Algorithmic Approach to the Interpretation of Renal Biopsy

Basic stains required for LM H&E

• Glomerular: exudative lesions

• Tubular: tubular epithelial damage

• Interstitial: edema, inflammation

• Vascular: inflammation

Methanamine-silver (Jones stain)

• Glomerular: GBM spikes, double contours, breaks in GBM/Bowman’s capsule

• Tubular: tubulitis

• Interstitial: Fibrosis

• Vascular: internal elastic lamina

PAS

• Glomerular: GBM thickening, capillary wall collapse, Bowman’s capsule, hyalinosis, sclerosis, mesangial cellularity and matrix increase, mesangiolysis, endo/extracapillary proliferation

• Tubular: tubular protein droplets, TBM thickening, tubulitis

• Vascular: hyaline arteriolosclerosis

Masson trichrome

• Glomerular: immune deposits, thrombi, fibrin, platelets

• Tubular: tubular atrophy

• Interstitial: fibrosis • Vascular: thrombi

Routine antibody panel for IF

• IgG immune complex disease, Anti-GBM disease

• IgA IgA nephropathy, HSP, Liver disease, SLE

• IgM Waldenstrom’s macroglobulinemia, mixed cryoglobulinemia

• C1q C1q nephropathy, SLE

• C3 Dense deposit disease, C3 mesangial GN, resolving PIGN

• Fibrinogen Necrotizing lesion, thrombotic microangiopathy, crescents

• Kappa & Lambda Monoclonal Ig deposition disease, amyloidosis

• C4d (transplant) Humoral rejection

Descriptive terms and patterns of glomerular injury

Related to distribution

Focal Involving less than 50% of glomeruli by LM

Diffuse Involving 50% or more of glomeruli by LM

Segmental Involving a portion of the glomerular tuft

Global Involving the entire glomerular tuft

Descriptive terms and patterns of glomerular injury

Related to Structure

Obsolescence Total loss of normal glomerular architecture due to replacement by

sclerosis

Sclerosis Increased collagenous extracellular matrix expanding the mesangium,

occluding capillary lumina or forming adhesions to Bowman’s capsule

Fibrinoid necrosis Disruption of structure, with degeneration of local cells, extracellular matrix

and the basement membrane, often associated with fibrin deposition

Lobular Hypersegmentation of the normal lobular architecture of the normal

glomerular capillary tuft due to intracapillary hypercellularity or significant

mesangial expansions

Mesangiolysis Dissolution or attenuation of mesangial matrix and degeneration of

mesangial cells, often associated with glomerular capillary aneurysms

Mesangial interposition Extension of mesangial cells in the peripheral glomerular capillary

walls in the space located between endothelial cells and GMB

(subendothelial zone)

Descriptive terms and patterns of glomerular injury

Related to Structure Hyalinosis Accumulation of glassy, refractile acellular material/plasmatic insudation

(PAS positive, methenamine-silver negative) which contains serum

proteins, other glycoproteins and lipids

Glomerular capillary collapse Retraction of glomerular tuft with closure of capillary lumina and

wrinkling and thickening of glomerular capillary walls

Glomerular capillary aneurysm Capillary lumen balloons out and appears ectatic due to

degeneration of mesangial cells and matrix (mesangiolysis)

Wire-loops Thickened glomerular capillary walls with a rigid appearance (wire-loop-like)

due to the presence of large and confluent subendothelial immune deposits

Tram-tracking/GBM reduplication Double contoured appearance of glomerular capillary walls

on PAS/silver stains due to the presence of deposits and

mesangial interposition between the endothelium and the

original GBM with creation of a new inner (subendothelial

side) basement-membrane-like material

Descriptive terms and patterns of glomerular injury

Related to Cell proliferation

Mesangial hypercellularity Presence of 3 or more mesangial and/or inflammatory cells per

mesangial area away from the vascular pole in a section that is

2-3 micron in thickness (WHO definition)

Endocapillary hypercellularity Increased cellularity within the confines of GMB composed of

endothelial cells, mesangial cells and /or inflammatory cells,

resulting in luminal narrowing or occlusion

Intracapillary hypercellularity Hypercellularity present in both mesangium and endocapillaries

Crescent The build-up of more than 2 layers of cells within Bowman’s

space caused by the proliferation of parietal cells, podocytes and

inflammatory cells, often with fibrin and collagen deposition.

Adhesion/synechia Localized narrow bridges of connective tissue between

glomerular tufts and Bowman’s capsule

Membranoproliferative Glomerular capillary wall thickening due to mesangial

interposition and duplication of GMB

Descriptive terms and patterns of glomerular injury

Related to Deposits

Intramembranous Within the GBM

Mesangial Within the mesangial matrix

Subendothelial Between the GBM and the endothelium

Subepithelial/epimembranous Between the GBM and podocytes

Humps Subepithelial electron-dense immune-type deposits with

a cigar-or dome-like appearance

Descriptive terms and patterns of tubulointerstitial and vascular injury

Tubules

Tubulitis Lymphocytes or other inflammatory cells infiltrating tubular epithelium

Tubular atrophy Tubular involution/obsolescence due to ischemia, obstruction, toxic or

inflammatory injury with different LM appearances including classic

atrophy, endocrine and thyroidization changes

Tubular casts Various coagulated proteins and other elements in tubular lumens usually

but not exclusively seen in distal nephron

Hydropic degeneration/ Fine regular cytoplasmic vacuolization of the proximal tubules

Osmotic nephrosis

Descriptive terms and patterns of tubulointerstitial and vascular injury

Tubules

Hyaline droplet PAS/silver-positive protein reabsorption droplets because of increased

protein loss by glomeruli

Fatty change Finely vacuolated cytoplasm with clear vacuoles in the cytoplasm of tubular

epithelium in which the lipid has been dissolved out during preparation of

paraffin sections

Hypokalemic change Large irregular sized coarse clear vacuoles in the cytoplasm of tubular

epithelial cells, especially the distal tubular cells

Intranuclear inclusions Seen in nuclei with various morphology depending on etiology, often

associated with viral infections (CMV, BK polyomavirus and adenovirus),

can be observed in tubular epithelial cell regeneration and lead

nephropathy

Descriptive terms and patterns of tubulointerstitial and vascular injury

Interstitium

Edema Increased extracellular fluid in the interstitium resulting in increased spacing

between tubules

Interstitial foam cells Macrophages with cytoplasm lipid-containing vacuoles

Inflammation Infiltration of lymphocytes, plasma cells, and often eosinophils and

neutrophils with associated tubular injury

Fibrosis Interstitial expansion by collagen

Granuloma Collection of epithelioid histiocytes with/with out surrounding multinucleated

giant cells and lymphocytes

Descriptive terms and patterns of tubulointerstitial and vascular injury

Vessels

Intimal thickening Fibrous thickening of the intimal layer, usually in a concentric configuration

and associated with varying degrees of luminal stenosis

Hyaline sclerosis Accumulation of PAS-positive/silver-negative material in the intima and /or

media resulting in a characteristic “glassy” acellular refractile change in

small arteries and arterioles

Endothelialitis/endarteritis Infiltration of mononuclear cells under arterial and arteriolar

endothelium

Arteritis Necrosis, fibrinoid degeneration and inflammation of arteries with

leukocytoclasia and disruption of internal elastic lamina

Vasculitis Necrosis, fibrinoid degeneration and leukocytoclastic inflammation of

arteries, arterioles and veins

Components of Native Kidney Biopsy Pathology Report

Light microscopy

• Presence and relative proportion of renal capsule, cortex, medulla, pelvic

urothelial lining and others (i.e., skeletal muscle, liver, intestine)

• Total number of glomeruli and the number/percentage of globally sclerotic

glomeruli if any

• Description of diagnostic morphology lesions/changes/patterns in glomeruli,

tubules, interstitium and vessels

• Description of important or relevant negative findings

Components of Native Kidney Biopsy Pathology Report

Immunofluorescence microscopy

• Total number of glomeruli and the number of globally sclerotic glomeruli if

present

• Description of positive or negative results for each Ig and complement

components in glomeruli

• Description of the location, stain pattern and intensity of the deposits in

glomeruli

• Description of immunoreactants in tubulointerstitial compartment and

vessels if present

Components of Native Kidney Biopsy Pathology Report

Electron microscopy

• Total number of glomeruli and the number of globally sclerotic glomeruli if

present

• Description of glomerular abnormalities/changes

• Description of the location, number, size, appearance/substructure of

electron dense deposits if present

• Description of degree of foot process effacement

• Description of relative changes in tubulointerstitial and vascular component

Components of Native Kidney Biopsy Pathology Report

Diagnosis

• Including morphologic pattern plus a particular pathogenic or

clinicopathologic category of the disease

Comment

• Clinicopathologic correlation

• List of differential diagnoses if necessary

• Pertinent histologic prognostic indicators

• Activity/chronicity indices of lupus nephritis

Components of Renal Transplant Biopsy Pathology Report

Light microscopy

• Glomeruli: glomerulitis, fibrin thrombosis, double contours, and other

glomerular lesions

• Tubules: tubular injury, inflammation (tubulitis), nuclear atypia/inclusions

• Interstitium: nature and degree of cellular infiltrate (i.e., edema, activated

mononuclear cell, malignant cells, leukocytes in peritubular capillaries)

• Vessels: endarteritis, myocyte necrosis, thrombi, nodular hyaline, intimal elastosis

Components of Renal Transplant Biopsy Pathology Report

Immunofluorescence microscopy

• C4d staining in peritubular capillaries

Components of Renal Transplant Biopsy Pathology Report

Electron microscopy

• Glomerular abnormalities

• Viral particles

• Peritubular capillary basement membrane multilayering

Components of Renal Transplant Biopsy Pathology Report

Diagnosis

• Including a particular patholonic or clinicopathologic category of the disease

(Banff Classification for Renal Transplant Pathology)

Comment

• Clinicopathologic correlation

• List of differential diagnoses if necessary

• Pertinent histologic prognostic indicators