|Year : 2012 | Volume
| Issue : 2 | Page : 76-78
Focal segmental glomerulosclerosis in concurrent association with renal clear cell carcinoma
GV Ramesh Prasad1, Serge Jothy2
1 Department of Medicine, University of Toronto, and Division of Nephrology, St. Michael's Hospital, Toronto, Canada
2 Department of Laboratory Medicine, University of Toronto, St. Michael's Hospital, Toronto, Canada
|Date of Web Publication||21-Sep-2013|
G V Ramesh Prasad
Department of of Medicine, University of Toronto, Division of Nephrology, St. Michael's Hospital, 61 Queen Street East, 9th Floor, Toronto, ON M5C 2T2
Source of Support: None, Conflict of Interest: None
Malignancies are sometimes associated with the development of proteinuria and the nephrotic syndrome. A 59-year-old Caucasian male university professor was referred for evaluation of renal insufficiency to the nephrologist three months after unilateral radical nephrectomy for clear cell renal carcinoma. Post nephrectomy, he was found to have significant proteinuria with a 24-hour urine collection revealing 1.38 g of glomerular protein. Histological sections of the noncancerous areas of the resected kidney were then examined which revealed focal segmental glomerulosclerosis. The patient was given angiotensin-converting enzyme inhibitor therapy. Six years later, the 24-hour urine protein excretion was 0.32 g and there has been no recurrence of his renal carcinoma. Patients undergoing nephrectomy for renal carcinoma should have routine urinalysis and a 24-hour urine collection ordered if protein is detected. Noncancerous portions of renal tissue can be reviewed at tumor resection or nephrectomy, so that biopsy of the remaining kidney is not necessary.
Keywords: Cancer, chronic renal failure, focal segmental glomerulosclerosis, malignancy, renal cell carcinoma
|How to cite this article:|
Ramesh Prasad G V, Jothy S. Focal segmental glomerulosclerosis in concurrent association with renal clear cell carcinoma. J Acad Med Sci 2012;2:76-8
|How to cite this URL:|
Ramesh Prasad G V, Jothy S. Focal segmental glomerulosclerosis in concurrent association with renal clear cell carcinoma. J Acad Med Sci [serial online] 2012 [cited 2020 Jan 25];2:76-8. Available from: http://www.e-jams.org/text.asp?2012/2/2/76/118665
| Introduction|| |
Malignancies are sometimes associated with the development of proteinuria and the nephrotic syndrome.  Renal disease may precede the diagnosis of malignancy, and so, the diagnosis of nephrotic syndrome in adults over 50 years should prompt the consideration of malignancy as the underlying cause.  Glomerulopathies can be seen with both solid organ tumors and hematological malignancies, with membranous nephropathy being the most common variety.  However, cases of focal segmental glomerulosclerosis (FSGS) have been reported in association with solid organ tumors such as melanoma, sarcoma, esophageal cancer, breast cancer,  Wilms' tumor,  and lung cancer,  as well as plasma cell disorders  and acute leukemia.  We present a case of renal cell carcinoma (RCC) that was synchronously associated with FSGS, highlighting this particular association and emphasizing that a percutaneous biopsy of the solitary remaining kidney may not be necessary for establishing the nature of the cancer-associated glomerular disease.
| Case Report|| |
A 59-year-old Caucasian male university professor was referred for evaluation of renal insufficiency to the nephrologist three months after unilateral radical nephrectomy for renal cell carcinoma (RCC). His past medical history was significant for two superficial melanomas resected 14 and 10 years earlier from his left ear and neck, respectively, which were not followed by chemotherapy or radiation. He was generally healthy, apart from suffering from long-standing migraine headaches and osteoarthritis of the hip. As part of a routine annual medical evaluation, he was found to have an elevated serum creatinine level of 141 mmol/L (1.6 mg/dL) compared to 123 mmol/L (1.4 mg/dL), two years earlier. There was no history of dysuria, visible hematuria, or foaming of the urine. Subsequent ultrasonography revealed a 3.3 × 2.8 × 2.7 hypoechoic mass in the upper pole of the left kidney; kidney size was normal and there was no hydronephrosis. Apart from confirmation of the presence of a mass, computerized tomography (CT) scanning also showed some obstruction of the upper pole calyces but no vascular or extracapsular spread. Skin examination was normal and there was also no evidence of distant metastatic disease. Due to the past history of melanoma, however, the patient underwent ultrasound-guided percutaneous biopsy of the tumor. This was complicated by gross hematuria that necessitated close observation; however, this resolved spontaneously. Histological examination revealed clear cell carcinoma, Fuhrman grade 3 [Figure 1]. Tumor cells stained positive for low-molecular weight keratin, but were negative for vimentin, HB45, and S-100. A few weeks later, he underwent left radical nephrectomy; the ipsilateral adrenal gland was left in situ. The procedure was well tolerated. Gross examination of the specimen revealed a 6 cm round yellow tumor mass with areas of focal hemorrhage and necrosis on cross section. Histological examination confirmed renal clear cell carcinoma. There was no evidence of hilar vascular invasion or lymph node spread. Postoperatively, the serum creatinine rose from 141 to 203 mmol/L (1.6 to 2.3 mg/dL), and after this was sustained for two months, he was referred to the nephrologist for assessment.
|Figure 1: Histology of the renal tumor. Large trabeculae of tumor cells are separated by vascular channels. The tumor cells have a clear cytoplasm and there is a moderate degree of nuclear pleomorphism. (Hematoxylin and eosin stain, ×200 magnification)|
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His current medications included Cafergot and acetaminophen for migraines. He was an occasional smoker for a few years until 35 years earlier. There was no family history of cancer or kidney disease. On physical examination, he was moderately obese (body mass index: 33 kg/m 2 ), with a blood pressure of 150/100 mmHg, a scar on his neck related to past dissection for melanoma, and a healed left flank wound. There was no edema. There were no other significant abnormalities. Urine examination revealed 1+ protein by dipstick, with no blood. Microscopy was entirely unremarkable. Subsequent laboratory testing revealed a serum creatinine of 203 mmol/L (2.3 mg/dL), hemoglobin 13.5 g/dL, albumin 3.8 g/dL, fasting total cholesterol 6.29 mmol/L (249 mg/dL), and triglycerides 5.11 mmol/L (453 mg/dL). A 24-hour urine collection revealed 1.38 g of protein. Serum immunoelectrophoresis was unremarkable and urine immunoelectrophoresis revealed a glomerular pattern of proteinuria.
Histological sections of the noncancerous areas of the kidney were examined and revealed FSGS [Figure 2]. Segmental sclerotic changes were present in less than 20% of glomeruli. There were no histological changes of the collapsing or tip variants of FSGS. There was also mild focal segmental mesangial hypercellularity. Owing to the fact that the specimen was previously fixed only in formalin, testing by immunofluorescence was not possible.
Immunohistochemistry showed a lack of expression of the RCC tumor marker (hybridoma clone PN-15, Cell Marque, California, USA) in the glomeruli and positive staining in the tumor cells. Electron microscopic evaluation, limited by artifacts from deparaffinization of the tissue specimen, showed no typical deposits, but there were segmental areas of glomerular capillary collapse and accumulation of matrix and electron dense material. Overall, the histopathological changes in the nontumoral part of the kidney can be classified in the 'Not Otherwise Specified' category, according to a recent classification of FSGS.  This type of FSGS is associated with, but is not specific for, obesity.
|Figure 2: Histology of the glomerular lesion. More than half of the glomerular capillary loops are replaced by fibrosis. (Hematoxylin and eosin stain, ×200 magnification)|
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The patient was given quinapril 20 mg/day and atorvastatin 10 mg/day. Over the next six years, blood pressure control was achieved with increases in the dose of quinapril and the addition of hydrochlorothiazide 25 mg/day. A reduction in cholesterol level to less than 5.2 mmol/L (200 mg/dL) was achieved after a switch to rosuvastatin 10 mg/day. He was also given aspirin 81 mg/day. After regular clinical and imaging surveillance for six years, there has been no recurrence of his melanoma or RCC. He remains clinically well. After six years, his serum creatinine was 247 mmol/L (2.8 mg/dL) and 24-hour urine protein excretion 0.32 g.
| Discussion|| |
RCC is associated with glomerular syndromes, including membranous nephropathy  and IgA nephropathy.  In addition, FSGS has also been reported with RCC.  The prevalence rate of FSGS in RCC has not been established with precision. A retrospective evaluation of cancer-adjacent tissue from 60 resected kidneys with RCC revealed IgA nephropathy in 11 and FSGS in five specimens.  Specimens from 21 kidneys were reported as normal, and none showed membranous nephropathy.  A prior literature review demonstrated FSGS in 6/24 cases of Wilms' tumor, at least 23 of whom had suspected concurrent renal disease.  The prognosis of FSGS in association with cancer is variable. Although details of clinical follow-up are limited, preoperative 'symptoms' persisted in all 5/60 patients with FSGS and RCC, for a minimum of 18 and a maximum of 51 months.  Similarly, death was reported in three, and remission in one out of six cases of FSGS with Wilms' tumor.  Another report described progressive renal disease in two patients, and stable renal function in two patients with FSGS and varied solid organ tumors.  Our patient has demonstrated 72 months of follow-up with control of proteinuria, slow progression of chronic renal insufficiency, and no cancer recurrence.
RCC occasionally induces antigen-antibody complex formation that can lead to immune complex deposition in the tumor.  One study revealed similar isotypes of immunoglobulin deposition in the tumor and glomeruli both in patients with IgA nephropathy and FSGS.  This may suggest an immunological mechanism for the development of FSGS with RCC, but this is by no means established. On the contrary, immunoglobulin and complement deposition can be a consequence rather than the cause of FSGS. Also, secondary FSGS can occur in conjunction with conditions characterized by maladaptive hemodynamic alterations and glomerulomegaly, as well as conditions not associated with these changes but other conditions such as lipid abnormalities and alterations in intraglomerular coagulation.  Unless tumor mass replaces more than half of the renal parenchyma, hyperfiltration is unlikely to explain FSGS in patients with synchronous RCC. Speculation that FSGS represents a paraneoplastic phenomenon in this situation is based on the finding that many cancer cells can synthesize growth factors, , some of which have been associated with the development of FSGS in animal models.  Despite this, a paraneoplastic nature to FSGS remains uncertain since this would require a relationship of disease severity to tumor activity, and resolution with tumor remission. Similar to a previous study,  we have not performed a biopsy of the remaining kidney to determine the long-term natural history of FSGS post malignancy, primarily for ethical reasons. However, establishing the nature of the glomerular lesion concurrent with RCC is important, since renal functional prognosis and therapeutic decisions may depend on this. For example, although comparative data are lacking, the prognosis with secondary minimal change disease may be quite different from that of secondary FSGS or crescentic glomerulonephritis.
This case illustrates several clinical diagnostic and management paradigms. First, in addition to the more commonly associated membranous nephropathy or IgA nephropathy, FSGS can be associated with solid organ tumors including RCC, although in this case FSGS could have also been due to obesity. Second, for patients with RCC, a case can be made for performing a urinalysis routinely and ordering a subsequent 24-hour urine collection if protein is detected. Arrangements can then be made for a review of noncancerous renal tissue at the time of tumor resection or nephrectomy. Third, if proteinuria is detected post unilateral nephrectomy, biopsy of the remaining solitary kidney may not be necessary. Rather, subject to the limitations imposed by prior tissue processing, review of the noncancerous parts of the resected kidney may reveal the glomerular diagnosis. Finally, although long-term prognosis is highly variable, this case demonstrates that the long-term renal functional prognosis with cancer-associated FSGS can be very good.
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[Figure 1], [Figure 2]