Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells

Figures & data

Figure 1. Selected histological findings: (A) and (B) hematoxylin-eosin stains. (A) photomicrograph showing normal lining thickness with increased stromal cellularity in part due to infiltrating large mononuclear cells. The arrow points to large macrophages within focal amyloid deposits (patient 1). (B) Example of mild focal lining hyperplasia and juxta-intimal pericapillaritis occasionally seen in the specimen from patient 2. (C) and (D) Detection of amyloid by Congo Red stain (patient 1). (C) Typical carmine red deposits as seen in bright field view. (D) Typical birefringence seen under polarizing light. (E–G) Immunohistochemical detection of kappa light chain (patient 1). There is diffuse deposition of kappa (E), but not of lambda (F) light chains, consistent with AL amyloidosis. G, negative control.

Figure 2. Immunohistochemical findings. Immunohistochemical stains for CD68, CD3, CD20 and CD38. Chromogen, DAB (brown). Original magnification, 100×. Left panel: synovial biopsy from patient 1. Middle panel: paraffin-embedded synovial fluid sediment from patient 1. Right panel: synovial biopsy from a patient with RA with active disease despite treatment with disease-modifying antirheumatic drugs.

Figure 3. Cluster analysis of the 2 MAA specimens with respect to RA, OA and normal synovium. Expression values in the synovial subintima (number of positive staining cells per mm²) of CD68, CD3, CD20, CD38, Ki-67 and vWF for MAA (n = 2), RA (n = 24), OA (n = 26) and normal synovium (n = 15) were used to construct a hierarchical tree of clusters for all specimens. The MAA specimens fall within a cluster of OA specimens and are clearly separated from the RA specimens.

Table 1. Demographic and laboratory data.

Measurement	Patient 1	Patient 2
Age (years)	58	77
Sex	Male	Male
Blood leukocytes (4.5–10 × 10^3/mm^3)	9.7	10.6
Differential count	82% P, 11% L, 6.8% M	90% P, 5.6% L, 4.7% M
Hemoglobin (13.5–16.5 g/dl)	10.2	9.6
Platelets/mm^3 (100–450 × 10^3)	162	227
ESR (0–20 mm/h)	54	91
RF (IU/ml, normal < 20)	<20	<20
ANA	Negative	Negative
SF cell count	2500/mm^3	“few mononuclear cells”
SF differential cell count	6% P, 17% L, 77% synovial lining cells	n/d
Serum IgA (45–300 mg/dl)	1150	82.6
Serum IgM (50–300 mg/dl)	25	24.1
Serum IgG (600–1500 mg/dl)	326	1910
SPEP	IgA κ and κ free light chain monoclonal bands	IgG κ monoclonal band

ANA, antinuclear antibodies; ESR, erythrocyte sedimentation rate; L, lymphocytes; M, monocytes; ND, not determined; P, polymorphonuclear cells; RF, rheumatoid factor; SF, synovial fluid; SPEP, serum protein electrophoresis.

Table 2. Summary of histomorphometric results.

	Vessels* (vWF)	Ki-67†	CD68†	CD3†	CD20†	CD38†
Case 1	52.8	17.0	233	80.5	0.0	0.0
Case 2	48.4	36.8	390	52.5	0.0	0.6
RA (n = 24)	119 (45.3)	200 (169)	542 (234)	574 (416)	245 (240)	585 (451)
OA (n = 26)	84.6 (33.2)	30.8 (26.6)	148.9 (81.6)	69.8 (60.6)	22.3 (38.7)	25.3 (51.8)
Normal (n = 15)	58.9 (8.1)	8.1 (6.2)	45.8 (29.6)	18.6 (20.6)	2.2 (4.3)	0.2 (0.6)

Values for RA, OA and Normal are summarized from previous publications (5–8).

*Mean positive staining vessels per mm² (±SD).

†Mean positive staining cells per mm² (±SD).

Figure 4. Amyloid phagocytosis in synovial tissue from patient 1. (A) and (B) Immunohistochemial detection of CD68+ macrophages (brown) engulfing (A) and interdigitating with (B) amorphous amyloid deposits (original magnification 400×). (C) and (D) Ultrastructural findings. (C) Phagocyte reacting to and surrounding a mass of amyloid (a); magnification approximately 12 000×. (D) Cell with completed amyloid phagocytosis; magnification approximately 7000×. Images were acquired with a Zeiss EM-10 transmission electron microscope, using thin sections from epoxy-embedded tissue. Tissue was obtained during the same biopsies as in Figure 1. Abbreviation: a, amyloid.