Isolated Splenic Metastases from Renal Cell Carcinoma 11 Years after Surgery

Splenic metastases are rare and usually occur in cases of disseminated disease. We report a case of a patient who had isolated splenic metastases with a previous history of left nephrectomy due to a renal cell carcinoma 11 years before. The aim of this report is to describe the case and review the literature of isolated splenic metastases due to renal carcinoma. This case emphasizes the importance of considering splenic metastatic disease even after many years of diagnosis of renal cell carcinoma.


Introduction
Splenic tumors, primary or metastatic, are rare and most commonly caused by haematological malignancies. e most frequent primary tumors that metastasize to the spleen are malignant melanoma, breast cancer, and lung and ovarian carcinoma [1], and it is usually a part of a disseminated metastatic disease. Metastatic disease is common in renal-cell carcinoma (RCC), and it is frequent to the lungs, bone, liver, adrenal glands, stomach, pancreas, brain, and contralateral kidney [2]. However, isolated splenic metastases from RCC are extremely rare. To the best of our knowledge, there are less than 20 cases of isolated splenic metastases from RCC reported in the literature [1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16]. e aim of this report is to describe a case of an adult patient with a previous history of left nephrectomy due to an RCC who had isolated splenic metastases 11 years after the primary renal tumor.

Case Report
A 48-year-old man complained of intermittent pain in the left flank that started 4 months ago, and it was associated with nausea. Physical examination was normal, except for mild discomfort in the upper abdomen. Laboratory studies were also within normal limits.
He had a previous history of RCC ( Figure 1) when he underwent left nephrectomy 11 years before (pT2, pV0, and pN0; Fuhrman grade 1). e RCC infiltrated beyond the renal capsule, but it was contained within the Gerota's fascia. Pathology showed a subtype of clear cell RCC. He also had a history of B-cell non-Hodgkin lymphoma on the scalp 8 years earlier, which was treated with surgery and radiotherapy.
Abdominal computed tomography (CT) with intravenous contrast was requested to evaluate his symptoms. CT scan demonstrated two heterogeneous hypovascular splenic masses with necrotic areas, situated in the posteroinferior portion. e lesions extended through the splenic capsule and abutted the left diaphragm ( Figure 2). Magnetic resonance imaging (MRI) was requested for further evaluation and demonstrated the splenic masses, with lobulated contours, heterogeneous signal intensity, and central necrotic areas (Figure 3). e splenic masses measured 4.5 cm and 5.8 cm. Additionally, a whole-body positron emission tomography scan (PET/CT) was performed, and it revealed an increase in FDG uptake within the splenic mass (SUV: 9.0), without other suspicious lesions (Figure 4). e patient underwent splenectomy. On pathological examination, the spleen had two yellowish lesions ( Figure 5), measuring up to 6.0 cm. On histopathological analysis, areas of tumoral necrosis, angiolymphatic invasion, and focal involvement of the diaphragm were observed. Immunohistochemistry assay was positive for CK8/18, CD10, PAX8, and vimentin, being consistent with metastases of clear cell RCC (Figures 6 and 7). It is important to note that PAX8 fixation was positive for nuclear staining although weak likely due to poor splenic parenchyma fixation (Figure 7(c)). e patient is in his 3rd month after surgery with complete resolution of his symptoms and in a good general health condition.

Discussion
Splenic metastases are rare and usually occur in cases of disseminated disease. Isolated splenic metastases from RCC are extremely rare. is rarity might be explained by several theories related to the anatomical, histological, and immunological characteristics of the spleen. e theories include the following: (a) sharp angle of the splenic artery, which may impair the migration of the tumor emboli to the spleen; (b) physiological rhythmic contractile activity of the spleen, squeezing out the tumor emboli; (c) absence of afferent lymphatics, which could bring tumor cells; and (d) high concentration of lymphoid tissue in the spleen, resulting in antitumor activity [3].
ere is an estimation that 18% of patients with RCC have metastasis at diagnosis (synchronous metastasis), and after surgical excision, 20%-30% of patients with localized tumors experience relapse [17]. e majority of recurrences (85%) occur within the first 3 years of follow-up. e most common sites of metastatic disease from RCC are the lungs, bone, lymph node, and liver [18].
Isolated spleen metastases may be underestimated, considering that the patients are often asymptomatic or oligosymptomatic. However, recently, more cases of isolated splenic metastases have been diagnosed due to the widespread use of diagnostic imaging modalities. Splenic metastases originating from RCC may be detected synchronously with the renal tumor in 30% of the cases [9]  or soon after its diagnosis. However, they can also arise several years after the treatment of the primary tumor as presented in our case. Isolated splenic metastases from RCC are extremely rare, and to the best of our knowledge, up to now, there are less than 20 cases reported in the literature [1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Table 1 summarizes the main studies that reported the cases of splenic metastases from RCC [1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16]. e average age of patients with splenic metastases from RCC was 62 years, ranging from 29 to 75 years, and the majority were men (11/14, 78%). e majority of the renal primary tumors was in the left kidney (10/14, 71%), which led to a hypothesis of direct spread of the tumor cells rather than haematogenous metastasis; however, the Gerota's fascia was intact in the majority of the tumors [10] similar to our case which suggests that it is an isolated metastasis rather than a case of local recurrence. Patients with splenic metastases from RCC were asymptomatic (6/14, 43%) or had abdominal pain or constitutional symptoms, such as fever, fatigue, weight loss, and anemia. e splenic renal Although not all lesions were PET/CT avid, it is a useful tool to investigate other lesions in other organs, which may change the management in these cases.
According to the literature, there is a survival benefit to an aggressive approach and a complete surgical resection of the primary tumor and metastatic sites, when technically feasible, may offer the best opportunity for cure [19]. e vast majority of the patients described in the literature underwent surgical resection. Among the reports that described the patient outcome, 2 patients died 5 and 12 months after the detection of splenic metastases and 9 patients were alive up to 2 years of follow-up.
is case report emphasizes the importance of considering splenic metastases from RCC even in patients without disseminated disease and many years after the primary tumor diagnosis. is case also stresses the need of extended follow-up since early diagnosis and treatment may improve patients' outcome and reduce morbidity, especially considering that complete surgical resection is the main curative treatment.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
Davi dos Santos Romão and Natally Horvat contributed equally to this study. DSR, NH, MCG, ESA RBDM, PCCV, and MCCM contributed to data curation and methodology. DSR, NH, and MCCM were responsible for project administration, supervision, writing the original draft, and reviewing and editing. DSR and NH contributed equally for formal analysis and visualization. MCCM was responsible for the conceptualization of the study.