56050 Clin Pathol 1994;47:560-561 Mixed systemic in a patient receiving long term haemodialysis J Clin Pathol: first published as 10.1136/jcp.47.6.560 on 1 June 1994. Downloaded from J Fernandez-Alonso, C Rios-Camacho, A Valenzuela-Castaiio, W Hernanz-Mediano

Abstract A 64 year old woman had been receiving mild cardiomegaly with left myocardic hyper- haemodialysis for 11 years. She had a trophy; calcification of the mitral valve and history of chronic renal failure, caused aortic cusps; adhesive fibrous pericarditis; by probable chronic , and scleroatrophic kidneys with cystic dialysis arthropathy. She died of acute transformation; haemorrhagic colitis; pul- pulmonary oedema and haemorrhage. At monary oedema; and inactive necropsy, histological, immunohisto- in the medium lobe of the right lung. No chemical, and ultrastructural studies malignancies or were found. showed widespread viscernl deposits of Microscopic examination of tissues fixed in fP,-microglobulin (#,-M) and AA . 10% buffered formalin, disclosed abundant amorphous eosfnophilic material which (7 Clin Pathol 1994;47:560-561) stained with alkaline Congo red and showed apple-green dichroism under polarised light. The amyloid had infiltrated the vessel walls of Beta,-microglobulin (f,-M1) amyloidosis that visceral organs (gastrointestinal tract, liver, predominantly affects perineural and peri- spleen, , heart, urinary bladder, and articular structures, joints, and bone is common kidneys) and skin; muscular layers of the in patients receiving long term haemodialysis.' gastrointestinal tract and urinary bladder; and Systemic deposits of fl,-M amyloid have also myocardium, pericardium, and peritoneum. been reported. Initially, these findings were Amyloid deposits were particularly heavy in considered clinically unimportant.2 Subse- the auricular myocardium. quently, however, some investigators showed In the vessel walls amyloid was found in the that extra-articular deposits of fl,2-M amyloid muscular layer and in the subendothelial can cause serious clinical problems.'4 On the space where it appeared as nodules protruding other hand, non-fl,2-M type amyloidosis also into the vascular lumen. An intense foreign appears in patients receiving haemodialysis, body giant cell reaction was found around the http://jcp.bmj.com/ and this is generally attributed to concomitant scattered submesothelial nodules. disease.2 5 Immunohistochemical studies using the We report a patient who had been receiving avidin-biotin complex method were per- haemodialysis for 11 years with dialysis asso- formed on serial sections of the paraffin wax ciated amyloid arthropathy in whom a post embedded samples of stomach, ventricular mortem examination showed systemic deposits and auricular myocardium, pericardial and of AA and fl,2-M amyloid. peritoneal nodules. Monoclonal antibodies to on September 30, 2021 by guest. Protected copyright. amyloid A (AA), and polyclonal f,-M, pre- albumin, K and A light chains (Dako) were Case report applied. For positive controls, substitution of A 64 year old woman with no history of tuber- the antibodies with TRIS-buffered saline, and culosis, multiple myeloma, malignancy, alkaline Congo red staining of tissue samples , bronchiectasis, chronic inflam- were also used. matory bowel disease, or articular inflamma- Only anti-AA and fl,-M antibodies reacted tory disease, was diagnosed with end stage positively with the amyloid. In the stomach Department of renal failure for probable chronic pyelonephri- both antibodies stained the amyloid of the Pathology, Hospital tis in 1978. She required haemodialysis from muscularis propia with anti-AA showing a Universitario Virgen del Rocio, Sevilla, December 1979. In March 1988 she received more diffuse pattern of staining than anti-fl,- Spain right-sided carpal tunnel decompression for M; in subserosal nodules 32-M was mainly J Femandez-Alonso carpal tunnel syndrome. A biopsy specimen observed in the periphery; AA appeared in the Nephrology Service obtained at the operation showed amyloid core (figure). In the vessels of all samples anti- C Rios-Camacho deposits of 4,-M type. During the same year a fl,-M seemed to be generally confined to the Service parathyroidectomy was performed because of subendothelial amyloid, and anti-AA stained A Valenzuela-Castanio W Hernanz-Mediano secondary hyperparathyroidism. Two abdomi- the other layers of the wall. In the myo- Correspondence to: nal fat biopsy specimens taken in 1988 and cardium the amyloid reacted positively only J Femandez-Alonso, Dpto. 1989 showed no amyloid deposits. In 1990 with anti-AA, while in the auricular de Anatomia Patol6gica, Hospital Universitario she had recurring infections of the arteriove- myocardium both antibodies appeared inter- Virgen del Rocio, Avda. nous fistule for seven months. She died that mingled. Manuel Siurot s/n, 41013- Sevilla, Spain year because of acute pulmonary oedema and Electron mycroscopic studies carried out Accepted for publication intestinal bleeding. on formalin fixed auricular myocardium 3 November 1993 The principal macroscopic findings were: showed interstitial curvilinear microfibrils Mixed systemic amyloidosis in a patient receiving long term haemodialysis 561

Figure (a) Gastric waUl: around the fl,2-M amyloid deposits. Giant cell muscle layer and subserosal nodule are positively reaction to fl,2-M, a common finding in the stained with anti-AA synovium, has occasionally been described in complex). (avidin-biotin visceral deposits.69 J Clin Pathol: first published as 10.1136/jcp.47.6.560 on 1 June 1994. Downloaded from (b) Gastic wall (serial as chronic pyelo- section): positive staining Several factors, such with anti-fl2-M in the nephritis, bronchiectasis, repetitive infections periphery ofthe subserosal of the arteriovenous fistule, and haemodialysis nodule, and in the could explain the presence of AA amyloid in muscular layer (avidin- ~~~- this case, though it is difficult to ascribe its biotin complex). development to one of them. It seems unlikely that bronchiectasis could account for AA amyloidosis because of the absence of previ- ous history and its inactive character. In a review of 45 consecutive necropsies with bronchiectasis we found AA amyloidosis in -tt. .v"Z.&~ four cases, all of them with clinical and patho- logical evidence ofactive disease (unpublished data). As regards chronic pyelonephritis, AA >. V amyloidosis has scarcely been reported in the absence of stag horn calculi or spinal cord g ;e dt iv*n er44 injury.10 No conditions were present in this case. The patient had had repeated infections of ,,~~~~~~~~~~~~~~~~~~~~~~~~~~~~~tczl. the arteriovenous fistule for seven months before her death, but it is difficult to consider those infectious episodes as the cause of AA amyloidosis in such a short time. A constant synthesis of AA protein induced by the leucocyte pyrogen produced by haemodialysis might be another possible mechanism for the development of AA amyloidosis in this patient.

We thank Mr M Hermida for kindly performing immunohisto- chemical techniques and Mr F Fuentes for his photographic assistance. samyloid osisad to ase d a ilect http://jcp.bmj.com/

1 Kleinman KS, Coburn JW. Amyloid syndromes associated with hemodialysis. Int 1989;35:567-75. 2 Noel LH, Zingraff J, Bardin T, Atienza C, Kuntz D, Drueke T. Tissue distribution of dialysis amyloidosis. Clin Nephrol 1987;27:175-8. 3 Arakawa M, Gejyo F, Oohara K, Homma N. Systemic deposition of Beta-2 microglobulin amyloid. In: Gejyo tion for the osteoarticular system,' but in F, Brancaccio D, Bardin T, eds. Dialysis amyloidosis. Milan: Wichtig Editore, 1989:111-8. on September 30, 2021 by guest. Protected copyright. 4 Maher ER, Hamilton Dutoit S, Baillod RA, Sweny P, cause serious clinical complications.34 In our Moorhead JF. Gastrointestinal complications of dialysis patient clinical manifestations of visceral related amyloidosis. Br MedJ 1988;297:265-6. 5 Morita T, Kamimura A, Hirasawa Y. Amyloid deposits in until the amyloidosis were absent, at least patients on long-term hemodialysis are not always beta-2- episode of heart failure that led her to death. microglobulin related. Nephron 1988;50: 171-2. 6 Takahashi S, Morita T, Koda Y, Murayama H, Hirasawa It is worth out several in pointing findings Y. Gastrointestinal involvement of dialysis-related amy- this case. Firstly, the results of the histologi- loidosis. Clin Nephrol 1988;30: 168-71. 7 Linke RP, Kunet U, Lobeck H, Hampl H, Eulitz M. and ultrastruc- cal, immunohistochemical, Chemical analysis of beta,-microglobulin derived amy- tural studies showed the presence of systemic loid in patients on long-term hemodialysis. In: Isobe T, Arali S, Uchino F, Kito S, Tsubura E, eds. Amyloid an deposits of both (X28-M and AA) amyloidosis. New York: Plenum, 1988:611-6. which happens only rarely.7 Secondly, both 8 Campistol JM, Cases A, Torras A, Soler M, Muiioz- Gomez J, Montoliu J, et al. Visceral involvement of amyloids showed a distinctive tissular distribu- dialysis amyloidosis. Am Nephrol 1987;7:390-3. tion, with /12-M being preferentially located in 9 Mazanec K, McClure J, Bartley CJ, Newbould MJ, Ackrill P. Systemic amyloidosis of P,-microglobulin type. Y Clin the subendothelium of the vessels, as noted Pathol 1992;45:832-3. before,8 and surrounding the AA amyloid 10 Caravaca F, Herrera JM, Pizarro JL, Arrobas M, Robles R, Saez-Santamaria J. Systemic amyloidosis (type AA) in deposits in the mesothelial nodules. Finally, end-stage renal failure patients due to chronic an intense giant cell reaction was present pyelonephritis. Nephron 1991;59:510-1.