Art of Medicine: Plasma Cell Rich Interstitial Nephritis

The above painting shows plasma cell rich interstitial inflammation with lymphocytic and plasma cell tubulitis, findings that can be seen in plasma cell rich interstitial nephritis.  Acute interstitial nephritis can have an inflammatory infiltrate with lymphocytes, plasma cells, eosinophils, neutrophils, and/or histiocytes.  Greater than 10 percent plasma cells would be considered “plasma cell rich”.  An H & E stained section of a plasma cell rich infiltrate is shown below.

The differential diagnosis for a plasma cell rich interstitial nephritis in native kidney biopsies includes drug reactions, Sjögren’s syndrome, chronic pyelonephritis, and IgG4-related kidney disease.  IgG4-related kidney disease is characterized by greater than 10 IgG4 positive plasma cells per high power field on a renal biopsy.  Tubular basement membrane IgG deposits, subepithelial IgG4 deposits, and storiform fibrosis are other common findings.  Serum IgG4 levels are nearly always elevated, and the disease is often systemic.  Other organ systems that can be involved include submandibular and parotid salivary glands, orbit, lymph nodes, pancreas, retroperitoneum, lung, aorta, and bile duct (Cornell, 2019).

Less common causes of plasma cell rich tubulointerstitial inflammation include renal infiltrates in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (Houghton et al, 2006), HIV infection (Melica et al, 2012), multicentric Castleman disease (Zoshima et al, 2016), light chain-mediated acute tubular interstitial nephritis due to plasma cell dyscrasia (Gu et al, 2006), and lupus nephritis (Houghton et al, 2006).

Plasma cell rich interstitial inflammation can also occur in renal allografts, with either polyomavirus nephritis (JC or BK viral infection) or rejection, both of which impart a poor prognosis.   Plasma cell rich rejection is frequently associated with mixed antibody-mediated and acute T cell mediated rejection.  Seventy five percent of cases are associated with a positive DSA (Desvaux et al, 2004).  Resistance to steroid pulse therapy is common in these cases.

Plasma cell rich infiltrate from a case of plasma cell rich interstitial nephritis (due to IgG4-related kidney disease).

References:

Cornell LD.  IgG4-related kidney disease.  Diagnostic Pathology: Kidney Diseases, Third Edition.  Eds: Colvin RB and Chang A.  Elsevier (2019).  ISBN: 978-0-323-66108-9.

Desvaux D, Le Gouvello S, Pastural M, Abtahi M, Suberbielle C, Boeri N, Remy P, Salomon L, Lang P, Baron C.  Acute renal allograft rejections with major interstitial oedema and plasma cell-rich infiltrates: high gamma-interferon expression and poor clinical outcome.  Nephrol Dial Transplant 2004 April; 19 (4): 933-999.

Gu X, Herrera GA.  Light chain-mediated acute tubular interstitial nephritis: a poorly recognized pattern of renal disease in patients with plasma cell dyscrasia.  Archives in Pathology and Laboratory Medicine 2006 Feb; 130: 165-169.

Houghton DC, Troxell ML.  An abundance of IgG4 plasma cells is not specific for IgG4-related tubulointerstitial nephritis.  Modern Pathology 2011; 24: 1480-1487.

Melica G, Matignon M, Desvaux D, Audard V, Copie-Bergnman C, Lang P, Levy Y, Grimbert P.  Acute interstitial nephritis with predominant plasmacytic infiltration in patients with HIV-1 infection.  American Journal of Kidney Disease 2012 May; 59 (5): 711-714.

Zoshima T, Yamada K, Hara S, Mizushima I, Yamagishi M, Harada K, Sato Y, Kawano M.  Multicentric castleman disease with tubulointerstitial nephritis mimicking IgG4-related disease: two case reports.  American Journal of Surgical Pathology 2016 April; 40 (4): 495-501.