Enlarged lymph node with partial or total replacement of normal architecture by deposits of acellular amorphous material with the characteristic features of amyloid or of other proteinaceous substances.

Amyloid lymphadenopathy.

The prevalence of lymph node involvement in primary or secondary amyloidosis is estimated at 17% to 37% of cases (1,2); however, very rarely is amyloid lymphadenopathy the major or only organ presentation (2,3,4,5). Among 40,000 lymph node biopsies recorded in the Lymph Node Registry in Kiel, amyloid lymphadenopathy was the presenting feature in only 10 (6).

Amyloid appears to be deposited in lymph nodes independently of its distribution in other tissues (7). A case of large mesenteric lymph node masses with deposits of amyloid A λ-protein in the context of systemic amyloidosis was described (8). Conversely, lymph nodes draining organs heavily affected by amyloidosis may be entirely unaffected (9). More often than amyloid, other proteinaceous substances, representing different by-products of abnormal immune reactions, may be deposited in the lymph nodes during the course of various diseases, including long-standing rheumatoid arthritis (10), immunoblastic lymphadenopathy (11), follicular lymphoma (12,13), plasmacytoid lymphoma (14), Hodgkin disease (15), and even Kikuchi disease in acquired immune deficiency disease (AIDS) patients (16). Such substances may be related to amyloid, but they differ from it histologically and ultrastructurally (5). The morphologic alterations of the involved lymph nodes are similar, regardless of the nature of the deposited substance, which cannot be ascertained under the light microscope without special stainings. Almost all cases reported had immunoglobulin (Ig) abnormalities, generally hypergammaglobulinemia, with elevated levels of IgM or IgA (5,8). Amyloid appears fibrillar on electron microscopy and exhibits a β-pleated sheet structure on roentgenographic diffraction, which determines its characteristic staining and optical features (17,18,19). Thus, amyloid binds Congo red and shows green birefringence under polarized light when stained with Congo red (20). Among the proteins that form β-pleated sheets, those derived from Ig light chains are designated AL. The two isotypes of AL, λ and κ, are designated Aλ and Aκ, respectively (19). Within the AL groups, light chains of the λ class are more often associated with amyloid than are light chains of the κ class (21). A second group is characterized by amyloid fibril protein AA and is associated with reactive or secondary amyloidosis.

In 90% of cases of primary amyloidosis, a monoclonal M protein is present in serum, urine, or cerebrospinal fluid (22). In 20% of patients with AL amyloidosis, an association with multiple myeloma is noted (22). The identification of AL protein in the amyloid of a lymph node indicates the presence of plasma cell dyscrasia with amyloidosis, idiopathic amyloidosis, or a lymphoproliferative neoplasm. For such patients, further investigation would include bone marrow examination, investigation of light chains in the urine, and serum protein studies (23). The identification of AA protein in a proteinaceous lymphadenopathy suggests reactive systemic amyloidosis, which may be associated with various conditions, including rheumatoid arthritis (10), ankylosing spondylitis, Crohn disease, tuberculosis, osteomyelitis, leprosy, and neoplasia (23) more often lymphoma (12,13,14,15). In 22% (10 of 44) of uremic patients with lymphadenopathy, lymph node amyloid deposits,
usually type AA, were found in vascular, follicular, or diffuse patterns (24). AL amyloid can cause abrupt hemorrhagic lymph node swelling that is followed by incomplete waning (25).