A 74-year-old man was referred to the urology department due to a palpable, painless, rigid mass on his left testicle. Scrotal ultrasound revealed a hypervascular testicular lesion during a color Doppler examination. Testicular tumor markers, such as α-fetoprotein, lactate dehydrogenase, and β-human chorionic gonadotropin were within the normal ranges. Other laboratory findings included normocytic anemia with a hemoglobin level of 10.8 g/dl (reference range [RR], 12–16 g/dl) and hematocrit of 31.7% (RR, 35%–46%), and a platelet count of 410 × 103/µl (RR, 130–400 × 103/µl). The patient was scheduled for a left orchiectomy (Figure 1A). Results of the histopathologic examination of frozen sections were consistent with a diagnosis of clear cell renal cell carcinoma (ccRCC) with a Fuhrman grade of G3 (Figure 1B–1G). A computed tomography scan showed bilateral renal tumors with a clinical TNM Classification of Malignant Tumors of T4N1M1 (Figure 1H). Based on the prognostic model of the International Metastatic Renal Cancer Database Consortium (IMDC), the patient’s disease stage was classified as poor-risk due to the bilateral, locally advanced tumors. It was not possible to perform nephron-sparing surgery on either side. The patient was referred for systemic therapy; however, the disease was progressive, and he died 2 months later.

Figure 1. A – postoperative visual examination of the testicle cut in length, with visible tumor masses and necrotic foci; B–G – microscopic examination of metastatic renal cell carcinoma of the testicle. Tumor samples were morphologically analyzed and photographed using an Olympus BX43 light microscope equipped with an Olympus SC50 digital camera, revealing mixed patterns of hollow tubules, cysts, alveoli, and well-vascularized nests. Polygonal tumor cells had slightly eosinophilic to abundant clear cytoplasm. Metastatic tumors showed mixed patterns of tubules and cysts. The residual testicular parenchyma showed decreased spermatogenesis, tubular atrophy, and fibrosis (hematoxylin and eosin staining, scale bar 20 µm) (B). Analysis of immunohistochemistry staining (scale bar 20 µm) revealed that the metastatic renal cell carcinoma was positive for CD 10 (C), negative for CD 30 (D), positive for CK PAN (E), negative for CK 7 Cytokeratin (F), and positive for PAX 8 (G). H – cross-sectional computed tomography scan presenting the tumor localized bilaterally in the kidneys (arrows)

Patients with RCC develop metastases in 33% of cases, while 25% of them have metastatic disease at the time of diagnosis.1 The median survival time for metastatic RCC (mRCC) is 6 to 10 months, and the 5-year survival rate is 5%. The most common histologic type is ccRCC, which occurs in 87% of mRCC cases.2 Breaching of the basement membrane (BM) and extracellular matrix (ECM) appears to be the crucial mechanism during tumor invasion that leads to metastasis formation. Matrix metalloproteinases and heparinase, which are expressed in RCC cells, are responsible for the destruction of the main components of the BM and ECM.3 RCC can affect many areas of the body, most commonly the lungs (71%), lymph nodes (49%), and bones (36%).2 RCC metastasis to the testes is extremely rare. Based on previous reports on testicular metastases of RCC, the ipsilateral testicle is more commonly affected. The spread pattern of RCC is mainly through blood vessels. The way RCC cells reach the testes is not clear; however, it is believed that they descend to the gonad through the testicular vein in the cases of ipsilateral mRCC or, more regionally, via the ipsilateral renal capsular veins, then to the Batson plexus, contralateral renal capsular veins, and finally to the spermatic cord vessels and the gonad in the cases of contralateral mRCC.4 Most patients with mRCC require a cytoreductive nephrectomy as well as palliative and systemic treatments. According to the results of the CARMENA (NCT00930033) and SURTIME (NCT01099423) randomized clinical trials, in mRCC patients with an intermediate- and poor-risk prognosis based on the IMDC prognostic model, the primary tumor should be treated with upfront immunotherapy-based combination therapy. In the individuals with a clinical response to systemic therapy, a subsequent cytoreductive nephrectomy may be considered.5 In the patients unfit for surgery, mRCC must be treated systemically with vascular endothelial growth factor receptor inhibitors, tyrosine kinase inhibitors, and immunotherapies.