Intra- and extracellular crystal deposition in a case of amyloid light chain amyloidosis.

Abstract

A 78-year-old patient presented with a two-month history of increasing shortness of breath and bilateral leg oedema. Clinical examination found atrial fibrillation and fluid overload. A chest X-ray showed pulmonary oedema and bilateral pleural effusions. An echocardiogram demonstrated thickened cardiac walls and a restrictive cardiomyopathy, suggestive of cardiac amyloidosis. Further investigation showed an abnormal serum free light chain ratio of 0·055 (kappa 18·5 mg/l, lambda 337 mg/l), but with no detectable paraprotein. Cardiac magnetic resonance imaging showed concentric left ventricular hypertrophy with altered gadolinium kinetics with interatrial septal thickening and bi-atrial dilatation. Biopsy of the affected organ would not have been easy. As amyloid light chain (AL) amyloidosis can be associated with myeloma or other B-cell neoplasms, the patient underwent a bone marrow aspirate and trephine biopsy. Whilst non-diagnostic, the aspirate showed an increase in plasma cells at 9% with a further population of monomorphic forms. Trephine biopsy specimen histology was consistent with the aspirate, with plasma cells accounting for 5–10% of cells. These were lambda light chain-restricted and also expressed cyclin D1. Amyloid deposition was seen within blood vessels within the interstitium. Strikingly, intracytoplasmic crystalline structures were identified within many of the abnormal plasma cells. These were rectangular crystals with clear pink staining on haematoxylin and eosin (H&E) staining (top, x100 objective), but interestingly they did not stain with Congo red. Many were within the plasma cells on a CD79a stain (bottom, x100 objective); others were free within the interstitium. Some were fragmented. While intracytoplasmic immunoglobulin deposition is not infrequent and can commonly be a feature of a plasma cell neoplasm, it generally takes a globular form, such as Russell bodies or Mott cells; crystalline forms within plasma cells occur only rarely. Crystal formation within plasma cells has been reported in some reactive conditions and, occasionally, in myeloma.