Nephropathology
Slide Seminar: Case 2
European Congress of Pathology
30.8.2011
Anne Raisanen-Sokolowski, MD, PhD
Transplantation Laboratory
Helsinki University Central Hospital
Helsinki, Finland
Patient data 1
• 53 years old, previously healthy male
• One year ago vision began to worsen,
diagnosed and treated as iritis
• Thereafter fever (ad 39°C) and malaise
for 6 months.
• He suffered malfunction of intestine,
edema in the lower extremities and
muscle weakness, loss of appetite,
weight loss
Patient data 2
• The patient presented with:
 tingling in finger tips and polyneuropathy by
ENMG
 hepatosplenomegalia
• Ultrasound: several focal defects in liver,
suspicion of metastasis
• Biopsy: necrosis -> suspicion of Tbc ->
treatment started -> laboratory findings negative
• Ascites
 Hypogonadism (low testosterone)
Patient data 3
• The patient presented with:
 paraproteinemia in plasma (kappa light
chain, 3-10 g/l)
• crista biopsy 10% plasma cells
 hematuria (>20 erytrocytes/hpf)
 proteinuria (dU-Prot 0,32-0,42 g/day,
P-Alb 27 g/l, Crea 103 mmol/l)
 Cachexia
• Kidney biopsy taken
Immunofluoresence study
• Performed in frozen sections
• IgG, IgA, IgM, C3, C1q, fibrinogen,
kappa and lambda were negative
Biopsy findings
• Glomeruli
 lobular and mesangial proliferation
 GBM duplication, mesangial interposition
 no immune deposit (IF and EM negative)
• Tubuli and vessels
 unremarkable
Diagnosis
• Membranoproliferative
glomerulonephritis associated with
POEMS syndrome
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Polyneuropathy
Organomegaly (hepatosplenomegaly)
Endocrinopathy (hypogonadism)
M-component (kappa light chain) in plasma
Skin lesions (none)
Nakamoto et al: A spectrum of clinicopathological features of nephropathy associated with
POEMS syndrome. NDT 1999: 14:2370-2378
POEMS syndrome 1
• POEMS syndrome is a rare
paraneoplastic syndrome secondary to
plasma cell dyscrasia
 Usually lambda light chain (95%)
• Incidence peaks in 5th and 6th decade
of life, unlike multiple myeloma (7-8th)
Dispenzieri: POEMS syndrome. Blood Reviews 2007: 21, 285-299
POEMS syndrome 2
• Complex pathogenesis: elevation of
proangiogenic and proinflammatory
cytokines are hallmarks of this disorder
• Patients with POEMS have elevated
VEGF levels in plasma, serum, ascites
and cerebrospinal fluid
Dispenzieri: POEMS syndrome. Blood Reviews 2007: 21, 285-299
POEMS syndrome 3
• VEGF is the dominant driving cytokine
 Targets endothelial cells and induces an
increase in vascular permeability
 Important in angiogenesis and
osteogenesis
 VEGF is expressed by osteoblasts, in bone
tissue, macrophages, tumor cells (including
plasma cells), megakaryocytes and
platelets
 IL-1b and IL-6 stimulate VEGF production
Dispenzieri: POEMS syndrome. Blood Reviews 2007: 21, 285-299
Pathological features of
POEMS nephropathy
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Glomerular enlargement
Cell proliferation and swelling
Mesangial loosening and mesangiolysis
Microaneurysms
Nodular-like lesions
Infiltration of plasma cells and mononuclear cells
Tubular atrophy and interstitial fibrosis
Acute tubular necrosis
No immune deposits
Nakamoto et al: A spectrum of clinicopathological features of nephropathy associated with POEMS
syndrome. NDT 1999: 14:2370-2378
Treatment
• No randomized, controlled trials in POEMS
• Radiation therapy, chemotherapy,
corticosteroids, anti-VEGF mAb
(Bevacizumab, Avestin) and stem cell
transplantation
• Case Patient received cyclic chemotherapycorticosteroids-Bevacizumab treatment for 11
months, remission -> autologous stem cell
transplantation 3/2011 ->5/2011 in remission
Dispenzieri: POEMS syndrome. Blood Reviews 2007: 21, 285-299
If we knew what we were doing
it would not be called research
A. Einstein
Midnight Sun in Pyhatunturi, Lapland, July 14, 2011 at 23.28