Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review

Abstract

Background: TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever and/or elevated serum C-reactive protein, renal dysfunction, and organomegaly. Case Presentation: A 28-year-old woman with fever, weight gain of 13 kgs, lower extremity edema, hepatosplenomegaly, and multicentric peripheral lymphadenopathy was referred to our center. Laboratory investigations revealed anemia, thrombocytopenia, creatinine at 1.19 mg/dL and hypoalbuminemia at 33 g/L. Proteinuria was measured at 2 g/day including albuminuria at 1.5 g/day. Urinary sediment examination found leukocyturia at 44,000/mL and hematuria at 645,000/mL. Vascular endothelial growth factor (VEGF) level was elevated. A cervical lymph node biopsy found features consistent with the mixed histopathological subtype of iMCD. A renal biopsy revealed a membranoproliferative glomerulonephritis (MPGN) pattern. We initiated 3 days of methylprednisolone pulse-therapy at 1,000 mg per day, followed by prednisone 1 mg/kg/day and evolution was favorable. Review of Literature: 19 iMCD patients with TAFRO syndrome had undergone a renal biopsy: 8 cases with author's diagnosis consistent with MPGN-like and 11 cases of thrombotic microangiopathy (TMA)-like glomerulopathy without fibrin thrombi in glomerular capillaries or arterioles and without typical biological signs. Clinical, biological, and outcome characteristics were similar between the cases described as having MPGN and TMA-like presentation. After a thorough review of histopathological descriptions for each case, MPGN lesions seems to be the consequences of chronic glomerular endothelial injury in persistent TMA. We suspect that VEGF and IL-6 play a key role in the physiopathology of the spectrum of renal involvement from TMA-like to MPGN observed in TAFRO syndrome. Conclusion: We present a Caucasian iMCD patient with TAFRO syndrome with renal insufficiency secondary to MPGN, which might be secondary to a chronic TMA-like disease. We suspect that there is a continuum between TMA and MPGN lesions in TAFRO syndrome favored by VEGF and IL-6.

Keywords: TAFRO syndrome; VEGF; idiopathic multicentric Castleman disease; interleukin-6; membranoproliferative glomerulonephritis; thrombotic microangiopathy glomerulopathy.

Figure 1

Mixed histopathological subtype of Castleman disease. (A) Follicles are characterized by an atrophic germinal center with few lymphocytes, radially penetrated by blood vessels (lollipop follicle). HES 100x (B) the small lymphocytes of the mantle zones are arranged in concentric rings around the germinal center. Silver impregnation after Gordon-Sweet 100x.

Figure 2

Representative photomicrographs from kidney biopsy of the case: membranoproliferative glomerulonephritis pattern. (A) Increased lobulation with intracapillary hypercellularity by macrophages and neutrophils. Masson's Trichrome 400x. (B) Thickening of capillary due to multiple double contours. Mild mesangial proliferation. Silver impregnation after Jones 400x. Mild. (C) Segmentary granular capillary walls deposits for IgM. Immunofluorescence (IF) 400x. (D) Mild endomembranous deposits for Lambda light chains. IF 400x. (E) Mild endomembranous deposits for Kappa light chains. IF 400x. (F) Ultrastructural study showed moderate subendothelial dense deposits without subepithelial neither intra-membranous deposits x1293.