Nephrol Dial Transplant (2001) 16: 2270–2271
Images in Nephrology
(Section Editor: G. H. Neild)
Macrophage and platelet-infiltrated glomerulonephritis
with interstitial angiofollicular hyperplasia in a patient
with POEMS syndrome
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 3800uml with 34% lymphocytes. There was
no protein, sugar or blood in the urine. Blood urea
nitrogen (BUN) was 46 mgudl, serum creatinine (sCr)
1.9 mgudl and creatinine clearance (Ccr) 18 mlumin.
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 formalinfixed paraffin sections, glomerular macrophages
detected with an anti-CD68 monoclonal antibody
were found on average in as many as 25 cells per
Correspondence and offprint requests to: Haruyoshi Yoshida, MD,
Department of Clinical Laboratory Medicine and Nephrology,
Fukui Medical University, Matsuoka, Fukui 9101193, Japan.
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.
#
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.
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 a (TNFa), IL-1b and platelet-derived
growth factor (PDGF), and which may also contribute
to mesangial and capillary proliferation. Cytokines
such as IL-6, IL-1b, vascular endothelial growth factor
(VEGF) and platelet-derived endothelial cell growth
factor (PD-ECGF) play an important role in POEMS
syndrome and in angiogenesis w1–3x. Since IL-6 and
IL-1b are secreted by clonally expanded lymphocytes
and macrophages w4x, and VEGF and PD-ECGF
are produced by platelets as well as infiltrating cells
w3,5x, we speculate that the combination of these cytokines induced the formation of MPGN-like glomerulopathy, as well as angiofollicular hyperplasia in
this patient.
2001 European Renal Association–European Dialysis and Transplant Association
Glomerulonephritis with hyperplasia in POEMS syndrome
2271
(a)
(a)
(b)
(b)
(c)
(c)
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, 3 200 (a, b) and 3 400 (c).
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, 3 160 (a) and 3 200 (b, c).
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