (5/6) and calretenin stain then negative for carcinoembryonic antigen stain; and the diagnosis of metastatic malignant mesothelioma of the tunica vaginalis testis was confirmed [Figure 4]. One month later, the proteinuria disappeared and the prednisone dosage was progressively decreased over 6 months, while furosemide was continued at a dose of 40 mg/day. A combination of chemotherapeutic regimen including cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 was subsequently given about 3-week with intervals for a total of six cycles. Re-staging work-up performed after 6 cycles of chemotherapy; showed a reduction of the size of the enlarged lymph node and maintenance therapy with pemetrexed was decided. Six months after his discharge, the patient remains asymptomatic and the primary malignancy remains quiescent.
|Figure 2: Convex-probe endobronchial ultrasound image showing an enlarged right hilar lymph node (yellow arrow) 2.5 cm in diameter as well as the hyperchoic needle (red arrow) within the lymph node|
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|Figure 3: Mediastinal lymph node metastasis (H and E, original magnification ×100). Tumor cells are polygonal with well-defined cell membranes and dense eosinophilic cytoplasm (inset H and E, ×60)|
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|Figure 4: Mediastinal lymph node metastasis from mesothelioma of testis. The tumor cells are positive for calretinin by immunohistochemistry (original magnification ×40)|
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| > Discussion|| |
Mesothelioma of the tunica vaginalis testis arises from the serosal membrane of the tunica vaginalis, and has a mesenchymal origin. Most mesotheliomas primarily, involve the pleura and secondarily, the peritoneum representing 68-85% and 9.1-24.1% of all malignant mesothelioma cases, respectively.  Mesothelioma of the tunica vaginalis testis is a very rare malignant tumor accounting for 0.3-5% of mesothelioma seen. It usually occurs in middle-aged to elderly males (mean: 53.5 years), however about 10% of the patients were younger than 25 years.  Although the pathophysiology is unclear, asbestos exposure and long-standing hydrocele have been implicated in the development of malignant mesothelioma of the tunica vaginalis.  Despite this form of mesothelioma being very localized, it is still associated with dismal outcomes for the patient and only 5% of patients surviving beyond 5 years.  Lymph nodes such as inguinal, retroperitoneal and supraclavicular, lung and liver include the most frequent metastatic sites when the disease rapidly progresses. 
Given the rarity of the testicular mesothelioma, it is difficult to obtain precise information about what is the most appropriate treatment. Radical inguinal orchidectomy seems to be the mainstay of treatment. Adjuvant chemotherapy and radiotherapy may yield increased survival rates in advanced disease, although their therapeutic value has not adequately been evaluated. ,
Paraneoplastic glomerulopathy is a well-known manifestation and rarely, associated with pleural mesothelioma. Particularly, it is exceptionally rare in testicular mesothelioma.  The diagnosis of paraneoplastic nephritic syndrome is valid, when the following criteria are met: (a) No evidence of other etiologies of the nephritic syndrome, (b) time relationship between the diagnosis of nephritic syndrome and cancer, (c) tumor treatment associated with a decrease of renal symptoms, and (d) tumor recurrence associated with an increase in renal symptoms and proteinuria. A causal relationship is suggested, if proteinuria develops either 6 months before or after the diagnosis of malignancy. In our case, the glomerulopathy was very sensitive to corticosteroids, it occurred 3 years after the diagnosis of the primary malignancy, but concomitantly with its recurrence and it did not decrease with tumor control and did not recur when the mesothelioma escaped treatment. Moreover, other recognized causes of nephritic syndrome were excluded.
In the present case, a right hilar lymphadenopathy was identified on whole-body CT scan nearly 3 years after surgical treatment. Hence, a convex-probe EBUS was promptly carried out since, it has been established as a standard technique for the diagnosis of hilar or mediastinal lymphadenopathy.  EBUS with TBNA (EBUS-TBNA) can be performed with the patient under moderate sedation in an outpatient setting thus obviating the need for performance of more invasive tests, such as mediastinoscopy. Multiple studies have reported excellent sensitivity and specificity of EBUS-TBNA, comparable with those reported for mediastinoscopy.  In addition, real-time EBUS-TBNA provides high diagnostic accuracy since sufficient cytologic material or tissue specimen can be obtained thus allowing the cytopathologist to precisely make the diagnosis by using ancillary testing (e.g. immunohistochemistry, molecular analysis). The use of EBUS-TBNA in the present case enabled, the diagnosis of metastatic testicular mesothelioma through immunohistochemical analysis of adequate samples thus avoiding futile surgical diagnostic procedures. 
| > Conclusion|| |
This case describes a patient with malignant mesothelioma of testis, that is metastasized to the mediastinum presenting as an asymptomatic solitary lymph node enlargement, without initially involving anatomic structures lined by mesothelium, such as pleura, pericardium and peritoneum. Bronchoscopy with EBUS-TBNA appears to be the preferred method for the assessment of mediastinal lymphadenopathy. The high diagnostic accuracy, the minimally invasive technique and the lower complication rate associated with EBUS-TBNA are additional arguments for its use as the first mediastinal procedure. Chest physicians should be aware of this novel technique that greatly simplifies the diagnosis of any lymph node mediastinal enlargement.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]