Myeloma cast nephropathy with diffuse amyloid casts without systemic amyloidosis: two cases report

Abstract

Background: Multiple myeloma (MM) is a plasma-cell derived hematologic malignant disease. The malignant proliferating plasma cells secrete massive monoclonal immunoglobulins which lead to various pathologic types of renal injury. Myeloma cast nephropathy (MCN) is the most common histopathologic lesion with the worst renal prognosis. Rarely, the free light chains in the protein casts can form amyloid fibrils. Here, we reported two rare cases of MCN with diffuse amyloid casts.

Case presentation: Case 1: A 54-year-old Chinese man presented with a 4-year history of multiple myeloma, proteinuria and hematuria. He had monoclonal IgAλ plus free λ spike in both serum and urine. He had been on chemotherapy for 4 years and maintained normal serum creatinine until 11 months ago. Then, his renal function deteriorated and he went on hemodialysis 4 months before admission. Renal biopsy showed diffuse amyloid casts in the tubular lumens, without any obvious amyloid deposits in other kidney compartments or signs of extra-renal amyloidosis. The amyloid fibrils formed around mononuclear cells which were CD68 negative. According to the morphology and location, these mononuclear cells were considered as tubular epithelial cells. The patient was maintained on chemotherapy and hemodialysis. He died 8 months after renal biopsy. Case 2: A 58-year-old Chinese man presented with a one-and-a-half-year history of proteinuria and slowly rising serum creatinine. He had monoclonal IgDλ spike in both serum and urine. Amyloid casts were observed in the tubular lumens and mononuclear cells could be identified in the center of some casts. There were no amyloid deposits in other kidney compartments and no sign of systemic amyloidosis. The patient also had fine granular deposits along the tubular basement membrane with λ linear staining along tubular basement membrane suggesting light chain deposition disease. He was treated with bortezomib-based chemotherapy followed by lenalidomide-based chemotherapy and achieved very good partial remission (VGPR). After 27 months of follow-up, the patient still showed no signs of systemic amyloidosis.

Conclusions: These 2 cases of MCN with diffuse amyloid casts have different histopathologic characteristics from the usual myeloma casts and tubular epithelial cells might play important roles in the pathogenesis.

Keywords: Amyloid; Multiple cast nephropathy; Multiple myeloma.

Fig. 1

Renal biopsy findings of case 1. a showed IgA linear staining along glomerular capillary wall and tubular basement membrane (× 200). b showed λ linear staining along glomerular capillary wall and tubular basement membrane (× 200). c showed λ was strong positive on the protein casts (× 200). d showed minimal mesangial proliferation of the glomeruli (PASM+Masson, × 400). e showed PAS negative protein casts in the tubular lumen (PAS, × 400). f showed fibrillary structure in the peripheral of the protein casts (PASM+Masson, × 400). g showed mononuclear cells in the center of the protein casts (H&E, × 400). h showed the protein casts was Congo red positive (Congo red staining, × 200). i showed the protein revealed apple-green birefringence with polarized microscopy (Congo red staining, × 200). j showed normal glomerular without fine granular deposits along the capillary wall (× 6000)

Fig. 2

Renal biopsy findings of patient 2. a showed λ linear staining along glomerular capillary wall and tubular basement membrane (× 200). b showed mild segmental mesangial proliferation of glomeruli (PASM+Masson, × 400). c showed fibrillary structure in the peripheral of the protein casts and mononuclear cells in the center (PASM+Masson, × 400). d showed the protein cast was Congo-red positive (× 400). e showed no deposit in the glomeruli on electron microscopy (× 15,000). f showed fine granular deposits along the tubular basement membrane (× 12,000)

Fig. 3

Immunohistochemistry staining of CD68 of patient 1. The mononuclear cells in the center of the amyloid casts were CD 68 negative. (CD68 + PAS, × 400)