Immunohistochemical classification of amyloid in surgical pathology revisited.

We aimed to reassess the suitability of immunohistochemical classification of amyloid in surgical pathology. One hundred sixty-nine biopsies from 121 patients diagnosed with amyloid during the period from 1994 to 2004 were included. Amyloid was classified immunohistochemically, using antibodies directed against amyloid P-component, AA amyloid, apolipoprotein AI, fibrinogen, keratoepithelin, lactoferrin, lysozyme, beta2-microglobulin (beta2M), immunoglobulin-derived lambda-light and kappa-light chains, and transthyretin. Amyloid was most commonly present in biopsies from the hepatogastrointestinal tract. The deposits were classified immunohistochemically in 156 (92%) biopsies. In 13 biopsies of 12 patients, amyloid remained unclassified. AL amyloidosis was diagnosed in 76 (45%) biopsies and was further categorized into AL amyloid of kappa-light chain origin [32 (42%) biopsies] or lambda-light chain origin [20 (26%)]. In 24 (32%) biopsies, the amyloid deposits did not show unequivocal staining for lambda-light or kappa-light chain. However, these cases were categorized as "probably AL amyloid, not otherwise specified", because no other antibody showed unequivocal staining of the amyloid deposits. AA amyloidosis was diagnosed in 32, ATTR amyloidosis in 21, and AApoAI amyloidosis in 3 biopsies. Other types of amyloid included AKer and ALac amyloids each in 1, and ALys and ACal amyloids each in 2 biopsies. Abeta2M amyloid was not diagnosed in any case. Immunohistochemical classification of amyloid still poses problems. Although classification of AA, AApoAI, ALys, ALac, and ATTR amyloids is relatively straightforward, classification of AL amyloid and rare hereditary amyloidoses is a serious obstacle and sometimes even impossible when conclusive clinical information or additional protein biochemical or molecular biologic studies are not available.