Sites Of Renal Cell Carcinoma Research Articles

Uncommon muscle metastatic sites of renal cell carcinoma

Introduction. Renal cell carcinoma (RCC) is the most common malignant renal tumor. It has a tendency for spreading to unusual and distant sites, such as the orbit, paranasal sinuses, thyroid gland, heart, skin, and muscles. Skeletal muscle metastases are accounting for only 0.4% of all metastatic localizations. Following CT, they may be presented in five different radiology types of lesions. The aim of our case was CT evaluation of rare skeletal muscle metastatic localizations of RCC, following the time interval of their occurrence in relation to the appearance of the primary tumor, with emphasis on metastases in the levator ani muscle, since this metastatic localization of RCC has not been recorded in the previous literature. Case outline. We present a 66-year-old man after partial nephrectomy, due to a primary diagnosis of RCC. Three years after the initial diagnosis, multiple distant metastases were verified at typical localizations, as well as rare localizations such as muscles, including levator ani. Conclusion. Advanced metastases in uncommon locations are most often accompanied by a poor prognosis, therefore the further algorithm includes monitoring the whole clinical and radiological status. Metastases in the levator ani muscle have been recorded for the first time in this report. Taking into account that this muscle has very important functions, such as supporting and raising the pelvic visceral structures, as well as having control of the flow of urine and defecation, it is of great importance to include this localization in the CT evaluation.

Extracellular vesicles secreted from bone metastatic renal cell carcinoma promote angiogenesis and endothelial gap formation in bone marrow in a time-dependent manner in a preclinical mouse model.

Bone is a major metastatic site of renal cell carcinoma (RCC). Recently, it is well recognized that bone metastatic tumor cells remodel bone marrow vasculature. However, the precise mechanism underlying cell-cell communication between bone metastatic RCC and the cells in bone marrow remains unknown. Extracellular vesicles (EVs) reportedly play crucial roles in intercellular communication between metastatic tumor cells and bone marrow. Therefore, we conducted the current study to clarify the histological alteration in vascular endothelium in bone marrow induced by EVs secreted from bone metastatic RCC cells as well as association between angiogenesis in bone marrow and bone metastasis formation. We established a bone metastatic RCC cell line (786-O BM) by in vivo selection and observed phenotypic changes in tissues when EVs were intravenously injected into immunodeficient mice. Proteomic analysis was performed to identify the protein cargo of EVs that could contribute to histological changes in bone. Tissue exudative EVs (Te-EVs) from cancer tissues of patients with bone metastatic RCC (BM-EV) and those with locally advanced disease (LA-EV) were compared for in vitro function and protein cargo. Treatment of mice with EVs from 786-O BM promoted angiogenesis in the bone marrow in a time-dependent manner and increased the gaps of capillary endothelium. 786-O BM EVs also promoted tube formation in vitro. Proteomic analysis of EVs identified aminopeptidase N (APN) as a candidate protein that enhances angiogenesis. APN knockdown in 786-O BM resulted in reduced angiogenesis in vitro and in vivo. When parental 786-O cells were intracardially injected 12 weeks after treatment with786-O BM EVs, more bone metastasis developed compared to those treated with EVs from parental 786-O cells. In patient samples, BM-EVs contained higher APN compared to LA-EV. In addition, BM-EVs promoted tube formation in vitro compared to LA-EVs. EVs from bone metastatic RCC promote angiogenesis and gap formation in capillary endothelium in bone marrow in a time-dependent manner.

Renal cell carcinoma in renal transplant recipients: Is there a role for screening?

10528 Background: Renal transplant (RT) recipients are at an increased risk of developing renal cell carcinoma (RCC), mainly due to iatrogenic immunosuppression and changes in immune surveillance. Most RCCs in RT recipients arises from the native kidney, but rarely may arise from the allograft. RCC post-RT can adversely affect allograft function and long-term survival. Screening for RCC in RT recipients is controversial and is not routinely done. Methods: We performed a retrospective chart review of RT recipients who underwent transplantation between January 1, 1999, and December 31, 2019. The following data were collected: Baseline demographic variables, cause of end-stage renal disease (ESRD), duration of dialysis prior to RT, type of RT (cadaveric vs. living donor), immunosuppressive regimen, site of RCC (native kidney vs transplanted kidney), time from RT to diagnosis of RCC, stage and Fuhrman grade, tumor histology, RCC treatment, and RCC-related mortality. RCC stage at diagnosis and survival were compared between patients who were screened versus those who were not. Results: Among 1998 RT recipients who underwent transplantation at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC); 16 patients (0.8%) developed RCC. An additional 4 patients with RCC who underwent RT elsewhere but received follow up at MHH TMC were also included. Therefore, a total of 20 patients with post-RT RCC were identified, of whom 75% were men. Subject races included White (20%), Black (50%), Hispanic (20%), and Asian (10%). The median age was 56 years. Median duration of dialysis prior to RT was 36 months (range, 1–120). Median time to RCC diagnosis post-RT was 96 months (range, 16–312). Histologies included clear cell (75%), papillary (20%), and chromophobe (5%) RCC. RCC developed in the native kidney in 60% and in the allograft in 40% of the patients. Post-RT RCC patients were divided into those who underwent regular screening (n = 12) and no screening (n = 8). The regular screening group (n = 12) underwent ultrasound or computerized tomography annually or every 2 years. All of these patients had early-stage disease at presentation: stage I (n = 11) or II (n = 1). All patients who had RCC detected by screening were cured by nephrectomy (n = 10) or cryotherapy (n = 2). In patients who had no screening post RT, 37.5% had stage I, 25% had stage III, and 37.5% had stage IV RCC. Two patients with stage IV RCC died from metastatic disease. The RCC-related mortality was 0% in patients who were screened, compared to 25% in patients who had no screening. Conclusions: All RT recipients who had RCC diagnosed based on screening had an early diagnosis and no RCC-related mortality. Screening for RCC in RT recipients is an effective tool for early diagnosis and to reduce RCC-related mortality. Further research into the cost-effectiveness of screening is imperative.

Expert consensus on diagnosis and treatment of renal cell cancer bone metastasis (2021 edition)

Bone is a common metastatic site of renal cell carcinoma (RCC), with about 30% of metastatic RCC patients are suffering from bone metastasis. More than 70% of RCC patients with bone metastasis may experience skeletal related events (SREs), which may severely impair patients' quality of life and even shorten their survival time. Therefore, SREs prevention has become one of the treatment objectives of RCC bone metastasis. Bone-modifying agents are the basic treatment of bone metastases in addition to anti-tumor therapy. The treatment of RCC bone metastasis also requires multi-disciplinary team and individualized comprehensive treatment strategies. To standardize the diagnosis and treatment of RCC bone metastasis in China, the expert group of Genitourinary Oncology Committee, Chinese Anti-cancer Association has formulated the expert consensus for the reference of clinical practice, to improve the general therapeutic level of RCC with bone metastasis and benefit more patients.

A rare case of syncronous solitary para-pharyngeal metastasis of clear cell carcinoma in a patient with small renal mass.

Unusual metastatic sites of renal cell carcinoma (RCC) are not infrequent. We report a rare case of solitary pharyngeal metastasis as first presentation of RCC. A 74 years-old man was referred to our hospital due to rapidly progressive dyspnoea and dysphagia. Physical examination showed a large right para-pharyngeal mass. Imaging findings showed a 5.5 cm mass, suspicious for malignancy, which extended to right para and retro-pharyngeal spaces with compression of the major right cervical vessels, C2-C3 vertebral bodies osteolysis, dural sac compression and dislocation. Futhermore, a small (2.6 × 2 cm) mass located at the upper pole of the right kidney was shown. Patient underwent partial trans-oral removal of the mass. Pathological examination and immunochemistry resulting strongly suggestive for metastatic RCC. Considering the metastatic stage of the tumour and the rapidly progressive clinical worsening with poor performance status, we offered the patient a palliative treatment with tyrosine kinase and cytoreductive radiotherapy on vertebral bodies. The patient developed a rapidly progressive multifocal metastatic disease and died 4 months after the presentation. We think that our case is noteworthy for some aspects. Firstly, pharyngeal localizations of RCC are very rare and this is the first case of solitary pharyngeal metastasis. Secondly, this metastatic lesion was really particular because it was synchronous and twice as big than the primary tumour. Thirdly, this case is consistent with previous evidence that synchronous compared with metachronous metastasis RCC is associated with adverse effect on outcome and response to targeted treatment.

Bone Metastasis in Renal Cell Carcinoma Patients: Risk and Prognostic Factors and Nomograms.

Background Bone metastasis (BM) is one of the common sites of renal cell carcinoma (RCC), and patients with BM have a poorer prognosis. We aimed to develop two nomograms to quantify the risk of BM and predict the prognosis of RCC patients with BM. Methods We reviewed patients with diagnosed RCC with BM in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Multivariate logistic regression analysis was used to determine independent factors to predict BM in RCC patients. Univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors for BM in RCC patients. Two nomograms were established and evaluated by calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results The study included 37,554 patients diagnosed with RCC in the SEER database, 537 of whom were BM patients. BM's risk factors included sex, tumor size, liver metastasis, lung metastasis, brain metastasis, N stage, T stage, histologic type, and grade in RCC patients. Currently, independent prognostic factors for RCC with BM included grade, histologic type, N stage, surgery, brain metastasis, and lung metastasis. The calibration curve, ROC curve, and DCA showed good performance for diagnostic and prognostic nomograms. Conclusions Nomograms were established to predict the risk of BM in RCC and the prognosis of RCC with BM, separately. These nomograms strengthen each patient's prognosis-based decision making, which is critical in improving the prognosis of patients.

Metastatic renal cell carcinoma: a clinicopathological analysis of 196 cases

Objective: To analyze the clinico pathological features, differential diagnosis and prognosis of metastatic renal cell carcinomas. Methods: The clinical data, histology, immunophenotype and follow-up data of 196 patients with metastatic renal cell carcinoma diagnosed from 1994 to 2017 at the Department of Pathology, Changhai Hospital, Naval Military Medical University, Shanghai, China were analyzed retrospectively. Results: There were 142 males and 54 females, with a median age of 61 years. The top three metastatic sites for the 196 cases of metastatic renal cell carcinoma were lung (31.1%, 61/196), bone (29.1%, 57/196) and digestive system (19.4%, 38/196). Among the pathological subtypes of metastasis, the proportion of clear cell renal cell carcinoma was 94.4% (185/196) and that of type II papillary renal cell carcinoma was 3.6% (7/196). The TFE3 translocated renal cell carcinoma and congestive tubular carcinoma were rare, with 3 cases and 1 case, respectively. CK, vimentin, CAⅨ and CD10 were expressed in all metastatic clear cell renal cell carcinomas. CK7, CD10 and P504s were expressed in papillary renal cell carcinomas. TFE3 was expressed in TFE3 translocated renal cell carcinoma. The collecting duct carcinoma was positive for HCK. Conclusions: Lung metastasis and bone metastasis are still the most frequent metastatic sites of renal cell carcinoma. Five years after primary lesion resection may be the high risk time for metastasis. Most of the metastases are solitary when they are first identified. To better diagnose and identify the renal origin of a metastatic renal cell carcinoma, one should consider morphological characteristics, clinical history information of the metastasis and the combined immunohistochemistry of CK, vimentin, CD10, CK7, TFE3, PAX2 and PAX8.

S1603 Ampullary Mass from Metastatic Renal Cell Carcinoma Presenting as Acute Pancreatitis

INTRODUCTION: Renal cell carcinoma (RCC) is a heterogenous group of cancers that originate from renal tubular epithelial cells. Metastatic disease most commonly affects the lungs or bone. In rare cases, there may be metastasis to the ampulla of Vater, which can result in acute pancreatitis. Although there have been few case reports of recurrent RCC presenting as a periampullary mass, none have presented with acute pancreatitis. CASE DESCRIPTION/METHODS: A 61-year old male presented with a 1-day history of periumbilical and epigastric pain radiating to the back, nausea, and vomiting. Past medical history was notable for clear cell carcinoma of the left kidney with pulmonary metastasis. Physical examination revealed tenderness in periumbilical and epigastric regions without rebound or guarding. Liver function tests were significant for a bilirubin of 3.2 mg/dL, alkaline phosphatase of 777 U/L, and an ALT of 659 U/L. Serum lipase was 5,862 U/L. Gallbladder ultrasound revealed sludge and common bile duct dilation to 12 mm. An abdominal CT scan showed pancreatic tail edema and peripancreatic fat infiltration. Endoscopic retrograde cholangiopancreatography (ERCP) showed ulceration of the major papilla and a large, periampullary mass. A stricture of distal common bile duct at the ampulla was also present. A sphincterotomy was performed and a temporary, plastic biliary stent was placed. The lower one-third of the common bile duct and ampulla were biopsied and cytology was consistent with metastatic renal cell carcinoma. DISCUSSION: Although RCC appears to have a predilection for certain organs, metastatic disease can present in many places. Metastasis to the ampulla of Vater is rare, and there are very few reported cases. Despite limited data, it is believed that renal cell carcinoma with metastasis to the ampulla of Vater has a more favorable prognosis compared to other sites. Of the reported cases, symptoms of biliary obstruction such as nausea, vomiting, abdominal pain, and jaundice were the most common presentations. To our knowledge, this is the first reported case of an ampullary mass from renal cell carcinoma resulting in acute pancreatitis. Treatment of these patients should focus on fluid resuscitation and pain control, ERCP with sphincterotomy and stent placement, and coordination with oncology services. It is difficult to provide absolute estimates of patient prognosis, although relative ones can be made when comparing to other sites of RCC metastasis.Figure 1.: H&E (×400): At high magnification, the atypical cells have round to oval nuclei with prominent nucleoli and voluminous clear cytoplasm. They are separated by delicate blood vessels with associated extravasated red cells and inflammatory cells.

Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma.

We aimed to assess an "Immunological Profile (IP)" including CD8+ and FoxP3+ T lymphocytes for renal cell carcinoma (RCC) to evaluate its effects on tumor pathological characteristics, disease progression, and survival. Adjacent normal and intratumoral specimens from 42 patients who had undergone radical nephrectomy for RCC were analyzed for counts of CD8+ and FoxP3+ T lymphocytes by immunohistochemistry. Tissue from both sites were evaluated and scored separately according to low (0) or high (1) expression of CD8 and FoxP3. A total score (min: 0, max: 4) was assigned to each patient. Thereafter, patients were divided into two groups for clinicopathologic and survival stratification based on score (IPWeak 0-2; and IPStrong 3-4). Survival curves were constructed using the Kaplan-Meier method, and a multivariable Cox regression model was used for overall survival (OS) and progression-free survival (PFS). The mean follow-up was 54.73 ± 21.34months. Poor RCC characteristics including pT3-T4, tumor necrosis, lymphovascular invasion, lymph node involvement, and larger tumor size were significantly more common in the IPWeak patients compared to IPStrong (p < 0.05). Kaplan-Meier analysis showed that IPWeak patients had worse OS (62.5 vs. 100%; p = 0.006) and PFS (50 vs. 94.4%; p = 0.002) compared to IPStrong patients. In multivariable analysis, IPWeak (HR 8.64; 95% CI 1.09-68.05, p = 0.042) and high tumor node metastasis stage (HR 45.33; 95% CI 4.69-437.68, p < 0.001) were significant independent predictors of poor PFS. Assessment of IP including CD8+ and FoxP3+ T lymphocytes in adjacent normal and intratumoral sites in RCC may serve as a good predictive marker for PFS.

Expert consensus on renal cell carcinoma with bone metastasis (2020 Edition)

Bone is the second most common metastatic site of renal cell carcinoma (RCC), about 35-40% of metastatic RCC patients are associated with bone metastasis. Bone metastasis can cause pain, pathological fracture, spinal cord compression, hypercalcemia and other skeletal related events (SREs), which may seriously affect patients' quality of life. RCC patients with bone metastasis, for whom drug therapy alone is less effective and the prognosis is poor, required multi-disciplinary team (MDT) and individualized comprehensive treatment to reduce or delay the onset of SRE, to maintain the quality of life and to extend the time of disease control and survival. In order to update the worldwide treatment progress in RCC with bone metastasis timely, and to improve the standardized diagnosis and treatment of such patients in China, the diagnosis and therapy for bone metastasis of malignant tumor and skeletal-related event expert group formulates "Expert consensus on renal cell carcinoma with bone metastasis (2020 Edition)" .

Differential expressions of PD-1, PD-L1 and PD-L2 between primary and metastatic sites in renal cell carcinoma

BackgroundIn clinical practice, the detection of biomarkers is mostly based on primary tumors for its convenience in acquisition. However, immune checkpoints may express differently between primary and metastatic tumor. Therefore, we aimed to compare the differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastatic sites of renal cell carcinoma (RCC).MethodsPatients diagnosed with RCC by resection or fine needle aspiration of metastasis were included. Immunohistochemistry (IHC) was applied to detect PD-1, PD-L1 and PD-L2 expressions. SPSS 22.0 was applied to conduct Chi-square, consistency tests and Cox’s proportional hazards regression models. GraphPad Prism 6 was used to plot survival curves and R software was used to calculate Predictive accuracy (PA).ResultsIn the whole cohort (N = 163), IHC results suggested a higher detection rate of PD-L1 in the metastasis than that of the primary site (χ2 = 4.66, p = 0.03), with a low consistent rate of 32.5%. Among different metastatic tumors, PD-1 was highly expressed in the lung/lymph node (65.3%) and poorly expressed in the brain (10.5%) and visceral metastases (12.5%). PD-L1 was highly expressed in lung/lymph node (37.5%) and the bone metastases (12.2%) on the contrary. In terms of survival analysis, patients with PD-1 expression either in the primary or metastasis had a shorter overall survival (OS) (HR: 1.59, 95% CI 1.08–2.36, p = 0.02). Also, PD-L1 expression in the primary was associated with a shorter OS (HR 2.55, 95% CI 1.06–6.15, p = 0.04). In the multivariate analysis, the predictive accuracy of the whole model for PFS was increased from 0.683 to 0.699 after adding PD-1.ConclusionPD-1, PD-L1 and PD-L2 were differentially expressed between primary and metastatic tumors. Histopathological examination of these immune check points in metastatic lesions of mRCC should be noticed, and its accurate diagnosis may be one of the effective ways to realize the individualized treatment.

Differential expression of TIM-3 between primary and metastatic sites in renal cell carcinoma

BackgroundDue to the significant heterogeneity of renal cell carcinoma (RCC), immune checkpoints may express differently between primary and metastatic tumor. We aimed to evaluate the differential expression of TIM-3 between the primary and metastatic sites of RCC.MethodsCases of RCC with metastases resected or biopsied at West China Hospital between January 2009 and November 2016 were included. Clinicopathological parameters were retrospectively extracted. SPPS 22.0, GraphPad Prism 6 and R statistical software were applied for data analysis.ResultsA total of 163 cases were included. Immunohistochemical results showed that the overall detection rate of TIM-3 was 56.4% (92/163). The detection rate of TIM-3 in the primary (53.0%, 44/83) was numerically higher than that of the metastasis (42.6%,79/174). Although the concordance rate of TIM-3 between the primary and metastasis was as high as 66.3% (55/83) in the paired cohort, a significant statistically difference of TIM-3 expression between the primary and metastasis was observed (χ2 = 4.664, p = 0.002), with a poor consistency (Kappa = 0.331, p = 0.002). Subsequent survival analysis suggested that TIM-3 expression either in the primary or metastatic tumor was associated with longer progression-free survival (PFS) (HR: 0.67, 95% CI 0.45–0.99, P = 0.02) and overall survival (OS) (HR: 0.52, 95% CI 0.33–0.82, P < 0.001). The expressions of TIM-3 in the primary, metastatic tumors and patients treated with targeted agents all played as favorable factors for PFS and OS. Further multivariate analysis showed that, in the whole cohort, TIM-3 expression in metastatic tumor increased the predicted accuracy (PA) of the whole model of PFS from 74.7 to 75.6% (P = 0.02). For OS, the PA of whole model was increased from 78.1 to 81.1% by adding TIM-3 expression in the metastasis (P = 0.005). The same trends were also observed in paired patients and patients treated with targeted agents. In conclusion, the expression difference between the primary and metastatic tumor of TIM-3 was significant. Biopsy or resection of the metastases may provide a more accurate biological information for clinician’s decision-making and the patient’s prognosis. What’s more, the role of TIM-3 in the RCC still remains controversy, further study are needed to verify the conclusion.

18F-FDG PET/CT detects Metastatic Renal Cell Carcinoma Masquerading as Primary Breast Malignancy.

We present the case of a 36-year-old woman who underwent 18F-FDG PET/CT with suspicion of a primary breast malignancy. However, PET/CT detected an occult renal cell carcinoma with metastases to the thyroid, breast, lungs and lymph nodes. Thyroid and breast metastases are atypical metastatic sites of renal cell carcinoma. Breast metastases from extra mammary tissue are extremely rare, more so from renal cell carcinoma. Histopathologic confirmation of the breast lesions is imperative to avoid unnecessary mastectomy and imaging can help in raising the suspicion of metastatic involvement versus primary breast malignancy.

Time-dependent change of relapse sites of renal cell carcinoma after curative surgery

Time-dependent change of relapse sites of renal cell carcinoma after curative surgery

Differential expressions of PD-1, PD-L1, and PD-L2 between the primary and metastatic sites in renal cell carcinoma.

616 Background: To evaluate the differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastatic sites of renal cell carcinoma (RCC), and to find potential factors influencing expression difference. Methods: We included cases of RCC histologically diagnosed at West China Hospital between January 2009 and November 2016. Clinicopathological data were retrospectively extracted. SPPS 22.0 and GraphPad Prism 6 statistical software were used for data analysis. Kaplan-Meier was used to analyze PFS and OS. R software was used to calculate predictive accuracy (PA). Results: A total of 163 patients were included in this study. Immunohistochemistry results suggested significant differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastasis, with a higher detection rate of the primary than metastasis. Meanwhile, the concordance rate of PD-L1 between the primary and metastasis was only 32.5% (27/83), with a significant statistically difference (χ2 = 4.664, p = 0.031) and poor consistency (Kappa = 0.229, p = 0.031). PD-1 and PD-L1 were highly expressed in the lung/lymph node and PD-L2 was highly expressed in visceral metastases. Survival analysis suggested that PD-1 positive either in the primary or metastasis was a poor prognostic factor for OS (HR: 1.59, 95% CI 1.08-2.36, P = 0.0195). The expression of PD-L1 in the primary was a poor prognostic factor for OS (HR 2.55, 95% CI 1.06-6.15, P = 0.0373). Although the predictive effect of PD-L1 expression on OS was not statistically significant in TKI treated patients, the OS time was shorter in PD-L1-positive patients than those negative (median OS 19.0 vs 41.0 months). In the whole cohort, the PA value of COX regression analysis was 0.683 for PFS, and the addition of PD-1 expression in the primary increased the PA value to 0.699. Conclusions: The assessment of immunological checkpoint-related protein in primary tumor may not be able to provide adequate information for clinicians to evaluate or predict the patient's treatment-related efficacy and prognosis. Biopsy or resection of the metastases may provide a more accurate biological information for clinician's decision-making and the patient's prognosis.

Time-dependent change in relapse sites of renal cell carcinoma after curative surgery.

We investigated time-dependent changes in the relapse features of renal cell carcinoma (RCC) after curative surgery. Between 1985 and 2015, 1398 patients with RCC (1226 clear cell RCC, 89 papillary RCC, and 53 chromophobe RCC) underwent curative surgery at Yokohama City University Hospital and its affiliated hospitals. We retrospectively reviewed the clinicopathologic factors of patients with relapse after surgery. Median follow-up was 56.3months. Recurrence occurred in 245 patients (217 clear cell RCC, 12 papillary RCC, and 3 chromophobe RCC). Papillary RCC and chromophobe RCC had no recurrence beyond 5years after surgery, but 20 cases of clear cell carcinoma had recurrence beyond 10years after surgery. The typical recurrence sites of clear cell RCC were lung (46.6%), bone (17.9%), liver (7.6%), and lymph nodes (6.5%). The proportion of recurrences at these typical sites was 83.9% for recurrences within 5 years, 76.3% between 5 and 10 years, and 40.0% beyond 10years. In contrast, the proportion of retroperitoneal organ recurrence, including contralateral kidney, pancreas, and adrenal glands, increased with increasing time after surgery. Interestingly, the hazard ratio of typical site relapse decreased whereas that of retroperitoneal organ relapse increased in a time-dependent manner. In summary, clear cell RCC showed potential to relapse beyond 10years after surgery. Recurrence at typical sites decreased whereas retroperitoneal organ recurrence increased in a time-dependent manner. Clinicians should check for recurrence at various sites beyond 10 years, especially in clear cell RCC.

Late Solitary Acrometastasis of the Hands as Unusual Metastatic Site of Renal Cell Carcinoma: A Case Report and Literature Review

Skeletal metastases from renal cell carcinoma (RCC) are common, but its metastasis to the digital extremities is rare. The lesion presents diagnostic and therapeutic challenges because of the mimicry of other benign skeletal diseases resulting in difficulties in prompt recognition of diagnosis. We here report a 62 year-old male patient with RCC metastatic to a metacarpal bone presenting with pain and swelling of left hand after 8 years’ follow-up at stable disease without any recurrences. The pathological cytology from the swelling site revealed findings consistent with metastatic clear cell carcinoma.

Clinical significances and prognostic value of cancer stem-like cells markers and vasculogenic mimicry in renal cell carcinoma

The aim of this study was to investigate the clinical significances and prognostic value of CD133 and CD44 (markers of cancer stem-like cells, CSCs), and vasculogenic mimicry (VM) in renal cell carcinoma (RCC). Immunohistochemistry was performed to detect CD133 and CD44 expression and VM in 110 RCC patients proven to exhibit de novo metastases after radical nephrectomy. In RCC, positive rates of 27.3%, 20.9%, and 21.8% were obtained for CD44, CD133, and VM, respectively. CD44 was significantly associated with tumor size, grade, stage, and histological type. CD44 expression may serve as a predictor of the number of metastases sites in RCC. CD133 expression correlated with tumor grade, stage, histological type, and tumor location. VM was positively associated with tumor grade and stage. Microvessel density (MVD) positively corresponded to tumor size, grade, and stage. CD133 expression was not associated with MVD, but significantly correlated with VM. CD44 expression correlated marginally with VM, but was found to have a significantly association with MVD. A close relationship between CSCs, MVD, and VM was established. The overall survival times of patients with CD133-high positive, CD44-high positive, VM-positive, and MVD <43 were lower than that of the patients with low positive, negative, and MVD ≥43. Tumor grade and presence of VM were independent prognostic factors of RCC. Findings show that higher CSCs and VM was correlated with more aggressive clinicopathologic. VM was an independent unfavorable prognostic factor. The authors consistently observed that CSCs may be related to angiogenesis and vasculogenic mimicry.

Sclerotic osseous metastases from renal cell carcinoma

This case series describes and illustrates three cases of sclerotic osseous metastases from untreated renal cell carcinoma (RCC). RCC is commonly metastatic to the skeleton but almost always produces lytic metastases, with only three prior reports of sclerotic metastases identified in the literature. Sclerotic metastasis causing low back pain was the initial disease presentation in two of the three patients in this case series and the first manifestation of metastatic disease in one. The most common metastatic sites of RCC, i.e., retroperitoneal lymph nodes, lung, and liver, were not identified in any of the cases, and skeletal involvement with epidural extension was the only site of metastasis in two. Pathologic specimens from all three cases revealed RCC of high nuclear grade.

Distribution of metastatic sites in renal cell carcinoma: a population-based analysis

We assessed the distribution of site-specific metastases in patients with renal cell carcinoma (RCC) according to age. Moreover, we evaluated recommendations proposed by guidelines and focused specifically on bone and brain metastases. Patients with metastatic RCC (mRCC) were abstracted from the Nationwide Inpatient Sample (1998-2007). Age was stratified into four groups: <55, 55-64, 65-74 and ≥ 75 years. Cochran-Armitage trend test and multivariable logistic regression analysis tested the relationship between age and the rate of multiple metastatic sites. Finally, we examined the rates of brain or bone metastases according to the presence of other metastatic sites. In 11,157 mRCC patients, the rate of multiple metastatic sites decreased with increasing age (P < 0.001). This phenomenon was confirmed in patients with lung, bone, liver and brain metastases (all P ≤ 0.01). The rate of bone metastases was 10% in patients with exclusive abdominal metastases and 49% in patients with abdominal, thoracic and brain metastases. The rate of brain metastases was 2% in patients with exclusive abdominal metastases and 16% in patients with thoracic and bone metastases. The proportion of patients with multiple metastatic sites is higher in young patients. The rates of bone (10%-49%) and brain (2%-16%) metastases are nonnegligible in mRCC patients.