Biopsy Findings

7/27/2019 Biopsy Findings

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Biopsy findings12 December 2012

18:33

1: Immune deposits in glomeruli can be seen on LM,

as they are large and are widespread.

On LM, the deposits have a glassy, hyper eosinophilic,

on H &E.

With special stains :

STAIN DEPOSIT MESANGIUM

& BM

Tichrome Red

(fuchsinophilic)

Blue

Jones

methenamine

silver

Pink Black

Methenamine

silver + Masson

Ponceau stain

Red Black

Jones methenamine silver

Sites of immune deposits:1. Mesangium common: all classes2. Subendothelial : class 3 & 4 Wire loops: deposits large enough to

completely involve the peripheral

circumference of the glomerular capillary-

produce a rigid, refractile thickening of the

glomerular capillary wall in hematoxylin-eosin

stained sections

Lupus nephritis class IV. Glomerular capillary walls are

segmentally thickened by wire-loop deposits. An

intraluminal deposit forms a hyaline thrombus in one

capillary, and there is global endocapillary

proliferation.

Lupus nephritis class IV. PAS stain highlights the

thickening of the glomerular capillary walls by

numerous subendothelial deposits.

3. regularly distributedsub epithelial deposits arethe defining feature of membranous lupus

nephritis class V

4. Intracapillary: hyaline thrombi. Class 3 & 4.misnomer, as they are not fibrin thrombi.

Composition similar to subendothelial immune

deposit. actually in continuity with large

subendothelial deposits in a deeper plane of

section. Common in class 4, particularly with

extensive wire loops. Also have exuberant

endocap proliferation.


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Differentiating from fibrin:

a. special stains for fibrin: modified Fraser Lendrum stain -- more sensitive

and specific phosphotungstic acid hematoxylin [PTAH] stain--

less sensitiveb. On H&E:

Fibrin Darkly eosinophilicfibrillar appearance

Hyaline

thrombi

Lightly eosinophilic, homogenous

glassy smooth structure.

Significance of hyaline thrombi:

a: severe disease

b: associated APLA syndrome.

Jones methenamine stain

Massons trichrome stain

2: Mesangial & endocapillary proliferation:

Response to immunedeposits in above areas.

Poor correlation between size & extent of mesangial

immune deposit and degree of mesangial

proliferation.

Endocapillary proliferation:

proliferation of endothelial cells & mesangialcells together with infiltrating PMN-->

narrows/occludes glomerular capillary lumen.

Focal and segmental or diffuse and global. LM identifies only PMN. IHC & EM identifies

other cells also. Good correlation between extent of immune

deposit, complement activation and

proliferative response. No direct correlation between proliferative

response and renal function. On the other hand, the number of macrophages

(as well as tubular macrophages) in a second

renal biopsy taken 6 months following therapy

has been found to correlate well with outcome


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3: Necroses:

Feature of class 3 and 4 LN only. Focus of smudgy fibrinoid obliteration of the

glomerular tuft, which is often associated with

any or all of the following:

deposition of intracapillary fibrin, glomerular basement membrane rupture

or gap formation, and

apoptosis of infiltrating neutrophilsforming pyknotic or karyorrhectic nuclear

debris

Usually segmental, but >1 glomerular lobulemay be involved.

Cellular crescents frequently directly overlie theaffected lobule.

Correlates with low serum CH50 levels, andmore severe proteinuria.

Jones methenamine silver stain of BM:

segmental rupture of BM.

4: Hematoxylin bodies:

Common in necrotising lesions the only truly pathognomonic lesion in lupus

nephritis Extremely uncommon, 2% biopsy specimen

from lupus patients. rounded, smudgy, lilac-staining structures that

are generally smaller than normal nuclei

Isolated or clustered., with indistinct borders. Hematoxylin bodies are the tissue equivalent of

the LE body and consist of naked nuclei whose

chromatin has been altered by binding to ANA,

probably after exposure of the nuclei to theambient circulation in the course of individual

cell death in necrotizing lesions. Owing to their

nuclear origin, they are Feulgen positive. Difference from pyknosis:


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Hematoxylin body Indistinct border Iliac hyaline coloration

Pyknosis Smaller , darkly basophilic

5: Cellular crescents

In class 3 & 4 active LN only.

Definition: aggregates comprising two or morelayers of proliferating visceral and parietal

epithelial cells with infiltrating mononuclearcells lining one fourth or more of the interior

circumference of Bowman's capsule.

TUBULES & INTERSTITIUM:

Changes common in class 4, followed by 3

Less common in class 5.

Least in class 1 &2.

Lesions can be acute or chronic. Due to inflammatory

process or edema.

a: pts with nephrotic range proteinuria : In PCT:

intracytoplasmic lipid resorptiondroplets, appearing as clear

vacuoles in H&E.

Protein resorption droplets :eosinophilic & strongly PAS positive

& trichrome red. Referred to as hyaline

degeneration. Interstitial foam cells in few cases.

Active tubulointerstitial lesions : in class 4 & 3. infiltrate of mononuclear leucocytes, L,M,

plasma cells present along with edema.

Neutrophils and eosinophils are rare. Sometimes, lymphocytic infiltration of

tubules (= tubulitis +) and tubular

epithelial degenerative and regenerative

changes +. Rarely, hematoxylin bodies ingested by

neutrophils are identified in tubular

lumens

Casts of neutrophils, erythrocytes, andshed tubular epithelial cells are readilyidentified in active class III or IV lupus

nephritis Intratubular oval fat bodies consisting of

lipid-laden desquamated epithelial cells

are most common in cases with severe

nephrotic proteinuria Immune deposits : seen in

Tubular basement membrane, any part. Interstitial capillary BM : specific Interstitial collagen.

VASCULAR LESION IN LUPUS NEPHRITIS:

Arteriosclerosis and arteriolosclerosis Uncomplicated vascular immune deposits Noninflammatory necrotizing vasculopathy (so-

called lupus vasculopathy) Thrombotic microangiopathy

o Associated with HUS/TTP syndromeo Associated with antiphospholipid

antibodieso Associated with scleroderma/mixed

connective tissue disease Necrotizing vasculitis (PAN type)


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associated with a higher rate of progression to renal

failure.

Uncomplicated Vascular Immune Deposits :

most common renal vascular lesion immune complex deposition in the walls of

small arteries and arterioles The affected vessels usually appear normal by

light microscopy Diagnosis requires the demonstration of

granular deposits of immunoglobulin (IgG, IgM,

and IgA in various combinations), often

associated with C1q or C3

most common in the more active proliferativeclasses

usually clinically silent, and they have not beenfound to confer a higher risk of hypertension or

progressive renal disease.Noninflammatory necrotizing vasculopathy: Less common. affects predominantly preglomerular arterioles ,

interlobular arteries (less common). Vessels narrowed, sometimes occluded by

abundant intimal and luminal deposits of glassy

eosinophilic material that may extend into the

media

This mterial is red on trichrome stain; showsfocal reactivity for fibrin on lendrum and PTAH

stain. Endothelium is swollen/denuded Degeneration and loss od myocytes, no

inflammatory infiltration of the vessel wall. IF: variable deposition of Ig, complements,

antigens combined processes of vascular immune

deposition and intravascular coagulation

contribute to their morphogenesis.

Severe HTN common in these pts, acceleratesthe vascuolopathy; carries ominous prognosis

H&E stain and lendrum stain of lupus

vasculopathy.

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Biopsy Findings