CRP-57: Difference between revisions - Pathology Education Instructional Resource

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'''CRP-57'''

==Clinical History==

The patient is a 47 year old female.

History of SLE and focal proliferative glomerulonephritis by 1991 biopsy (done elsewhere). Status post treatment with Cytoxan and prednisone. Hepatitis C positive. Urinary sediment shows 1-20 RBC. BUN 88, creatinine 2.8.

==Gross Description:==

==Gross Description==

Received in transport media are two cores measuring 11 and 12 mm in length and 2 mm in diameter. Two 1-mm pieces are taken for EM. The remaining 11-mm piece is submitted for immunofluorescence, and the remaining 10-mm piece is submitted for light microscopy.

==Pathology==

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<peir-vm>specialcrp/CRP-057_Trichrome</peir-vm>

<div class="usermessage mw-customtoggle-diagnosis" style="cursor:pointer"> Microscopic Description, Immunofluorescence, and Electron Microscopy.</div>

<div class="usermessage mw-customtoggle-diagnosis" style="cursor:pointer"> Microscopic Description, Immunofluorescence, and Electron Microscopy</div>

==Microscopic Description:==

==Microscopic Description==

===Light Microscopy:===

===Light Microscopy===

The specimen consists of a fragment of renal cortex that contains seventy-one glomeruli in the three levels. Sixteen of these are obsolete. The remaining glomeruli are similar and show marked diffuse endocapillary and mesangial cell proliferation with accentuation of the lobular pattern. A number of the glomeruli contain hyaline thrombi within the peripheral capillary loops. One glomerulus on the second levels show markedly thickened and eosinophilic segmental capillary basement membranes, suggestive of wire loops. No glomerular necrosis is noted, and there are no cellular or fibrous crescents. The silver stain shows numerous examples of mesangial interposition with double contours. There is diffuse moderate interstitial fibrosis with corresponding tubular dropout. There is moderate focal tubular atrophy in the remaining tubules. Mononuclear inflammatory cells are present throughout the interstitium, but tubulitis is not identified. A number of the small arteries show marked mucinous intimal thickening with almost completely obliteration of the lumen. Some of these arterioles contain hyaline thrombi. The interlobular arteries generally show marked mucinous fibroplasia with severe compromise or complete obliteration of the lumen. The silver stain does not show significant “onion-skinning". There is no vasculitis or necrosis in any of the vessels. No definite fibrin thrombi or trapped red cells are identified in any of these vessels.

===Immunofluorescence:===

===Immunofluorescence===

There are twelve glomeruli in the sections. There is finely granular and amorphous focal, segmental staining for IgG, IgM, Clq, C3 and kappa and lambda light chains. There is no glomerular staining for IgA. There is both capillary loop and mesangial staining in the glomeruli. Occasional thrombi identified in the glomeruli and arterioles show stain strongly for IgG, IgM and kappa light chain. The glomerular staining is graded 2+ for IgG, IgM and kappa light chain; the staining for Clq, C3 and lambda light chain is only 1+. There is no staining of the tubular basement membranes.

===Electron Microscopy===

Two thick sections are available. The glomeruli are similar to those described above and show diffuse proliferation with occasional thrombi in the glomeruli and arterioles. Ultrastructural examination reveals increased mesangial matrix and occasional mesangial deposits. Numerous examples of mesangial interposition are noted, and there is deposition of new basement membrane material in many of the capillary loops. Numerous subendothelial deposits, as well as large intraluminal electron dense deposits, are identified. Very high magnification of these deposits demonstrates a distinct substructure that consists of curved and annular arrays, consistent with cryoglobulins. No intramembranous or subepithelial deposits are identified. There is diffuse effacement of the epithelial cell foot processes.

=~~==Electron Microscopy:===~~

</div></div>

Kidney, needle biopsy

- Membranoproliferative glomerulonephritis secondary to mixed cryoglobulinemia.

~~</div></div>~~

- Severe arteriolar and arterial sclerosis.

These features are most consistent with cryoglobulinemic membranoproliferative glomerulonephritis. The immunofluorescence pattern would be extremely atypical for diffuse proliferative lupus glomerulonephritis. The light microscopic changes in the vessels are more consistent with long-standing severe hypertension rather than malignant hypertension. The degree of tubulointerstitial scarring combined with the severe vascular injury suggests a very poor prognosis for this kidney.

~~<spoiler text="Diagnosis~~ and ~~Comments">~~

Discussion (Addendum):

Immunoperoxidase staining for hepatitis C antigen was performed on this tissue. There was diffuse positive staining in most of the tubular epithelial cells, but this appeared to be non-specific staining. Most of the glomeruli showed positive staining, generally within capillary loops and along the endothelial surfaces of the capillary basement membranes. A control stain of liver was adequate. However, due to the generally diffuse staining in the tubular epithelium, a second control stain was performed on a renal biopsy from a patient who definitely did not have hepatitis C. This stain also showed diffuse tubular epithelial cell staining, but there was no staining whatsoever in the glomeruli. Therefore, the glomerular staining in this biopsy (S98-08233) appears to be genuine.

</spoiler>

@@ Line 1: / Line 1: @@
 '''CRP-57'''
 ==Clinical History==
+The patient is a 47 year old female.
+History of SLE and focal proliferative glomerulonephritis by 1991 biopsy (done elsewhere).  Status post treatment with Cytoxan and prednisone.  Hepatitis C positive.  Urinary sediment shows 1-20 RBC.  BUN 88, creatinine 2.8.
-==Gross Description:==
+==Gross Description==
+Received in transport media are two cores measuring 11 and 12 mm in length and 2 mm in diameter.  Two 1-mm pieces are taken for EM.  The remaining 11-mm piece is submitted for immunofluorescence, and the remaining 10-mm piece is submitted for light microscopy.
 ==Pathology==
@@ Line 14: / Line 17: @@
 <peir-vm>specialcrp/CRP-057_Trichrome</peir-vm>
-<div class="usermessage mw-customtoggle-diagnosis" style="cursor:pointer"> Microscopic Description, Immunofluorescence, and Electron Microscopy.</div>
+<div class="usermessage mw-customtoggle-diagnosis" style="cursor:pointer"> Microscopic Description, Immunofluorescence, and Electron Microscopy</div>
 <div class="mw-collapsible mw-collapsed" id="mw-customcollapsible-diagnosis">
 <div class="mw-collapsible-content">
-==Microscopic Description:==
+==Microscopic Description==
-===Light Microscopy:===
+===Light Microscopy===
+The specimen consists of a fragment of renal cortex that contains seventy-one glomeruli in the three levels.  Sixteen of these are obsolete.  The remaining glomeruli are similar and show marked diffuse endocapillary and mesangial cell proliferation with accentuation of the lobular pattern.  A number of the glomeruli contain hyaline thrombi within the peripheral capillary loops.  One glomerulus on the second levels show markedly thickened and eosinophilic segmental capillary basement membranes, suggestive of wire loops.  No glomerular necrosis is noted, and there are no cellular or fibrous crescents.  The silver stain shows numerous examples of mesangial interposition with double contours.  There is diffuse moderate interstitial fibrosis with corresponding tubular dropout.  There is moderate focal tubular atrophy in the remaining tubules.  Mononuclear inflammatory cells are present throughout the interstitium, but tubulitis is not identified.  A number of the small arteries show marked mucinous intimal thickening with almost completely obliteration of the lumen.  Some of these arterioles contain hyaline thrombi. The interlobular arteries generally show marked mucinous fibroplasia with severe compromise or complete obliteration of the lumen.  The silver stain does not show significant “onion-skinning".  There is no vasculitis or necrosis in any of the vessels.  No definite fibrin thrombi or trapped red cells are identified in any of these vessels.
-===Immunofluorescence:===
+===Immunofluorescence===
+There are twelve glomeruli in the sections.  There is finely granular and amorphous focal, segmental staining for IgG, IgM, Clq, C3 and kappa and lambda light chains.  There is no glomerular staining for IgA.  There is both capillary loop and mesangial staining in the glomeruli.  Occasional thrombi identified in the glomeruli and arterioles show stain strongly for IgG, IgM and kappa light chain.  The glomerular staining is graded 2+ for IgG, IgM and kappa light chain; the staining for Clq, C3 and lambda light chain is only 1+. There is no staining of the tubular basement membranes.
+===Electron Microscopy===
+Two thick sections are available.  The glomeruli are similar to those described above and show diffuse proliferation with occasional thrombi in the glomeruli and arterioles.  Ultrastructural examination reveals increased mesangial matrix and occasional mesangial deposits.  Numerous examples of mesangial interposition are noted, and there is deposition of new basement membrane material in many of the capillary loops.  Numerous subendothelial deposits, as well as large intraluminal electron dense deposits, are identified.  Very high magnification of these deposits demonstrates a distinct substructure that consists of curved and annular arrays, consistent with cryoglobulins.  No intramembranous or subepithelial deposits are identified. There is diffuse effacement of the epithelial cell foot processes.
-===Electron Microscopy:===
+</div></div>
+<spoiler text="Diagnosis and Comments">
+Kidney, needle biopsy
+- Membranoproliferative glomerulonephritis secondary to mixed cryoglobulinemia.
-</div></div>
+- Severe arteriolar and arterial sclerosis.
+These features are most consistent with cryoglobulinemic membranoproliferative glomerulonephritis.  The immunofluorescence pattern would be extremely atypical for diffuse proliferative lupus glomerulonephritis.  The light microscopic changes in the vessels are more consistent with long-standing severe hypertension rather than malignant hypertension.  The degree of tubulointerstitial scarring combined with the severe vascular injury suggests a very poor prognosis for this kidney.
-<spoiler text="Diagnosis and Comments">
+Discussion (Addendum):
+Immunoperoxidase staining for hepatitis C antigen was performed on this tissue. There was diffuse positive staining in most of the tubular epithelial cells, but this appeared to be non-specific staining. Most of the glomeruli showed positive staining, generally within capillary loops and along the endothelial surfaces of the capillary basement membranes. A control stain of liver was adequate. However, due to the generally diffuse staining in the tubular epithelium, a second control stain was performed on a renal biopsy from a patient who definitely did not have hepatitis C. This stain also showed diffuse tubular epithelial cell staining, but there was no staining whatsoever in the glomeruli. Therefore, the glomerular staining in this biopsy (S98-08233) appears to be genuine.
 </spoiler>