RPS Case of the Month
Dr. Alok Sharma
Renal Pathology and Electron Microscopy,
National Reference Laboratory
Dr Lal PathLabs Ltd,
New Delhi, India.
A 35 year old lady of Asian origin, presented with edema feet and facial puffiness. She gave history of persistent proteinuria since last one and a half years, which was initially sub nephrotic but had gradually increased to 6.2 gms/24 hours at last evaluation about three months back.
There was no history of joint pains, skin rashes, oral ulcers, alopecia or any other signs suggestive of connective tissue disorder.
Pedal edema and facial puffiness +, BP 146/88 mmHg (supine), Systemic examination- NAD
Urine – Albumin 4+, no hematuria, 24 hours urine protein 8.3 g
Serum ANA, anti dsDNA, ANCA, HIV, HBsAg, anti HCV- negative
Serum complement levels (C3 and C4) –WNL, Haematological profile -WNL
Urea: 44 mg% (15.7 mmol/L), Creatinine 1.4 mg% (123.76 m mol/L), Cholesterol 236 mg% (6.1 mmol/L)
USG abdomen: Mild ascites +, bilateral normal sized kidneys with well-maintained cortico medullary differentiation, no hydronephrosisIn view of persistent progressive proteinuria of adult onset, a renal biopsy was performed.
KIDNEY BIOPSY FINDINGS
Figure 1. Image for H&E stained section showing irregular “pale” appearing expansion of glomerular mesangial matrix with accentuated lobulation of capillary tuft.
Figure 2. Photomicrograph from PAS stained section showing the expanded mesangial areas are PAS negative. Glomerular capillaries appear thickened.
Figure 3. Image showing intense silver positive staining in the mesangial areas and thickened capillaries with focal reduplication/ splits (MPGN pattern)
Figure 4. Image from section stained with Masson’s Trichrome showing deep blue staining mesangial areas and thickened capillaries.
Figure 5. Transmission Electron Microscopy (TEM) from paraffin reprocessed tissue showing thickened GBM with remarkable subendothelial expansion.
Figure 6. TEM image shoeing accumulation of irregularly distributed fibrillary material and cellular debris in expanded subendothelial areas.
Figure 7. Higher magnification TEM images showing irregular bundles of banded Type 3 collagen fibrils in the mesangial and subendothelial areas
FINAL DIAGNOSISCollagenofibrotic glomerulopathy
Collagenofibrotic glomerulopathy (CG) is a rare condition characterized by deposition of abnormal Type III collagen fibres in the subendothelial space and mesangium of the glomerulus [1–7]. It was initially thought to be a variant of the nail–patella syndrome sans the skeletal abnormalities [8,9]. Later research revealed that CG was a novel type of hereditary glomerulopathy .
In the described cases, the patients ranged from 2–66 years of age, with no definite gender predilection. The most common clinical presentation was proteinuria with or without associated nephrotic syndrome, and minimal/mild alterations in renal function [4, 5]. The exact etiopathogenesis of this disease is not clear; however, the regional clustering of cases from Asia and occurrence of disease in siblings point towards role of environmental as well as genetic factors respectively . Several patients with CG were detected with elevated levels of serum procollagen III peptide, which is considered a marker of renal fibrosis and is elevated in patients with ESRD and widespread renal fibrosis.
Histopathological features include lobular accentuation or a nodular glomerulosclerosis pattern due to global expansion of the mesangium with thickening of the peripheral capillary walls. Mesangial cellularity however is usually insignificant /minimal. The expanded mesangium is weakly eosinophilic, PAS negative and non Congophilic. On Masson’s trichrome stain, the deposited material reveals blue staining and is variably but usually intensely argyrophilic (in contrast to amyloid). The capillary walls are thickened and show focal to widespread reduplication mimicking the MPGN pattern of injury. Usually, no endocapillary or extracapillary proliferation is seen in CG. Staining for immunoglobulins and complement components is generally negative, though a single case of CG associated with immune complex deposits has been reported .
Electron microscopy is essential to establish a definitive diagnosis of CG. There is massive accumulation of banded collagen in mesangial and sub-endothelial areas. The collagen fibrils are arranged in irregular bundles, show a distinct periodicity of 43–65 nm and appear curved, frayed, and worm and comma shaped when sectioned transversely [12-15]. Owing to their peculiar size and disposition these collagen bundles can be distinguished from other types of organized glomerular deposits, including amyloid, cryoglobulins, fibrillary glomerulonephritis and immunotactoid glomerulopathy . It is important to recognize small and scant fibrillary collagen bundles which may be seen within glomerulus in sclerosing processes and near hilum and not confuse these with CG, where collagen bundles are more abundant and morphologically atypical.
Currently, no specific treatment is available for the disease. There is limited experience of renal transplantation in patients with CG, however the outcome has been favourable in the reported cases .
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