Nephropathology Slide Seminar: Case 2 European Congress of Pathology 30.8.2011 Anne Raisanen-Sokolowski, MD, PhD Transplantation Laboratory Helsinki University.

Nephropathology Nephropathology Slide Seminar: Case 2Slide Seminar: Case 2European Congress of Pathology European Congress of Pathology

30.8.201130.8.2011

Anne Raisanen-Sokolowski, MD, PhDTransplantation Laboratory

Helsinki University Central HospitalHelsinki, Finland

Patient data 1Patient 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 2Patient 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 3Patient 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 studyImmunofluoresence study

• Performed in frozen sections• IgG, IgA, IgM, C3, C1q, fibrinogen,

kappa and lambda were negative

Biopsy findingsBiopsy findings

• Glomeruli lobular and mesangial proliferation GBM duplication, mesangial interposition no immune deposit (IF and EM negative)

• Tubuli and vessels unremarkable

DiagnosisDiagnosis

• Membranoproliferative glomerulonephritis associated with POEMS syndrome 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 1POEMS 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 2POEMS 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 3POEMS 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-1 and IL-6 stimulate VEGF productionDispenzieri: POEMS syndrome. Blood Reviews 2007: 21, 285-299

Pathological features of Pathological features of POEMS nephropathyPOEMS nephropathy

• 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 chemotherapy-corticosteroids-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

Midnight Sun in Pyhatunturi, Lapland, July 14, 2011 at 23.28

If we knew what we were doing it would not be called research A. Einstein