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MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS IN THE
SETTING OF MULTICENTRIC ANGIOFOLLICULAR LYMPH
NODE HYPERPLASIA (CASTLEMANS DISEASE)
COMPLICATED BY EVANS SYNDROME Gakiopoulou H,
Paraskevakou H, Marinaki S, Voulgarelis M,
Korkolopoulou P, Lazaris A, Tzirakis M, Stofas
A, Boletis J, Patsouris E A Department of
Pathology Medical School University of Athens,
Department of Nephrology, Laikon Hospital
Department of Pathophysiology, Medical School,
National University of Athens, Greece.

• INTRODUCTION
• Castlemans disease of the plasma cell or
  multicentric type is a systemic
  lymphoproliferative disorder with various
  clinical presentations and I
• incompletely understood etiology.1
• Multicentric Castlemans disease is
  infrequently associated with renal manifestations
  while the presence of overt nephrotic syndrome
  and/or
• acute renal failure due to an underlying
  glomerulopathy is a rare occurrence.2-10
• However, it appears to be etiologically related
  to the presence of Castlemans disease since
  resolution of glomerulopathy follows disease
• remission.3

• AIM
• To report on a rare case of the plasma cell
  variant of Castlemans disease complicated by
  autoimmune haemolytic anemia, autoimmune
• thrombocytopenia (Evans syndrome) and
  associated with a mixed nephrotic-nephritic
  syndrome and acute renal failure due to an
  underlying
• glomerulopathy with light microscopic and
  immunofluorescence findings compatible with
  membranoproliferative glomerulonephritis type I.
• To the best of our knowledge constellation of
  all these autoimmune disorders is reported for
  the first time.

• CASE REPORT
• A 17 year old male with a history of
  Castlemans disease of the plasma cell type,
  associated with autoimmune haemolytic anemia and
  
• autoimmune thrombocytopenia (Evans
  syndrome) presented with disease relapse
  associated with marked peripheral edema followed
  by rapid
• deterioration of renal function. Urine
  protein excretion was at 7,65 g/24hrs and
  urinanalysis showed active urinary nephritic
  sediment. Serum
• complement was decreased. Laboratory
  examination demonstrated low complement. Renal
  biopsy was performed.
• The renal biopsy specimen showed diffuse global
  mesangial hyperplasia of both matrix and cells
  (fig 1) with focal endocapillary proliferation
  and
• subsequent glomerular lobular accentuation
  (fig.1-3). Basement membranes of the glomerular
  capillaries were thickened and double contours
• were detected by PAS and Silver stains (fig.
  2-3 )
• Immunofluorescence immunohistochemistry
  revealed immunodeposits for IgG () (fig. 5),
  IgM (), C3 () (fig.6), C1q () (fig.4)
• and k light chain () with a predominantly
  peripheral, band-like subendothelial
  localization.
• Immunohistochemistry for VEGF, flk1, Flt-1,
  Flt-4 and IL-6 was negative. Immunohistochemistry
  for HHV8 was also negative in renal tissue.
• Taking into account the membranoproliferative
  pattern seen in light microscopy together with
  the immunofluorescence findings suggestive of
• activation of the classic complement pathway,
  a diagnosis of membranoproliferative
  glomerulolonephritis type I was supported. The
  patient
• was treated for the relapse of his primary
  disease with cyclophosphamide, vincristine,
  doxorubicin and prednisone aiming to also manage
  renal
• manifestations.

Figure 2
Figure 1
Figure 3
Figure 4
Figure 5
Figure 6

• DISCUSSION
• We report for the first time the constellation
  of several autoimmune disorders in association
  with Castlemans disease of the multicentric
  type autoimmune anemia, autoimmune
  thrombocytopenia (Evans syndrome) and
  membranoproliferative glomerulonephritis type I
• The well established role of cytokines (VEGF
  IL-6) in the pathogenesis of Castlemans disease
  might also be responsible for the morphological
  renal alterations mimicking a membranoproliferativ
  e pattern via mesangial and endothelial cell
  proliferation and/or injurious action to the
  glomerular endothelium.1,5,7
• However, the constellation in our case of
  several autoimmune disorders along with the
  negative immunostaining for IL-6, VEGF and its
  receptors, suggests a more generalized
  immunologic disturbance in multicentric Castleman
  disease which is supported by the following
  observations
• 1. The detection of various types of
  autoantibodies in previously reported cases of
  Castlemans disease - associated or not with
  renal manifestations like antiplatelet and
  anti-cardiolipin autoantibodies.1,10,11
• 2. The recently described case of an anti-GBM
  glomerulonephritis in a Castlemans disease
  patient 10 and the detection of
• anti-MPO antibodies in a previously reported
  case of crescentic glomerulonephritis seen in
  another Castlemans disease patient.9
• 3. The identification of a secreted autoantibody
  in cultured Castlemans tumor cells which reacts
  against epidermal proteins, in paraneoplastic
  pemphigus, a serious autoimmune skin disorder,
  seen in a Castlemans disease patient.12
• It is attractive to speculate that apart from
  the putative role of VEGF and IL6 in the
  pathogenesis of renal lesions, autoantibodies
  might be induced by active polyclonal B cells
  raised from Castlemans disease tumor.

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