CRP-49

CRP-49

Clinical History

The patient is a 73 year old white male. Positive ANA, positive anti-double stranded DNA. Active urinary sediment. Creatinine ranges from 1.4 to 1.8; urinary protein 1.2 g/ 24 hr.

Gross Description

Received in transport media are two cores measuring 22 and 12 mm n length and 2 mm in diameter. Two 1-mm pieces are taken for EM, and the remainder is bisected and divided equally for immunofluorescence and light microscopy.

Pathology

Case CRP-049 PASH

Microscopic Description, Immunofluorescence, and Electron Microscopy

Microscopic Description

Light Microscopy

The specimen consist of three fragments of renal cortex with small portions of medulla. There are thirty-nine glomeruli in the three levels examined. None of these are obsolete, and none show segmental sclerosis. About 30% of the glomeruli demonstrate mild ischemic atrophy with increased mesangial matrix and thickened and wrinkled capillary basement membranes. Silver stain, however, does not show spike formation or splitting along the capillary loops. There is no significant mesangial hypercellularity, and there are no segmental areas of necrosis or proliferation. There is diffuse moderate interstitial fibrosis with corresponding tubular dropout. Many of the remaining tubules are atrophic with chickened and wrinkled tubular basement membranes. There is moderate interstitial edema. However, the most striking feature in the biopsy is the marked mononuclear cell infiltrate throughout the interstitium. This is composed of lymphocytes and plasma cells with occasional eosinophils. Polymorphonuclear leukocytes are not identified. The infiltrate is associated with focal examples of mild tubulitis. A number of arterioles and small arteries are present in the biopsy. The arterioles show moderately severe hyaline thickening, and the larger arteries show moderate intimal fibrous thickening. There is no vasculitis, and no thrombi are identified.

Immunofluorescence

There are eight glomeruli in the sections. There is l+ mesangial staining for IgM and C3. There is no glomerular staining for IgG, IgA, C1q or light chains. Tubular epithelium and tubular basement membranes show 2+ granular staining for IgG, C3 and kappa and lambda light chains. There is no staining of the vessels.

Electron Microscopy

Two thick sections are available, but one contains no glomeruli. The other section contains three glomeruli, although one is obsolete. These are similar to those described above and show mild ischemic atrophy. There is an intense interstitial infiltrate of lymphocytes and plasma cells. Very few tubules are present, because most of the interstitium is fibrotic. Ultrastructural examination reveals moderate focal thickening and wrinkling of the capillary basement membranes, and there is diffuse fusion of the visceral epithelial cell foot processes. No electron dense deposits are identified in the glomeruli. Careful examination of the few tubules available in the section does not reveal any definite deposits consistent with immune complexes.

Diagnosis and Comments

Kidney, needle biopsy

- Immune complex-mediated acute interstitial nephritis.

- Moderate arterial and arteriolar sclerosis.

These findings are most consistent with immune complex-mediated acute interstitial nephritis. The granular nature of the immunofluorescence staining in the tubular basement membranes is more consistent with immune complex deposition rather than anti-basement membrane antibodies. The condition in which prominent TBM deposits are most often found is lupus nephritis. However, the lack of evidence in this biopsy for an immune complex-mediated glomerulopathy makes lupus nephritis extremely unlikely. The other two lesions generally mentioned in association with tubulointerstitial immunoglobulin-containing deposits are mixed cryoglobulinemia and Sjogren's syndrome. Sjogren's syndrome is definitely worth considering, since it may be associated with rather intense interstitial nephritis, as noted in this biopsy. The relatively preserved glomerular morphology makes a systemic vasculitis such as Wegener's granulomatosis or microscopic polyarteritis very unlikely.

An infiltrate is an accumulation of cells in the lung parenchyma--this is a sign of pneumonia.