Permanent Improvement of Renal Dysfunction and Proteinuria with Colchicine in a Patient with Tumoral Amyloidosis and Basal Cell Carcinoma

Abstract

Basal cell carcinoma and amyloid deposition was reported not uncommonly, but renal failure and nephrotic syndrome were rare. Here in, we reported a 72 years old male patient with nephrotic syndrome, renal failure and relatively small basal cell carcinoma. In this patient toumoral excision caused temporary improvement. When the proteinuria reappeared, due to amyloid deposition in toumoral tissue, colchicine was began. With colchicine therapy permanent improvement of nephrotic syndrome was achieved in follow-up 18 months.

• Proteinuria
• Colchicine
• Tumoral amyloidosis
• Basal cell carcinoma
• Renal dysfunction

Case Report

Benign and malignant tumors, including solid tumors, have been associated with nephropathy. Glomerular appearances are not specific for particular tumor type and there is no association between tumor load (tumor size or metastases) and nephropathy. Malignant disease may involve the kidney in a variety of different ways. Some of those ways are infiltration, ischemia, metastases, renal vein thrombosis, amyloidosis, glomerulopathy, concominant electrolyte disorders, and different types of glomerular disease. Basal cell carcinoma of the skin has a slow growing tumor course. Rare metastasis to lymph nodes or parenchymatous organs has been reported complicating with amyloidosis in the kidneys, lymph nodes, the spleen and intestines were also reported.[[1]] Herein we reported a case with relatively small basal cell carcinoma and renal dysfunction and nephrotic syndrome secondary to tumoral amyloidosis. In this patient tumoral excision first caused temporary improvement of kidney disease then it has been detected that consequent colchicine therapy also caused permanent improvement of nephrotic syndrome associated amyloidosis.

A 72-year-old male patient was admitted to the hospital with a 6-months history of periorbital and bilateral ankle edema. For the last 12 months he noticed a 2 × 1 cm ulceral skin lesion on his face. Chronic renal disease (etiology unknown) had been diagnosed before this admittance to our unit. He was afebrile generally edematous and normotensive (110/80 mmHg). Laboratory investigation were determined as follows: Hb, Hct, WBC within normal range, blood glucose 95 mg/dL, BUN 46 mg/dL, creatinine 3.9 mg/dL, total cholesterol 424 mg/dL, LDL 342 mg/dL, HDL 35 mg/dL, triglyceride 162 mg/dL, total protein 5.2 g/dL, albumin 2.4 g/dL, AST 20 IU/L, ALT 12 IU/L, Na 131 mEq/L, K 4.25 mEq/L, Calcium 7.1 mg/dL, phosphorus 3.6 mg/dL, ESR was 104 mm/h. Urinary sediments contained 4–5 epithelial cells, 1–2 red-blood cells per high-power field and fat bodies. The daily urinary protein excretion was 5.6 g. The creatinine clearance was 29 mL/min/1.73 m². A renal ultrasonography was normal. Rectal biopsy was negative for amyloidosis. Skin ulceral lesion on his face was totally excised. The histopathological diagnosis of this lesion was basal cell carcinoma. Lisinopril 5 mg/per day, atorvastatin 10 mg/per day, and acetyl salicylic acid 80 mg/per day, were started. One month after the initiation of therapy, his edema disappeared and his laboratory findings were as follows: BUN 15 mg/dL, serum creatinine 1.6 mg/dL, total protein 5.7 g/dL, serum albumin 2.9 g/dL, daily proteinuria 0.5 g. Generalized edema reappeared after two months, with proteinuria of 3.75 g/day, total protein 4.5 g/dL, serum albumin 2.4 g/dL, BUN 35 mg/dL, serum creatinine 1.4 mg/dL. Renal vein thrombosis was not detected on renal Doppler ultrasonography. His biopsy of ulceral skin lesion was re-evaluated and besides the basal cell carcinoma, amyloid deposition was found in the excised tissue. Colchicum dispert (1.5 mg/per day) was begun. On the 5th month of colchicine therapy edema and proteinuria had disappeared. By that time his laboratory findings included; BUN 20 mg/dL, serum creatinine 1.1 mg/dL, total cholesterol 181 mg/dL, HDL 51 mg/dL, LDL 114 mg/dL, triglyceride 82 mg/dL, total protein 7.9 g/dL, and serum albumin 3.9 g/dL. Eighteen months later he was very well, and his renal function and proteinuria were normal and negative respectively.

Glomerular injury in malignancy may be immunologically mediated or related to amyloid accumulation. Immunological pathogenesis of glomerulopathy in malignancy resembles the same features in immune complex diseases.[[2]] It has been reported that nephrotic syndrome and renal failure can develop due to amyloidosis associated with malignant disease including solid tumor, lymphoma, and basal cell carcinoma. Improvement or remission of glomerulopathy has been described after treatment or removal of those tumors. But some patients fail to improve even after remission or removal of the tumor.[[2]] In our case, renal function was regained and daily proteinuria regressed after one month from the excision of tumoral lesion. Then four weeks later, edema and heavy proteinuria developed again. At that time we thought that renal amyloidosis could be cause of this nephrotic range of proteinuria and, on tumoral tissue sample amyloidosis deposition was found.

It is well known that basal cell carcinoma samples may contain amyloid deposition. Congo red screening in a previous study demonstrated intra tumor amyloidosis deposits in 35 of 53 unselected cases of basal cell carcinoma.[[3]] Male patients had a higher amyloid positivity rate than female patients.[[3]] In the literature tumor-associated amyloidosis is particularly seen to be AA type in renal cell carcinoma.[[2]] Whereas there were some reports of amyloid deposits in basal cell carcinoma with permanganate resistance and did not contain AA protein. The deposits showed variable staining for immunoglobulin light chains of amyloid P component with a standard peroxidase–antiperoxidase staining method.[[4]] The other possibility might be speculated that intra tumor amyloid could have a neoplastic origin rather than not a secondary amyloidosis. Amyloid may be originated from the tumor cells as result of tumor apoptosis.[[3]], [[5]]

In another patient with a large basal cell carcinoma, systemic amyloidosis was also reported. In that patient, anemia, hypoproteinemia, and dyspnea were found.[[6]] In our case we did not perform renal biopsy. Colchicine dispert 1.5 mg per day was begun two months later of tumoral excision. By adding colchicine to lisinopril, atorvastatin and aspirin regimen, complete remission for renal dysfunction, and nephrotic syndrome was achieved. In the 18-month follow-up he had normal renal function and negative proteinuria. New tumoral lesion was not found. With this finding in summary, diagnosis of our patient was nephrotic syndrome due to systemic amyloidosis secondary to basal cell carcinoma. We did not find any information on the effect of colchicine on renal amyloidosis due to basal cell carcinoma. In summary we can conclude that:

1. Relatively small basal cell carcinoma may contain tumoral amyloid deposition and can cause renal failure and nephrotic syndrome due to amyloidosis.

2. Renal dysfunction and proteinuria may improve however cannot regress with the resection of malign tumor alone.

3. Colchicine can be effective in amyloidosis secondary to basal cell carcinoma and colchicine can reduce proteinuria via change of permeability of glomerular basal membrane or some permanent structural changes in the glomeruli.