Amyloid proximal tubulopathy and amyloid casts: An unusual finding in multiple myeloma

Abstract

Patients with multiple myeloma (MM) often develop renal manifestations. The majority of cases present as cast nephropathy, amyloid light-chain (AL) amyloidosis, and monoclonal immunoglobulin deposition disease. AL amyloidosis usually involves the glomeruli, blood vessels, and interstitium. It is extremely uncommon to find isolated intratubular deposition of AL amyloid. Our patient presented with rapid worsening of renal function due to isolated intratubular deposition of AL amyloid, where the biopsy revealed amyloid proximal tubulopathy and amyloid cast nephropathy. Our case provides new insights into the complicated pathophysiology of the abnormal light chains in MM. This case is, to our knowledge, the second case of amyloid proximal tubulopathy reported in literature.

Unusual morphology of amyloid cast nephropathy in renal biopsy portending poor prognosis

“…This hypothesis is in agreement with previous studies done by Shirahama and Cohen9 suggesting that proteolytic enzyme processing of immunoglobulin light chains within the lysosomes is central to amyloid fibril formation. Recently, Kurien and Fernando10 from India and Iliuta et al 11 from Canada have reported a similar case of amyloid cast with amyloid proximal tubulopathy. Proximal tubulopathy was not present in our case.…”

Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review

“… Friman C [ 10 ] 1970 1 a Distal Laminated ND No Yes in tumour, No in other organs Limas C [ 11 ] 1973 15 a convoluted tubules, loops of Henle, etc. Rimmed ND PTC cytoplasm in 3 cases No c Melato M [ 12 ] 1980 4 a ND Rimmed Laminated Homogeneous ND No No El-Zoghby Z [ 13 ] 2007 1 b ND Rimmed λ PTC cytoplasm Yes in BM and joint Nasr SH [ 14 ] 2008 1 b ND Rimmed λ No ND Sethi S [ 15 ] 2009 1 b ND Rimmed λ No No in BM Sharma A [ 16 ] 2014 1 b ND Rimmed λ No No in BM Kato H [ 6 ] 2015 1 b Distal Rimmed Laminated Homogeneous λ No ND Iliuta IA [ 17 ] 2016 1 b Many segments Homogeneous λ PTC cytoplasm ND Kurien AA [ 18 ] 2018 1...…”

“…In most cases, it has a lightly stained central area and a deeplystained burr-like edge, which is black, blue and fuchsia with PASM, Masson trichrome and PAS staining, respectively. Positive Congo red staining and electron microscopy can confirm its amyloid properties [ 15 , 16 , 18 , 19 ]. Under polarized light microscopy, ordinary light microscopy and fluorescence microscopy, Congo red staining exhibits apple green double refraction, brick red and bright red, respectively [ 19 ].…”

“…Electron microscopy shows numerous randomly arranged unbranched fibrils with a diameter of 8–12 nm in the amyloid structures of the casts [ 6 , 13 , 15 – 17 , 19 , 21 ]. Immunofluorescence or immunohistochemical examination reveals that the light chain in the cast has monoclonal properties, that is, only λ or κ light chain is present [ 6 , 13 – 16 , 18 – 21 ]. The morphological characteristics of the casts in Case 1 of this paper are completely consistent with those of LCAC above.…”

“…It is known that the free light chains with a low molecular weight (approximately 20–25 kDa) can pass through the glomerular filtration membrane, while the amyloid fibrils with larger size cannot. Therefore, it can be inferred that the LCACs are formed in the tubules [ 15 , 17 , 18 ]. There are two hypotheses.…”