Module 4 · Visual Grammar

Glomerular Pattern Recognition

Ten glomerular patterns — what you see, best modality, pathophysiologic meaning, and the differential each pattern opens.

Pattern first. Diagnosis second.

Name the tissue reaction — hypercellularity, capillary wall thickening, sclerosis, crescents, thrombi — before naming the disease it might belong to.

Mesangial hypercellularity

Glomerular pattern

Image placeholder — Mesangial hypercellularity

What you see: Increased mesangial cells (>3 per mesangial area away from vascular pole) with variable matrix expansion.
Best stain / modality: PAS and silver highlight the mesangial area.
Pathophysiologic meaning: Mesangial immune-complex deposition or proliferative response to injury.
Associated clinical syndromes: IgA nephropathy, lupus class II, resolving post-infectious GN, hematuria/proteinuria.
Differential diagnosis: IgA nephropathy, IgA vasculitis, lupus nephritis class II, MPGN with mesangial pattern.

Board-style question

Isolated mesangial hypercellularity with dominant mesangial IgA on IF most likely represents:

Endocapillary hypercellularity

Glomerular pattern

Image placeholder — Endocapillary hypercellularity

What you see: Capillary lumina occluded by increased intracapillary cells (endothelial, mesangial, and infiltrating leukocytes).
Best stain / modality: H&E and PAS; IF for immune identity.
Pathophysiologic meaning: Immune-complex-driven inflammatory infiltrate within capillary loops.
Associated clinical syndromes: Nephritic syndrome, post-infectious GN, lupus class III/IV, cryoglobulinemic GN.
Differential diagnosis: Post-infectious GN, lupus proliferative GN, MPGN, cryoglobulinemic GN.

Board-style question

Endocapillary hypercellularity with humps on EM and starry-sky IF pattern (IgG, C3) fits:

Membranous / capillary wall pattern

Glomerular pattern

Image placeholder — Membranous / capillary wall pattern

What you see: Diffuse capillary wall thickening without significant hypercellularity.
Best stain / modality: Silver (GBM spikes), PAS (thickened GBM); IF (granular capillary-wall IgG); EM (subepithelial deposits).
Pathophysiologic meaning: In-situ or trapped subepithelial immune-complex formation with GBM reaction.
Associated clinical syndromes: Nephrotic syndrome in adults.
Differential diagnosis: Primary (PLA2R/THSD7A) vs secondary membranous (lupus, malignancy, infection, drugs).

Board-style question

Which combination best identifies membranous nephropathy?

Crescentic pattern

Glomerular pattern

Image placeholder — Crescentic pattern

What you see: Extracapillary proliferation filling Bowman's space in ≥50% of glomeruli in classic 'crescentic GN'; any crescents warrant attention.
Best stain / modality: PAS and silver define Bowman's capsule; H&E shows cellular vs fibrous crescents.
Pathophysiologic meaning: Severe glomerular injury with rupture of GBM/Bowman's capsule and macrophage/parietal-epithelial-cell proliferation.
Associated clinical syndromes: Rapidly progressive glomerulonephritis (RPGN).
Differential diagnosis: Immune-complex (lupus, IgA, PIGN), pauci-immune (ANCA), anti-GBM.

Board-style question

Cellular crescents with pauci-immune IF and no EM deposits most likely reflect:

Necrotizing pattern

Glomerular pattern

Image placeholder — Necrotizing pattern

What you see: Segmental fibrinoid necrosis of the tuft, often with karyorrhexis and adjacent crescents.
Best stain / modality: H&E and silver; fibrin on IF/trichrome.
Pathophysiologic meaning: Focal capillary loop rupture with fibrinoid material; commonly co-occurs with crescents.
Associated clinical syndromes: RPGN — especially ANCA-associated vasculitis.
Differential diagnosis: ANCA-associated GN, anti-GBM, severe lupus nephritis.

Board-style question

Fibrinoid necrosis with cellular crescents is most classically associated with which serology?

Segmental sclerosis

Glomerular pattern

Image placeholder — Segmental sclerosis

What you see: Segmental collapse and sclerosis of a portion of the tuft with adhesions to Bowman's capsule.
Best stain / modality: PAS and silver to define sclerotic segments; trichrome for scar.
Pathophysiologic meaning: Podocyte injury/adaptation or scar from prior focal injury; FSGS is a lesion, not a single disease.
Associated clinical syndromes: Nephrotic-range proteinuria (primary FSGS); sub-nephrotic proteinuria in secondary/adaptive FSGS.
Differential diagnosis: Primary FSGS, secondary/adaptive FSGS (obesity, reflux, reduced nephron mass), genetic podocytopathies, healed focal GN.

Board-style question

Diffuse foot process effacement on EM with segmental sclerosis on LM suggests:

Global sclerosis

Glomerular pattern

Image placeholder — Global sclerosis

What you see: Entire tuft replaced by sclerotic matrix — often collapsed onto Bowman's capsule.
Best stain / modality: PAS/silver/trichrome for chronic scar.
Pathophysiologic meaning: End-stage response to any glomerular injury; also age-related.
Associated clinical syndromes: Marker of chronicity; contributes to prognosis independent of etiology.
Differential diagnosis: Age-related, hypertensive nephrosclerosis, end-stage of any GN.

Board-style question

The percentage of globally sclerotic glomeruli is most important for:

Double contours / MPGN pattern

Glomerular pattern

Image placeholder — Double contours / MPGN pattern

What you see: GBM duplication ('tram-tracks') with mesangial interposition and lobular accentuation of the tuft.
Best stain / modality: Silver and PAS show duplication; IF and EM define subtype.
Pathophysiologic meaning: Chronic endothelial injury and mesangial cell interposition — an injury pattern, not a diagnosis.
Associated clinical syndromes: Nephrotic + nephritic overlap; hematuria; low complements (immune-complex or C3-mediated).
Differential diagnosis: Immune-complex MPGN (hepatitis C, cryoglobulinemia, lupus), C3 glomerulopathy, TMA (healing phase), monoclonal Ig-mediated GN.

Board-style question

Double contours with C3-only IF and dense intramembranous deposits on EM fit:

Collapsing pattern

Glomerular pattern

Image placeholder — Collapsing pattern

What you see: Global or segmental capillary collapse with overlying podocyte hypertrophy and hyperplasia ('pseudocrescents').
Best stain / modality: PAS/silver for collapsed tuft; podocyte markers on IHC where available.
Pathophysiologic meaning: Severe podocyte injury with dysregulation; rapid progression.
Associated clinical syndromes: Nephrotic-range proteinuria with rapid decline in GFR.
Differential diagnosis: HIV-associated nephropathy, APOL1-associated collapsing FSGS, drug/toxin (e.g. pamidronate, interferon), viral (SARS-CoV-2).

Board-style question

'Pseudocrescents' composed of hyperplastic podocytes over collapsed tufts distinguish collapsing FSGS from:

Thrombotic microangiopathy (TMA) pattern

Glomerular pattern

Image placeholder — Thrombotic microangiopathy (TMA) pattern

What you see: Endothelial swelling, fibrin thrombi, fragmented RBCs, mesangiolysis; chronic phase shows double contours.
Best stain / modality: H&E for thrombi; silver/PAS for GBM duplication; fibrin on IF/trichrome.
Pathophysiologic meaning: Endothelial injury with intravascular thrombus formation and mechanical hemolysis.
Associated clinical syndromes: TMA syndromes (HUS, TTP, aHUS, secondary TMA), severe hypertension, drugs, transplant.
Differential diagnosis: Complement-mediated (aHUS), Shiga-toxin HUS, TTP, secondary TMA (malignant HTN, CNI, anti-VEGF).

Board-style question

Which finding is LEAST expected in acute TMA?

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