• Renal dysfunction stems from several pathologic effects of myeloma that may occur alone or in combination. Most important are obstructive proteinaceous casts, which often form in the distal convoluted tubules and the collecting ducts. The casts consist mostly of Bence Jones proteins along with variable amounts of complete immunoglobulin, Tamm-Horsfall protein, and albumin. Light chain deposition in the glomeruli or the interstitium, either as amyloid or linear deposits, also may contribute to renal damage. Completing the assault is hypercalcemia, which may lead to dehydration and renal stones, and frequent bouts of bacterial pyelonephritis, which stem in part from the hypogammaglobulinemia.
MORPHOLOGYMultiplemyelomausuallymanifestswithmultifocal destructive skeletal lesions thatmostcommonlyinvolvethevertebralcolumn,ribs,skull,pelvis,femur,clavicle,andscapula. Thelesionsariseinthemedullarycavity,erodecancellousbone,andprogressivelydestroythebonecortex.Bonedestructionoftenleadstopathologic fractures, mostfrequentlyinthevertebralcolumnorfemur.Thebonelesionsusuallyappearaspunched-out defects 1to4cmindiameter(
Fig.12.19A ).Microscopicexaminationofthemarrowshowsincreasednumbersofplasmacells,whichusuallyconstitutegreaterthan30%ofthecellularity.Myelomacellsmayresemblenormalplasmacellsbutmoreoftenshowabnormalfeaturessuchasprominentnucleoliorabnormalcytoplasmicinclusionscontainingimmunoglobulin(
Fig.12.19B ).Withdiseaseprogression,myelomacellsmayspreadtothevisceraandothersofttissuesites,andinterminalstagesaleukemicpicturemayemerge.
Renalinvolvement(myeloma nephrosis) isassociatedwithproteinaceouscastsconsistingmostlyofBenceJonesproteinsthatobstructthedistalconvolutedtubulesandthecollectingducts.Multinucleategiantcellsderivedfrommacrophagesusuallysurroundthecasts.Veryoftentheepithelial cells adjacent to the casts become necrotic or atrophic owingtothetoxiceffectsofBenceJonesproteins.Othercommonpathologicprocessesinvolvingthekidneyincludemetastatic calcification,stemmingfromboneresorptionandhypercalcemia;light chain (AL) amyloidosis,involvingtherenalglomeruliandvesselwalls;andbacterial pyelonephritis, secondarytotheincreasedsusceptibilitytobacterialinfections.Rarely,infiltratesofneoplasticplasmacellsareseenintherenalinterstitium.
Clinical Features. Clinical findings stem mainly from (1) the effects of plasma cells on the skeleton; (2) the production of excessive immunoglobulins, which often have abnormal physicochemical properties; and (3) the suppression of humoral immunity.
Bone resorption often leads to pathologic fractures and chronic pain. The attendant hypercalcemia can give rise to neurologic manifestations, such as confusion, weakness, and lethargy, and contributes to renal dysfunction. Decreased production of normal immunoglobulins sets the stage for recurrent bacterial infections. Of great significance is renal insufficiency, which trails only infections as a cause of death. Renal failure occurs in up to 50% of patients and is associated strongly with the presence and level of Bence Jones proteinuria, highlighting the importance of free light chains in renal disease. Certain light chains also are prone to cause amyloidosis of the AL type (Chapter 5), which can exacerbate renal dysfunction and deposit in other tissues as well.
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