Pathology of Organised Deposits

Fibrillary glomerulonephritis
By
Dr Noha El Anwar
Associate Professor of Pathology
Tanta University, Armed Forces College of Medicine
Definition / general
• Glomerular disease characterized by deposition of IgG (usually
polytypic) and infiltrative fibrils with a diameter of 12 - 24 nm
by electron microscopy
• Most cases (95%) are Congo red negative
• DNAJB9 has high sensitivity and specificity for fibrillary GN

Microscopic
• Most cases exhibit mesangial expansion with variable
hypercellularity or sclerosis; there is variability in the degree of
glomerular basement membrane duplication
(membranoproliferative pattern)
Glomerular basement
membranes and mesangium
are thickened by
amorphous, homogenous
material.
Contributed by Mandolin S. Ziadie,

M.D.
Glomerular basement
membranes and mesangium
are thickened by
amorphous, homogenous
material that stains bright
pink on PAS.
M.D.
DNAJB9 highlights
glomerular immune deposits
in fibrillary
glomerulonephritis (400x).

M.D.
Immunofluorescence description
• Mesangial and variable capillary wall staining for polyclonal IgG
and C3 is most common
Mesangial and variable

capillary wall deposits of
randomly organized fibrils
that range from 10 - 30 nm
in diameter
Differential diagnosis
• Cryoglobulinemic glomerulonephritis: serum cryoglobulin tests
positive, "pseudothrombi" in glomerular capillaries, granular
subendothelial / mesangial deposits and thrombi positive for IgM,
IgG and C3
Immunotactoid Glomerulopathy
• Glomerulopathy with microtubular deposits of IgG, typically > 30 nm in

diameter, arranged in parallel arrays andCongo red negative
ETIOLOGY/PATHOGENESIS
Unknown Mechanism
• Aggregration of immunoglobulins to form microtubules
• Activate complement
Clinical Issues
• Nephrotic syndrome, hematuria, and hypocomplementemia
• Associated with monoclonal gammopathy and hematologic
malignancy
Microscopic
• Mesangial expansion with eosinophilic, PAS-positive material
• Mesangioproliferative, membranoproliferative, membranous, and

endocapillary proliferative patterns
ANCILLARY TESTS
• Congo red stain negative
Immunofluorescence :with predominant IgG, with some cases showing IgA

or IgM
○ Majority have light chain restriction (70-90%)
○ C3 usually positive, and C1q less frequently positive

Electron microscopy
It shows microtubules organized
in parallel arrays (> 30 nm) with
hollow core
Top Differential Diagnoses
• Fibrillary glomerulopathy
• Cryoglobulinemic glomerulonephritis
• Fibronectin glomerulopathy
• Type III collagen glomerulopathy

DIFFERENTIAL DIAGNOSES
Fibrillary Glomerulopathy
• Randomly arranged fibrils with average thickness of 20 nm without
hollow core
• Polyclonal IF staining; commonly IgG4

Differential Diagnosis
Cryoglobulinemic Glomerulonephritis
• Serum positive for cryoglobulins; pseudothrombi
Fibronectin Glomerulopathy
• Fibrillar deposits < 30 nm; IgG negative
• Positive immunohistochemistry for fibronectin

Differential Diagnosis
Type III Collagen Glomerulopathy
• Periodic banded collagen fibrils by EM and type III collagen by IHC
Nail-Patella Syndrome
• Rare disorder with nail hypoplasia &/or bone abnormalities
• Periodic, sparse collagen fibrils by EM in GBM

Monoclonal Immunoglobulin Deposition Diseases
• MIDDs are systemic disorders characterized by deposition of

monoclonal immunoglobulins in many organs, but the kidneys are the
most commonly involved
• In most cases, light chains are the immunoglobulin components that

deposit in tissues, giving rise to LCDD.
• More recently, heavy chain-associated monoclonal deposition disease,

also referred to as heavy chain deposition disease (HCDD), has been
recognized
• Interestingly, the pathologic findings in both light and heavy chain

deposition diseases (LHCDDs) are quite similar
Clinical Presentation and Laboratory Findings
• The average age of patients with LCDD with renal manifestations is 55

to 60 years
• Most (more than 90%) present with proteinuria, and the average
protein excretion per 24 hours is in the nephrotic range (generally 4 to
5 g/d)
Light Microscopy
• The most characteristic finding in patients with LCDD is nodular glomerulopathy

that mimics the pattern of nodular glomerulosclerosis in diabetic nephropathy
• Capsular drop and hyaline cap lesions are not present in LCDD, and the absence of
these features helps in the differential diagnosis from diabetic nephropathy.
• In addition, the mesangial nodules in LCDD are more evenly distributed, although
there is significant variation depending on the stage of the disease process ,
whereas the nodules in diabetic nephropathy tend to be asymmetric.
Light Microscopy
• The mesangial nodules are argyrophilic and composed of extracellular matrix proteins
admixed with monotypic light chains
• Mesangial hypercellularity accompanies the increase in extracellular matrix in some of the

cases.
• The peripheral capillary walls are variably thickened, and the capillary wall alterations are
uneven from one glomerulus to the other and as well as within the same glomerulus.
• The thickened walls are a consequence of the subendothelial deposition of light chains
Light Microscopy
• There are a number of glomerular morphologic patterns, including mesangial,

membranoproliferative, and crescentic, that precede the nodular glomerulopathy.
• Progression from one of these “early” patterns to a classic nodular

glomerulosclerosis has been shown to occur over time using repeat kidney
biopsies.
• The light chain deposits, regardless of whether they are in renal or extrarenal sites,
are always Congo red negative.
Light Microscopy
• The extraglomerular changes may also be quite impressive. The tubular basement
membranes may be thickened and tortuous, as a result of deposition of light
chains, generally on the outer aspect of the tubular basement membranes
• Thickening of vessel walls by light chain deposits is seen in approximately 40% of

LCDD cases. In half of LCDD patients with vascular changes, concentric thickening
of the small and medium arteries accompanied by focal light chain deposits creates
a striking hyperplastic vasculopathy
Immunofluorescence
• Deposition of monoclonal light chains can be seen along the peripheral

capillary walls in the glomeruli, alongside the tubular basement
membranes, and in the vessel walls
• In most cases of LCDD, the pathogenic light chain is of kappa isotype.

Immunofluorescence
• No staining is noted for the other light chain, defining the monotypic
nature of the labeling pattern
• Staining for immunoglobulin heavy chains (IgG, IgM, and IgA) as well as
complement components C3 and C1q are typically negative
Electron Microscopy
• Light chain deposition manifested by granular to powdery electron-

dense material can be seen in all renal compartments especially in
cases with nodular glomerulosclerosis (advanced lesion).
Electron Microscopy
• Light chain deposition manifested by granular to powdery electron-

dense material can be seen in all renal compartments especially in
cases with nodular glomerulosclerosis (advanced lesion).
Distinguishing pathologic characteristics of different
types of organized glomerular deposits
42

Pathology of Organised Deposits

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Pathology of Organised Deposits

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Fibrillary glomerulonephritis

• Most cases (95%) are Congo red negative

• DNAJB9 has high sensitivity and specificity for fibrillary GN

Contributed by Mandolin S. Ziadie,

Contributed by Mandolin S. Ziadie,

Mesangial and variable

• Glomerulopathy with microtubular deposits of IgG, typically > 30 nm in

• Aggregration of immunoglobulins to form microtubules

• Associated with monoclonal gammopathy and hematologic

• Mesangial expansion with eosinophilic, PAS-positive material

• Mesangioproliferative, membranoproliferative, membranous, and

Immunofluorescence :with predominant IgG, with some cases showing IgA

○ Majority have light chain restriction (70-90%)

○ C3 usually positive, and C1q less frequently positive

Top Differential Diagnoses

• Type III collagen glomerulopathy

• Polyclonal IF staining; commonly IgG4

• Serum positive for cryoglobulins; pseudothrombi

• Fibrillar deposits < 30 nm; IgG negative

• Positive immunohistochemistry for fibronectin

• Periodic banded collagen fibrils by EM and type III collagen by IHC

• Rare disorder with nail hypoplasia &/or bone abnormalities

• Periodic, sparse collagen fibrils by EM in GBM

• MIDDs are systemic disorders characterized by deposition of

• In most cases, light chains are the immunoglobulin components that

• More recently, heavy chain-associated monoclonal deposition disease,

• Interestingly, the pathologic findings in both light and heavy chain

Clinical Presentation and Laboratory Findings

• The average age of patients with LCDD with renal manifestations is 55

• The most characteristic finding in patients with LCDD is nodular glomerulopathy

• Mesangial hypercellularity accompanies the increase in extracellular matrix in some of the

• There are a number of glomerular morphologic patterns, including mesangial,

• Progression from one of these “early” patterns to a classic nodular

• Thickening of vessel walls by light chain deposits is seen in approximately 40% of

• Deposition of monoclonal light chains can be seen along the peripheral

• In most cases of LCDD, the pathogenic light chain is of kappa isotype.

• Light chain deposition manifested by granular to powdery electron-

• Light chain deposition manifested by granular to powdery electron-

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