Immunoglobulin light and heavy chain amyloidosis AL/AH: renal pathology and differential diagnosis.

Among the varied and biochemically diverse group of protein folding disorders that are collectively known as the amyloidoses, AL-amyloidosis where deposits are derived from the immunoglobulin light chain fragments, is the most prevalent systemic form of the disease found in the western world. In contrast, AH-amyloidosis, resulting from the deposition of immunoglobulin heavy chains, is a rare disease with very few cases thus far reported. Both diseases primarily affect older individuals and are always associated with some form of plasma cell/B cell lymphoproliferative process. The overwhelming majority of monoclonal light chains are nephrotoxic leading to frequent renal involvement, although a wide variety of other organ systems may be involved. The most common clinical presentation is proteinuria and the disease is often diagnosed by renal biopsy. The kidneys are the most frequent site of amyloid fibril deposition in AL and light microscopic examination of Congo red stained sections is the prime means of detection. Electron microscopy may be helpful in the detection of small deposits and in the differentiation of amyloid from other types of renal fibrillar deposits. Current treatment of systemic amyloidoses depends upon the type of amyloid deposits; thus, accurate typing, using a panel of antibodies, is of paramount importance. While the differential diagnosis of amyloidoses continues to expand with increased awareness of hereditary types, currently, the main challenge is diagnosis of AL/AH with confidence. Future goals include the development of more precise and sensitive diagnostic tools. This chapter presents the pathology of AL/AH, current standards of diagnosis and the differential diagnosis. Whenever possible, the most recent references, considered as being particularly useful to clinicians and pathologists serving patients with renal amyloidosis, have been selected.