Membranoproliferative glomerulonephritis associated with Rosai-Dorfman disease

Abstract

Rosai-Dorfman disease is also known as sinus histiocytosis with massive lymphadenopathy. Extranodal Rosai-Dorfman disease has been reported in ~ 43% of cases; the most frequent extranodal sites - skin, soft tissue, bone, respiratory tract, and eye - are usually involved in association with lymphadenopathy. Lack of lymph node involvement is rare, especially when patients manifest renal disease. Here, we describe a patient who developed membranoproliferative glomerulonephritis when lymphadenopathy was absent. During follow-up for sinus histiocytosis, a 7-year-old Japanese boy developed proteinuria and hematuria. No renal abnormality was present in ultrasound imaging. Histologic examination of a renal biopsy specimen disclosed moderate mesangial proliferation, focal thickening of glomerular capillary walls, and mesangial interposition. Mononuclear cells infiltrated the interstitium. Immunofluorescence showed intense IgG, C3, and C4 reactivity in portions of the mesangium and glomerular capillary walls. Electron microscopy depicted nodular deposits in mesangial, endocapillary, and subepithelial areas. Immunohistochemistry for S-100 protein, CD68, and lysozyme was positive within the interstitium. CD1a staining was absent. These findings were diagnostic for membranoproliferative glomerulonephritis. Multidrug therapy, including methylprednisolone and mizoribine, improved urinary findings and induced complete remission of both diseases. To the best of our knowledge, this is the first report of Rosai-Dorfman disease complicated by renal disease in the absence of concurrent nodal involvement. Clinicians should be alert to this diagnostic possibility.

Keywords: Langerhans-cell histiocytosis; Rosai-Dorfman disease; children; cytokines; membranoproliferative glomerulonephritis; mizoribine.

Figure 1.. Radiologic findings in the patient at the age of 9 months. Axial contrast-enhanced computed tomography shows left cervical adenopathy (arrows).

Figure 2.. Immunohistochemistry findings. A cervical lymph node biopsy specimen displays nodal involvement by RDD. Immunohistochemical staining for S-100(+) is positive (A), while staining for CD1a is negative (original magnification, ×400) (B).

Figure 3.. Histologic findings at 7 years. The renal biopsy specimen shows enlargement of a glomerulus with mesangial proliferation, thickening of segmental capillary walls, mesangial interposition (thick red arrows) and double contours (thin arrow). Periodic acid-Schiff (PAS) stain (original magnification, ×400).

Figure 4.. Immunofluorescence findings. Immunofluorescence shows intense IgG (A) and C3 (B) deposition in the mesangium and the focally in glomerular capillary walls (circle and arrow) (original magnification, ×400). No glomerular IgA, IgM, C1q, or fibrinogen deposition is demonstrated.

Figure 5.. Electron microscopic findings at 7 years. Nodular deposits (arrows) are shown in mesangial, endocapillary, and subepithelial areas (original magnification, ×7,000).

Figure 6.. Immunohistochemical findings in the kidney upon repeat biopsy. Infiltration of mononuclear cells in the interstitium identified by staining for S-100 (A), CD68 (B), and lysozyme (C). CD1a staining is negative in the same area (magnification, ×400) (D).