As clinical management depends on the type of amyloid, characterization of amyloid deposits is required in every specimen. This can be achieved by immunohistochemistry [39], and with higher specificity and sensitivity, with mass spectrometry-based proteomics [30, 40]. It is also important to investigate the lymphoid component for evidence of an underlying B-cell or plasma cells proliferative disorder. Flow cytometry-based immunophenotyping is often challenging,especially in lymph nodes extensively replaced by amyloid deposits. Therefore, immunohistochemistry to detect neoplastic B-cells and/or plasma cells is recommended. Immunohistochemistry tests should include standard workup for low-grade B-cell lymphomas including staining for cytoplasmic immunoglobulin kappa and lambda light chains, and staining for additional markers such as CD56, Cyclin D1, and CD117 often aberrantly expressed by systemic plasma cell disorders. Using such a comprehensive approach, the presence of a clonal B-cell or plasma cell population can be demonstrated in most cases of AL amyloidosis involving the lymph nodes (Fig. 32.3). However, in some cases the neoplastic infiltrate can be very subtle and can only be detected by careful examination or only by molecular techniques. Significantly higher proportion of AL amyloidosis of lymph nodes are associated with IgM paraproteinemia (2–4 % of systemic AL amyloidosis compared to 20–30 % in lymph node amyloidosis) [30, 31]. Consistent with this, the underlying B-cell neoplasm is more frequently diagnosed as a lymphoplasmacytic lymphoma rather than a pure plasma cell neoplasm.

By mass spectrometry-based proteomics, the exact constitution of amyloid deposits can be identified. Mass spectrometry not only identifies the type of amyloid but also provides detailed information regarding the light chain variable usage and the presence or absence of an immunoglobulin heavy chain component [30]. Interestingly, most cases of AL amyloidosis involving the lymph nodes appear to be composed of both heavy and light chain components. In contrast, amyloid deposits in other organs frequently involved by systemic AL amyloidosis such as the heart or the kidneys are primarily composed of light chains without a heavy chain component. Although the reasons for this difference remain unclear, it is likely that the heavy chain component which has a larger molecular size can be deposited locally in the extracellular environment where it is produced, whereas only the smaller size light chain component can be transported to distant sites.