Biopsy Findings

Biopsy findings
12 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 Blue (fuchsinophilic) Jones Pink Black methenamine silver Methenamine Red Black silver + Masson Ponceau stain
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.
Jones methenamine silver
Lupus nephritis class IV. PAS stain highlights the thickening of the glomerular capillary walls by numerous subendothelial deposits.
Sites of immune deposits: 1. Mesangium common: all classes 2. Subendothelial : class 3 & 4 Wire loops: deposits large enough to completely involve the peripheral circumference of the glomerular capillaryproduce a rigid, refractile thickening of the glomerular capillary wall in hematoxylin-eosin stained sections
3. regularly distributed sub epithelial deposits are the 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.
Differentiating from fibrin: a. special stains for fibrin: modified Fraser Lendrum stain -- more sensitive and specific phosphotungstic acid hematoxylin [PTAH] stain-less sensitive b. On H&E: Fibrin Darkly eosinophilic fibrillar appearance Hyaline Lightly eosinophilic, homogenous thrombi glassy smooth structure. Significance of hyaline thrombi: a: severe disease b: associated APLA syndrome.
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 & mesangial cells 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
Jones methenamine stain
Jones methenamine silver stain of BM: segmental rupture of BM. 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 neutrophils forming pyknotic or karyorrhectic nuclear debris 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
Usually segmental, but >1 glomerular lobule may be involved. Cellular crescents frequently directly overlie the affected lobule. Correlates with low serum CH50 levels, and more severe proteinuria.
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 the ambient circulation in the course of individual cell death in necrotizing lesions. Owing to their nuclear origin, they are Feulgen positive. Difference from pyknosis:
Hematoxylin body Pyknosis
Indistinct border Iliac hyaline coloration Smaller , darkly basophilic
5: Cellular crescents In class 3 & 4 active LN only.
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 resorption droplets, appearing as clear vacuoles in H&E. Protein resorption droplets : eosinophilic & strongly PAS positive & trichrome red. to as hyaline Referred degeneration. Interstitial foam cells in few cases.
Definition: aggregates comprising two or more layers of proliferating visceral and parietal epithelial cells with infiltrating mononuclear cells lining one fourth or more of the interior circumference of Bowman's capsule.
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, and shed tubular epithelial cells are readily identified 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 (socalled lupus vasculopathy) Thrombotic microangiopathy o Associated with HUS/TTP syndrome o Associated with antiphospholipid antibodies o Associated with scleroderma/mixed connective tissue disease Necrotizing vasculitis (PAN type)
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 proliferative classes usually clinically silent, and they have not been found 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
Severe HTN common in these pts, accelerates the vascuolopathy; carries ominous prognosis
H&E stain and lendrum vasculopathy.
stain of lupus
This mterial is red on trichrome stain; shows focal 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.

Biopsy Findings

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Biopsy Findings

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Biopsy findings

12 December 2012 18:33

Jones methenamine silver

Massons trichrome stain

Jones methenamine stain

Hematoxylin body Pyknosis

Indistinct border Iliac hyaline coloration Smaller , darkly basophilic

5: Cellular crescents In class 3 & 4 active LN only.

H&E stain and lendrum vasculopathy.

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