Metachronous contralateral testicular and bilateral adrenal metastasis of chromophobe renal cell carcinoma: a case report and review of the literature

Metachronous contralateral testicular and bilateral adrenal metastasis of chromophobe renal cell carcinoma: a case report and review of the literature first-author corresp ‡Corresponding Author ‡Corresponding Author †E-mail:ligonghui1970@hotmail.com †E-mail:ligonghui1970@hotmail.com ligonghui1970@hotmail.com Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China Chromophobe renal cell carcinoma (ChRCC) metastatic to the testis has not, to the best of our knowledge, been reported in the literature. Nor have there been reports of delayed bilateral adrenal metastasis of ChRCC. Here we report a case of metachronous contralateral testicular and bilateral adrenal metastasis of ChRCC in a 70-year-old man who underwent right radical nephrectomy for RCC six years ago. He was admitted to the hospital because of left intrascrotal enlargement of two-month duration. Ultrasonography revealed a mass in the upper pole of the left testis. Computed tomography (CT) showed irregular masses in the bilateral adrenal area. Left radical orchiectomy and laparoscopic bilateral adrenalectomy were performed. The pathologic examination showed metastatic ChRCC in the left testis and bilateral adrenal gland. Postoperative follow-up showed that the patient had survived for at least 56 months without recurrence. The case highlights the unique behavior of RCC with an unusual site of metastasis and favorable survival after multiple metastasectomy. Renal cell carcinoma (RCC) Testicular metastasis Adrenal metastasis Metastasectomy Introduction 1 It has been reported that testicular metastasis from renal cell carcinoma (RCC) is predominantly ipsilateral and invariably on the left side. It usually presents simultaneously with the renal primary tumors or precedes the diagnosis of renal tumors (Nabi et al., 2001 2001 ). The histological subtype of RCC metastatic to the testis almost always shows clear cell carcinoma (Datta et al., 2001 2001 ; Steiner et al., 1999 1999 ). Only one case of metachronous contralateral testicular metastasis from RCC has been reported (Nabi et al., 2001 2001 ), and no case of chromophobe RCC (ChRCC) metastatic to the testis was reported, to the best of our knowledge. Delayed bilateral adrenal metastasis of RCC is also very rare (Antonelli et al., 2006 2006 ; Bonnet et al., 2008 2008 ). To date, there have been no reports on delayed bilateral adrenal metastasis of ChRCC. Here we report a case of metachronous contralateral testicular and bilateral adrenal metastasis of ChRCC and review the literature. Case report 1 A 70-year-old male patient was admitted to the hospital because of left intrascrotal enlargement of two-month duration. He underwent right radical nephrectomy for right RCC in a local hospital six years ago. Physical examination revealed a palpable mass of the left testis with 4 cm×3 cm×2 cm in size. Superficial lymph nodes were not palpable. Serum alpha fetoprotein (AFP) and β-human chorionic gonadotropin (β-HCG) were within normal limits. B-ultrasound showed a 3.9 cm×2.8 cm mass in the left testis. A positive computed tomography (CT) (Fig. 1 1 ) scan of the abdomen revealed that total right nephrectomy had been done, and irregular masses were seen in bilateral adrenal areas. The right adrenal mass was 7.7 cm×5.5 cm in size and the left one 5.6 cm×6.0 cm. Single photon emission computed tomography (SPECT) of bone showed no bony metastasis. The patient underwent left radical orchiectomy. The pathologic examination showed ChRCC of the left testis (Fig. 2 2 ). Immunohistochemistry of the left testicular tumor was positive for intra-cellular cytokeratin and vimentin. The patient accepted laparoscopic bilateral adrenalectomy seven days after left radical orchiectomy. The pathological findings indicated metastatic ChRCC of the bilateral adrenal glands. His postoperative course was uneventful. Postoperative follow-up showed that the patient had survived for at least 56 months without recurrence (Fig. 3 3 ). Left down arrow showed renal chromophobe cell carcinoma. Right upper arrow showed testicular convoluted seminiferous tubule (×100) Discussion 1 The incidence rate of secondary testicular tumors ranges from 0.3% to 3.6% (Dieckmann et al., 1988 1988 ). The most frequent origin of them is the prostate (Dutt et al., 2000 2000 ; Llarena Ibarguren et al., 2008 2008 ). Very rarely, intrascrotal metastasis from RCC has been reported (Schmorl et al., 2008 2008 ). The pathologic diagnosis of RCC metastatic to the testis almost always reveals a clear cell tumor (Datta et al., 2001 2001 ; Steiner et al., 1999 1999 ). After radical nephrectomy, approximately 25% of RCC patients developed metachronous metastasis (Bonnet et al., 2008 2008 ), among whom less than 2% presented with metastasis confined to the adrenal glands (Antonelli et al., 2006 2006 ; Siemer et al., 2004 2004 ). In a recent study, a series of 1179 patients were treated for RCC, and it was found that the global incidence of adrenal metastasis among those patients was 3.7%, of which 1.9% were ipsilateral, 1.5% contralateral, 0.3% bilateral, 2.7% synchronous with the renal tumor, and only 1% metachronous (Antonelli et al., 2006 2006 ). The incidence rate of metachronous bilateral adrenal metastasis from RCC is even more rare. There have only been three cases reported (Antonelli et al., 2006 2006 ; Bonnet et al., 2008 2008 ). And there are no reports concerning delayed bilateral adrenal metastasis of ChRCC. ChRCC is biologically a tumor of low malignant potential with a 5-year survival rate of 78% to 100% and a 10-year survival rate of 80% to 90% (Amin et al., 2008 2008 ). Metastasis of ChRCC constitutes less than 5% of all ChRCC cases and less than 1% of all metastatic RCC (Choueiri et al., 2008 2008 ). Patients with ChRCC are more likely to experience liver metastasis (Hoffmann et al., 2008 2008 ). Treatment modalities for metastatic RCC are limited. Chemotherapy and radiotherapy have proven to have low response rates. Immunotherapeutic combination regimens are currently being examined in clinical trials, including cytokine therapy combined with interleukin-2 (IL-2) and interferon-α (IFN-α), or targeted agents such as multitargeted tyrosine kinase inhibitors (TKIs), mammalian target of rapamycin (mTOR) inhibitors, and the monoclonal antiangiogenic antibodies. Most of the studies were focused on clear cell RCC and only a few on the ChRCC (Choueiri et al., 2008 2008 ; Guevremont et al., 2009 2009 ; Motzer et al., 2008 2008 ). Although these agents show a consistent efficacy in clinical trials, surgery remains the only known curative therapy for RCC. Several studies described surgical intervention for metastatic RCC and showed that metastasectomy promoted long-term survival in the patients with a solitary metastasis (Bonnet et al., 2008 2008 ; Daliani et al., 2009 2009 ; Eggener et al., 2008 2008 ; Swanson, 2004 2004 ). Median survival for metastatic RCC varied from 23 months (Kierney et al., 1994 1994 ) to 41 months in patients with resected solitary metastatic lesions (Wroński et al., 1996 1996 ). It remains a topic of debate whether metastasectomy is feasible for the patients who have nonsolitary lesions of RCC metastasis. A study showed that, compared to resection of nonsolitary lesions, resection of solitary metastasis did not necessarily lead to longer survival. However, an interval shorter than two years between primary tumor and metastases was correlated with a shorter disease-specific survival (van der Poel et al., 1999 1999 ). The laparoscopic approach to adrenal malignancy still remains controversial. More recently, some authors considered laparoscopic adrenalectomy (LA) to be safe for metastatic adrenal lesions, with equivalent long-term oncological outcomes to the open surgery and an additional benefit of being less invasive. LA has been recommended as a feasible initial approach for isolated adrenal metastasis (Bonnet et al., 2008 2008 ; Porpiglia et al., 2004 2004 ; Moinzadeh and Gill, 2005 2005 ). Moinzadeh and Gill ( 2005 2005 ) reported that 31 patients underwent a total of 33 LAs for adrenal carcinoma and no operative mortality was reported. One case was electively converted to open surgery. Mean tumor size was 5 cm (ranging from 1.8 to 9 cm). There were metastatic cancers in 26 cases and primary adrenal malignancy in 7 cases according to the pathological findings. Cancer specific survival at a median follow-up of 42 months was 53% and a 5-year actuarial survival was 40%. Seven patients had local recurrence (23%). There was no port site metastasis. We have accomplished LA for five patients with adrenal metastatic tumors. The mean follow-up was 18 months (from 3 to 56 months). Among the five patients, there was no endoperitoneal or trocar port-site seeding found, though one case died of systemic dissemination of the disease 14 months after the operation. We consider LA a feasible option following the principles of oncological surgery. Adrenalectomy for metastasis, with intent of prolonging survival, should be offered to patients with favourable tumor biology. Nevertheless, further investigations are required to evaluate the appropriateness of this operation. In conclusion, we present a very rare case that highlights the unique behavior of RCC with an unusual metastatic site and favorable survival after multiple metastasectomy. We consider that, when the metastatic RCC is resectable, it should be surgically treated. The patients with chromophobe histological subtype or a long interval between primary tumor and metastases may live longer with no recurrence after metastasectomy. References MB Amin , GP Paner , I Alvarado-Cabrero , AN Young , HJ Stricker , RH Lyles , H Moch . Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases . Am J Surg Pathol , 2008 . 32 ( 12 ): 1822 - 1834 . 18813125 DOI: 10.1097/PAS.0b013e3181831e68 http://doi.org/10.1097/PAS.0b013e3181831e68 . Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases A Antonelli , A Cozzoli , C Simeone , D Zani , T Zanotelli , E Portesi , S Cosciani Cunico . Surgical treatment of adrenal metastasis from renal cell carcinoma: a single-centre experience of 45 patients . BJU Int , 2006 . 97 ( 3 ): 505 - 508 . 16469016 DOI: 10.1111/j.1464-410X.2006.05934.x http://doi.org/10.1111/j.1464-410X.2006.05934.x . Surgical treatment of adrenal metastasis from renal cell carcinoma: a single-centre experience of 45 patients S Bonnet , S Gaujoux , M Leconte , JM Thillois , F Tissier , B Dousset . Laparoscopic adrenalectomy for metachronous metastasis from renal cell carcinoma . World J Surg , 2008 . 32 ( 8 ): 1809 - 1814 . 18330621 DOI: 10.1007/s00268-008-9539-3 http://doi.org/10.1007/s00268-008-9539-3 . Laparoscopic adrenalectomy for metachronous metastasis from renal cell carcinoma TK Choueiri , A Plantade , P Elson , S Nergrier , A Ravaud , S Oudard , M Zhou , BI Rini , RM Bukowski , B Escudier . Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma . J Clin Oncol , 2008 . 26 ( 1 ): 127 - 131 . 18165647 DOI: 10.1200/JCO.2007.13.3223 http://doi.org/10.1200/JCO.2007.13.3223 . Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma DD Daliani , NM Tannir , CN Papandreou , X Wang , S Swisher , CG Wood , DA Swanson , CJ Logothetis , E Jonasch . Prospective assessment of systemic therapy followed by surgical removal of metastases in selected patients with renal cell carcinoma . BJU Int , 2009 . 104 ( 4 ): 456 - 460 . 19338544 DOI: 10.1111/j.1464-410X.2009.08490.x http://doi.org/10.1111/j.1464-410X.2009.08490.x . Prospective assessment of systemic therapy followed by surgical removal of metastases in selected patients with renal cell carcinoma MW Datta , TM Ulbright , RH Young . Renal cell carcinoma metastatic to the testis and its adnexa: a report of five cases including three that accounted for the initial clinical presentation . Int J Surg Pathol , 2001 . 9 ( 1 ): 49 - 56 . 11469344 DOI: 10.1177/106689690100900108 http://doi.org/10.1177/106689690100900108 . Renal cell carcinoma metastatic to the testis and its adnexa: a report of five cases including three that accounted for the initial clinical presentation KP Dieckmann , W Düe , V Loy . Intrascrotal metastasis of renal cell carcinoma. Case reports and review of the literature . Eur Urol , 1988 . 15 ( 3-4 ): 297 - 301 . 3063545 . Intrascrotal metastasis of renal cell carcinoma. Case reports and review of the literature N Dutt , AW Bates , SI Baithun . Secondary neoplasms of the male genital tract with different patterns of involvement in adults and children . Histopathology , 2000 . 37 ( 4 ): 323 - 331 . 11012739 DOI: 10.1046/j.1365-2559.2000.00983.x http://doi.org/10.1046/j.1365-2559.2000.00983.x . Secondary neoplasms of the male genital tract with different patterns of involvement in adults and children SE Eggener , O Yossepowitch , S Kundu , RJ Motzer , P Russo . Risk score and metastasectomy independently impact prognosis of patients with recurrent renal cell carcinoma . J Urol , 2008 . 180 ( 3 ): 873 - 878 . 18635225 DOI: 10.1016/j.juro.2008.05.006 http://doi.org/10.1016/j.juro.2008.05.006 . Risk score and metastasectomy independently impact prognosis of patients with recurrent renal cell carcinoma C Guevremont , C Jeldres , P Perrotte , PI Karakiewicz . Sorafenib in the management of metastatic renal cell carcinoma . Curr Oncol , 2009 . 16 ( Suppl. 1 ): S27 - S32 . 19478894 . Sorafenib in the management of metastatic renal cell carcinoma NE Hoffmann , MD Gillett , JC Cheville , CM Lohse , BC Leibovich , ML Blute . Differences in organ system of distant metastasis by renal cell carcinoma subtype . J Urol , 2008 . 179 ( 2 ): 474 - 477 . 18076920 DOI: 10.1016/j.juro.2007.09.036 http://doi.org/10.1016/j.juro.2007.09.036 . Differences in organ system of distant metastasis by renal cell carcinoma subtype PC Kierney , JA van Heerden , JW Segura , AL Weaver . Surgeon’s role in the management of solitary renal cell carcinoma metastases occurring subsequent to initial curative nephrectomy: an institutional review . Ann Surg Oncol , 1994 . 1 ( 4 ): 345 - 352 . 7850534 DOI: 10.1007/BF02303572 http://doi.org/10.1007/BF02303572 . Surgeon’s role in the management of solitary renal cell carcinoma metastases occurring subsequent to initial curative nephrectomy: an institutional review R Llarena Ibarguren , J García-Olaverri Rodríguez , I Azurmendi Arin , I Olano Grasa , C Pertusa Peña . Metachronic testicular metastasis secondary to clear cell renal adenocarcinoma . Arch Esp Urol , 2008 . 61 ( 4 ): 531 - 533 . 18592774 DOI: 10.4321/S0004-06142008000400012 http://doi.org/10.4321/S0004-06142008000400012 . Metachronic testicular metastasis secondary to clear cell renal adenocarcinoma A Moinzadeh , IS Gill . Laparoscopic radical adrenalectomy for malignancy in 31 patients . J Urol , 2005 . 173 ( 2 ): 519 - 525 . 15643237 DOI: 10.1097/01.ju.0000149038.89467.30 http://doi.org/10.1097/01.ju.0000149038.89467.30 . Laparoscopic radical adrenalectomy for malignancy in 31 patients RJ Motzer , B Escudier , S Oudard , TE Hutson , C Porta , S Bracarda , V Grünwald , JA Thompson , RA Figlin , N Hollaender , 等 . Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial . Lancet , 2008 . 372 ( 9637 ): 449 - 456 . 18653228 DOI: 10.1016/S0140-6736(08)61039-9 http://doi.org/10.1016/S0140-6736(08)61039-9 . Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial G Nabi , MA Gania , MC Sharma . Solitary metachronous contralateral testicular metastasis from renal cell carcinoma . Indian J Pathol Microbiol , 2001 . 44 ( 4 ): 487 - 488 . 12035375 . Solitary metachronous contralateral testicular metastasis from renal cell carcinoma F Porpiglia , C Fiori , R Tarabuzzi , G Giraudo , C Garrone , M Morino , D Fontana , RM Scarpa . Is laparoscopic adrenalectomy feasible for adrenocortical carcinoma or metastasis? . BJU Int , 2004 . 94 ( 7 ): 1026 - 1029 . 15541121 DOI: 10.1111/j.1464-410X.2004.05098.x http://doi.org/10.1111/j.1464-410X.2004.05098.x . Is laparoscopic adrenalectomy feasible for adrenocortical carcinoma or metastasis? P Schmorl , H Ostertag , S Conrad . Intratesticular metastasis of renal cancer . Der Urologe A , 2008 . 47 ( 8 ): 1001 - 1003 . DOI: 10.1007/s00120-008-1738-x http://doi.org/10.1007/s00120-008-1738-x . Intratesticular metastasis of renal cancer S Siemer , J Lehmann , J Kamradt , T Loch , K Remberger , U Humke , M Ziegler , M Stöckle . Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy . J Urol , 2004 . 171 ( 6 ): 2155 - 2159 . 15126776 DOI: 10.1097/01.ju.0000125340.84492.a7 http://doi.org/10.1097/01.ju.0000125340.84492.a7 . Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy G Steiner , D Heimbach , E Pakos , S Müller . Simultaneous contralateral testicular metastasis from a renal clear cell carcinoma . Scand J Urol Nephrol , 1999 . 33 ( 2 ): 136 - 137 . 10360459 DOI: 10.1080/003655999750016168 http://doi.org/10.1080/003655999750016168 . Simultaneous contralateral testicular metastasis from a renal clear cell carcinoma DA Swanson . Surgery for metastases of renal cell carcinoma . Scand J Surg , 2004 . 93 ( 2 ): 150 - 155 . 15285568 . Surgery for metastases of renal cell carcinoma HG van der Poel , JA Roukema , S Horenblas , AN van Geel , FM Debruyne . Metastasectomy in renal cell carcinoma: a multicenter retrospective analysis . Eur Urol , 1999 . 35 ( 3 ): 197 - 203 . 10072620 DOI: 10.1159/000019849 http://doi.org/10.1159/000019849 . Metastasectomy in renal cell carcinoma: a multicenter retrospective analysis M Wroński , E Arbit , P Russo , JH Galicich . Surgical resection of brain metastases from renal cell carcinoma in 50 patients . Urology , 1996 . 47 ( 2 ): 187 - 193 . 8607231 DOI: 10.1016/S0090-4295(99)80413-0 http://doi.org/10.1016/S0090-4295(99)80413-0 . Surgical resection of brain metastases from renal cell carcinoma in 50 patients 10.1631/jzus.B0900250 2009-08-13 2010-04-19 2010-02-22 2022-01-05 Copyright © Zhejiang University and Springer-Verlag Berlin Heidelberg 2010 2010 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 05 11