The contributions of electron microscopy to the understanding and diagnosis of plasma cell dyscrasia-related renal lesions

Electron microscopy has been crucial in the definition of many renal diseases. Ultrastructural evaluation has been instrumental in the characterization of many of the morphological manifestations of plasma cell dyscrasia-related renal lesions. Although it is recognized that there is controversy in regards to what the term multiple myeloma specifically refers, for the purposes of this article, myeloma and plasma cell dyscrasia are used interchangeably without consideration to perhaps significant conceptual differences that may exist between the two. Although distal nephron obstructive nephropathy ("myeloma kidney") was rather accurately defined solely on the basis of light microscopic findings and the association of AL-amyloidosis with underlying myeloma was confirmed using histochemical stains, the more subtle and intricate expressions of plasma cell dyscrasia-associated pathology required the electron microscope for proper characterization. The fibrillary nature of amyloid was discerned ultrastructurally, and detecting its characteristic ultrastructural features remains paramount to make a definitive diagnosis of amyloidosis when evaluating difficult cases. Pristine light- and heavy-chain deposits were objectively confirmed as immunomorphological correlates were depicted by immunofluorescence and at the ultrastructural level, substantiating the findings. Tubular interstitial alterations in these disorders other than cast nephropathy were firmly documented when careful ultrastructural studies were conducted experimentally and using clinical material. Likewise, electron microscopy has also played an important role in assessing vascular pathology in these conditions, especially when changes are focal, segmental, subtle, or such that they are easily confused with other pathological entities by light microscopy. Had it not been for the electron microscope, a clear definition of the immunomorphological scope of plasma cell dyscrasia-associated lesions, as understood currently, would not have been possible. Immunoelectron microscopy has provided a welcome added dimension, allowing a thorough characterization by expanding merely morphological data and providing exquisite immunomorphological correlations. This review highlights the role that electron microscopy has played and continues playing in the characterization of plasma cell dyscrasias-related renal lesions.