Macrophage and platelet-infiltrated glomerulonephritis with interstitial angiofollicular hyperplasia in a patient with POEMS syndrome
(Section Editor: G. H. Neild)
Toshihiko Machiguchi1,
Haruyoshi Yoshida2, and
Tadao Tamura
Department of Internal Medicine, Himeji National Hospital, Himeji, Japan
Keywords: angiofollicular hyperplasia; interleukin-6; interstitial nephritis; macrophage infiltration; platelet aggregation; POEMS syndrome
A 49-year-old woman was admitted to our hospital with low-grade fever and leg oedema. She had muscle weakness with numbness, mild organomegaly (of thyroid gland, heart, liver and spleen), hypothyroidism, polyclonal gammopathy with elevated IgG and IgM levels, and skin sclerosis with hyperpigmentation especially in the extremities. White blood cell count was low at 3800/µl with 34% lymphocytes. There was no protein, sugar or blood in the urine. Blood urea nitrogen (BUN) was 46 mg/dl, serum creatinine (sCr) 1.9 mg/dl and creatinine clearance (Ccr) 18 ml/min. She had received no analgesics or NSAIDs. Serum and 24-h urinary interleukin-6 (IL-6) levels were within normal limits.
A renal biopsy showed a membranoproliferative glomerulonephritis (MPGN) but without immune deposits in any of the 12 glomeruli obtained (Figure 1a
). On immunoenzyme staining of formalin-fixed paraffin sections, glomerular macrophages detected with an anti-CD68 monoclonal antibody were found on average in as many as 25 cells per glomerulus (Figure 1b
). Platelet aggregates, detected by a monoclonal anti-glycoprotein IIIa (gpIIIa) antibody, were observed segmentally in glomerular capillaries, with some segments of strong positivity (Figure 1c
). There was focal tubular atrophy, with moderate to severe interstitial fibrosis and mononuclear cell infiltration including plasma cells. In addition, lymphoid follicular hyperplasia penetrated by an arborizing vessel, that is angiofollicular hyperplasia, was observed in the cortical interstitium (Figure 2a
). Interstitial macrophages were present, with prominent infiltration in angiofollicular hyperplasia (Figure 2b
). Type IV collagen detected by a relevant monoclonal antibody was demonstrated as a tubular pattern in angiofollicular hyperplastic lesion (Figure 2c
). Vascular wall thickening with hyalinization was present in small arteries and arterioles.

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Fig. 1. Representative glomerular photographs of periodic-acid Schiff (PAS) staining exhibiting MPGN-like glomerular lesions (a), and immunoenzyme stainings (dark brown colour) of CD68-positive macrophages with prominent endocapillary infiltration (b) and glycoprotein IIIa-positive platelets with severe intracapillary aggregation (c). Original magnification, x200 (a, b) and x400 (c).
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Fig. 2. Angiofollicular lymphoid hyperplasia in the cortical interstitium (PAS staining) (a), associated with severe CD68-positive macrophage infiltration (b) and tubular distribution of type IV collagen (c) by immunoenzyme staining (dark brown colour). Original magnification, x160 (a) and x200 (b, c).
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We describe a case of POEMS syndrome associated with MPGN-like glomerulopathy with prominent macrophage infiltration and platelet aggregation, and with severe interstitial nephritis with angiofollicular hyperplasia. Both macrophages and platelets in glomerular capillaries may cause endothelial damage, mediated by inflammatory cytokines such as tumour necrosis factor
(TNF
), IL-1ß and platelet-derived growth factor (PDGF), and which may also contribute to mesangial and capillary proliferation. Cytokines such as IL-6, IL-1ß, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) play an important role in POEMS syndrome and in angiogenesis [13]. Since IL-6 and IL-1ß are secreted by clonally expanded lymphocytes and macrophages [4], and VEGF and PD-ECGF are produced by platelets as well as infiltrating cells [3,5], we speculate that the combination of these cytokines induced the formation of MPGN-like glomerulopathy, as well as angiofollicular hyperplasia in this patient.
Notes
1 Present address: Department of Internal Medicine, Osaka Red Cross Hospital, Osaka, Japan. 
2 Present address: Department of Clinical Laboratory Medicine and Nephrology, Fukui Medical University, Fukui, Japan. 
Correspondence and offprint requests to: Haruyoshi Yoshida, MD, Department of Clinical Laboratory Medicine and Nephrology, Fukui Medical University, Matsuoka, Fukui 9101193, Japan. 
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