RPS Case of the Month
Aasma Nalwa, MD; Vikarn Vishwajeet, MD, DM
All India Institute of Medical Science,
EM images: Dr. Alok Sharma, National Reference Laboratory, Dr. Lal PathLabs Ltd.,
New Delhi, India.
A 40-year female of Asian origin, known hypertensive with hypothyroidism for the past 10 years was on irregular medications. She presented with nephrotic range proteinuria and renal dysfunction for the past 6 months. She had 8.6 g/24 hours urinary protein and was on hemodialysis twice weekly for the past month.
She was not diabetic and had no history of rash, joint pain, oral ulcers. On physical examination, her Blood Pressure was 180/100 mm Hg.
Serum Creatinine 4.7mg%, Albumin 2.7 g/dL. Her serum complement C3 was persistently low (66.3) and C4 was within normal limits.
Kidney Biopsy Findings: The tissue was examined at 10 levels of sections with H&E, PAS, Trichrome, and Jones Silver stains. Sections showed linear cores cortex and medulla showing 17 glomeruli, none globally sclerosed. All the glomeruli were displaying lobule formation in an MPGN pattern due to nodular mesangial expansion with thickened capillary walls. No apple-green birefringence was seen on polarization with Congo red staining. Tubular basement membranes were thickened and tortuous. Moderate interstitial fibrosis tubular atrophy comprising approximately 40-45% of the biopsied parenchyma was seen. No fractured casts were seen. Arteries showed moderate arteriosclerosis.
Immunohistochemistry for kappa and lambda light chains displayed kappa predominance in the mesangial nodules, outer aspect of tubular basement membranes and vessel walls.Tissue was processed for transmission electron microscopy and one glomerulus and accompanying tubulointerstitium were analyzed. Granular "powdery” confluent electron-dense deposits were seen in the Subendothelial and mesangial areas. Many tubules show thickened basement membranes with "powdery" electron-dense deposits along their basement membranes.
Figure 1. On low power view all the glomeruli display nodular mesangial expansion with irregular thickening of the tubular basement membranes (H&E x100)
Figure 2. High power view of a representative glomerulus with nodular mesangial expansion by eosinophilic glassy material. (H&E x400).
Figure 3. Photomicrograph shows thickening of the tubular basement membranes of the non-atrophic tubules
Figure 4. By IHC, the same field exhibits staining of glomeruli and tubular basement membranes for ĸ light chain and negative for λ light chain
Figure 5. Granular deposits with ĸ light chain are seen in the Mesangium which does not stain with λ light chain
Figure 6. Linear staining (red arrows) of tubular basement membranes suggestive of deposits with ĸ light chain is seen. In the same field, no staining is seen with IHC for λ light chain
Figure 7. TEM image shows electron-dense, non-fibrillary, linear punctate deposits on TBM
FINAL DIAGNOSISLight chain Deposition Disease, ĸ light chain restricted
Monoclonal immunoglobulin deposition diseases (MIDD) are multi-systemic disorders characterized by the deposition of monoclonal immunoglobulins in various organs. Light chain deposition disease (LCDD) is the most commonly diagnosed form of MIDD with kidneys being the most commonly involved organs . The patients presenting with LCDD with renal manifestations are usually older adults in the sixth and seventh decades of life. Although there is no gender predilection, males are affected slightly more than females . Clinically, the renal manifestations present as nephrotic range proteinuria (30% of cases), microscopic hematuria, hypertension and rarely, renal tubular acidosis. Patients may also present with primary plasma cell abnormalities and extrarenal manifestations of LCDD. The extrarenal organs commonly affected by LCDD are the liver and heart (1,2).
Free light chains are rapidly cleared from the serum and are filtered by the kidneys, making them a prominent target for deposition of the light chains . These light chains get deposited in the mesangium and along the glomerular and tubular basement membranes. The mesangial cells secrete extracellular matrix and enzymes such as matrix metalloproteinases to maintain the glomerulus. The extracellular matrix proteins such as tenascins and monotypic light chains cause nodular mesangial expansion [1,3]. The light chain deposits are non-fibrillary, Periodic acid-Schiff positive and do not stain with Congo Red. Linear staining for monoclonal light chains (either ĸ or λ) by immunofluorescence or immunohistochemistry with the presence of electron-dense granular, punctate deposits in the glomerulus (mesangium and glomerular basement membranes), and tubular basement membranes ultrastructurally is diagnostic of LCDD [4,5]. 40-60% of the patients with LCDD have overt multiple myeloma at the time of diagnosis and may present with concurrent cast nephropathy [1,2]. M spike on serum or urine protein electrophoresis is seen in approximately 50% of patients.Renal transplants have been successful in preventing recurrence of the disease if the production of the precursor protein is controlled or eliminated before transplantation. Without effective treatment, the recurrence may occur within weeks to years after transplantation .
The RPS promotes excellence in diagnosis, fosters basic, clinical and translational research, encourages training and education in renal disease, sponsors US based and international conferences and symposia, and brings news and updates pertaining to renal pathology to its members around the world.
Office of the Secretary
Virginie Royal, MD
Office of the Treasurer
Carla Ellis, MD, MS.
Mailing address: 1440 W. Taylor St. # 734, Chicago, IL, USA Fax: +1 (312) 281-0029