IgGκ light and heavy chain amyloidosis secondary to a B‐cell lymphoproliferative disorder, whole picture on a renal biopsy

Abstract

A 87-year-old man without any significant history was hospitalized in the nephrology department due to diffuse swelling. Blood and urine analysis revealed a full nephrotic syndrome (serum albumin 1.1 g/dL, urine protein-to-creatinine 0.6 g/mmol) without acute kidney injury (serum creatinine 91 μmol/L) associated with an IgGκmonoclonal protein (3.5 g/ dL, serum-free light chain [LC] ratio 21.8, 30% of LC on urine electrophoresis). Serumcalciumwas in normal range. Haemoglobin level was 11.6 g/ dL, platelet count was normal and white blood cells also except a moderate lymphocytosis (4.5 × 10/μL). CT scanner and radiological assessment were normal. Bone marrow puncture revealed 88% of mature B cells. Blood and bone marrow lymphocyte immunophenotyping (IgGκ+CD19 + CD20 + CD22 + CD23 − CD10 − CD5−) supported the diagnosis of extra-nodal marginal zone B-cell lymphoma (MZBCL). Renal biopsy showed together primary amyloidosis composed of heavy and LC (AHL) and renal infiltration by mature B-cell of theMZBCL (Figure 1). Transthoracic echocardiogram revealed ventricular wall thickening probably due to amyloidosis. Rituximab and bendamustine were started allowing an improvement of the general condition and a progressive regression of the nephrotic syndrome. This case combines several extremely unusual entities. First, AHL is a very uncommon type of amyloidosis compared with the classical LC presentation, to this date, less than 20 cases have been reported. Second, usually deposits consisted of IgGλ or IgAκ, and to our knowledge, our observation is the first reported case of IgGκ AHL. Third, AHL is mostly caused by plasma cell dyscrasia but rarely secondary to B-cell lymphoproliferative disorder, a MZBCL in our case. Unlike B-cell lymphoproliferative disorder, plasma cell dyscrasia is almost always associated with a M-protein, thus renal lesion related to monoclonal immunoglobulin deposit is most often related to plasma cell dyscrasia while kidney involvement in-B cell lymphoproliferative disorder is most often related to tumoral infiltration. Of the 19 cases of AHL published in the literature, 16were related to plasma cell proliferation, two caused by lymphoplasmocytic lymphoma (LPL) and one associated with chronic lymphoid leukaemia (CLL). One of the LPL associated with an IgGλ AHL was lung-restricted for both the lymphomatous infiltrate and the amyloidosis, the other was associated with IgMλ renal AHL, the presence of a renal infiltrate not being specified, lastly CLL was associated with renal infiltrate and IgGλ AHL. Finally, the simultaneous presence of both the cause (the lymphoma identified by the interstitial infiltrate) and consequence (the amorphous glomerular material) on the same picture is particularly illustrative and instructive.