Rare presentation of kappa light chain proximal tubulopathy with fibrillar aggregates

Introduction/Objective Patients with dysproteinemias may show a spectrum of renal alterations due to organized deposits of excess immunoglobulins, including primary amyloidosis, myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, and light chain proximal tubulopathy (LCPT). Among the least common is LCPT, which shows ultrastructural cytoplasmic light chain inclusions with crystalline morphology or rarely fibrillar aggregates. We present the case of a patient with LCPT with fibrillar aggregates that is the only such case registered in our large academic surgical pathology electronic database. Our aim is to increase understanding and recognition of this rare variant. Methods/Case Report A 73-year-old man presented with 540 mg/day proteinuria, serum creatinine 5.73 mg/dL, platelets 178,000/cc, and 20% plasma cells in his bone marrow biopsy specimen. Kidney needle biopsy cores examined by light, fluorescent and transmission electron microscopy (EM) showed kappa light chain cast nephropathy and kappa LCPT with fibrillary aggregates, the latter requiring unmasking of kappa epitopes using pronase-treated paraffin sections. Congo red stain was negative. By EM, proximal tubules contained intracellular bundles of tightly aggregated fibrils with mean fibril diameter of 7.7 +/- 1.6 nm. Individual bundles were variably shaped as round, oval, spicular or irregular blobs. Fibrils were not seen in glomeruli. Results (if a Case Study enter NA) NA Conclusion This rare presentation of LCPT with fibrillar aggregates reinforces the utility of renal biopsy diagnosis that includes careful ultrastructural examination of renal tubules. In the absence of EM, the unique fibrillar organization of these cytoplasmic light chain aggregates would otherwise go unrecognized.

MO929KIDNEY TRANSPLANTATION IN MONOCLONAL IMMUNOGLOBULIN DEPOSITION DISEASE: A REPORT OF 6 CASES

Background and Aims Monoclonal immunoglobulin deposition disease (MIDD) is a systemic rare condition that usually leads to end stage renal disease. Treatment of patients with a bortezomib-based regimen followed by autologous stem cell transplantation (ASCT) has been increasingly used, with improvements in the response rates and the renal graft outcomes in kidney transplant recipients Method Retrospective study of 6 patients diagnosed of MIDD with complete response but not renal response after hematologic treatment that underwent kidney transplant in our institution between 2010 and 2019. Results A total of 6 patients (5 women) were analyzed, with mean age at diagnosis of 47 years (range 40-53). At presentation their mean eGFR was 18 mL/minute (range 9-25) and mean proteinuria of 5.5 g (range 0.290-12.5). The deposit was kappa type except in 1 case (heavy and light lambda type chains). In all of them there was an absence of monoclonal component in blood and urine but positive immunofixation in 5 cases (2 only in urine). 3 started chronic hemodialysis during admission and the others at 3, 5 and 44 months after diagnosis. As hematological treatment, all received bortezomib followed by ASCT, being under complete hematological response at the time of kidney transplant. It was performed at 28 months on average from ASCT (range 11-42), with mean kappa/lambda ratio of 2.6 (range 1.33-3.75). 3 patients received induction with thymoglobulin and 3 with basiliximab, followed by triple therapy with tacrolimus + prednisone + mTOR inhibitor (4 patients) or mycophenolate (2 patients). During a median follow-up of 20,5 months from kidney transplant and 54 months from ASCT, 1 patient experienced hematologic relapse and 2 had hematologic progression (one of them with MIDD relapse in the allograft) requiring treatment. The patient with organ relapse received Daratumumab monotherapy achieving complete hematologic response but graft failure. The other 5 patients had functional graft with median serum creatinine 1.68 mg/dl. Conclusion In patients with MIDD and sustained complete hematologic response, a kidney transplant can be considered. The optimal approach to treatment of hematologic relapse or recurrence of MIDD after kidney transplant remains to be determined

Randall-Type Monoclonal Immunoglobulin Deposition Disease: New Insights into the Pathogenesis, Diagnosis and Management

Randall-type monoclonal immunoglobulin deposition disease (MIDD) is a rare disease that belongs to the spectrum of monoclonal gammopathy of renal significance (MGRS). Renal involvement is prominent in MIDD, but extra-renal manifestations can be present and may affect global prognosis. Recent data highlighted the central role of molecular characteristics of nephrotoxic monoclonal immunoglobulins in the pathophysiology of MIDD, and the importance of serum free light chain monitoring in the diagnosis and follow-up disease. Clone-targeted therapy is required to improve the overall and renal survival, and the achievement of a rapid and deep hematological response is the goal of therapy. This review will focus on the recent progress in the pathogenesis and management of this rare disease.

From light chain deposition to multiple myeloma – Case report and literature review

Monoclonal gammopathies consist of a broad spectrum of diseases, ranging from asymptomatic monoclonal gammopathy of undetermined significance to multiple myeloma (MM). Multiple myeloma is a malignant plasma cell disorder and accounts for 10% of all hematological malignancies and 1% of all malignancies. Differential diagnosis may be challenging, considering the variety of clinical entities with similar behavior. About 15­‑20% of MM only secretes monoclonal light chains, called light chain MM, which is associated with poorer outcome. Two intermediate concepts were recently introduced, monoclonal gammopathy of renal significance (MGRS) and a wider concept of monoclonal gammopathy of clinical significance (MGCS). The former behaves as a clonal proliferative disorder with associated nephrotoxicity, but does not have the hematological criteria for MM, while MGCS expands this concept to other organs. A subtype of MGCS is monoclonal immunoglobulin deposition disease, a multisystemic disorder characterized by light or heavy chain deposition of monoclonal immunoglobulin in various organs and encompasses three clinical entities: Light­‑Chain, Light­‑ and Heavy­‑Chain, and Heavy­‑Chain Deposition Disease (LCDD, LHCDD and HCDD, respectively). We describe an unusual case of LCDD in which MM was subsequently considered although the proposed criteria are not met. We demonstrate the variability of clinical­‑pathological presentation of LCDD, requiring a rapid decision­‑making, particularly in terms of kidney and survival outcomes.